Muhammad Husnain

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Scholarly Contributions

Chapters

• Husnain, M., Zhang, Y., & Rosenblatt, J. (2021). The Role of Breg Cells in Modulating the Antitumor Immune Response. In Cancer Immunotherapy Principles and Practice, Second Edition. New York: NY: Demos Medical Publishing.

Journals/Publications

• Barker, K., Barker, K., Marco, T., Marco, T., Husnain, M., Husnain, M., Katsanis, E., & Katsanis, E. (2025). Addition of Phosphorous and IL6 to m-EASIX Score Improves Detection of ICANS and CRS, as Well as CRS Progression. Cancers, 17(Issue 6). doi:10.3390/cancers17060918
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  Introduction: Cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) are both serious complications of CAR-T therapy associated with endothelial dysfunction, prompting prior use of a modified version of the endothelial activation and stress index (m-EASIX) to predict the occurrence of severe ICANS and CRS. Previous studies have linked both hypophosphatemia and elevated IL6 levels to CRS and ICANS. Our study aimed to enhance the early prediction of both syndromes by integrating phosphorous and IL-6 both together and separately into the m-EASIX score. Methods: Forty-two patients with non-Hodgkin’s lymphoma presenting for CAR-T treatment were used to generate three variations in the m-EASIX score, assessing performance for the clinically actionable time points of day +0 through day +3. Results: The addition of phosphorous through the P-m-EASIX improved the predictive capabilities for the occurrence of ICANS, most notably on day +1 (AUC 89.6%; p = 0.0090, OR of 2.23; p = 0.0096) compared to the m-EASIX (AUC 80.8%; p = 0.0047, OR 1.72; p = 0.0046). The P-m-EASIX also showed enhanced predictive capabilities for the occurrence of CRS, with peak discriminatory function on day +3 (AUC 92.0%; p =
• Channar, A., Naqvi, S. A., Khan, M. A., Bibi, A., Saxena, A., Tripathi, N., Iftikhar, A., Raina, A., Khakwani, K. Z., Riaz, I. B., & Husnain, M. (2025). Efficacy and Safety of Quadruplet Therapy in Newly Diagnosed Transplant-Eligible Multiple Myeloma: A Systematic Review and Meta-Analysis. Cancer reports (Hoboken, N.J.), 8(4), e70171.
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  The treatment landscape for multiple myeloma continues to evolve. Recently, the addition of anti-CD38 monoclonal antibodies (mAbs) to the triplet regimen, comprising a proteasome inhibitor, an immunomodulatory agent, and a steroid, for transplant-eligible newly diagnosed multiple myeloma (TENDMM) has shown promising results.
• Filioglou, D., Santa-Cruz, N., Leite, G. S., Davini, D. W., Cracchiolo, M. J., Baker, F. L., Husnain, M., Simpson, R. J., Voudouris, V., & Katsanis, E. (2025). A Triple Oral Combination of Bendamustine, Acalabrutinib, and Venetoclax Demonstrates Efficacy Against Mantle Cell Lymphoma In Vitro and In Vivo. Cancers, 17(11).
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  : Bendamustine (BEN) combined with rituximab (RTX) remains a standard first-line therapy for transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL). Meanwhile, novel targeted therapies such as Bruton tyrosine kinase inhibitors (BTKis) are increasingly used in the treatment of relapsed/refractory (R/R) MCL. We recently reported that a novel oral formulation of BEN exhibits comparable efficacy to the intravenous counterpart. In this study, we investigated the efficacy of oral BEN administered alone or in combination with the oral BCL-2 inhibitor Venetoclax (VEN) and/or the oral BTKi Acalabrutinib (ACAL), against two human MCL cell lines (Jeko-1 and Z-138) representative of the R/R disease subtype. : We performed in vitro analyses using MTS viability and Annexin V/PI apoptosis assays. For the in vivo studies, all treatments were administered via oral gavage in xenograft mouse models. Therapeutic efficacy was evaluated by monitoring tumor growth and survival. : BEN induced significant cytotoxicity in both cell lines at low, clinically relevant concentrations. In contrast, VEN demonstrated limited efficacy as monotherapy, with Z-138 showing sensitivity only at high doses. However, combining BEN with VEN with or without ACAL, enhanced apoptosis and cytotoxicity, with more pronounced effects in Z-138. In vivo, oral BEN significantly reduced tumor growth and prolonged survival in both xenograft models. In the Z-138 model, the addition of VEN ± ACAL further improved survival outcomes. : Our findings support the efficacy of oral BEN as both a monotherapy and as part of an all-oral treatment regimen for MCL. These results warrant further investigation into the clinical potential of oral BEN, particularly in combination with targeted agents.
• Filioglou, D., Santa-Cruz, N., Leite, G. S., Davini, D. W., Cracchiolo, M. J., Baker, F. L., Husnain, M., Simpson, R. J., Voudouris, V., & Katsanis, E. (2025). A Triple Oral Combination of Bendamustine, Acalabrutinib, and Venetoclax Demonstrates Efficacy Against Mantle Cell Lymphoma In Vitro and In Vivo. Cancers, 17(Issue 11). doi:10.3390/cancers17111889
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  Background/Objectives: Bendamustine (BEN) combined with rituximab (RTX) remains a standard first-line therapy for transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL). Meanwhile, novel targeted therapies such as Bruton tyrosine kinase inhibitors (BTKis) are increasingly used in the treatment of relapsed/refractory (R/R) MCL. We recently reported that a novel oral formulation of BEN exhibits comparable efficacy to the intravenous counterpart. In this study, we investigated the efficacy of oral BEN administered alone or in combination with the oral BCL-2 inhibitor Venetoclax (VEN) and/or the oral BTKi Acalabrutinib (ACAL), against two human MCL cell lines (Jeko-1 and Z-138) representative of the R/R disease subtype. Methods: We performed in vitro analyses using MTS viability and Annexin V/PI apoptosis assays. For the in vivo studies, all treatments were administered via oral gavage in xenograft mouse models. Therapeutic efficacy was evaluated by monitoring tumor growth and survival. Results: BEN induced significant cytotoxicity in both cell lines at low, clinically relevant concentrations. In contrast, VEN demonstrated limited efficacy as monotherapy, with Z-138 showing sensitivity only at high doses. However, combining BEN with VEN with or without ACAL, enhanced apoptosis and cytotoxicity, with more pronounced effects in Z-138. In vivo, oral BEN significantly reduced tumor growth and prolonged survival in both xenograft models. In the Z-138 model, the addition of VEN ± ACAL further improved survival outcomes. Conclusions: Our findings support the efficacy of oral BEN as both a monotherapy and as part of an all-oral treatment regimen for MCL. These results warrant further investigation into the clinical potential of oral BEN, particularly in combination with targeted agents.
• Hameed, M., Iftikhar, A., Abbas, S., Faiz, Z., Ayoobkhan, F. S., Siddiqui, S., Elahi, M. A., Khadim, S., Anwer, F., & Husnain, M. (2025). Plasmablastic Lymphoma-A Crosstalk Between Myeloma and Lymphoma. Clinical lymphoma, myeloma & leukemia, 25(10), e799-e808.
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  Plasmablastic lymphoma (PBL) is a rare type of large B-cell lymphoma that primarily affects immunocompromised individuals, often associated with viral infections such as Human Immunodeficiency Virus (HIV) and Epstein-Barr Virus (EBV). The diagnosis of PBL is often difficult to ascertain due to its overlapping clinical and pathological features with multiple myeloma and large B cell lymphoma. The primary organs of involvement are typically the gastrointestinal system, lymph nodes, oral mucosa, with some involvement of the skin. This review explores the critical aspects of plasmablastic lymphoma, including its clinical features, diagnosis, treatment options, and the latest advancements for this rare disease. Understanding plasmablastic lymphoma is necessary for healthcare professionals and patients alike to improve the outcomes and quality of life for those affected by this aggressive form of lymphoma.
• Hossain, N. M., Ahn, K. W., Patel, J., Lian, Q., Abid, B., Al Nughmush, A., Bacher, U., Bi, X., Hashmi, S. K., Hilal, T., Husnain, M., Khimani, F., Maziarz, R. T., Modi, D., Ram, R., Rizzieri, D., Sica, R. A., Steinberg, A., Vij, R., , Shadman, M., et al. (2025). Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS. British Journal of Haematology, 207(Issue 3). doi:10.1111/bjh.70020
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  CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a pivotal part of the treatment algorithm for large B-cell lymphoma (LBCL) in the second- and third-line settings based on numerous clinical trials. However, these studies included very few patients with a diagnosis of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS) and it is unclear if outcomes are similar to those observed with more common LBCL histologies. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we identified 111 HGBCL-NOS patients who received CAR-T therapy. The cytokine release syndrome (CRS) rate was 74% (7.7% grade 3+), median onset was 4 days (1–17) and immune effector cell-associated neurotoxicity syndrome rate was 45.2% (22.6% grade 3+), median onset was 7 days (1–17). At 2 years post-CAR-T infusion, the probability of overall survival and progression-free survival were 41.6% and 28.7% respectively. The 2-year non-relapse mortality and relapse/progression were 3.1% (95% confidence interval [CI]: 0.6–7.6) and 68.1% (95% CI: 57.9–77.6) respectively. Our analysis illustrates that patients with HGBCL-NOS represent a particularly difficult group to treat, even with CAR-T therapy. We observed that one third of patients achieved a durable response; however, the overall results were less favourable, with lower overall response rate, overall survival and progression-free survival as compared to published reports on LBCL.
• Hossain, N. M., Ahn, K. W., Patel, J., Lian, Q., Bilal Abid, M., Al Nughmush, A., Bacher, U., Bi, X., Hashmi, S. K., Hilal, T., Husnain, M., Khimani, F., Maziarz, R. T., Modi, D., Ram, R., Rizzieri, D., Sica, R. A., Steinberg, A., Vij, R., , Shadman, M., et al. (2025). Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS. British journal of haematology, 207(3), 1011-1018.
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  CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a pivotal part of the treatment algorithm for large B-cell lymphoma (LBCL) in the second- and third-line settings based on numerous clinical trials. However, these studies included very few patients with a diagnosis of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS) and it is unclear if outcomes are similar to those observed with more common LBCL histologies. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we identified 111 HGBCL-NOS patients who received CAR-T therapy. The cytokine release syndrome (CRS) rate was 74% (7.7% grade 3+), median onset was 4 days (1-17) and immune effector cell-associated neurotoxicity syndrome rate was 45.2% (22.6% grade 3+), median onset was 7 days (1-17). At 2 years post-CAR-T infusion, the probability of overall survival and progression-free survival were 41.6% and 28.7% respectively. The 2-year non-relapse mortality and relapse/progression were 3.1% (95% confidence interval [CI]: 0.6-7.6) and 68.1% (95% CI: 57.9-77.6) respectively. Our analysis illustrates that patients with HGBCL-NOS represent a particularly difficult group to treat, even with CAR-T therapy. We observed that one third of patients achieved a durable response; however, the overall results were less favourable, with lower overall response rate, overall survival and progression-free survival as compared to published reports on LBCL.
• Husnain, M., Vina, E., Ali, M. S., Suhaib, M., Rehman, M. E., Gondal, F., Iftikhar, A., Ahmad, R. U., & Razzaq, F. (2025).

  Chimeric Antigen Receptor T-cell therapy in systemic lupus erythematosus and other autoimmune diseases: a literature review

  . J Rheum Dis. doi:10.4078/jrd.2025.0075
• Ritter, J., Marco, T., Angeletti, M., Barnett, D., Horak, H., & Husnain, M. (2025). Autologous hematopoietic stem cell transplantation in severe, refractory stiff person syndrome: a case series. Bone Marrow Transplantation, 60(Issue). doi:10.1038/s41409-025-02686-z
• Ritter, J., Marco, T., Angeletti, M., Barnett, D., Horak, H., & Husnain, M. (2025). Autologous hematopoietic stem cell transplantation in severe, refractory stiff person syndrome: a case series. Bone marrow transplantation, 60(10), 1387-1389.
• Asghar, K., Zafar, M., Holland, E., Abduljabbar, A. B., Albagoush, S. A., Asghar, N., Sood, A., Dufani, J. M., Thirumalaredy, J., DeVrieze, B., Tauseef, A., & Husnain, M. (2024). A systematic review and meta-analysis on utilizing anti-CD19 chimeric antigen receptor T-cell therapy as a second-line treatment for relapsed and refractory diffuse large B-cell lymphoma. Frontiers in oncology, 14, 1407001.
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  Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting.
• Cracchiolo, M. J., Davis, L., Matiatos, A. P., Davini, D. W., Husnain, M., Simpson, R. J., Voudouris, V., & Katsanis, E. (2024). Comparable Efficacy of Oral Bendamustine versus Intravenous Administration in Treating Hematologic Malignancies. Research square.
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  The purpose of this study was to analyze potential differences in antitumor efficacy and pharmacokinetics between intravenous (IV) bendamustine (BEN) and a novel orally administered bendamustine agent (PO) that is utilizing the beneficial properties of superstaturated solid dispersions formulated in nanoparticles.
• Cracchiolo, M. J., Davis, L., Matiatos, A. P., Davini, D. W., Husnain, M., Simpson, R. J., Voudouris, V., & Katsanis, E. (2024). Comparable efficacy of oral bendamustine versus intravenous administration in treating hematologic malignancies. Cancer chemotherapy and pharmacology, 94(3), 361-372.
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  The purpose of this study was to analyze potential differences in antitumor efficacy and pharmacokinetics between intravenous (IV) bendamustine and a novel orally administered (PO) bendamustine agent that is utilizing the beneficial properties of superstaturated solid dispersions formulated in nanoparticles.
• Ayaz, A., Naqvi, S. A., Farooq, S., Sickora, K., Wazir, M. H., Hajj, M. E., Lateef, T. S., Masood, A., Amin, S., Rajkumar, C., Patel, M., Husnain, M., Riaz, I. B., & Mir, S. A. (2023). Cardiovascular (CV) Mortality Among Adults Diagnosed with Leukemias: A Retrospective Cohort Study. Blood, 142(Supplement 1), 2426-2426. doi:10.1182/blood-2023-190472
• Barker, K., Koza, S., Katsanis, E., & Husnain, M. (2023). Hypophosphatemia and pre-infusion thrombocytopenia as biomarkers for CRS and ICANS after CAR T therapy. Bone marrow transplantation, 58(11), 1267-1269.
• Filioglou, D., Husnain, M., Khurana, S., Simpson, R. J., & Katsanis, E. (2023). Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?. Frontiers in Immunology, 14(Issue). doi:10.3389/fimmu.2023.1329850
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  The most common lymphodepletion regimen used prior to infusion of chimeric antigen receptor-T cells (CAR-T) is cyclophosphamide (CY) in combination with fludarabine (Flu) (CY-FLU). While cyclophosphamide (CY) possesses lymphotoxic effects, it concurrently preserves regulatory T cell activity, potentially affecting the efficacy of CAR-T cells. Moreover, the use of fludarabine (FLU) has been linked to neurotoxicity, which could complicate the early detection of immune effector cell-associated neurotoxicity syndrome (ICANS) observed in CAR-T cell therapy. Given the ongoing shortage of FLU, alternative lymphodepleting agents have become necessary. To date, only a limited number of studies have directly compared different lymphodepleting regimens, and most of these comparisons have been retrospective in nature. Herein, we review the current literature on lymphodepletion preceding CAR-T cell therapies for lymphoid hematologic malignancies, with a specific focus on the use of bendamustine (BEN). Recent evidence suggests that administering BEN before CAR-T cell infusion yields comparable efficacy, possibly with a more favorable toxicity profile when compared to CY-FLU. This warrants further investigation through randomized prospective studies.
• Ghafoor, B., Masthan, S. S., Hameed, M., Akhtar, H. H., Khalid, A., Ghafoor, S., Allah, H. M., Arshad, M. M., Iqbal, I., Iftikhar, A., Husnain, M., & Anwer, F. (2023). Waldenström macroglobulinemia: a review of pathogenesis, current treatment, and future prospects. Annals of hematology.
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  Waldenström macroglobulinemia (WM) is a chronic B-cell lymphoproliferative disorder characterized by lymphoplasmacytic cell overgrowth in the bone marrow and increased secretion of IgM immunoglobulins into the serum. Patients with WM have a variety of clinical outcomes, including long-term survival but inevitable recurrence. Recent advances in disease knowledge, including molecular and genetic principles with the discovery of MYD88 and CXCR4 mutations, have rapidly increased patient-tolerable treatment options. WM patients may benefit from chemotherapy regimens that include rituximab-based regimens, alkylating drugs, proteasome inhibitors, monoclonal antibodies, and drugs targeting Bruton tyrosine kinase inhibitors. In light of these advancements, patients can now receive treatment customized to their specific clinical characteristics, focusing on enhancing the depth and durability of their response while limiting the adverse effects. Despite the rapidly developing therapeutic armament against WM, a lack of high-quality evidence from extensive phase 3 trials remains a significant challenge in the research. We believe clinical outcomes will keep improving when new medicines are introduced while preserving efficacy and minimizing toxicity.
• Mian, A., Naqvi, S. A., Ayaz, A., Husnain, M., Aljama, M. A., Mohyuddin, G. R., Koehn, K., Mohan, M., Bin Riaz, I., & Chakraborty, R. (2023). Incidence of second primary malignancies in patients with multiple myeloma receiving anti-CD38 monoclonal antibodies: A systematic review and meta-analysis. Leukemia research, 131, 107324.
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  Anti-CD38 monoclonal antibodies (mAbs) are commonly used for treating newly diagnosed and relapsed/refractory (r/r) multiple myeloma (MM). However, concerns have been raised about the occurrence of second primary malignancies (SPMs) in patients receiving anti-CD38 mAbs. Assessing the safety data for rare adverse events like SPMs is challenging because individual clinical trials are typically focused on the primary endpoint. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) published between January 2005 and April 2022, including patients with newly diagnosed or r/r MM. Our aim was to compare SPM rate with the use of anti-CD38 mAb-based regimens with other anti-myeloma regimens. After a median follow-up of 35.3 months (range: 8.2-56.2), we found that exposure to anti-CD38 mAbs was associated with an increased risk of developing SPMs compared to the control group (6.8% vs. 5.2%; Peto odds ratio [OR]: 1.53 [95% confidence interval (CI): 1.20-1.95]; I= 0%, p-value for heterogeneity= 0.44). This increased risk was primarily driven by non-melanoma cutaneous cancers (92 vs. 47; Peto OR: 1.77 [95% CI: 1.25-2.51]; I = 0%, p-value for heterogeneity = 0.54). However, there was no significant difference in the incidence of solid tumors (including malignant melanoma) (OR: 1.28 [95% CI: 0.85-1.95]) or hematologic SPMs (OR: 1.86; [95% CI: 0.81-4.27]). In conclusion, the use of anti-CD38 mAb-based combination regimens is associated with a higher risk of non-invasive cutaneous SPMs, but not solid tumors or hematologic SPMs. The increased occurrence of non-invasive cutaneous SPMs may be due to enhanced monitoring resulting from longer treatment duration with anti-CD38 mAbs.
• Mian, A., Naqvi, S. A., Ayaz, A., Husnain, M., Aljama, M. A., Mohyuddin, G. R., Koehn, K., Mohan, M., Riaz, I. B., & Chakraborty, R. (2023). Incidence of second primary malignancies (SPMs) in patients with multiple myeloma (MM) receiving anti-CD38 monoclonal antibodies (mAbs): A systematic review and meta-analysis.. Journal of Clinical Oncology, 41(16_suppl), e24078-e24078. doi:10.1200/jco.2023.41.16_suppl.e24078
• Naqvi, S. A., Asghar, K., Thirumalareddy, J., Asghar, N., Husnain, M., Chakraborty, R., Devrieze, B., Mathews, A., Riaz, I. B., & Aljama, M. (2023). Efficacy of Maintenance Therapies By Prognostic Subgroups in Post-Transplant Newly Diagnosed Multiple Myeloma Patients: A Systematic Review and Network Meta-Analysis. Blood, 142(Supplement 1), 3348-3348. doi:10.1182/blood-2023-190200
• Wu, C., Manchen, P., Edelman, A., Husnain, M., Katsanis, E., Fuchs, D., Stephens, L., & Khurana, S. (2023). Refractory Pure Red Blood Cell Aplasia Secondary to Major ABO-Incompatible Allogeneic Stem Cell Transplantation Successfully Treated With Daratumumab. Journal of hematology, 12(6), 277-282.
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  Pure red cell aplasia (PRCA) is a rare hematologic phenomenon that is usually associated with inherited genetic mutations such as in Diamond-Blackfan anemia. However, due to the emergence of allogenic stem cell transplantation in the treatment of various malignant and non-malignant disorders, the incidence of PRCA has increased. PRCA following hematopoietic stem cell transplant (HSCT) is more commonly seen in the setting of a major ABO-incompatible transplant. Treatment of allo-HSCT induced PRCA can be initially supportive as it takes time for the bone marrow to fully recover. However, prolonged and/or failure of the bone marrow to recover, significantly increases patient's risk of iron overload in the setting of frequent transfusions. Iron deposition can potentially lead to severe life-threatening multiorgan involvement which can be fatal. Therefore, earlier recognition and intervention with immunomodulators in patients who undergo frequent transfusions can be beneficial to mitigate this risk. Here, we present a case with severe transfusion-dependent PRCA following major ABO-incompatible allo-HSCT successfully treated with daratumumab.
• Aljama, M. A., Asghar, N., Ayaz, A., Chakraborty, R., Fatima, S., He, H., Husnain, M., Ijaz, H., Naqvi, S. A., & Riaz, I. (2022). Post Autologous Stem Cell Transplant Maintenance in Patients with Newly Diagnosed Multiple Myeloma: A Network Meta-Analysis. Blood, 140(Supplement 1), 10111-10113. doi:10.1182/blood-2022-170869
• Asghar, N., Husnain, M., Naqvi, S. A., Paludo, J., Riaz, I. B., & Sipra, Q. U. (2022). Anti-CD19 chimeric antigenic receptor T cell as a second-line therapy for patients with relapsed/refractory diffuse large B-cell lymphoma.. Journal of Clinical Oncology, 40(16_suppl), e19502-e19502. doi:10.1200/jco.2022.40.16_suppl.e19502
• Chakraborty, R., Siddiqi, R., Willson, G., Gupta, S., Asghar, N., Husnain, M., Aljama, M. A., Behera, T. R., Anwer, F., Perrot, A., & Riaz, I. B. (2022). Impact of autologous transplantation on survival in patients with newly diagnosed multiple myeloma who have high-risk cytogenetics: A meta-analysis of randomized controlled trials. Cancer, 128(12), 2288-2297.
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  Despite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high-dose therapy (HDT) consolidation on overall survival (OS) or progression-free survival (PFS) in patients who have high-risk cytogenetics. The authors performed a meta-analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk.
• Chakraborty, R., Siddiqi, R., Willson, G., Gupta, S., Asghar, N., Husnain, M., Aljama, M. A., Behera, T. R., Anwer, F., Perrot, A., & Riaz, I. B. (2022). Impact of autologous transplantation on survival in patients with newly diagnosed multiple myeloma who have high‐risk cytogenetics: A meta‐analysis of randomized controlled trials. Cancer, 128(12), 2288-2297. doi:10.1002/cncr.34211
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  Background: Despite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high-dose therapy (HDT) consolidation on overall survival (OS) or progression-free survival (PFS) in patients who have high-risk cytogenetics. The authors performed a meta-analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk. Methods: All RCTs in patients who had newly diagnosed myeloma from 2000 to 2021 that compared upfront HDT versus standard-dose therapy (SDT) consolidation were included. The primary objective was to assess the difference in HDT efficacy between standard-risk and high-risk cytogenetics in terms of the OS or PFS log(hazard ratio) (HR). The pooled OS and PFS HR was calculated according to cytogenetic-risk subgroup using a random-effects model, and heterogeneity (I2) (the percentage of total observed variability explained by between-study differences) was assessed using an interaction test. Results: After screening 3307 citations, 6 RCTs were included for PFS analysis, and 4 were included for OS analysis. The median follow-up ranged from 3.1 to 7.8 years. The pooled OS HR for HDT versus SDT consolidation in patients with standard-risk and high-risk cytogenetics was 0.90 (95% confidence interval [CI], 0.70-1.17; I2 = 0%) and 0.66 (95% CI, 0.45-0.97; I2 = 0%), respectively. The difference in HDT efficacy in terms of OS between standard-risk and high-risk patients was statistically significant in favor of the high-risk group (P for interaction =.03). The pooled PFS HR for HDT versus SDT was 0.65 (95% CI 0.56-0.76; I2 = 0%) versus 0.52 (95% CI, 0.33-0.83; I2 = 55%), respectively. The difference in HDT efficacy in terms of PFS between standard-risk and high-risk patients was not significant (P for interaction =.25). Conclusions: The magnitude of OS benefit with upfront HDT is cytogenetics-dependent. Patients with high-risk cytogenetics should preferably receive upfront rather than delayed HDT consolidation. Lay Summary: Upfront autologous stem cell transplantation improves overall survival in patients with newly diagnosed myeloma harboring high-risk cytogenetics.
• Chineke, I., Hassab, M., Husnain, M., & Kumar, A. (2022). Anti-CD 19 CAR-T Cell Therapy with Tisagenlecleucel for Ritcher Syndrome. Blood, 140(Supplement 1), 12796-12797. doi:10.1182/blood-2022-167450
• Dhaliwal, A., Husnain, M., Kumar, A., Mann, S., & Persky, D. O. (2022). Tisagenlecleucel for secondary CNS lymphoma, a case series.. Journal of Clinical Oncology, 40(16_suppl), e19507-e19507. doi:10.1200/jco.2022.40.16_suppl.e19507
• Katsanis, E., Stea, B., Kovacs, K., Truscott, L., Husnain, M., Khurana, S., Roe, D. J., & Simpson, R. J. (2022). Feasibility and Efficacy of Partially Replacing Post-Transplantation Cyclophosphamide with Bendamustine in Pediatric and Young Adult Patients Undergoing Haploidentical Bone Marrow Transplantation. Transplantation and cellular therapy, 28(7), 390.e1-390.e10.
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  Post-transplantation cyclophosphamide (PT-CY) is the most widely applied graft-versus-host disease (GVHD) prophylaxis regimen in T-cell replete haploidentical bone marrow transplantation (haplo-BMT). Although PT-CY has met with great success in the haplo-BMT arena by suppressing GVHD, patients without acute GVHD have high relapse rates. One strategy to reduce relapse rates being explored by others is a dosage reduction of PT-CY. We have taken a different approach in evaluating whether partially replacing PT-CY with post-transplantation bendamustine (PT-BEN) would be advantageous, an idea based on our preclinical research identifying several beneficial immunomodulatory properties of BEN. We therefore initiated and completed a Phase Ia trial to evaluate the progressive substitution of PT-CY with PT-BEN (ClinicalTrials.gov identifier NCT02996773). We compared outcomes between 13 patients with high-risk hematologic malignancies who received PT-CY/BEN and 31 contemporaneous haplo-BMT recipients treated with the same myeloablative conditioning regimens but receiving only PT-CY. We found that partial replacement of PT-CY with PT-BEN (PT-CY/BEN) on day +4 was well tolerated and associated with significantly earlier trilineage engraftment. We also report favorable trends toward significant improvements on univariate and multivariate analyses with PT-CY/BEN compared with PT-CY with respect to rates of chronic GVHD (hazard ratio [HR], .08; 95% confidence interval [CI], .005 to 1.11; P = .06), and GVHD-free relapse-free survival (GRFS) (HR, .22; 95% CI, .05 to .86; P = .039). Our human trial has now transitioned to Phase Ib, which will further evaluate the safety and potential benefits of PT-CY/BEN. Herein we also expand our pediatric, adolescent, and young adult experience to 31 patients, demonstrating overall survival, progression-free survival, and GRFS at 3 years of 85.6%, 76.1%, and 58.2%, respectively, in a largely racial/ethnic minority cohort. PT-CY/BEN appears to be a promising treatment option that requires further evaluation.
• Ahmad, N., Anjum, A., Durrani, A. Z., Husnain, M., Iqbal, M. Z., Jabbar, A., Khan, J. A., Khan, A., Usman, S., & Usman, M. (2021). Molecular epidemiology of Coxiella Brunetii in small ruminants in Punjab, Pakistan: a novel reporting analytical cross sectional study.. Tropical animal health and production, 53(1), 68.
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  Coxiella burnetii, an intracellular zoonotic bacterium, causes query (Q) fever in ruminants. Its role has never been elucidated in small ruminants from Pakistan. The current study is designed to (a) determine the prevalence of coxiellosis in small ruminants, (b) evaluate the association of various potential risk factors and biomarkers in the occurrence of Coxiella burnetii, (c) and determine phylogeny and genetic variability of its various isolates identified during the study. For this purpose, 320 blood samples from sheep (n = 160) and goats (n = 160) were collected from 9 Union Councils of district Kasur, Punjab, and processed for DNA extraction. C. burnetii was confirmed by amplification of IS1111 transposase gene with an amplicon size of 294 bp. The results showed that the overall positive percentage of C. burnetii is 36.87% (sheep: 46.9% and goats: 30%). The phylogenetic tree was also constructed which described the possible origin of this pathogen from environment. Besides, after translation into amino acid, the resultant alignment showed several unique changes at position numbers 18 and 27 in the isolates from goats and at 27 and 66 from those of sheep. These mutations can have major impact on the infectious characteristics of this pathogen. Furthermore, different potential risk factors and clinical biomarkers like age, tick infestation, abortion, mastitis, and infertility were also studied and found that these are significantly (p < 0.05) associated with the occurrence of coxiellosis. It is concluded from the study that C. burnetii is endemic in small ruminants in Punjab, Pakistan. The outcomes of this study are alarming for scientific community as well as for policy makers because coxiellosis is an emerging threat to both humans and animals in this region due to its interspecies transmission ability.
• Beitinjaneh, A., Benjamin, C. L., Goodman, M., Husnain, M., Jimenez, A. M., Komanduri, K. V., Kwon, D., Lekakis, L. J., Pereira, D., Plate, T., & Wang, T. P. (2021). Post-Transplant Cyclophosphamide (PTCy) Is Associated with Improved Clinical Outcomes in HLA-Mismatched Unrelated Donor (MMUD) Hematopoietic Stem Cell Transplantation (HCT). The University of Miami Experience. Transplantation and Cellular Therapy, 27(3), S238-S239. doi:10.1016/s2666-6367(21)00298-0
• Beitinjaneh, A., Carollo, D., Goodman, M., Husnain, M., Jimenez, A. M., Komanduri, K. V., Kwon, D., Lekakis, L. J., Patel, P. M., Pereira, D., Saul, M. E., Saul, E. E., Tomita-barber, J. F., & Wang, T. P. (2021). Clinical Outcomes in Acute Myeloid Leukemia (AML) Patients (Pts) Carrying Isocitrate Dehydrogenase (IDH1-2) Mutations Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HCT). Transplantation and Cellular Therapy, 27(3), S147-S148. doi:10.1016/s2666-6367(21)00181-0
• Beitinjaneh, A., Carollo, D., Goodman, M., Husnain, M., Jimenez, A. M., Komanduri, K. V., Kwon, D., Lekakis, L. J., Pereira, D., Saul, E. E., & Wang, T. P. (2021). Impact of Pre-Transplant Molecular Measurable Residual Disease (MMRD) and European Leukemianet (ELN) Genetic Classification in Clinical Outcomes for Acute Myeloid Leukemia (AML) Patients (Pts) Undergoing Allogeneic Stem Cell Transplantation (alloHCT). Transplantation and Cellular Therapy, 27(3), S148-S149. doi:10.1016/s2666-6367(21)00184-6
• Bryce, A. H., Costello, B. A., He, H., Herasevich, V., Ho, T. H., Husnain, M., Joseph, R. W., Liu, H., Maheswari, D., Montori, V. M., Murad, M. H., Naqvi, S. A., Pagliaro, L. C., Riaz, I. B., Ryu, A. J., Siddiqi, R., Singh, P., Sipra, Q. U., Wang, Z., & Yao, Y. (2021). A framework for living evidence synthesis in cancer: Living, interactive network meta-analysis for first-line treatment of metastatic renal cell carcinoma (mRCC).. Journal of Clinical Oncology, 39(6_suppl), 335-335. doi:10.1200/jco.2021.39.6_suppl.335
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  335Background: Systematic reviews are outdated quickly when the evidence is rapidly evolving as the process is laborious and there is little incentive for primary author team of an index SRMA to up...
• Hashmi, H., Husnain, M., Khan, A., & Usmani, S. Z. (2021). CD38-Directed Therapies for Management of Multiple Myeloma. ImmunoTargets and therapy, 10, 201-211.
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  The survival outcomes for multiple myeloma have improved several-fold in the past two decades, primarily due to the introduction of therapies with novel mechanisms of action including immunomodulatory agents, proteasome inhibitors, stem cell transplant and monoclonal antibodies in the schema of therapy. Antibody-based therapies targeting the surface marker CD38, namely daratumumab and isatuximab, have emerged as being highly effective as single agents as well as in combination regimens for both newly diagnosed and relapsed settings. Herein, the authors summarize the most recent data with both the current and emerging CD38-directed therapies in multiple myeloma.
• Riaz, I. B., He, H., Ryu, A. J., Siddiqi, R., Naqvi, S. A., Yao, Y., Husnain, M., Narasimhulu, D. M., Mathew, J., Sipra, Q. U., Vandvik, P. O., Joseph, R. W., Liu, H., Wang, Z., Herasevich, V., Singh, P., Hussain, S. A., Ho, T. H., Bryce, A. H., , Pagliaro, L. C., et al. (2021). A Living, Interactive Systematic Review and Network Meta-analysis of First-line Treatment of Metastatic Renal Cell Carcinoma. European urology, 80(6), 712-723.
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  Identifying the most effective first-line treatment for metastatic renal cell carcinoma (mRCC) is challenging as rapidly evolving data quickly outdate the existing body of evidence, and current approaches to presenting the evidence in user-friendly formats are fraught with limitations.
• Adil, S., Asghar, N., Babiker, H. M., Bryce, A. H., Husnain, M., Hwang, S. R., Maheswari, D., Murad, M. H., Raina, A., Riaz, I. B., Siddiqi, R., Singh, P., & Sipra, Q. U. (2020). Treatment of metastatic castration sensitive prostate cancer (mCSPC) by disease volume: A systematic review and a meta-analysis.. Journal of Clinical Oncology, 38(15_suppl), e17539-e17539. doi:10.1200/jco.2020.38.15_suppl.e17539
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  e17539Background: Chemotherapy with Docetaxel (D) or androgen pathway inhibition (API) with Abiraterone Acetate plus prednisone (AAP), Aplautamide(APA) and Enzalutamide(E) are acceptable, FDA appro...
• Aguirre, L. E., Ali, R., Arshad, J., Beitinjaneh, A., Byrnes, D. M., Carollo, D., Goodman, M., Husnain, M., Jimenez, A. M., Komanduri, K. V., Lekakis, L. J., Mohammed, Y. N., Pereira, D. L., Ramdial, J., Saul, E. E., & Wang, T. P. (2020). Pre-transplant molecular minimal residual disease (MMRD) is associated with inferior outcomes in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation.. Journal of Clinical Oncology, 38(15_suppl), 7547-7547. doi:10.1200/jco.2020.38.15_suppl.7547
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  7547Background: Allogeneic Stem Cell Transplant (alloSCT) continues to be the optimal consolidation strategy for many patients with AML; cytogenetic and molecular abnormalities are known predictors...
• Alderuccio, J. P., Chapman, J. R., Husnain, M., Iyer, S. G., Kuker, R., Lossos, I. S., Reis, I. M., Vega, F., & Zhao, W. (2020). Clinical and radiological characteristics of patients with pulmonary marginal zone lymphoma: A single center analysis.. Cancer medicine, 9(14), 5051-5064. doi:10.1002/cam4.3096
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  Pulmonary marginal zone lymphoma (PMZL) is the most common non-Hodgkin lymphoma affecting the lung. PMZL is usually an indolent disease. Clinical and radiological variables associated with shorter survival are largely unknown and no consensus exists on preferred treatment strategy in PMZL. Herein we aimed to identify clinical and radiological features associated with shorter survival and inferior treatment outcomes. Forty patients with PMZL were analyzed. FDG-avid disease was evident in most patients (93%) with staging PET/CT (n = 15). With a median follow-up in treated patients (n = 38) of 8.4 years (range 0.07-18.44), the median progression-free survival (PFS) and overall survival (OS) were 7.5 years (95% CI 1.8-9.5) and 15.7 years (95% CI 9.3-NE) respectively. Shorter PFS was observed in patients who presented at diagnosis with elevated LDH, B symptoms, advanced stage and failed to achieve complete response (CR) after initial treatment. Patients with multifocal lung disease, extrapulmonary MZL and cavitary lesions on CT scans exhibited shorter PFS. Nevertheless, no clinical or radiologic findings were associated with shorter OS. All patients treated with surgery (n = 4) and radiation therapy (n = 3) achieved and remained in CR. No higher grade transformations occurred during the follow-up period. PMZL exhibited excellent outcomes with a 15-year PMZL-related OS of 94.9% (95% CI: 81.25%-98.7%). Radiation therapy and surgery are potentially curative strategies in localized PMZL.
• Bayati, M. J., Husnain, M., Luo, Z., Rosenblatt, J. D., & Zhang, Y. (2020). Abstract 3333: EMT-6 tumor conditioned Breg cells inhibit NK cell proliferation and cytotoxic activity. Immunology, 80, 3333-3333. doi:10.1158/1538-7445.am2020-3333
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  Purpose: Breg (B regulatory) cells have been implicated in suppression of anti-tumor response in murine and human solid tumors. Prior studies in our laboratory demonstrated that murine EMT-6 breast carcinoma is rejected in B cell deficient mice (BCDM), but not in wild type (WT) mice, due to an enhanced immune response. Tumor infiltrating B cells (TIL-B), and normal splenic B cells co-cultured with EMT-6 (EMT6-B), express LAP/TGF-β, PD-L1, and suppress CD8+ and NK cell proliferation in vitro. Increased CD8+ and NK cell infiltration into the tumor bed is seen in BCDM. BCDM tumor rejection is abrogated by NK depletion. We studied EMT6-B effects on NK cell phenotype, proliferation and cytokine expression in vitro and in vivo. Experimental design: Normal splenic B cells were co-cultured with mitomycin C treated EMT-6, and Breg phenotype, and effects on NK cell phenotype and proliferation and cytokine function were studied in vitro and in vivo. Results: EMT6-B but not WT splenic B cells inhibited CFSE labeled CD49b+ NK cell proliferation in response to IL-15 in dose dependent fashion. EMT-6-B suppressed expression of CD226 and NKG2D activating receptors on NK cells, and increased expression of PD-1 and PD-L1 respectively. EMT6-B suppressed the induction of IFNγ+/CD49b+ NK cells following PMA/ION stimulation as assayed by intracellular flow cytometry (10%±1.2 to 2%±0.5) and also suppressed IL-2 induced induction of IFNγ+/CD49b+ NK cells (70%±5 to 20%±7.8). EMT-6 and CT26 colon carcinoma conditioned B cells, but not C166 endothelial cell conditioned B cells suppressed NK degranulation (IFNγ+/CD107a+ NK cells). EMT6-B inhibited YAC-1 cell induced NK cell degranulation, and killing of YAC-1 targets, more effectively than naive B cells (40%±6.2 to 18%±5.1) (P=0.05). NK suppression was inhibited by anti-PD-L1, and anti-TGF-β antibody. EMT6-B expressed increased FasL compared to splenic B cells, and induced NK apoptosis as measured by 7AAD/Annexin-V staining. Blocking antibody to FasL decreased NK apoptosis, and restored NK cell proliferation. Infiltrating NK cells in the EMT6 tumor bed demonstrated increased PD-1 compared to splenic and TDLN NK cells, and higher levels of IFN-γ, CD107a, and Granzyme B in BCDM vs. WT mice. EMT6 expressed high levels of CD155 NK inhibitory ligand compared to C166 endothelial cells. The EMT-6 tumor bed contained higher levels of CD19+CD155+ B cells (22% / tumor bed vs 6% / TDLN, vs 9%/ spleen). BCDM expressed higher levels of CD226+/Ki67+ NK cells in spleen compared to WT splenic NK cells. Antibodies to Fas-L, TGF-beta, and PD-L1 partially restored anti-tumor response in WT mice and decreased tumor growth. Conclusions: EMT-6 TIL-B or normal B cells conditioned by EMT-6 coculture acquire an NK suppressive phenotype which inhibits NK cell activation, proliferation, degranulation and cytotoxic function. Targeting of Breg-NK interactions may improve anti-tumor immune response. Citation Format: Yu Zhang, Muhammad Husnain, Zhifen Luo, Mahmood Al Bayati, Joseph D. Rosenblatt. EMT-6 tumor conditioned Breg cells inhibit NK cell proliferation and cytotoxic activity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3333.
• Alderuccio, J. P., Zhao, W., Desai, A., Ramdial, J., Gallastegui, N., Kimble, E., Fuente, M. I., Husnain, M., Rosenblatt, J. D., Alencar, A. J., Schatz, J. H., Moskowitz, C. H., Chapman, J. R., Vega, F., Reis, I. M., & Lossos, I. S. (2019). Short survival and frequent transformation in extranodal marginal zone lymphoma with multiple mucosal sites presentation.. American journal of hematology, 94(5), 585-596. doi:10.1002/ajh.25446
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  Between 11 and 37% of extranodal marginal zone lymphoma (EMZL) patients present with disease involvement in multiple mucosal sites (MMS). We analyzed 405 EMZL patients seen between 1995 and 2017: 265 (65.4%) patients presented with stage I disease, 49 of 309 (15.8%) patients with bone marrow involvement, and 35 of 328 (10.7%) patients with monoclonal gammopathy (MG). Forty-three (10.6%) patients had MMS presentation, which was more frequently seen in patients aged >60 years (55.8%). Five (17.9%) of 28 MMS patients had MG. MMS patients commonly exhibited the International Prognostic Index (IPI) >2 (79.1%), Follicular Lymphoma International Prognostic Index (FLIPI) >2 (39.5%), and Mucosa-Associated Lymphoid Tissue Lymphoma International Prognostic Index (MALT-IPI) 2-3 (60.5%). Both MMS presentation and MG were associated with shorter survival univariately. In multivariable Cox regression models, shorter progression-free survival (PFS) and overall survival (OS) were observed in patients with MMS (hazard ratio [HR] = 3.08 and 2.92, respectively), age ≥60 years (HR = 1.52 and 2.45, respectively), and in patients who failed to attain a complete remission following initial therapy (HR = 3.27 and 2.13, respectively). Elevated lactate dehydrogenase was associated with shorter PFS (HR = 1.92), while anemia (HR = 2.46) was associated with shortened OS. MALT-IPI ≥2 (HR = 2.47 and 4.75), FLIPI >2 (HR = 1.65 and 2.09), and IPI >2 (HR = 2.09 and 1.73) were associated with shorter PFS and OS, respectively. Higher grade transformation (HGT) occurred in 11 (25.6%) MMS patients with a 5-year cumulative incidence of 13.2% (95% CI 4.7-26.1%). EMZL patients with MMS presentation represent a novel clinical subset associated with shorter PFS, OS, and higher incidence of HGT that needs novel therapeutic approaches.
• Husnain, M., Babiker, H. M., Borad, M. J., & Riaz, I. B. (2019). Erratum: Oncolytic virotherapy including Rigvir and standard therapies in malignant melanoma [Corrigendum].. Oncolytic virotherapy, 8, 1. doi:10.2147/ov.s196145
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  [This corrects the article on p. 11 in vol. 6, PMID: 28224120.].
• Husnain, M., Mackrides, N., Vega, F., Paez-escamilla, M., Markoe, A. M., Harbour, J. W., & Lossos, I. S. (2019). CD4+/CD8+ immunophenotype switching as a marker for intraocular and CNS involvement in mycosis fungoides.. Leukemia & lymphoma, 60(5), 1308-1311. doi:10.1080/10428194.2018.1526376
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  Mycosis Fungoides (MF), the most common cutaneous T cell lymphoma, is usually indolent and characterized by slow progression from patches to plaques and tumor formation with systemic dissemination....
• Husnain, M., Riaz, I. B., Gondal, F. R., Raina, A., Islam, M., Lopes, G., Malik, S. U., & Sipra, Q. U. (2019). CDK4/6 inhibitors in advanced hormone receptor-positive/HER2-negative breast cancer: A network meta-analysis (NMA) of randomized controlled trials (RCTs).. Journal of Clinical Oncology, 37(15_suppl), e12545-e12545. doi:10.1200/jco.2019.37.15_suppl.e12545
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  e12545Background: Palbociclib(P), Ribociclib(R) and Abemaciclib(A) in combination with Endocrine therapy (ET) have demonstrated progression free survival (PFS) in patients with metastatic hormone r...
• Husnain, M., Valdes, M., Hoffman, J. E., Lekakis, L. J., & Wang, T. P. (2019). Multiple Myeloma in a Patient with ANKRD26-Related Thrombocytopenia Successfully Treated with Combination Therapy and Autologous Stem Cell Transplant.. Case reports in hematology, 2019, 9357572. doi:10.1155/2019/9357572
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  Ankyrin repeat domain-containing protein 26- (ANKRD26-) related thrombocytopenia is a rare, autosomal dominant condition caused by ANKRD26 gene mutation. ANKRD26-related thrombocytopenia is characterized by moderate thrombocytopenia with minimal bleeding, normal platelet size, and dysmegakaryopoiesis on bone marrow evaluation. ANKRD26 mutation has been previously associated with myeloid malignancies, including acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. We report the first case of multiple myeloma in a patient with ANKRD26 related thrombocytopenia. The patient was successfully treated with contemporary combination therapy followed by melphalan-conditioned autologous stem cell transplant for his multiple myeloma despite preexisting thrombocytopenia.
• Riaz, I. B., Faridi, W., Husnain, M., Malik, S. U., Gondal, F. R., Xie, H., Yadav, S., Kohli, M., & Sipra, Q. U. (2019). Adjuvant Therapy in High-Risk Renal Cell Cancer: A Systematic Review and Meta-analysis.. Mayo Clinic proceedings, 94(8), 1524-1534. doi:10.1016/j.mayocp.2019.01.045
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  To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating risk-benefit for adjuvant postoperative treatments in high-risk renal cell carcinoma by assessing reported disease-free survival (DFS), overall survival (OS), toxicity, and quality of life..A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant RCTs (from database inception through May 15, 2018). The results of the ATLAS trial were published while writing this manuscript, and the manuscript was updated accordingly. A generic variance-weighted random effects model was used to derive estimates for efficacy and common adverse effects. Heterogeneity was assessed using the Cochran Q statistic and was quantified using the I2 test..Adjuvant therapy with tyrosine kinase inhibitors compared with placebo was observed to have a DFS hazard ratio [HR] of 0.92 (95% CI, 0.83-1.01) and an OS HR of 1.01 (95% CI, 0.89-1.15) (4 RCTs; 4417 patients). Analysis of DFS for sunitinib compared with placebo (n=1909) in the adjuvant setting detected an HR of 0.90 (95% CI, 0.67-1.19). Increased risk of grade 3 or 4 adverse events (relative risk [RR]=2.6; 95% CI, 2.28-2.97), diarrhea (RR=9.89; 95% CI, 4.22-23.14), fatigue (RR=3.11; 95% CI, 1.86-5.18), hypertension (RR=3.63; 95% CI, 2.99-4.41), and palmar/plantar dysesthesia (RR=2.70; 95% CI, 2.47-2.96) was observed..Adjuvant vascular endothelial growth factor tyrosine kinase inhibitors in high-risk renal cell carcinoma did not improve OS or DFS, and there was a significant increased risk of toxicity in greater than half of the patients, leading to a decline in quality of life.
• Riaz, I. B., Husnain, M., Raina, A., Khan, A., Akhtar, M., Wang, Z., Murad, M. H., Leon-ferre, R. A., & Sipra, Q. U. (2019). Short versus long duration of adjuvant trastuzumab (T) in HER2+ breast cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).. Journal of Clinical Oncology, 37(15_suppl), e12057-e12057. doi:10.1200/jco.2019.37.15_suppl.e12057
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  e12057Background: Several RCTs have evaluated a shorter duration of T ( < 12 months) with hopes of similar efficacy, reduced cardiotoxicity, cost and burden of treatment. Of the 5 major studies, PE...
• Riaz, I. B., Malik, S. U., Husnain, M., Ain Riaz Sipra, Q. U., Faridi, W., Gondal, F. R., Ho, T., Yadav, S., Wang, Z., & Kohli, M. (2019). HSR19-108: A Meta-Analysis of Randomized Controlled Trials (RCTs) for Efficacy and Safety of Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors (VEGF-TKIs) Adjuvant Therapy in High-Risk Renal Cell Cancer (RCC). Journal of the National Comprehensive Cancer Network, 17(3.5), HSR19-108. doi:10.6004/jnccn.2018.7233
• Ahman, F., Akbar, S., Ali, Z., Anwer, F., Bilal, J., Gondal, F. R., Husnain, M., Iftikhar, A., Javed, A., Mcbride, A., Riaz, I. B., Singh, P., Sipra, Q. U., Umar, M., & Zahid, U. (2018). Role of one, two and three doses of high-dose chemotherapy with autologous transplantation in the treatment of high-risk or relapsed testicular cancer: a systematic review.. Bone Marrow Transplantation, 53(10), 1242-1254. doi:10.1038/s41409-018-0188-3
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  Approximately 20–30% of patients with metastatic germ cell cancers (GCCs) can develop relapsed or refractory (RR) disease, about 40–50% of patients who relapse after salvage chemotherapy may reach long-term remission. The goal of this review was to identify patients who appear to benefit from high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). To access this, we performed a systematic medical literature review to evaluate the effectiveness of HDCT in the frontline setting, as well as in patients with RR testicular cancer. We searched databases for interventional clinical studies and identified 5883 studies. We selected 49 studies for inclusion, which included a total of 5985 patients. Seventeen studies reported results of newly diagnosed poor-risk GCC patients and 32 studies reported results of RR patients. For newly diagnosed patients with poor prognostic predictors, a risk adjusted strategy using unfavorable tumor marker decline with initial standard chemotherapy regimen and upfront HDCT demonstrated improved outcomes. Our data suggest a minimum of two HDCT cycles with ASCT should be standard of care for patients with RR GCC. Failure of HDCT results in a poor prognosis with only 10% of patients achieving lasting remission with salvage therapy.
• Faridi, W., Gondal, F. R., Husnain, M., Kohli, M., Malik, S., Riaz, I. B., Sipra, Q. U., Xie, H., & Yadav, S. (2018). A meta-analysis of randomized controlled trials for efficacy and safety of vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) adjuvant therapy in high-risk renal cell cancer (RCC).. Journal of Clinical Oncology, 36(15_suppl), 4567-4567. doi:10.1200/jco.2018.36.15_suppl.4567
• Husnain, M., Arshad, A., Ashrani, A. A., Bhattacharjee, S., Kaluski, E., Khan, S. U., Riaz, I. B., & Riaz, A. (2018). TCT-819 Patent Foramen Ovale Closure versus Medical Therapy after Cryptogenic Stroke-A Systematic Review and Meta- Analysis. Journal of the American College of Cardiology, 72(13), B326-B327. doi:10.1016/j.jacc.2018.08.2057
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  The optimal therapeutic strategy for prevention of cryptogenic stroke among patients with PFO remained unclear. We conducted a meta-analysis to investigate the relative safety and efficacy of device closure versus medical therapy in patients with patent foramen ovale (PFO). Five randomized trials
• Husnain, M., Park, W., Ramos, J. C., Johnson, T. E., Chan, J., Dasari, A., Mudad, R., & Hosein, P. J. (2018). Complete response to ipilimumab and nivolumab therapy in a patient with extensive extrapulmonary high-grade small cell carcinoma of the pancreas and HIV infection.. Journal for immunotherapy of cancer, 6(1), 66. doi:10.1186/s40425-018-0379-x
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  Immune checkpoint inhibitors (CPIs) have shown promising results in many solid tumors. There are limited data on the safety and efficacy of these drugs in HIV infected patients as they have traditionally been excluded from CPIs clinical trials..We present a case of an HIV-positive patient with extensive extrapulmonary high-grade small cell carcinoma who was treated with dual CPIs (nivolumab and ipilimumab) with a complete response to therapy and with a manageable safety profile. We performed a comprehensive literature review identifying 62 total HIV positive cases treated with CPIs showing this to be a potentially safe option in HIV-positive patients..HIV infection is not an absolute contraindication to CPI therapy. Our case and others provide justification for ongoing trials of CPI therapy in patients with HIV infection, a group that has traditionally been excluded from clinical trials.
• Ibrahim, M., Siddique, S., Rehman, K., Husnain, M., Hussain, A., Azam, F., & Akash, M. S. (2018). Comprehensive Analysis of Phytochemical Constituents and Ethnopharmacological Investigation of Genus Datura.. Critical reviews in eukaryotic gene expression, 28(3), 223-283. doi:10.1615/critreveukaryotgeneexpr.2018022531
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  The genus Datura comprises wild shrub plants that belong to the Solanaceae family. Naturally, they possess both medicinal and poisonous properties due to the presence of many biologically active phytochemical constituents. Traditionally, Datura had been used for mystic and religious purposes, as a natural drug to treat asthma, pain, gout, boils, abscesses, and wounds, and as psychoactive infusions and fumitories. Different Datura species exhibit diverse ethnopharmacological activities against different diseases, and many ancient and traditional cultures have used various forms of Datura to treat ailments and to prevent many diseases. In this article, we comprehensively summarize various phytochemical constituents isolated from Datura, their pharmacological properties against different diseases, parts of the plants used as traditional therapeutic agents, regions where they are located, and botanical descriptions of different Datura species. The ethnopharmacological properties of Datura may provide new insights for discovery and development of natural drugs. Further research is needed for the investigation of mechanisms of action and to develop safety profiles of the phytochemical constituents isolated from Datura species.
• Peterson, S. L., Husnain, M., Pollack, T., Pimentel, A., Loaiza-bonilla, A., Westendorf-overley, C., Anthony, L., Goel, G., Kudrimoti, M., Tzeng, C. D., Hosein, P. J., Desimone, P. A., Dineen, S. P., & Ratermann, K. L. (2018). Neoadjuvant Nab-paclitaxel and Gemcitabine in Borderline Resectable or Locally Advanced Unresectable Pancreatic Adenocarcinoma in Patients Who Are Ineligible for FOLFIRINOX.. Anticancer research, 38(7), 4035-4039. doi:10.21873/anticanres.12692
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  Combination nab-paclitaxel/gemcitabine (AG) is superior to gemcitabine in patients with metastatic pancreatic cancer (PC). There are limited data for AG in borderline resectable (BR) or locally advanced pancreatic cancer (LAPC). Herein, we report our experience with neoadjuvant AG for BR/LAPC in patients ineligible for FOLFIRINOX..This retrospective series, included patients with BR/LAPC who received AG as neoadjuvant therapy for 3-4 months followed by radiation, then re-evaluation for surgery..Between 10/2013-2/2018, 32 patients (22 BR, 10 LAPC) were treated with this approach. Median age was 70 years. Nine patients were converted to resectability by imaging; six had R0 resections (19%), five (16%) achieved a partial response and 24 (75%) had stable disease..In this small series, the R0 resection rate and response rate were 19% and 16% respectively. These data suggest that neoadjuvant AG may be an alternate option for patients ineligible for FOLFIRINOX.
• Amaraneni, A., Husnain, M., Riaz, I. B., Iftikhar, A., Akbar, F., Anwer, F., Chan, O., Mcbride, A., & Zahid, U. (2017). A Review of Autologous Stem Cell Transplantation in Lymphoma.. Current hematologic malignancy reports, 12(3), 217-226. doi:10.1007/s11899-017-0382-1
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  Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20-30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients..There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL. Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.
• Bilal, J., Husnain, M., & Sipra, Q. U. (2017). Dextrocardia With Situs Inversus and Levo-Transposition of Great Vessels.. The American journal of the medical sciences, 353(6), e11. doi:10.1016/j.amjms.2016.10.007
• Husnain, M., Akbar, S., Ali, Z., Anwer, F., Gondal, F. R., Javed, A., Riaz, I. B., Singh, P., Sipra, Q. R., & Umar, M. (2017). High Dose Chemotherapy with Autologous Stem Cell Transplant in Treatment of Germ Cell Tumors: A Systematic Review and Meta-Analysis. Biology of Blood and Marrow Transplantation, 23(3), S269-S270. doi:10.1016/j.bbmt.2016.12.516
• Husnain, M., Ali, Z., Anwer, F., George, L., Hamadani, A. A., Hua, A., Mcbride, A., Puvvada, S. D., Rahman, B., Raina, A., Riaz, I. B., Spira, Q. R., Umar, M., & Zahid, U. (2017). Anti-CD 19 and Anti- CD 20 Chimeric Antigen Receptor-Modified T Cells for B-Cell Malignancies: A Systematic Review and Meta-Analysis. Biology of Blood and Marrow Transplantation, 23(3), S164. doi:10.1016/j.bbmt.2016.12.277
• Husnain, M., Anwer, F., George, L., Hamadani, A. A., Hua, A., Kamal, M. U., Mcbride, A., Puvvada, S. D., Rahman, B., Raina, A., Riaz, I. B., Sipra, Q. R., Zahid, U., & Zeeshan, A. (2017). Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis.. Immunotherapy, 9(12), 979-993. doi:10.2217/imt-2017-0062
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  Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 chimeric antigen receptor-T therapy for B-cell hematologic malignancies. A total of 16 studies with 195 patients were identified. The pooled analysis showed an overall response rate of 61% (118/195) with complete response of 42% (81/195) and partial response of 19% (37/195). Major adverse events were cytokine release syndrome 33%, neurotoxicity 33% and B-cell aplasia 54%. Collectively, the results indicate encouraging response in relapsed/refractory B lymphoma and leukemia, especially in acute lymphoblastic leukemia (ALL) patients.
• Husnain, M., Anwer, F., Gondal, F. R., Raina, A. I., & Riaz, I. B. (2017). Quetiapine Associated Thrombotic Thrombocytopenic Purpura: A Case Report and Literature Review.. American journal of therapeutics, 24(5), e615-e616. doi:10.1097/mjt.0000000000000456
• Husnain, M., Anwer, F., Khan, M. S., Mazursky, K., & Riaz, I. B. (2017). Bone lymphoma with multiple negative bone biopsies.. JAAPA : official journal of the American Academy of Physician Assistants, 30(9), 27-29. doi:10.1097/01.jaa.0000521135.38539.f4
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  This article describes a 71-year-old man with right knee pain, prerenal azotemia, hypercalcemia, and a mass in the distal femur. Although testing, including bone marrow biopsy, initially ruled out myeloma, an open surgical biopsy eventually confirmed the diagnosis as lymphoma involving the bone with classic histologic findings of mature B-cell neoplasm of germinal cell origin.
• Husnain, M., Babiker, H. M., Borad, M. J., & Riaz, I. B. (2017). Oncolytic virotherapy including Rigvir and standard therapies in malignant melanoma.. Oncolytic virotherapy, 6, 11-18. doi:10.2147/ov.s100072
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  The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor), nivolumab (IgG4 PD-1 inhibitor), pembrolizumab (IgG4 PD-1 inhibitor) and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor) and trametinib (MEK inhibitor), as they yielded improved responses and survival in malignant melanoma patients. This is certainly a burgeoning time in immunotherapy drug development, and the aforementioned efforts along with the recent US Food and Drug Administration approval of talimogene laherparepvec (T-VEC), a recombinant oncolytic herpes virus, have paved the way to exploring the role of additional oncolytic viruses, such as the echovirus Rigvir, as new and innovative treatment modalities in patients with melanoma. Herein, we discuss the current standard of care treatment in melanoma with an emphasis on immunotherapy and oncolytic viruses in development.
• Husnain, M., Riaz, I. B., Anwer, F., Hasan, N., Lim, M., Mcbride, A., Persky, D. O., Shaukat, A. A., & Zahid, U. (2017). Donor origin CAR T cells: graft versus malignancy effect without GVHD, a systematic review.. Immunotherapy, 9(2), 123-130. doi:10.2217/imt-2016-0127
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  CD19, CD20 chimeric antigen receptor T (CAR T) cell therapy has shown promising results for the treatment of relapsed or refractory hematological malignancies. Best results have been reported in acute lymphoblastic leukemia patients with a complete response rate above 80%. Patients who received donor-derived CAR T cells for the relapsed malignancy after stem cell transplantation (allogenic hematopoietic stem cell transplant) were identified from the published trials. A total of 72 patients from seven studies were treated with donor-derived CAR T cells. Only five out of 72 patients (6.9%) developed graft versus host disease. Use of donor-derived CAR T cell for relapse prophylaxis, minimal residual disease clearance or salvage from relapse is therefore highly effective, and risk of graft versus host disease flare is very low. Side effects include cytokine release syndrome, tumor lysis syndrome, B-cell aplasia along with CNS toxicity.
• Luni, F. K., Riaz, H., Khan, A. R., Riaz, T., Husnain, M., Riaz, I. B., Khan, M. S., Taleb, M., Kanjwal, Y., Cooper, C. J., & Khuder, S. A. (2017). Clinical outcomes associated with per-operative discontinuation of aspirin in patients with coronary artery disease: A systematic review and meta-analysis.. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, 89(7), 1168-1175. doi:10.1002/ccd.26807
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  Postoperative state is characterized by increased thrombotic risk by virtue of platelet activation. Whether aspirin ameliorates this risk in patients with established coronary artery disease undergoing cardiac or noncardiac surgery is unknown. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiac events (MACE) and the risk of bleeding in patients with early (3-5 or more days before surgery) vs. late discontinuation(
• Byrne, R. A., Cassese, S., Finn, A. V., Hsu, C. H., Husnain, M., Lee, K. S., Lee, J. Z., Riaz, I. B., Riaz, H., Samady, H., & Thai, H. (2016). Temporal Trends in Strut-Level Optical Coherence Tomography Evaluation of Coronary Stent Coverage: A Systematic Review and Meta-Analysis.. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, 88(7), 1083-1093. doi:10.1002/ccd.26374
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  We sought to pool data from all studies with reported strut-level data in human subjects evaluated by optical coherence tomography (OCT) surveillance and to compare the aggregate data of stent strut coverage on a longitudinal temporal timeline from initial implantation for different coronary stent subtypes..Delayed strut coverage following drug-eluting stent (DES) implantation is an important contributor to late stent thrombosis (LST). OCT can detect stent strut coverage..We conducted a systematic search of published or presented studies reporting OCT stent strut coverage of bare-metal stents (BMS) and DES in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials to June 2014. Data from 3,515 patients with strut-level data on 731,761 struts were analyzed..The temporal kinetics of strut coverage differed according to stent type. The rate of strut coverage, reflected by the calculated regression coefficient, was found to be the highest in BMS, followed by early generation zotarolimus-eluting stent, everolimus-eluting stent, newer-generation zotarolimus-eluting stent, paclitaxel-eluting stent, and sirolimus-eluting stent (p < 0.0001)..Aggregate rates of stent strut coverage assessed by OCT surveillance differed according to stent type. The clinical implications of these differences require further study but may underlie the differences in rates of stent thrombosis observed in clinical trials with different stent types. © 2015 Wiley Periodicals, Inc.
• Husnain, M., Agarwal, A., Barkett, N., Kurtin, S. E., & Riaz, I. B. (2016). Refractory IgD Multiple Myeloma Treated with Daratumumab: A Case Report and Literature Review.. Case reports in oncological medicine, 2016(Issue), 2490168. doi:10.1155/2016/2490168
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  Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients. We report a case of 40-year-old man with immunoglobulin D (IgD) multiple myeloma whose disease was refractory to at least 5 different chemotherapy regimens including proteasome inhibitors and immunomodulatory drugs. The clinical studies assessing daratumumab did not include any patients with IgD myeloma which is a rare form of multiple myeloma and to our knowledge is the first study reporting use of daratumumab in IgD myeloma.
• Husnain, M., Ali, Z., Anwer, F., Geoge, L., Hamadani, A. A., Hua, A., Kamal, M. U., Mcbride, A., Rahman, B., Raina, A., Riaz, I. B., Saleh, A. A., Sipra, Q. R., & Zahid, U. (2016). Anti-CD 19 and Anti- CD 20 Chimeric Antigen Receptor-Modified T Cells for B-Cell Malignancies: A Systematic Review and Meta-Analysis. Blood, 128(22), 5163-5163. doi:10.1182/blood.v128.22.5163.5163
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  Background: Chimeric antigen receptor (CAR) modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. CD19 and CD20 targeted CAR constructs from several different institutions have demonstrated consistently high anti-tumor efficacy in children and adults with relapsed B-cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL). We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 CAR-T therapy for B-cell hematologic malignancies. Methods: Literature search was performed using MEDLINE (Ovid SP and PubMed), EMBASE, The Cochrane Library, Scopus and Web of Science. We conducted meta-analysis using random effects model using Comprehensive Metaanalysis 3.0. Heterogeneity was assessed using Q-statistic and it was quantified using I2statistic. Results: After a comprehensive literature search 4476 studies were identified and finally 15 eligible studies involving 121 patients were included in the final systematic review. The infused CAR T-cell dose was in the range of 0.76 x 106 to 3 x 107 cells/kg in seven trials and in the range of 0.8 x 107 cells to 3.3 x 109 cells/m2in 6 trials. Among 106 patients, the overall response to treatment after CAR T-cell infusion were 33% complete remission (CR), 30 % partial remission (PR), 21% stable disease (SD), and 8% progressive disease (PD). Three studies described response to immunotherapy as minimal residual disease negative (MRD-) and as no evidence of disease (NED) and after including it, the overall CR was 38%. Major adverse events included fever (38%), hypotension (23%), chills (29%), rigor (28%), fatigue 17% and dyspnea 10%. One patient died from cytokine release syndrome, which is potentially serious complication. Neurological symptoms require prompt recognition and management. Conclusion: CAR T cell therapy is a promising treatment for refractory and relapsed hematological malignancies. The durable responses of CAR T cell therapy help integrate it in standard treatment protocols. Patients who are refractory to standard salvage chemotherapy or relapse after allo - HSCT have overall poor prognosis and can potentially achieve remission again with CAR T cell therapy. Disclosures McBride:Sanofi: Research Funding. Anwer:Seattle Genetics: Other: Advisory Board Participant; Incyte: Speakers Bureau.
• Husnain, M., Anwer, F., Chan, O., Okolo, O., & Riaz, I. B. (2016). Outcome of Immune-Suppressive Therapy (IST) and Hematopoietic Stem Cell Transplantation (SCT) in Patients with Aplastic Anemia: A Retrospective Single Center Experience. Blood, 128(22), 5081-5081. doi:10.1182/blood.v128.22.5081.5081
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  Background Aplastic anemia (AA), characterized by bone marrow failure resulting in pancytopenia, is a rare condition with an incidence rate of 2-3 cases per million per year internationally(Montane et al., 2008). Treatment consists of immune-suppressive therapy (IST), hematopoietic stem cell transplantation (SCT), or both depending on patient factors such as age and comorbidities. Some studies suggest patients who received SCT from alternative transplant donor, specifically matched unrelated donor (MUD), may experience similar outcomes as the time-tested matched related donor (MRD)(Kennedy-Nasser et al., 2006, Buchholz et al., 2008). We compare the survivals of our patients under different treatments and further examine how transplant donor types affect outcomes. Methods We retrospectively retrieved the medical records of patients with the ICD-9 and ICD-10 code of aplastic anemia in their diagnosis seen at the University of Arizona Cancer Center/University Medical Center at Tucson, Arizona from 1990 to 2016. There are 104 patients returned with these search criteria. After chart review, patients who did not have aplastic anemia or with insufficient data for analysis were removed, leaving a total of 65 patients in the cohort. Survival analyses with 95% confidence intervals (CI) were estimated by Kaplan-Meier method and compared by log-rank test. P-values less than 0.05 were considered to be statistically significant. All statistical analyses were performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria). Results A total of 65 patients were included in the study with 25 males (38%) and 40 female (62%). Median age at diagnosis was 22 years ranging from 1 to 64 years. Overall survival (OS) was 70%+/-7.2 (95% CI, 56.8-85.3). Patients were divided into 3 treatment categories including those who had received IST only (13/65, 20%), transplant only (41/65, 63%), and combination (11/65, 17%). OS for each category was 92%+/-7.4, 64%+/-8.5, and 82%+/-11.6, respectively as shown in Figure1A(p=0.321). Applying the same analysis on patients who had received treatment in the last decade from 2007 and beyond showed improved outcomes for those who had received transplant only (9/29, 31%) with OS of 73%+/-17% as demonstrated in Figure1B(p Conclusions Our findings suggest IST remains the treatment method with the highest OS for those who are eligible. Advances in supportive care during transplant period in the last decade translate to better outcomes for these patients. For those who are appropriate for SCT, MRD is the optimal donor choice. References BUCHHOLZ, S., DAMMANN, E., KOENECKE, C., STADLER, M., FRANZKE, A., BLASCZYK, R., BREMER, M., KRAUTER, J., HERTENSTEIN, B., GANSER, A. & EDER, M. 2008. Allogeneic stem cell transplantation from related and unrelated donors for aplastic anaemia in adults--a single-centre experience. Ann Hematol, 87, 551-6. KENNEDY-NASSER, A. A., LEUNG, K. S., MAHAJAN, A., WEISS, H. L., ARCE, J. A., GOTTSCHALK, S., CARRUM, G., KHAN, S. P., HESLOP, H. E., BRENNER, M. K., BOLLARD, C. M. & KRANCE, R. A. 2006. Comparable outcomes of matched-related and alternative donor stem cell transplantation for pediatric severe aplastic anemia. Biol Blood Marrow Transplant, 12, 1277-84. MONTANE, E., IBANEZ, L., VIDAL, X., BALLARIN, E., PUIG, R., GARCIA, N., LAPORTE, J. R., CATALAN GROUP FOR STUDY OF, A. & APLASTIC, A. 2008. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica, 93, 518-23. Disclosures Anwer:Seattle Genetics: Other: Advisory Board Participant; Incyte: Speakers Bureau.
• Husnain, M., Riaz, I. B., Akbar, S., Ali, Z., Anwer, F., Gondal, F. R., Javed, A., Kamal, M. U., Singh, P., & Sipra, Q. R. (2016). High Dose Chemotherapy with Autologous Stem Cell Transplant in Treatment of Germ Cell Tumors: A Systematic Review and Meta-Analysis. Blood, 128(22), 5829-5829. doi:10.1182/blood.v128.22.5829.5829
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  Background: Cure rates for the poor risk, relapsed and refractory germ cell tumors are only 25 % with conventional dose chemotherapy. High Dose Chemotherapy (HDCT) followed by rescue stem cell transplant has since been studied in randomized controlled trails for the IGCCG poor risk group patients and for the relapsed and refractory testicular cancer patients. We conducted a meta-analysis of all prospective Phase II and III trials studying the role of high dose chemotherapy in germ cell tumors. Methods: Literature search was conducted using methods described in the PRISMA statement. Medline (PubMed and Ovid SP), Embase, Cochrane Central Register of Controlled Clinical Trials(CENTRAL) and Cochrane Database of Systematic Review (CDSR) were searched from the inception of these databases till present. We performed a meta-analysis using Comprehensive Meta-analysis 3.0 using random effects model. The heterogeneity was assessed using I2values and sensitivity analysis was performed to explain the heterogeneity where present. Results: After a comprehensive literature search 4440 studies were identified and finally 35 studies were included in the final analysis. 14 studies involving 905 patients with IGCCG poor risk germ cell cancer were treated with high dose chemotherapy. 44 % (398) patients were able to achieve CR with HDCT with HR of o.48 (0.33-0.62) p=0.75. The overall survival (OS) and Progression free survival (PFS ) were 0.62 (0.54-0.69, p=0.004) and 0.60 (0.52-0.68 p=0.011) respectively. 21 studies involving 1153 patients with relapsed and or refractory germ cell cancer were identified. CR rate with HDCT was 32 % (374 patients) with HR of 0.32 (0.26-0.40, p=0.00). The results for OS failed to show any significant results with HR of 0.52 (0.44-0.60, p=0.67) but was significant for PFS with HR of 0.60 (0.52-0.67, p=0.01). Conclusion: High dose chemotherapy followed by HSCT showed significant OS and PFS for IGCCG poor risk category germ cell tumors and significant CR and PFS for relapsed and or refractory germ cell cancer group. Disclosures Anwer:Incyte: Speakers Bureau; Seattle Genetics: Other: Advisory Board Participant.
• Husnain, M., Movahed, M. R., Kollampare, S., Lee, J. Z., Luni, F. K., Riaz, I. B., & Suryanarayana, P. (2014). Presence of anomalous coronary seen on angiogram is not associated with increased risk of significant coronary artery disease.. The International journal of angiology : official publication of the International College of Angiology, Inc, 23(4), 243-6. doi:10.1055/s-0034-1384839
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  It is unclear if anomalous coronary arteries are at higher risk for atherosclerosis. The link between anomalous coronary artery and early coronary artery disease has been suggested. The aim of this study is to determine whether the coronary artery anomaly predisposes to development of significant coronary disease. Using retrospective chart review, patients with documented anomalous coronary arteries recognized during coronary angiography between years 2000 to 2007 were analyzed. Prevalence of significant atherosclerotic coronary artery disease (defined as more than 50% luminal narrowing) was compared between normal and anomalous coronaries. A total of 147 patients with anomalous coronary arteries were found. Right coronary artery was the most common anomalous artery 128 of 148 (86.5%) in our dataset. There was no difference in the occurrence of atherosclerosis between anomalous and nonanomalous coronaries. Significant atherosclerosis was present in 59 of the 148 anomalous coronary arteries (37.8%), and 112 of the 293 nonanomalous coronary arteries (38.2%, p = 0.9). On the basis of our study, there is no evidence that anomalous coronary arteries predispose to significant coronary artery disease in comparison to normal coronary arteries.
• Riaz, I. B., Husnain, M., & Ateeli, H. (2014). Recurrent thrombosis in a patient with Lesch-Nyhan syndrome.. The American journal of medicine, 127(7), e11-2. doi:10.1016/j.amjmed.2014.01.033
• Riaz, I. B., Husnain, M., Asawaeer, M., Bilal, J., Lee, K. S., Pandit, A., Riaz, H., & Shetty, R. (2014). Meta-analysis of revascularization versus medical therapy for atherosclerotic renal artery stenosis.. The American journal of cardiology, 114(7), 1116-23. doi:10.1016/j.amjcard.2014.06.033
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  The aim of the study was to compare the efficacy of revascularization versus medical therapy in patients with atherosclerotic renal artery stenosis (ARAS). ARAS is the most common cause of secondary hypertension and is associated with several complications, such as renal failure, coronary artery disease, cardiac destabilization, and stroke. Medical therapy is the cornerstone for management of ARAS; however, numerous trials have compared medical therapy with revascularization in the form of percutaneous renal artery angioplasty (PTRA) or percutaneous renal artery angioplasty with stent placement (PTRAS). Medline (PubMed and Ovid SP), Embase, Cochrane Central Register of Controlled Clinical Trials (CENTRAL), and Cochrane Database of Systematic Review (CDSR) were searched till present (November 2013) to identify clinical trials where medical therapy was compared with revascularization (PTRA or PTRAS). We performed a meta-analysis using a random effects model. The heterogeneity was assessed using I2 values. The initial database search identified 540 studies and 7 randomized controlled trials, and 2,139 patients were included in the final analysis. Angioplasty with or without stenting was not superior to medical therapy with respect to any outcome. The incidence of nonfatal myocardial infarction was 6.74% in both the stenting and medical therapy group (odds ratio=0.998, 95% confidence interval 0.698 to 1.427, p=0.992), and incidence of renal events in stenting population was found to be 19.58% versus 20.53% in medical therapy (odds ratio=0.945, 95% confidence interval 0.755 to 1.182, p=0.620). In conclusion, PTRA or PTRAS does not improve outcomes compared with medical therapy in patients with ARAS. Future studies should investigate to identify patient subgroups that may benefit from such an intervention.
• Husnain, M., Kern, K. B., Lee, K. S., Lee, J. Z., Lotun, K., Riaz, I. B., & Riaz, H. (2013). TCT-847 Strut Level Optical Coherence Tomography Evaluation of Coronary Stent Strut Coverage Temporal Trends: A Systematic Review. Journal of the American College of Cardiology, 62(18), B255-B256. doi:10.1016/j.jacc.2013.08.1601
• Riaz, I. B., Husnain, M., Dhoble, A., Hsu, C. H., Lee, K. S., Lee, J. Z., Lotun, K., & Mizyed, A. (2013). Transcatheter patent foramen ovale closure versus medical therapy for cryptogenic stroke: a meta-analysis of randomized clinical trials.. BMC cardiovascular disorders, 13(1), 116. doi:10.1186/1471-2261-13-116
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  There is an association between cryptogenic stroke and patent foramen ovale (PFO). The optimal treatment strategy for secondary prevention remains unclear. The purpose of this study was to analyze aggregate data examining the safety and efficacy of transcatheter device closure versus standard medical therapy in patients with PFO and cryptogenic stroke..A search of published data identified 3 randomized clinical trials for inclusion. The primary outcome was a composite end-point of death, stroke and transient-ischemic attack (TIA). Pre-defined subgroup analysis was performed with respect to baseline characteristics including age, sex, atrial septal aneurysm and shunt size. Data was synthesized using a random effects model and results presented as hazard ratios (HRs) with 95% confidence intervals (CIs)..A cohort of 2,303 patients with a history of cryptogenic stroke and PFO were randomized to device closure (n = 1150) and medical therapy (n = 1153). Mean follow-up was 2.5 years. Transcatheter closure was not superior to medical therapy in the secondary prevention of stroke or TIA in intention-to-treat analysis (HR: 0.66, 95% CI: 0.43 to 1.01; p = 0.056). However, the results were statistically significant using per-protocol analysis (HR: 0.64, 95% CI: 0.41 to 0.98; p = 0.043). Males had significant benefit with device closure (HR: 0.48, 95% CI: 0.24 to 0.96; p = 0.038)..In this meta-analysis, using intention-to-treat analysis, transcatheter device closure of PFO was not superior to standard medical therapy in the secondary prevention of cryptogenic stroke. Transcatheter closure was superior using per-protocol analysis.

Poster Presentations

• Husnain, M. (2021, December). Non-Relapse Mortality in TP53-Mutated MDS/AML - a Multi-Center Collaborative Study. American Society of Hematology. Atlanta, GA.

Reviews

• Filioglou, D., Husnain, M., Khurana, S., Simpson, R. J., & Katsanis, E. (2023. Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?(p. 1329850).
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  The most common lymphodepletion regimen used prior to infusion of chimeric antigen receptor-T cells (CAR-T) is cyclophosphamide (CY) in combination with fludarabine (Flu) (CY-FLU). While cyclophosphamide (CY) possesses lymphotoxic effects, it concurrently preserves regulatory T cell activity, potentially affecting the efficacy of CAR-T cells. Moreover, the use of fludarabine (FLU) has been linked to neurotoxicity, which could complicate the early detection of immune effector cell-associated neurotoxicity syndrome (ICANS) observed in CAR-T cell therapy. Given the ongoing shortage of FLU, alternative lymphodepleting agents have become necessary. To date, only a limited number of studies have directly compared different lymphodepleting regimens, and most of these comparisons have been retrospective in nature. Herein, we review the current literature on lymphodepletion preceding CAR-T cell therapies for lymphoid hematologic malignancies, with a specific focus on the use of bendamustine (BEN). Recent evidence suggests that administering BEN before CAR-T cell infusion yields comparable efficacy, possibly with a more favorable toxicity profile when compared to CY-FLU. This warrants further investigation through randomized prospective studies.