Sharad Khurana

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Journals/Publications

• Khurana, S. (2024). Evaluation of Novel Targets, Including CC-Chemokine Receptor 4, in Adult T-Cell Acute Lymphoblastic Leukemia/Lymphoma: A Mayo Clinic Clinical and Pathologic Study. Archives of Pathology & Laboratory Medicine.
• Khurana, S., Heckman, M., Craig, F., Cochuyt, J., Greipp, P., Rahman, Z., Sproat, L., Litzow, M., Foran, J., & Jiang, L. (2024). Evaluation of Novel Targets, Including CC-Chemokine Receptor 4, in Adult T-Cell Acute Lymphoblastic Leukemia/Lymphoma A Mayo Clinic Clinical and Pathologic Study. Archives of Pathology and Laboratory Medicine, 148(4). doi:10.5858/arpa.2022-0482-oa
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  • Context.—Unlike B-cell acute lymphoblastic leukemia/ lymphoma (ALL/LBL), there have been few therapeutic advances in T-cell ALL (T-ALL)/LBL, an aggressive ALL/LBL subtype. Objective.—To perform a focused tissue array study to elucidate tumor markers of therapeutic potential in T-ALL/LBL. Design.—Using immunohistochemistry, we evaluated expression of leukemic antigens of interest, specifically CC-chemokine receptor 4 (CCR4), among others, on available remnant diagnostic material, including tumor tissue slides obtained from formalin-fixed, paraffin-embedded preserved tissues. Results.—Our analysis identified, for the first time, expression of CCR4 in T-ALL/LBL in 11 of 27 cases (40.7%) and confirmed common expression of BCL2, CD38, and CD47, as reported previously. We also identified the expression of CD123 in 4 of 26 cases (15.4%), whereas BCL6 and PDL1 were expressed in a small number of T-ALL/ LBL cases. The potential novel target CCR4 was significantly more common in the Pre/Pro-T immunophenotypic subtype, 6 of 9 (66.7%, P ¼ .01). No additional differences in clinical and epidemiologic variables were noted among positive or negative CCR4 cases. Conclusions.—These findings support preclinical and clinical testing of therapies targeting CCR4, CD47, BCL2, CD38, and CD123 in T-ALL/LBL, and may help guide the development of targeted clinical trials in T-ALL/LBL, a rare disease in urgent need of novel therapies.
• Wakefield, C., Hansen Smith, M., Dashkevych, U., Proytcheva, M., & Khurana, S. (2024). Clinical, Phenotypic and Molecular Characterization of Fusion Positive Myeloid Malignancies. Journal of medical cases, 15(9), 250-255.
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  The identification of a fusion has been seen in about 6% of patients with T lymphoblastic leukemia (T-ALL). It has been described at a lower frequency in B-lymphoblastic leukemia (B-ALL) patients as well. To our knowledge, this is the first case report documenting a fusion in a patient with newly diagnosed myelodysplastic syndrome (MDS) as identified by next-generation sequencing (NGS). A case report by Wang et al recently described a case report of the first fusion in a patient with newly diagnosed acute myeloid leukemia (AML). This shows that this specific translocation is not isolated to lymphoid malignancies, and can be associated with myeloid malignancies as well. The potential use of tyrosine kinase inhibitors (TKIs) as a line of treatment for patients who harbor this translocation makes this finding of particular interest. However, while there have been individual reports noting the effect of TKIs in T-ALLs with fusions, additional research is needed to fully understand the role of this mutation in myeloid derived malignancies, and its corresponding treatment and prognostic implications.
• Wakefield, C., Smith, M., Dashkevych, U., Proytcheva, M., & Khurana, S. (2024). Clinical, Phenotypic and Molecular Characterization of NUP214-ABL1 Fusion Positive Myeloid Malignancies. Journal of Medical Cases, 15(9). doi:10.14740/jmc4286
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  The identification of a NUP214-ABL1 fusion has been seen in about 6% of patients with T lymphoblastic leukemia (T-ALL). It has been described at a lower frequency in B-lymphoblastic leukemia (B-ALL) patients as well. To our knowledge, this is the first case report documenting a NUP214-ABL1 fusion in a patient with newly diagnosed myelodysplastic syndrome (MDS) as identified by next-generation sequencing (NGS). A case report by Wang et al recently described a case report of the first NUP214-ABL1 fusion in a patient with newly diagnosed acute myeloid leukemia (AML). This shows that this specific translocation is not isolated to lymphoid malignancies, and can be associated with myeloid malignancies as well. The potential use of tyrosine kinase inhibitors (TKIs) as a line of treatment for patients who harbor this translocation makes this finding of particular interest. However, while there have been individual reports noting the effect of TKIs in T-ALLs with NUP214-ABL1 fusions, additional research is needed to fully understand the role of this mutation in myeloid derived malignancies, and its corresponding treatment and prognostic implications.
• Asghar, N., Masood, A., Dhaliwal, A., Khurana, S., Davis, J., Hashmi, H., & Husnain, M. (2023). Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review of Literature. Clinical lymphoma, myeloma & leukemia, 23(1), 15-21.
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  Relapsed/refractory central nervous system (CNS) lymphoma, whether primary or secondary, is associated with poor prognosis with currently available treatment modalities, including high-dose chemotherapy-autologous stem cell transplantation. The pivotal ZUMA-1 and JULIET trials that led to FDA approval of Axicabtagene ciloleucel and Tisagenlecleucel for relapsed refractory large cell lymphoma excluded patients with CNS involvement due to concerns of increased toxicity. However, TRANSCEND study for Lisocabtagene maraleucel in relapsed refractory large cell lymphoma allowed patients with CNS involvement and reported manageable CNS toxicities in these patients. In the real-world experience, chimeric antigen receptor T-cell (CAR T) therapy has been deemed safe and effective for these patients with poor prognosis. In this systematic review, we analyzed available literature to evaluate the role of CAR T-cell therapy in both primary and secondary CNS lymphoma using Embase, Cochrane, and PubMed databases. A total of 14 studies, including 8 retrospective analyses and 6 prospective studies/clinical trials, were included in the qualitative synthesis to study the safety and efficacy of CAR T. Based on our analysis, CAR T-cell therapy appears to be associated with reasonable efficacy and a manageable safety for primary and secondary CNS lymphoma.
• Filioglou, D., Husnain, M., Khurana, S., Simpson, R., & Katsanis, E. (2023). Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?. Frontiers in Immunology, 14. 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.
• Khurana, S., Heckman, M. G., Craig, F. E., Cochuyt, J. J., Greipp, P., Rahman, Z. A., Sproat, L. Z., Litzow, M., Foran, J. M., & Jiang, L. J. (2023). Evaluation of Novel Targets, Including CC-Chemokine Receptor 4, in Adult T-Cell Acute Lymphoblastic Leukemia/Lymphoma. Archives of pathology & laboratory medicine.
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  Unlike B-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL), there have been few therapeutic advances in T-cell ALL/LBL, an aggressive ALL/LBL subtype.
• Rein, L. A., El Chaer, F., Yuda, J., Shimoda, K., McCloskey, J., Takami, A., Haque, T., Ichii, M., Shirane, S., Fukaya, M., Scandura, J. M., Bradley, T., Vachhani, P., Tabayashi, T., Green, S., Cheung, S., Bose, P., Khurana, S., O'Connell, C. L., , Amanam, I., et al. (2023). Phase 1/2 Study of TP-3654, a Selective PIM1 Kinase Inhibitor: Preliminary Data Showed Clinical Activity and Cytokine Reductions in Relapsed/Refractory Myelofibrosis Patients. Blood, 142(Supplement 1), 626-626. doi:10.1182/blood-2023-180164
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  Background: PIM1 expression is significantly upregulated in hematologic malignancies including myelofibrosis (MF) and has been shown to play a role in modulating the activity of cytokine induced PI3K/AKT and JAK/STAT pathways. The distinct clinical features of MF are partly attributed to the elevated circulating cytokines; a subset of which are shown to correlate with poor prognosis. TP-3654, an oral investigational highly selective PIM1 kinase inhibitor, is currently being evaluated in a phase 1/2 study in patients (pts) with relapsed/refractory MF. In preclinical studies, TP-3654 alone and in combination with ruxolitinib showed spleen size and bone marrow (BM) fibrosis reduction in murine MF models. Importantly, TP-3654 also showed reduction of cytokine response genes and serum TGF-β in progenitor cells and JAK2V617F murine MF model, respectively. Methods: This phase 1/2 study evaluates the safety and efficacy of TP-3654 monotherapy in pts with MF (NCT04176198). Key eligibility criteria include primary or secondary MF; previously treated with or ineligible for JAK inhibitor treatment; DIPSS intermediate 1, 2 or high-risk MF; platelet ≥25x10 9/L; splenomegaly (≥450 cm 3 by imaging); and ≥2 measurable symptoms per MFSAF v4. The study aims to identify the MTD and/or RP2D of TP-3654 monotherapy and to assess safety, clinical activity (spleen volume reduction [SVR], total symptom score [TSS] improvement), PK, and PD markers (cytokine profile, BM fibrosis etc.). We investigated the patterns of similarity of 43 cytokines changes after 12 weeks of TP-3654 treatment using principal component analysis (PCA). Results: As of 20 June 2023, a total of 23 pts enrolled across 5 dose levels in the phase 1 dose escalation part. At baseline, median age 73 years (range 61, 80), spleen volume 2008.2 cm 3 (range 609, 6006), TSS 20.8 (range 4, 62), platelet 115 x10 9/L (range 64, 520), hemoglobin 10.1 g/dL (range 5.9, 13.7; 5 pts requiring transfusion). All pts, except one, had received ≥1 prior JAK inhibitor treatment (median 12.9 months [range 2.3, 81.0]). Median duration of TP-3654 treatment was 14.9 weeks (range 2, 96). No DLT occurred. Treatment-related adverse events (TRAEs) occurring in ≥20% of pts included grade 1/2 nausea, vomiting, and diarrhea. Grade 3 TRAEs were diarrhea (n=1) and platelet count decreased (n=2). Mean hemoglobin and platelet counts remained stable throughout the 24-week treatment period. SVR observed in 10 of 13 evaluable pts treated for ≥12 weeks (median best change -11%, range +97% to -63%); 3 pts showed ≥35% SVR. TSS improvement were observed in 12 of 13 evaluable pts (median best change -70%, range +9 to -100%); 7 pts showed ≥50% TSS response (Fig 1A); 5 pts had durable response for ≥12 weeks. Broad reductions in cytokines observed as early as within the first 24 hours after TP-3654 treatment. At week 12, pts with higher cytokine reductions correlated with greater TSS improvement. Two components of the PCA, PC1 and PC7, include MF associated cytokines such as IL-8, IL-18, CD40, ENRAGE amongst others, were reduced with TP-3654 treatment and these reductions correlated with symptom improvement (Fig 1B). BM fibrosis was reduced in one pt who also achieved spleen and symptom responses, showed MF associated cytokine reductions, and is on active treatment for 2 years. Conclusions: This preliminary data of TP-3654 in relapsed/refractory MF pts showed early signs of clinical activity including spleen volume reduction, TSS improvement, and correlating cytokine reductions. TP-3654 is well tolerated with limited myelosuppressive adverse events. Enrollment is ongoing as monotherapy and current data support the development of TP-3654 in combination with JAK inhibitors given the preliminary clinical activity and minimal cytopenia.
• Shahzad, M., Hussain, A., Tariq, E., Anwar, I., Faisal, M. S., Syed, L., Karam, A., Chaudhary, S. G., Ahmed, N., Bansal, R., Khurana, S., Singh, A. K., Byrd, K. P., Hematti, P., Abhyankar, S. H., McGuirk, J. P., & Mushtaq, M. U. (2023). Outcomes of Tyrosine Kinase Inhibitors Maintenance Therapy with or without Allogeneic Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in First Complete Remission: A Systematic Review and Meta-Analysis. Clinical lymphoma, myeloma & leukemia.
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  We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) maintenance therapy with or without allogeneic hematopoietic stem cell transplantation (HSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in first remission (CR1). A literature search was performed on PubMed, Cochrane, and Clinical trials.gov. After screening 1720 articles, 12 studies were included. Proportions and odds ratios (OR) with 95% confidence intervals (CI) were computed. I provides an estimate of the percentage of variability in results across studies that is due to real differences and not due to chance. Of 1039 patients, 635 (61%) had TKI alone and 404 (39%) patients had HSCT followed by TKI. At 3 years, a trend towards poor overall survival (OS; OR 0.67, 95% CI 0.39-1.15, I = 68%), (disease-free survival; OR 0.58, 95% CI 0.26-1.29, I = 76%), and higher relapse rate (RR; OR = 2.52, 95% CI = 1.66-3.83, I = 26%) was seen with TKI alone compared to HSCT-TKI. Although HSCT followed by TKI maintenance in Ph+ ALL has long been considered standard of care, the introduction of potent third-generation TKIs and bispecific T-cell engagers such as Blinatumomab has significantly improved outcomes while sparing the need for HSCT in newly diagnosed patients.
• 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.
• 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.
• Khurana, S., Shahzad, M., Chaudhary, S. G., Zafar, M. U., Hassan, M. A., Hussain, A., Ali, F., Anwar, I., Ahmed, M., Ahmed, N., Rauf, M. A., Anwar, F., Hematti, P., Callander, N. S., Abhyankar, S. H., McGuirk, J. P., & Mushtaq, M. U. (2022). Impact of COVID‐19 in hematopoietic stem cell transplant recipients: A systematic review and meta‐analysis. Transplant Infectious Disease, 24(2). doi:10.1111/tid.13792
• Khurana, S., Simpson, R. J., Roe, D. J., Husnain, M., Truscott, L. C., Kovacs, K., Stea, B., & Katsanis, E. (2022). Feasibility and Efficacy of Partially Replacing Post-Transplantation Cyclophosphamide with Bendamustine in Pediatric and Young Adult Patients Undergoing Haploidentical Bone Marrow Transplantation. Biology of Blood and Marrow Transplantation. doi:10.1016/j.jtct.2022.04.015
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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.
• Shahzad, M., Chaudhary, S. G., Zafar, M. U., Hassan, M. A., Hussain, A., Ali, F., Anwar, I., Ahmed, M., Ahmed, N., Khurana, S., Rauf, M. A., Anwar, F., Hematti, P., Callander, N. S., Abhyankar, S. H., McGuirk, J. P., & Mushtaq, M. U. (2022). Impact of COVID-19 in hematopoietic stem cell transplant recipients: A systematic review and meta-analysis. Transplant infectious disease : an official journal of the Transplantation Society, 24(2), e13792.
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  Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of mortality and morbidity with coronavirus disease 2019 (COVID-19) due to severe immune dysfunction.
• Bojanini Molina, L., Khurana, S., Melody, M., Jiang, L., & Roy, V. (2021). Low-Dose Methotrexate Causing Fatal Pancytopenia in a Patient With Severe Malnutrition. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 27(8S), S764-S765.
• Shahzad, M., Siddiqui, R. S., Anwar, I., Chaudhary, S. G., Ali, T., Naseem, M., Ahmed, T. F., Ahmed, Z., Khurana, S., Ahmed, N., Balusu, R., Singh, A. K., Hematti, P., Callander, N. S., Abhyankar, S. H., McGuirk, J. P., & Mushtaq, M. U. (2021). Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis. Transplantation and cellular therapy, 27(10), 877.e1-877.e8.
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  Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) characterized by multilineage cytopenia in the absence of mixed donor chimerism (
• Beltran, M., Foran, J. M., Gil, Y., Khurana, S., Kumar, R., & Lewis, J. T. (2020). Nonimmunoglobulin Crystal-Storing Histiocytosis (CSH): Case Report and Literature Review.. Case reports in hematology, 2020, 8856411. doi:10.1155/2020/8856411
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  Crystal-storing histiocytosis (CSH) is an uncommon condition in which histiocytes accumulate a crystalline matter within their cytoplasm. Generally, those crystals are composed of either monoclonal or polyclonal immunoglobulin chains, which have a strong association with an underlying lymphoproliferative or plasma cell disorder (LP-PCD). Rarely, CSH has been reported as local or generalized manifestation of a variety of benign disorders. These cases are associated with crystals composed of nonimmunoglobulin substances. We are reporting an exceptional case of a local colonic CSH with Charcot-Leyden crystals. This patient underwent a screening colonoscopy that detected some polyps. The biopsy reported tubular adenomas, with a markedly dense, transmural inflammatory infiltrates, which were predominantly composed of eosinophils and crystal-storing histiocytes containing Charcot-Leyden crystals. The patient had a negative workup for LP-PCD and autoimmune conditions, including a normal skeletal survey and bone marrow aspirate/biopsy. The only positive laboratory workup was an elevated absolute eosinophil count and a positive IgG anti-Strongyloides antibody. Giving those findings, this parasitic infection is the most likely etiology of the CSH in our patient. Although there was an initial negative evaluation for LP-PCD, close monitoring of patients with either immunoglobulin or nonimmunoglobulin CSH is recommended.
• Khurana, S., Melody, M. E., Ketterling, R. P., Peterson, J. F., Luoma, I. M., Vazmatzis, G., Tun, H. W., Foran, J. M., & Jiang, L. (2020). Molecular and phenotypic characterization of an early T-cell precursor acute lymphoblastic lymphoma harboring PICALM-MLLT10 fusion with aberrant expression of B-cell antigens. Cancer Genetics, 240(Issue). doi:10.1016/j.cancergen.2019.11.002
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  T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is usually diagnosed based on the presence of immature lymphoid marker terminal deoxynucleotidyl transferase (TdT), and T-cell specific markers, specifically CD3, by immunohistochemistry (IHC) staining on bone marrow and/or extramedullary tissue. We present a novel, TdT and CD3 negative, aggressive early T-cell precursor LBL (ETP-LBL) initially misdiagnosed as a high grade B-cell lymphoma due to expression of CD79a and the erroneous detection of BCL2/IGH fusion. The patient was eventually evaluated using molecular diagnostic techniques, including fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) assays that demonstrated PICALM-MLLT10 fusion and a NOTCH1 mutation in the absence of BCL2/IGH fusion. The use of NGS, specifically mate-pair sequencing (MPseq), subsequently confirmed an in-frame PICALM-MLLT10 fusion. Our retrospective analysis showed that PICALM-MLLT10 fusion has no association with CD3/TdT negativity, as 6/49 T-ALL/LBL cases from Mayo Clinic database (01/1998–09/2018), including this case, were noted to have PICALM-MLLT10 fusion; however, none of the other cases were associated with CD3/TdT negativity. We emphasize the importance of a comprehensive hematopathologic evaluation including multiple molecular studies for the appropriate interrogation and classification of a difficult acute leukemia diagnosis, and to prevent potential diagnostic errors of clinical significance.
• Khurana, S., Sluzevich, J. C., He, R., Reimer, D. K., Kharfan-Dabaja, M. A., Foran, J. M., & Jiang, L. (2020). Association between High-grade Myelodysplastic Syndrome and Cutaneous Langerhans Cell Histiocytosis Suggested by Next-Generation Sequencing. JAMA Dermatology, 156(Issue 7). doi:10.1001/jamadermatol.2020.0544
• Melody, M., Butts, E., Menke, D., Landolfo, K., Oken, K., Sher, T., & Khurana, S. (2020). Use of Tocilizumab in Management of Post-Operative Myelomonocytic Leukemoid Reaction. Leukemia Research Reports, 14(Issue). doi:10.1016/j.lrr.2020.100228
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  Interleukin 6 receptor (IL6R) inhibitor, tocilizumab, has been effectively used in the treatment of cytokine release syndrome in patients receiving chimeric antigen receptor T-cell therapy. Here we present a patient with chronic myelomonocytic leukemia (CMML) who developed a steroid refractory, post-operative myelomonocytic leukemoid reaction (PO-MMLR), effectively treated with tocilizumab. Although, further studies are needed to validate the effectiveness of tocilizumab in management of PO-MMLR, this case serves to provide a new management approach in treatment of this rare but lethal syndrome with no standardized treatment options.
• Ailawadhi, S., Dholaria, B. R., Khurana, S., Sher, T., Alegria, V., Paulus, A., Ailawadhi, M., Mehta, A., Chanan-Khan, A., & Roy, V. (2019). Outcomes of patients with simultaneous diagnosis of chronic lymphocytic leukaemia/small lymphocytic lymphoma and multiple myeloma. British Journal of Haematology, 185(Issue 2). doi:10.1111/bjh.15458
• Khurana, S., Baldeo, C., & Joseph, R. W. (2019). Inositol hexaphosphate plus inositol induced complete remission in stage IV melanoma: A case report. Melanoma Research, 29(Issue 3). doi:10.1097/cmr.0000000000000577
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  Inositol hexaphosphate (IP6) also called phytic acid is a polyphosphorylated carbohydrate naturally found in cereals, nuts, grains, and high-fiber-containing foods. It has been shown to inhibit the growth of many different tumor cell lines both in vitro and in vivo like colon, pancreas, liver, prostate, and even melanoma. Vitamin B inositol is a precursor of IP6 and another naturally occurring compound with anticancer properties. We present a case report of a patient with metastatic melanoma who declined traditional therapy and opted to try over the counter supplement IP6+inositol instead. To our surprise, the patient achieved a complete remission and remains in remission 3 years later. On the basis of this case and previous preclinical studies, we believe further research is indicated in exploring antiproliferative and potential immune stimulating effects of IP6+inositol in patients with metastatic melanoma.

Poster Presentations

• Khurana, S. (2023). Phase 1/2 Study of TP-3654, a Selective PIM1 Kinase Inhibitor: Preliminary Data Showed Clinical Activity and Cytokine Reductions in Relapsed/Refractory Myelofibrosis Patients. ASH.
• Khurana, S. (2023, December). Phase 1b/2 Study of Escalating Doses of the NEDD8 Activating Enzyme Inhibitor Pevonedistat Administered in Combination with Standard Induction Therapy (Cytarabine and Idarubicin) in Newly Diagnosed High Risk Acute Myeloid Leukemia.. ASH.

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.