Malvi Bipin Savani

Interests

No activities entered.

Courses

No activities entered.

Scholarly Contributions

Journals/Publications

• Mahmud, M., Munjal, A., Savani, M., Win, H., Rozell, U. A., & Arshad, J. (2024). Biomarker Testing and Role of Tyrosine Kinase Inhibitors and Immunotherapy for Esophageal Squamous Cell Carcinoma. Foregut: The Journal of the American Foregut Society. doi:10.1177/26345161241238748
  More info

  Esophageal squamous cell carcinoma (ESCC) constitutes an aggressive subset of esophageal cancers that portends a poor prognosis. Management of ESCC has been historically challenging due to the limited effective therapeutic options. Broadening our understanding of the molecular landscape and identifying reliable biomarkers are essential in early detection, monitoring disease response and advancing treatment strategies. Recently, immunotherapy and tyrosine kinase inhibitors have changed the treatment algorithm of ESCC. In this review, we explore the molecular landscape and biomarkers that can aid in the management of ESCC and discuss the role of immunotherapy and tyrosine kinase inhibitors in the treatment of ESCC.
• Cazeau, N., Palazzo, M., Savani, M., & Shroff, R. (2022). COVID-19 Vaccines and Immunosuppressed Patients With Cancer: Critical Considerations. Clin J Oncol Nurs, 26(4). doi:10.1188/22.CJON.367-373
  More info

  BACKGROUND: Patients with cancer are highly vulnerable to COVID-19 because of immunosup-pression from diseases and treatments. Emerging data characterize the impact of COVID-19 vaccines related to cancer malignancies and treatments. OBJECTIVES: This article provides a clinical foundation on the immune response to the COVID-19 vaccine associated with the impact of cancer and its related treatments. It reviews strategies for vaccine scheduling, Centers for Disease Control and Prevention recommendations, and nursing considerations when administering the vaccine to immunosup-pressed patients. METHODS: Research studies about immune responses to COVID-19 vaccines among immu-nosuppressed patients with hematologic and solid tumor malignancies were summarized. FINDINGS: Studies about the humoral immune responses of patients with cancer to COVID-19 vaccines help guide vaccination planning for this population. Critical nursing considerations for patients with cancer receiving COVID-19 vaccination are integral to the provision of optimal clinical oncology care during the pandemic.
• Pu, J., Savani, M., Huang, N., & Epner, E. (2022). Mantle cell lymphoma management trends and novel agents: where are we going?. Ther Adv Hematol, 13. doi:10.1177/20406207221080743
  More info

  The heterogeneity in disease pathology, the unpredictability in disease prognosis, and the variability in response to therapy make mantle cell lymphoma (MCL) a focus of novel therapeutic development. MCL is characterized by dysregulated expression of cyclin D1 through a chromosome t(11;14) translocation. MCL international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation status are currently utilized for prognostication. With advances in pharmacokinetic analysis and drug discovery, treatment strategy has evolved from chemotherapy to combination of targeted, epigenetic, and immune therapies. In this review, we discuss investigational and newly approved treatment approaches. In a short time, the US Food and Drug Administration (FDA) has approved five agents for the treatment of MCL: lenalidomide, an immunomodulatory agent; bortezomib, a proteasome inhibitor; and ibrutinib, acalabrutinib, and zanubrutinib, all Bruton kinase inhibitors. Epigenetic agents (e.g. cladribine and vorinostat), mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus and everolimus), and monoclonal antibodies and/or antibody-drug conjugates (e.g. obinutuzumab, polatuzumab, and ublituximab) are promising therapeutic agents currently under clinical trial investigation. Most recently, chimeric antigen receptor (CAR)-T cell therapy and bispecific T-cell engager (BiTE) therapy even open a new venue for MCL treatment. However, due to its intricate pathology nature and high relapse incidence, there are still unmet needs in developing optimal therapeutic strategies for both frontline and relapsed/refractory settings. The ultimate goal is to develop innovative personalized combination therapy approaches for the purpose of delivering precision medicine to cure this disease.
• Savani, M., & Shroff, R. T. (2022). Decision-Making Regarding Perioperative Therapy in Individuals with Localized Pancreatic Adenocarcinoma. Hematol Oncol Clin North Am. doi:10.1016/j.hoc.2022.07.003
  More info

  Pancreatic cancer is a fatal malignancy that is projected to emerge as the second leading cause of cancer-related death in the United States. Despite the critical advances in surgical strategies, radiographic techniques, and systemic therapy, the treatment modality has remained largely unchanged over the past two decades eliciting a dire need for clinical trials in improving quality of life and prolonging survival in this patient population. Emergence of innovative strategies including novel combination chemotherapy , immunotherapy , vaccines, small compound drugs , among others is avenues under investigation to improve perioperative outcomes in localized pancreatic cancer.
• Savani, M., Ahn, K., Chen, Y., Ahmed, S., Cashen, A. F., Shadman, M., Modi, D., Khimani, F., Cutler, C. S., Zain, J., Brammer, J., Rezvani, A., Fenske, T., Sauter, C., Kharfan-Dabaja, M., Herrera, A. F., & Hamadani, M. (2022). Impact of conditioning regimen intensity on the outcomes of peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma patients undergoing allogeneic transplant. Br J Haematol, 197(2). doi:10.1111/bjh.18052
  More info

  There have been no large studies comparing reduced-intensity/non-myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T-cell non-Hodgkin lymphoma (T-NHL) patients undergoing allogeneic transplant (allo-HCT). A total of 803 adults with peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma (age 18–65 years), undergoing allo-HCT between 2008–2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation-specific comorbidity index (HCT-CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79–1.29; p = 0.95). Similarly, non-relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61–1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98–1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92–1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3–4 acute graft-versus-host disease (HR = 0.67; 95% CI = 0.46–0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo-HCT for T-cell NHL.
• Evens, A. M., Danilov, A. V., Jagadeesh, D., Sperling, A., Kim, S. H., Vaca, R., Wei, C., Rector, D., Sundaram, S., Reddy, N., Lin, Y., Farooq, U., D’Angelo, C., Bond, D. A., Berg, S., Churnetski, M. C., Godara, A., Khan, N., Choi, Y. Y., , Yazdy, M. S., et al. (2021). Burkitt lymphoma in the modern era: real-world outcomes and prognostication across 30 US cancer centers. Blood. doi:10.1182/blood.2020006926
  More info

  Abstract We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P < .001) and without difference based on setting of administration (ie, inpatient vs outpatient). Outcomes were also improved at an academic vs community cancer center (3-year PFS, 67% vs 46%, P = .006; OS, 72% vs 53%, P = .01). In multivariate models, age ≥ 40 years (PFS, hazard ratio [HR] = 1.70, P = .001; OS, HR = 2.09, P < .001), ECOG PS 2 to 4 (PFS, HR = 1.60, P < .001; OS, HR = 1.74, P = .003), lactate dehydrogenase > 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates.
• Hanel, W., Chen, Y., Yu, M., Yang, D., Guo, L., Karmali, R., Burkart, M., Ciccosanti, C., David, K., Risch, Z., Murga-Zamalloa, C., Devata, S., Wilcox, R., Savani, M., Courville, E., Bachanova, V., Rabinovich, E., Peace, D., Osman, F., , Epperla, N., et al. (2021). Impact of initial chemotherapy regimen on outcomes for patients with double-expressor lymphoma: A multi-center analysis. Hematol Oncol, 39(4). doi:10.1002/hon.2902
  More info

  Diffuse large B-cell lymphoma featuring overexpression of MYC and B-Cell Lymphoma 2 (double expressor lymphoma, DEL) is associated with poor outcomes. Existing evidence suggesting improved outcomes for DEL with the use of more intensive regimens than R-CHOP is restricted to younger patients and based on limited evidence from low patient numbers. We retrospectively evaluated the impact of intensive frontline regimens versus R-CHOP in a multicenter analysis across 7 academic medical centers in the United States. We collected 90 cases of DEL, 46 out of 90 patients (51%) received R-CHOP and 44/90 (49%) received an intensive regimen, which was predominantly DA-EPOCH-R. Treatment cohorts were evenly balanced for demographics and disease characteristics, though the intensive group had a higher lactate dehydrogenase (LDH, 326 vs. 230 U/L p = 0.06) and presence of B-symptoms (50% vs. 22%, p = 0.01) compared to the R-CHOP cohort. There was no difference in PFS (median 53 vs. 38 months, p = 0.49) or overall survival (67 vs. not reached months, p = 0.14) between the R-CHOP and intensive therapy cohorts, respectively. On multivariate analysis, intensive therapy was associated with a hazard ratio of 2.35 (95% CI 0.74–7.41), though this was not statistically significant. Additionally, a subgroup analysis of intermediate high-risk lymphoma defined by IPI ≥3 did not identify a difference in survival outcomes between regimens. We conclude that in our multi-center cohort there is no evidence supporting the use of intensive regimens over R-CHOP, suggesting that R-CHOP remains the standard of care for treating DEL.
• Julian, R., Savani, M., & Bauman, J. E. (2021). Immunotherapy Approaches in HPV-Associated Head and Neck Cancer. Cancers. doi:10.3390/cancers13235889
• Mohty, R., Duléry, R., Bazarbachi, A. H., Savani, M., Hamed, R. A., Bazarbachi, A., & Mohty, M. (2021). Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J. doi:10.1038/s41408-021-00518-z
  More info

  Hodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody-drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field.
• Mohty, R., Savani, M., Brissot, É., & Mohty, M. (2021). Nutritional Supplements and Complementary/Alternative Medications in Patients With Hematologic Diseases and Hematopoietic Stem Cell Transplantation. Transplant Cell Ther. doi:10.1016/j.jtct.2021.03.011
  More info

  This perspective article discusses the various practices classified as complementary and alternative medicine (CAM) and reviews the benefits and uncertainties with respect to nutritional supplements in patients with hematological disease. It considers the high prevalence of CAM use especially among cancer survivors, particularly patients with hematologic malignancies and allogeneic stem cell transplant survivors, many of whom believe (because of extensive advertising) that supplements are anticancer/antitoxic agents, despite the paucity of evidence to support any benefit and the enormous cost to the individual. CAM constitutes various practices and nutritional behaviors including prayers, relaxation, spiritual healing, nutritional supplements, meditation, religious counseling, massage, and support groups. We highlighted the current literature regarding CAM practices and focused our discussion on the omnipresent nutritional supplements in particular to further expound on their benefits and adverse effects. As the number of survivors after HSCT increases over the next several years along with prevalence of CAM use, it becomes imperative to ascertain any beneficial potential, as well as toxicities associated with CAM use in this population.
• Savani, M., Dulery, R., Bazarbachi, A. H., Mohty, R., Brissot, E., Malard, F., Bazarbachi, A., Nagler, A., & Mohty, M. (2021). Allogeneic haematopoietic cell transplantation for myelofibrosis: a real‐life perspective. British Journal of Haematology, 195(4), 495-506. doi:10.1111/bjh.17469
• Savani, M., Oluwole, O. O., & Dholaria, B. (2021). New targets for CAR T therapy in hematologic malignancies. Best Pract Res Clin Haematol. doi:10.1016/j.beha.2021.101277
• Savani, M., Woerner, K., Bu, L., Birkenbach, M., & Skubitz, K. (2021). Pegylated liposomal doxorubicin-induced renal toxicity in retroperitoneal liposarcoma: a case report and literature review. Cancer Chemother Pharmacol, 87(2). doi:10.1007/s00280-020-04203-z
  More info

  Doxorubicin is one of the most active drugs for sarcoma. Pegylated liposomal doxorubicin (PLD) is a unique formulation of doxorubicin, which carries a more favorable toxicity profile in comparison with free doxorubicin. The main toxicity of PLD is hand–foot syndrome. Unlike free doxorubicin, PLD is unlikely to cause alopecia, nausea, myelosuppression, or cardiotoxicity. Additionally, no premedications are required. We describe the case of a 50-year-old man with advanced retroperitoneal liposarcoma who developed irreversible PLD-associated progressive renal failure requiring chronic hemodialysis due to a thrombotic microangiopathy. No cardiotoxicity was noted 84 months after he initiated PLD. This case describes a lesser known toxicity of PLD and may be a toxicity of long-term treatment with other liposomal drugs.
• Zayac, A., Evens, A. M., Danilov, A. V., Smith, S. D., Jagadeesh, D., Leslie, L. A., Wei, C., Kim, S. H., Naik, S., Sundaram, S., Reddy, N., Farooq, U., Kenkre, V. P., Epperla, N., Blum, K. A., Khan, N., Singh, D., Alderuccio, J. P., Godara, A., , Yazdy, M. S., et al. (2021). Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study. Haematologica. doi:10.3324/haematol.2020.270876
• Savani, M., Gençtürk, M., Shanley, R., Cayci, Z., Wilke, C., Warlick, E. D., He, F., Janakiram, M., Weisdorf, D. J., Brunstein, C. G., & Bachanová, V. (2020). Surveillance Imaging after Autologous Hematopoietic Cell Transplantation Predicts Survival in Patients with Diffuse Large B Cell Lymphoma. Biology of Blood and Marrow Transplantation. doi:10.1016/j.bbmt.2019.10.013
  More info

  The utility of surveillance imaging after autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory diffuse large B cell lymphoma (DLBCL) remains unclear. The purpose of this study was to determine whether surveillance imaging predicts survival after AHCT. At the University of Minnesota, serial imaging for early relapse detection has been used prospectively for all consecutive AHCT recipients treated since 2010. The present analysis included 91 AHCT recipients with DLBCL who underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scan at day +100 post-AHCT. 18F-FDG-PET parameters included the Deauville (D) 5-point scale, peak standardized uptake values (SUVmax), total legion glycolysis (TLG), and total metabolic tumor volume (TMTV). Survival of patients with clinically symptomatic versus asymptomatic radiographically detected relapsed DLBCL after AHCT was compared. Sixty patients experienced relapse; 35% was detected on day +100 surveillance PET scan. 5-year overall survival (OS) by 18F-FDG-PET scan at day +100 post-AHCT was significantly lower in D4 and D5 patients (37%; 95% confidence interval [CI], 14% to 100% versus 25%; 95% CI, 43% to 89%) compared with patients with D1 and D2 (62%; 95% CI, 43% to 89% versus 62%; 95% CI, 46% to 84%). TLG and TMTV were not prognostic. SUVmax at day +100 varied from 1.5 (D1) to 17.9 (D5). In multivariate analysis, only SUVmax was predictive of relapse and OS; mortality increased 1.8-fold with each SUVmax doubling (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.3; P < .01). At a median follow-up of 3.3 years (range, 1 to 12 years), lymphoma-related mortality was 1.8-fold higher among patients whose relapse was detected clinically (symptomatic) versus radiographically on surveillance scan (HR, 1.8; 95% CI, .9 to 3.4; P = .08). In patients with relapsed/refractory DLBCL, a routine PET imaging at day +100 post-AHCT detects asymptomatic relapse and high SUVmax identifies patients with poor expected survival of less than 1 year. Identifying this high-risk cohort can potentially highlight patients who might benefit from preemptive interventions to prevent or delay relapse.
• Mukhija, D., Savani, M., Shaikh, S., Shah, S., Rybicki, L., Winter, A., Jagadeesh, D., Gerds, A. T., Dean, R. M., Wilke, C., Sobecks, R., Pohlman, B., Bolwell, B. J., Kalaycio, M., Hamilton, B. K., Majhail, N. S., Hill, B. T., & Bachanová, V. (2019). Post-Transplant Radiation Had No Impact on Survival in Patients with Refractory or Relapsed Diffuse Large B-Cell Lymphoma. Biology of Blood and Marrow Transplantation. doi:10.1016/j.bbmt.2018.12.825
  More info

  IntroductionHigh-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) offers cure for appropriate patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) sensitive to chemotherapy. Post-AHCT consolidative radiation therapy (RT) has been associated with improved outcomes in R/R DLBCL patients with bulky [based on computed tomography (CT)] disease after AHCT. We and others have demonstrated that patients with a Deauville score 4-5 (high-risk) on pre-AHCT FDG positron emission tomography (PET) have significantly worse outcomes as compared to those with Deauville 1-3 (low risk). We here examined the impact of consolidative post-AHCT RT in R/R-DLBCL patients with high-risk functional imaging based on Deauville score) on pre-transplant FDG PET scan on AHCT outcomes. Therefore, we retrospectively studied the effect of post-ASCT RT within 6 months after ASCT on survival in patients with R/R-DLBCL with high-risk pre-ASCT PET scans.MethodsWe retrospectively studied 193 consecutive adult patients with R/R-DLBCL identified from the Cleveland Clinic and University of Minnesota who had available pre-transplant FDG PET scans and adequate clinical follow-up. PET scans were re-reviewed and scored Deauville 4-5 were considered high risk. Patients that died within 6 months of ASCT (n=20) were excluded from the final survival analyses. Univariate analysis was performed using the Kaplan-Meier method, and the log-rank test was used to compare the subgroups.ResultsThe mean (SD) age of diagnosis was 54 (11) years and 61% patients were male. The mean follow-up for alive patients was 43 (32.6) months. We identified 69 patients with pre-transplant Deauville scores 4 (n=41) or 5 (n=28). Seventeen (25%) received RT at median 58 days post AHCT (IQR 39-79 days). Receiving post-ASCT RT did not impact overall survival in univariable (Figure 1) or multivariable analyses adjusted for age and gender.ConclusionWithin the limits of the study design, we did not observe a benefit to RT on overall survival in patients with RR-DLBCL with high-risk pre-AHCT PET scans. Alternative treatment approaches for high risk patients based on pre-transplant PET should be investigated in prospective clinical trials.
• Savani, M., & Skubitz, K. (2019). Long-term Outcome After Doxorubicin and Ifosfamide Overdose in a Patient With Osteosarcoma and BARD1 Mutation. J Pediatr Hematol Oncol, 41(2). doi:10.1097/MPH.0000000000001264
  More info

  Current treatment of high-grade osteosarcoma consists of preoperative chemotherapy, typically using some combination of doxorubicin, cisplatin, ifosfamide, and/or high-dose methotrexate followed by surgical resection. In this report, we present a case of a 21-year-old woman with high-grade osteosarcoma of the chest wall who received 5 times the planned dose of doxorubin and 4 times the planned dose of ifosfamide. She survived this chemotherapy overdose after administration of dimethyl sulfoxide and phenobarbital. Despite the administration of 5 times the proposed dose of doxorubicin, the patient survived without cardiotoxicity, and later delivered a normal baby. Although there are many studies evaluating treatment for chemotherapy regimen-related toxicity, sparse data exist with respect to chemotherapy overdose and the appropriate course of action. This case further confirms the lower cardiotoxicity of continuous intravenous infusion of doxorubicin and provides support for the use of dimethyl sulfoxide in the prevention of toxicity in chemotherapy overdose.
• Savani, M., Gençtürk, M., Shanley, R., Cayci, Z., Wilke, C., Warlick, E. D., Weisdorf, D. J., Brunstein, C. G., & Bachanová, V. (2019). Surveillance PET 100 Days after Autologous Hematopoietic Cell Transplantation Identifies Diffuse Large B Cell Lymphoma Patients with Extremely Poor Survival. Biology of Blood and Marrow Transplantation. doi:10.1016/j.bbmt.2018.12.834
  More info

  IntroductionThe utility of surveillance imaging following auto-HCT in relapsed/refractory DLBCL remains unclear. Imaging is costly and exposes patients to radiation. Novel interventions are now available for patients relapsing after auto-HCT making early disease recognition crucial to intervene prior to clinical progression. We analyzed a cohort of auto-HCT recipients who were uniformly monitored with surveillance (18)F-FDG-PET CT at day 100 (Interquartile range (IQR): 97-103 days) post-HCT.ObjectivesWe explored the PET parameters including Deauville (D) and total metabolic tumor volume (TMTV) as predictors of relapse and survival after auto-HCT. In addition, we assessed outcomes of patients with clinically versus radiographically detected relapsed DLBCL after auto-HCT.Methods/ResultsWe included 131 DLBCL patients (median age 56 years) with available day 100 PET scan treated with auto-HCT between 2006-2016. Median follow-up was 3.3 years. Five-year cumulative incidence of relapse after auto-HCT was 50%, (95%CI 39 to 59) and overall survival (OS) was 51% (95% CI 41 to 63). Twelve (9%) relapsed prior to day 100 and 91 patients underwent surveillance PET/CT imaging at day 100. At time of surveillance re-staging most patients’ scores were D1 (22%) or D2 (55%) and 21 (23%) had a D≥3. Patients with D5 (n=12) had higher TMTV (137 cm3) compared to D4 (n=9, TMTV 12.5 cm3). 5-year OS in post-HCT D4 and D5 were only 37% (95%CI=14 to 100) and 25% (95%CI=43 to 89), respectively, whereas those with post-transplant D1 and D2 both had 5-year OS of 62%. Median survival in years for D1, D2, D4 and D5 were 6.0, 6.8, 4.7, and 1.2, respectively. Risk of death was 4 times higher in D5 patients relative to D1 (HR 4.10, 95%CI =1.56 to 10.77; p ≤ 0.01).The hazard ratio for death following relapse was 2-fold higher (HR 1.8 [95% CI 0.9 to 3.4]; p=0.08) if relapse was detected clinically versus only radiographically over a median follow-up time period of 3.3 years.ConclusionIn patients with relapsed/refractory DLBCL, PET scan D5 in day 100 post-HCT PET is associated with extremely poor survival ∼ 1 year. Identifying this high-risk cohort can potentially highlight patients that might benefit from cell therapy or other rescue treatment strategies.
• Savani, M., Murugan, P., & Skubitz, K. M. (2019). Long-term cure of soft tissue sarcoma with pegylated-liposomal doxorubicin after doxorubicin and ifosfamide failure. Clin Sarcoma Res. doi:10.1186/s13569-018-0111-0
• Savani, M., Upadhyay, K., & Talati, A. (2017). Characteristics and outcomes of very low birth weight infants receiving epinephrine during delivery room resuscitation. Resuscitation, 115. doi:10.1016/j.resuscitation.2017.03.009
  More info

  Background Delivery room resuscitation of very low birth weight infants can involve use of endotracheal or intravenous epinephrine. Data of the past 19 years were reviewed to identify the usage of epinephrine in delivery room and identify characteristics of these babies. Methods Neonates with ≤1500 g birthweight from January 1996 to August 2014 were reviewed. Infants born alive and admitted to NICU were eligible. Characteristics such as demographics, survival and outcomes were recorded. Variables significant at p ≤ 0.1 among neonates receiving epinephrine were further analyzed via multiple logistic regressions. Results Out of 5868 eligible neonates, 416 (7%) received epinephrine in the delivery room. The infants who received epinephrine were of lower estimated gestational age (25 vs. 28 wk) and lower birth weight (746 vs. 980 g). Gender, race and mode of delivery were comparable between the two cohorts. Survival was higher in non-epinephrine group (89.4 vs. 61.1%). Bacterial infection (24.3 vs. 18.4%) and combined grade 3 and 4 intraventricular hemorrhage (18.4 vs. 8.4%) were higher in epinephrine group. Use of epinephrine in the delivery room was associated with decreased survival even after controlling for birth weight, gestational age and low Apgar scores [Odd ratio – 0.48 with 95% CI (0.37–0.62), p 
• Clark, C. A., Savani, M., Mohty, M., & Savani, B. N. (2016). What do we need to know about allogeneic hematopoietic stem cell transplant survivors?. Bone Marrow Transplantation. doi:10.1038/bmt.2016.95
  More info

  Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for over 70 benign and malignant hematologic and immunological processes. Over the past several decades, significant technological and post-transplant supportive advances have been made, resulting in a decrease in early transplant mortality and continued growth in the population of allo-HSCT survivors. With the expansion in the number of long-term survivors, as well as of those considering a transplant, the focus of transplant medicine has been shifted significantly to include a more prominent role for the care of the 'long-term' survivor. These patients have survived the acute critical phase of transplantation and have potentially achieved remission from their primary disease, yet allo-HSCT patients do not return to pre-transplant health status. For survivors >2 years removed, the time of transplant all-cause mortality is four- to nine-fold higher than age-matched peers within the general population. These patients represent a distinct, high-risk population that must be monitored for long-term transplant complications, including chronic GvHD (cGvHD), multi-organ dysfunctions and secondary malignancies. This article will review in a non-exhaustive manner, the approach to long-term care of an allo-HSCT recipient.
• Jain, N., Savani, M., Agarwal, M., & Kadaria, D. (2016). Methimazole-induced insulin autoimmune syndrome. Ther Adv Endocrinol Metab. doi:10.1177/2042018816658396
• Jain, N., Savani, M., Agarwal, M., & Sands, C. W. (2016). Albiglutide-induced pancreatitis. Therapeutic Advances in Drug Safety. doi:10.1177/2042098616667352
  More info

  Albiglutide is an injectable glucagon-like peptide-1 (GLP-1) receptor agonist, approved by the US Food and Drug Administration (FDA) in 2014 for the treatment of type 2 diabetes mellitus (T2DM) [Prasad-Reddy and Isaacs, 2015]. Administered initially as a 30 mg subcutaneous (SC) once-weekly injection and subsequently as 50 mg SC to achieve glycemic targets, it provides effective glycemic control through an increase in glucose-dependent insulin secretion and a decrease in glucagon levels [Prasad-Reddy and Isaacs, 2015; Gallwitz, 2016; Madsbad, 2015]. In addition to reducing blood glucose, it also promotes weight loss by increasing satiety and delaying gastric emptying [Prasad-Reddy and Isaacs, 2015; Madsbad, 2015]. Owing to its long half-life of about 5 days, it allows the ease of once-a-week administration and improved adherence. [Madsbad, 2015]. Adverse effects reported from its use include upper respiratory tract infections, nausea, and diarrhea [Madsbad, 2015; Trujillo and Nuffer, 2014]. From the pooled data across the eight phase III HARMONY trials, pancreatitis was likely attributed to the use of albiglutide compared with placebo or comparative drugs. There is also an issued warning on the package insert against use in patients with a history of pancreatitis. To our knowledge no case of albiglutide-induced pancreatitis has been reported following FDA approval. We report the first case of a 59-year-old man who was diagnosed with albiglutide-induced pancreatitis and managed successfully at our medical center.
• Li, Z., Rubinstein, S. M., Thota, R., Savani, M., Brissot, É., Shaw, B. E., Majhail, N. S., Mohty, M., & Savani, B. N. (2016). Immune-Mediated Complications after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. doi:10.1016/j.bbmt.2016.04.005
  More info

  Hematopoietic stem cell transplantation (HSCT) has an integral role in the treatment of malignant and nonmalignant diseases. Long-term complications after HSCT have been well established and include graft-versus-host disease (GVHD), conditioning regimen-related toxicities, disease relapse, and infections. Immune-mediated phenomena are increasingly described after HSCT with clinically significant sequelae. Diagnosis is challenging because of features that overlap with other commonly reported post-transplantation complications. Patients who experience immune-mediated disease after HSCT tend to have poor outcomes. Early recognition of immune-mediated complications is imperative to reduce preventable morbidity and mortality. This review looks at the currently available literature on pathogenesis, incidence, risk factors, treatment, and outcomes of immune-mediated disease (other than GVHD) after HSCT.
• Savani, M., Guo, Y., Carbone, D., & Csiki, I. (2012). Sonic hedgehog pathway expression in non-small cell lung cancer. Ther Adv Med Oncol, 4(5). doi:10.1177/1758834012450362
  More info

  Activation of the hedgehog pathway is an important signaling mechanism crucial in embryogenesis and has strong links to carcinogenesis. This study investigates the expression of the Sonic hedgehog pathway molecules in non-small cell lung tumors as it relates to clinical outcome of various non-small cell lung cancers. Methods: A tissue microarray with 81 samples from 42 patients with various non-small cell lung cancer histologies was examined without the aid of laser microdissection. All samples were stained with antibodies directed against Sonic hedgehog, Ptch-1, Smoothened, and Gli-1. Results: Most of the tumor samples showed negative to weak expression of the pathway proteins (Sonic hedgehog, 38% negative to 20% weak; Ptch-1, 100% negative; Smoothened, 69% negative to 7% weak; Gli-1, 57% negative to 5% weak) compared with higher expression in normal lung epithelial cells. The same pathway expression did not correlate with clinical outcome. While our results do not provide any indication that the pathway molecules are correlated to overall patient survival possibly due to the limited sample size, our study shows minimum overexpression of Sonic hedgehog pathway in non-small cell lung cancer and this did not correlate clinically with patient outcome. © 2012, SAGE Publications. All rights reserved.