Somedeb Ball - Academia.edu (original) (raw)

Papers by Somedeb Ball

Research paper thumbnail of Luspatercept for Treatment of Lower Risk Myelodysplastic Syndromes: Real World Data Replicates Medalist Study Results and Confirms Activity Among Hypomethylating Agents and Lenalidomide Treated Patients

Research paper thumbnail of Sex Disparities in Myelodysplastic Syndromes: Genotype, Phenotype, and Outcomes

Clinical Lymphoma Myeloma and Leukemia

Research paper thumbnail of Post-Allogeneic Stem Cell Transplant Outcomes in Patients Treated with Hypomethylating Agent Plus Venetoclax Compared to CPX-351

Research paper thumbnail of Poster: MPN-521 Somatic Mutational Landscape and Clinical Response to Upfront Targeted Tyrosine Kinase Inhibitors Among Patients With Myeloid and Lymphoid Neoplasms With Eosinophilia and Rearrangements of PDGFRA, PDGFRB, FGFR1, JAK2, or FLT3

Clinical Lymphoma Myeloma and Leukemia

Research paper thumbnail of A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

Blood Advances, 2022

Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most pat... more Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after 6 months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (1) RUX dose <20 mg twice daily at baseline, months 3 and 6 (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.07-3.00; P = .03), (2) palpable spleen length reduction from baseline ≤30% at months 3 and 6 (HR, 2.26; 95% CI, 1.40-3.65; P = .0009), (3) red blood cell (RBC) transfusion need at months 3 and/or 6 (HR, 1.66; 95% CI, 0.95-2.88; P = .07), and (4) RBC transfusion need at a...

Research paper thumbnail of Incidence of Pleural Effusion with Dasatinib and the Effect of Switching Therapy to Bosutinib in Patients with Chronic Phase CML

Blood, 2021

Introduction: Dasatinib is a second generation tyrosine kinase inhibitor (TKI) which is approved ... more Introduction: Dasatinib is a second generation tyrosine kinase inhibitor (TKI) which is approved for treatment of chronic myeloid leukemia (CML). Pleural effusion (PE) is a unique toxicity associated with dasatinib use. The risk of development of PE with dasatinib was reported to be 6-9% per year in DASISION and 5-15% per year in CA180-034. At a 5 and 7 year follow up 28% and 33% of patients developed PE in DASISION and CA180-034, respectively (Cortes et. al. J Clin Onc 2016 and Shah et. al. Am J Hematol 2016). PE led to discontinuation of dasatinib in only 6% and 7% patients in DASISION and CA180-034, respectively. Alternative TKIs are required in these cases with the goal to avoid recurrence of PE. Recently, switching to bosutinib after development of a PE while on dasatinib has been shown to be associated with a 30% risk of developing a recurrent PE, higher than the reported rate in front line trials (Tribelli et. al. Ann Hematol 2019). Objective: The aim of this study was to ide...

Research paper thumbnail of Gender Disparities in Myelodysplastic Syndromes: Phenotype, Genotype, and Outcomes

Blood, 2021

BACKGROUND: Over the past 25 years research has shifted from predominantly focused on men to rese... more BACKGROUND: Over the past 25 years research has shifted from predominantly focused on men to research that includes both men and women. In addition, myelodysplastic syndromes (MDS) have only been included in the SEER registry since 2001 and are largely understudied. This has resulted in a knowledge gap in the difference in clinical phenotype, genotype, and outcomes between men and women diagnosed with MDS. The aim of this abstract is to identify those gender-based differences. METHODS: This was a retrospective study using a large MDS database at Moffitt Cancer Center. We compared baseline clinical and molecular characteristics and outcomes based on gender. Chi-square tests were used for comparing categorical variables and t-test for continuous variables. Kaplan-Meier method was used to compare survival. RESULTS: The Moffitt Cancer Center MDS data base includes 4413 patients among whom 2922 (66%) were men and 1658 (34%) were women. Table-1 summarizes baseline characteristics based on...

Research paper thumbnail of Mutations Highly Specific for Secondary AML Are Associated with Poor Outcomes in Patients with NPM1-Mutated ELN Favorable Risk AML

Blood, 2021

Background: NPM1 is commonly mutated in acute myeloid leukemia (AML) and represents a distinct en... more Background: NPM1 is commonly mutated in acute myeloid leukemia (AML) and represents a distinct entity under the WHO 2016 classification. It is one of the few mutations that can potentially support favorable risk by European LeukemiaNet (ELN) 2017 criteria. Mutations that are highly specific for secondary AML including SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2 (sMut) (Lindsley et al.) have been shown to confer poor prognosis. The impact of these mutations on NPM1-mutated AML warrants further investigation. Objective: In this study, we explore the outcomes in patients with NPM1-mutated AML. Methods: This was a retrospective study of NPM1-mutated AML patients who were diagnosed and treated at the Moffitt Cancer Center from 2013 to March 2021. Inclusion was restricted to NPM1-mutated patients with mutation analysis (NGS) performed at diagnosis (n=159). Kaplan-Meier, univariate, and multivariate analyses were performed. Results: Among 159 patients (78M/81F, median age 63 y...

Research paper thumbnail of Outcome with Hypomethylating Agent and Venetoclax Combination in Patients with Chronic Myelomonocytic Leukemia

Blood, 2021

Introduction: Hypomethylating agents (HMA) are commonly used in treatment of high risk chronic my... more Introduction: Hypomethylating agents (HMA) are commonly used in treatment of high risk chronic myelomonocytic leukemia (CMML), although only 40% patients (pts) respond. Decitabine failed to improve overall survival (OS) in comparison with hydroxyurea in proliferative CMML (Itzykson et al. 2020). Preliminary results have suggested safety and clinical activity of HMA and venetoclax combination (HMA-Ven) in a small CMML cohort (n=9; Morita et al. 2020). However, real world evidence lacks on efficacy of HMA-Ven and its impact on outcome in pts with CMML and post-CMML secondary acute myeloid leukemia (sAML). Methods: In this single center retrospective study, clinical and genomic data were collected from medical records of CMML pts treated with HMA-Ven at Moffitt Cancer Center. Treatment response was assessed with International Working Group criteria for CMML and European Leukemia Network 2017 criteria for post-CMML sAML. Survival estimates using Kaplan-Meier statistics and multivariate ...

Research paper thumbnail of A Focus on Phenotype and Genotype: Racial /Ethnic Disparities in Myelodysplastic Syndromes

Blood, 2021

Background: There is a paucity of research on racial and ethnic disparities in myelodysplastic sy... more Background: There is a paucity of research on racial and ethnic disparities in myelodysplastic syndromes (MDS). Research focused on racial and ethnic disparities for MDS is essential to improve knowledge and understanding to deliver racial and ethnic sensitive care. There are limited studies that delineate the incidence of cytogenetic and molecular features of MDS by race and ethnicity (Yan, et al. 2021, Ramadan, et al.,2016). The aim of this abstract is to report the difference in clinical phenotype, genotype and outcomes of White, Black and Hispanics from a large MDS data base. Methods: Adult patients were identified through the Moffitt Cancer Center MDS data base and divided into racial/ethnic categories. Fisher exact test and chi-square tests were used to compare categorical variables. Univariate survival analysis was estimated using the Kaplan-Meier method. Results: From analysis of 4414 patients with MDS, 4131 (93%) were White, 116 (3%) Black and 167 (4%) Hispanic. Table-1 sum...

Research paper thumbnail of Multicenter evaluation of efficacy and toxicity of venetoclax‐based combinations in patients with accelerated and blast phase myeloproliferative neoplasms

American Journal of Hematology, 2021

vaccine-induced antibodies against SARS-CoV-2 variants. Science. 2021;373(6561):1372-1377. doi:10... more vaccine-induced antibodies against SARS-CoV-2 variants. Science. 2021;373(6561):1372-1377. doi:10.1126/science.abj4176 11. Planas D, Veyer D, Baidaliuk A, et al. Reduced sensitivity of SARS-CoV2 variant delta to antibody neutralization. Nature. 2021;596:276-280. 12. Betton M, Livrozet M, Planas D, et al. Sera neutralizing activities against SARS-CoV-2 and multiple variants six month after hospitalization for COVID-19. Clin Infect Dis. 2021;73(6):e1337-e1344. doi:10. 1093/cid/ciab308 13. Wang Z, Schmidt F, Weisblum Y, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature. 2021;592:616-622. 14. Collier DA, De Marco A, Ferreira I, et al. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature. 2021;593:136-141. 15. Bergwerk M, Gonen T, Lustig Y, et al. Covid-19 breakthrough infections in vaccinated health care workers. N Engl J Med. 2021;385: 1474-1484. doi:10.1056/NEJMoa2109072 16. Brown CM, Vostok J, Johnson H, et al. Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections, associated with large public gatherings Barnstable County, Massachusetts, July 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1059-1062. 17. Farinholt T, Doddapaneni H, Qin X, et al. Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections. BMC Med. 2021;19:255. doi:10.1101/2021.06.28. 21258780

Research paper thumbnail of Dysautonomia: An Overlooked Neurological Manifestation in a Critically ill COVID-19 Patient

The American Journal of the Medical Sciences, 2020

Research paper thumbnail of Poster: MDS-229: Assessment of Baseline Clinical and Molecular Characteristics in Indolent Chronic Myelomonocytic Leukemia

Clinical Lymphoma Myeloma and Leukemia, 2021

Research paper thumbnail of Relation of hematologic inflammatory markers and obesity in otherwise healthy participants in the National Health and Nutrition Examination Survey, 2011–2016

Baylor University Medical Center Proceedings, 2020

This study investigated the association between hematologic inflammatory markers derived from com... more This study investigated the association between hematologic inflammatory markers derived from complete blood counts and obesity. We undertook a cross-sectional study that included self-reported healthy subjects above the age of 18 years from the 2011-2016 National Health and Nutrition Examination Survey, a US population database. Study parameters included mean corpuscular volume, red cell distribution width, mean platelet volume, total platelet count, neutrophil-to-lymphocyte ratio, plateletto-lymphocyte ratio, and systemic immune-inflammation index. Body mass index was used as an index of obesity and was correlated with each hematologic inflammatory marker. Our analysis found a statistically significant association between each inflammatory parameter and higher body mass indices. We demonstrated an association between complete blood count-derived indices of inflammation and obesity, and these results provide the basis for future studies using complete blood count-derived variables and outcomes in patients with some chronic diseases.

Research paper thumbnail of Risk of kidney toxicity with carfilzomib in multiple myeloma: a meta-analysis of randomized controlled trials

Annals of Hematology, 2020

The incidence and relative risk of kidney toxicity with carfilzomib in multiple myeloma (MM) has ... more The incidence and relative risk of kidney toxicity with carfilzomib in multiple myeloma (MM) has been incompletely characterized. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing carfilzomibbased with non-carfilzomib-based regimens in MM to investigate the risk of kidney toxicity. Point estimates were pooled in the form of risk ratios (RR) with 95% confidence intervals (CI) using the random-effects model. We identified four RCTs with 2954 patients. The median duration of treatment ranged from 16.3 to 88 weeks in carfilzomib arms. The cumulative rate of kidney toxicities in the carfilzomib arms was 21.3% for all grades and 8.3% for grades 3-5 toxicities, with acute kidney injury being the predominantly reported event. Patients receiving a carfilzomib-based regimen had a significantly higher risk of total kidney toxicity compared with those in the control arms, with pooled RR of 1.79 (95% CI, 1.43-2.23, p < 0.001) and 2.29 (95% CI, 1.59-3.30; p < 0.001), for all grades and grades 3-5 toxicities, respectively. Despite adjustment for the duration of exposure in treatment arms, pooled incidence rate ratios (IRR) for kidney toxicity was significantly increased in the carfilzomib arm compared with control (pooled IRR of 1.28 for all grades and 1.66 for grades 3-5 toxicity). Subgroup analysis based on carfilzomib dose, infusion length, and treatment setting did not identify any significant subgroup effect. Kidney toxicity is an important adverse effect of carfilzomib-based regimens. Prospective studies should investigate patient-, disease-, and treatment-related risk factors for severe kidney toxicities and impact on long-term outcome.

Research paper thumbnail of Risk of Renal Toxicities With Carfilzomib In Patients With Multiple Myeloma: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Clinical Lymphoma Myeloma and Leukemia, 2019

Conclusions: VRD with weekly bortezomib and low dose lenalidomide is a very effective and rapidly... more Conclusions: VRD with weekly bortezomib and low dose lenalidomide is a very effective and rapidly acting regimen that can induce deep hematologic responses within 3 months of therapy. However, toxicity of VRD in patients with AL amyloidosis is significant, despite the use of low doses of lenalidomide.

Research paper thumbnail of Solicitation for article submission by electronic journals

Baylor University Medical Center Proceedings, 2018

The business model, editorial policies, and content quality vary significantly in online medical ... more The business model, editorial policies, and content quality vary significantly in online medical journals. Some online journals have been labeled as predatory journals because their main effort involves collecting article processing charges with little interest in content, peer review, or manuscript presentation. Some of these journals send frequent email solicitations for submissions. One author affiliated with a department of internal medicine collected all email requests for submissions to online journals over a 6month period. These emails included 210 unique journal names that covered over 40 medical fields and requested 15 different article types. Most of these journals were not listed in PubMed or the Directory of Open Access Journals. One hundred and eighty two were on Beall's list of predatory journals. The median article processing charge was $1035. Faculty and trainees at medical schools receive multiple requests for submissions, but it is difficult to determine the quality of the journal sending these requests. At a minimum, a journal should be listed in the Directory of Open Access Journals and have very clear editorial and publication policies.

Research paper thumbnail of Topical 2′-Hydroxyflavanone for Cutaneous Melanoma

Cancers, 2019

2′-hydroxyflavanone (2HF) is a dietary flavonoid with anticancer activity towardsmultiple cancers... more 2′-hydroxyflavanone (2HF) is a dietary flavonoid with anticancer activity towardsmultiple cancers. Here, we report that topically applied 2HF inhibits the growth of intradermalimplants of melanoma in immunocompetent mice. 2HF induced apoptosis and inhibited the growthof the human SK-MEL-24 as well as murine B16-F0 and B16-F10 melanoma cell lines in vitro.Apoptosis was associated with depletion of caspase-3, caspase-9, and PARP1 in B16-F0 and SKMEL-24 cells. Caspase-9 and MEKK-15 were undetected even in untreated B16-F10 cells. Signalingproteins TNFα, and phospho-PDGFR-β were depleted in all three cell lines; MEKK-15 was depletedby 2HF in SK-MEL-24 cells. 2HF enhanced sunitinib (an MEK and PDGFR-β inhibitor) and AZD2461 (a PARP1 inhibitor) cytotoxicity. 2HF also depleted the Ral-regulated, stress-responsive,antiapoptotic endocytic protein RLIP76 (RALBP1), the inhibition of which has previously beenshown to inhibit B16-F0 melanoma growth in vivo. Functional inhibition of RLIP76 was ev...

Research paper thumbnail of Depression in heart failure: Intricate relationship, pathophysiology and most updated evidence of interventions from recent clinical studies

International Journal of Cardiology, Dec 1, 2016

Heart failure (HF) is a burgeoning chronic health condition affecting more than 20 million people... more Heart failure (HF) is a burgeoning chronic health condition affecting more than 20 million people worldwide. Patients with HF have a significant (17.1%) 30-day readmission rate, which invites substantial penalty in payment to hospitals from Centers for Medicare and Medicaid Services, as per the newly introduced Hospital Readmissions Reduction Program. Depression is one of the important risk factors for readmission in HF patients. It has a significant prevalence in patients with HF and contributes to the overall poor quality of life in them. Several behavioral (smoking, obesity, lack of exercise and medication noncompliance) and pathophysiological factors (hypercortisolism, elevated inflammatory biomarkers, fibrinogen, and atherosclerosis) have been found responsible for the adverse outcome in patients with HF and concomitant depression. Hippocampal volume loss noted in patients with acute HF exacerbations may contribute to the development of depressive symptoms in them. Screening for depression in HF patients continues to be challenging due to a considerable overlap in symptoms. Published trials on the use of antidepressants and cognitive behavioral therapy (CBT) have shown variable outcomes. Newer modalities like internet-based CBT have been tried in small studies, with promising results. A recent meta-analysis observed the beneficial role of aerobic exercise training in patients with HFrEF. Future long-term prospective studies may contribute to the formulation of a detailed screening and management guideline for patients with HF and depression. Our review is aimed to summarize the intricate relationship between depression and heart failure, with respect to their epidemiology, pathophysiological aspects, and optimal management approach.

Research paper thumbnail of Risk of Atrial Fibrillation with Ibrutinib in Patients with B-Cell Malignancies: An Updated Meta-Analysis of Phase III Randomized Controlled Trials

Blood, Nov 29, 2018

Introduction: Ibrutinib is an irreversible inhibitor of Bruton&amp;amp;#39;s tyrosine kinase ... more Introduction: Ibrutinib is an irreversible inhibitor of Bruton&amp;amp;#39;s tyrosine kinase which has become an important part of the therapeutic armamentarium for B-cell malignancies. Ibrutinib has been associated with an increased incidence of atrial and ventricular arrhythmias in studies. We conducted an updated systematic review and meta-analysis of all phase III randomized controlled trials (RCT) to determine the relative risk of atrial fibrillation (AF) associated with ibrutinib use, relative risk of high grade AF (grade 3-5), and to evaluate if the estimation of risk has changed with emergence of new data since prior reports on this adverse event. Methods: We performed a systematic search of PubMed, Embase, Web of Science, Scopus, Clinical Trials.gov, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews with appropriate keywords through 07/10/18, to find all RCTs comparing ibrutinib with other agents or placebo in patients with B-cell malignancies and also reporting AF as a treatment-emergent adverse event. The search strategy, study selection, data extraction, and analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. We pooled the point estimates using random effects model of the generic inverse-variance method described by Der Simonian and Laird. Statistical analyses were performed using the Stata/SE 15.1 (StataCorp LP, College Station, TX, USA). Results: A total of 6 phase III RCTs randomizing 1811 patients (pt; 935 on ibrutinib arms and 876 in the control arms) were included in the final analysis. Four trials were conducted in pts with CLL, one in pts with Waldenstrom macroglobulinemia and the other one in pts with mantle cell lymphoma. Characteristics of these trials are shown in Table 1. In 4 RCTs ibrutinib was compared with an active agent (i.e., ofatumumab, chlorambucil, temsirolimus, and rituximab) and in the other two trials, it was compared with placebo. Ibrutinib was administered as a 1st-line therapy in the RESONATE-2 trial and both as 1st line and in refractory cases in the iNNOVATE trial. The median duration of treatment across studies with ibrutinib was 17.7 months (range 9.4-38.7 months). The pooled risk ratio (RR) for all grade atrial fibrillation was 4.27 [95% confidence interval (CI): 2.26-8.06, p&amp;amp;amp;lt;0.001, I2=0.0%, figure 1A] in patients on ibrutinib across all B-cell malignancies, as compared to patients in the control arms. The overall incidence of high-grade (grade 3-5) AF was also significantly increased in the ibrutinib arms, as compared to control [pooled RR 4.85, 95% CI: 2.02-11.63, p&amp;amp;amp;lt;0.001, I2=0.0%, figure 1B]. In subgroup analysis of trials (n=4) in pts with CLL only, ibrutinib was again associated with a statistically significant increase in risk of all grade and high-grade AF [pooled RR 4.03, 95% CI: 1.99-8.15, p&amp;amp;amp;lt;0.001, I2=0.0%, figure 2A, and pooled RR 3.83, 95% CI: 1.29-11.42, p=0.016, I2=0.0%, figure 2B, respectively]. No publication bias was observed across all the studies included in final analysis. Conclusion: In agreement with prior reports, this updated meta-analysis confirmed that ibrutinib was associated with a significantly increased risk of all grade AF in pts with B-cell malignancies (RR 4.27). Our analysis shows that the risk of high grade AF (grade3-5) is also significantly increased with ibrutinib (RR 4.85). These pts need to be closely monitored for development of AF to help improve morbidity and mortality. Disclosures Short: Takeda Oncology: Consultancy. Maiti:Celgene Corporation: Other: Research funding to the institution.

Research paper thumbnail of Luspatercept for Treatment of Lower Risk Myelodysplastic Syndromes: Real World Data Replicates Medalist Study Results and Confirms Activity Among Hypomethylating Agents and Lenalidomide Treated Patients

Research paper thumbnail of Sex Disparities in Myelodysplastic Syndromes: Genotype, Phenotype, and Outcomes

Clinical Lymphoma Myeloma and Leukemia

Research paper thumbnail of Post-Allogeneic Stem Cell Transplant Outcomes in Patients Treated with Hypomethylating Agent Plus Venetoclax Compared to CPX-351

Research paper thumbnail of Poster: MPN-521 Somatic Mutational Landscape and Clinical Response to Upfront Targeted Tyrosine Kinase Inhibitors Among Patients With Myeloid and Lymphoid Neoplasms With Eosinophilia and Rearrangements of PDGFRA, PDGFRB, FGFR1, JAK2, or FLT3

Clinical Lymphoma Myeloma and Leukemia

Research paper thumbnail of A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

Blood Advances, 2022

Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most pat... more Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after 6 months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (1) RUX dose <20 mg twice daily at baseline, months 3 and 6 (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.07-3.00; P = .03), (2) palpable spleen length reduction from baseline ≤30% at months 3 and 6 (HR, 2.26; 95% CI, 1.40-3.65; P = .0009), (3) red blood cell (RBC) transfusion need at months 3 and/or 6 (HR, 1.66; 95% CI, 0.95-2.88; P = .07), and (4) RBC transfusion need at a...

Research paper thumbnail of Incidence of Pleural Effusion with Dasatinib and the Effect of Switching Therapy to Bosutinib in Patients with Chronic Phase CML

Blood, 2021

Introduction: Dasatinib is a second generation tyrosine kinase inhibitor (TKI) which is approved ... more Introduction: Dasatinib is a second generation tyrosine kinase inhibitor (TKI) which is approved for treatment of chronic myeloid leukemia (CML). Pleural effusion (PE) is a unique toxicity associated with dasatinib use. The risk of development of PE with dasatinib was reported to be 6-9% per year in DASISION and 5-15% per year in CA180-034. At a 5 and 7 year follow up 28% and 33% of patients developed PE in DASISION and CA180-034, respectively (Cortes et. al. J Clin Onc 2016 and Shah et. al. Am J Hematol 2016). PE led to discontinuation of dasatinib in only 6% and 7% patients in DASISION and CA180-034, respectively. Alternative TKIs are required in these cases with the goal to avoid recurrence of PE. Recently, switching to bosutinib after development of a PE while on dasatinib has been shown to be associated with a 30% risk of developing a recurrent PE, higher than the reported rate in front line trials (Tribelli et. al. Ann Hematol 2019). Objective: The aim of this study was to ide...

Research paper thumbnail of Gender Disparities in Myelodysplastic Syndromes: Phenotype, Genotype, and Outcomes

Blood, 2021

BACKGROUND: Over the past 25 years research has shifted from predominantly focused on men to rese... more BACKGROUND: Over the past 25 years research has shifted from predominantly focused on men to research that includes both men and women. In addition, myelodysplastic syndromes (MDS) have only been included in the SEER registry since 2001 and are largely understudied. This has resulted in a knowledge gap in the difference in clinical phenotype, genotype, and outcomes between men and women diagnosed with MDS. The aim of this abstract is to identify those gender-based differences. METHODS: This was a retrospective study using a large MDS database at Moffitt Cancer Center. We compared baseline clinical and molecular characteristics and outcomes based on gender. Chi-square tests were used for comparing categorical variables and t-test for continuous variables. Kaplan-Meier method was used to compare survival. RESULTS: The Moffitt Cancer Center MDS data base includes 4413 patients among whom 2922 (66%) were men and 1658 (34%) were women. Table-1 summarizes baseline characteristics based on...

Research paper thumbnail of Mutations Highly Specific for Secondary AML Are Associated with Poor Outcomes in Patients with NPM1-Mutated ELN Favorable Risk AML

Blood, 2021

Background: NPM1 is commonly mutated in acute myeloid leukemia (AML) and represents a distinct en... more Background: NPM1 is commonly mutated in acute myeloid leukemia (AML) and represents a distinct entity under the WHO 2016 classification. It is one of the few mutations that can potentially support favorable risk by European LeukemiaNet (ELN) 2017 criteria. Mutations that are highly specific for secondary AML including SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2 (sMut) (Lindsley et al.) have been shown to confer poor prognosis. The impact of these mutations on NPM1-mutated AML warrants further investigation. Objective: In this study, we explore the outcomes in patients with NPM1-mutated AML. Methods: This was a retrospective study of NPM1-mutated AML patients who were diagnosed and treated at the Moffitt Cancer Center from 2013 to March 2021. Inclusion was restricted to NPM1-mutated patients with mutation analysis (NGS) performed at diagnosis (n=159). Kaplan-Meier, univariate, and multivariate analyses were performed. Results: Among 159 patients (78M/81F, median age 63 y...

Research paper thumbnail of Outcome with Hypomethylating Agent and Venetoclax Combination in Patients with Chronic Myelomonocytic Leukemia

Blood, 2021

Introduction: Hypomethylating agents (HMA) are commonly used in treatment of high risk chronic my... more Introduction: Hypomethylating agents (HMA) are commonly used in treatment of high risk chronic myelomonocytic leukemia (CMML), although only 40% patients (pts) respond. Decitabine failed to improve overall survival (OS) in comparison with hydroxyurea in proliferative CMML (Itzykson et al. 2020). Preliminary results have suggested safety and clinical activity of HMA and venetoclax combination (HMA-Ven) in a small CMML cohort (n=9; Morita et al. 2020). However, real world evidence lacks on efficacy of HMA-Ven and its impact on outcome in pts with CMML and post-CMML secondary acute myeloid leukemia (sAML). Methods: In this single center retrospective study, clinical and genomic data were collected from medical records of CMML pts treated with HMA-Ven at Moffitt Cancer Center. Treatment response was assessed with International Working Group criteria for CMML and European Leukemia Network 2017 criteria for post-CMML sAML. Survival estimates using Kaplan-Meier statistics and multivariate ...

Research paper thumbnail of A Focus on Phenotype and Genotype: Racial /Ethnic Disparities in Myelodysplastic Syndromes

Blood, 2021

Background: There is a paucity of research on racial and ethnic disparities in myelodysplastic sy... more Background: There is a paucity of research on racial and ethnic disparities in myelodysplastic syndromes (MDS). Research focused on racial and ethnic disparities for MDS is essential to improve knowledge and understanding to deliver racial and ethnic sensitive care. There are limited studies that delineate the incidence of cytogenetic and molecular features of MDS by race and ethnicity (Yan, et al. 2021, Ramadan, et al.,2016). The aim of this abstract is to report the difference in clinical phenotype, genotype and outcomes of White, Black and Hispanics from a large MDS data base. Methods: Adult patients were identified through the Moffitt Cancer Center MDS data base and divided into racial/ethnic categories. Fisher exact test and chi-square tests were used to compare categorical variables. Univariate survival analysis was estimated using the Kaplan-Meier method. Results: From analysis of 4414 patients with MDS, 4131 (93%) were White, 116 (3%) Black and 167 (4%) Hispanic. Table-1 sum...

Research paper thumbnail of Multicenter evaluation of efficacy and toxicity of venetoclax‐based combinations in patients with accelerated and blast phase myeloproliferative neoplasms

American Journal of Hematology, 2021

vaccine-induced antibodies against SARS-CoV-2 variants. Science. 2021;373(6561):1372-1377. doi:10... more vaccine-induced antibodies against SARS-CoV-2 variants. Science. 2021;373(6561):1372-1377. doi:10.1126/science.abj4176 11. Planas D, Veyer D, Baidaliuk A, et al. Reduced sensitivity of SARS-CoV2 variant delta to antibody neutralization. Nature. 2021;596:276-280. 12. Betton M, Livrozet M, Planas D, et al. Sera neutralizing activities against SARS-CoV-2 and multiple variants six month after hospitalization for COVID-19. Clin Infect Dis. 2021;73(6):e1337-e1344. doi:10. 1093/cid/ciab308 13. Wang Z, Schmidt F, Weisblum Y, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature. 2021;592:616-622. 14. Collier DA, De Marco A, Ferreira I, et al. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature. 2021;593:136-141. 15. Bergwerk M, Gonen T, Lustig Y, et al. Covid-19 breakthrough infections in vaccinated health care workers. N Engl J Med. 2021;385: 1474-1484. doi:10.1056/NEJMoa2109072 16. Brown CM, Vostok J, Johnson H, et al. Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections, associated with large public gatherings Barnstable County, Massachusetts, July 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1059-1062. 17. Farinholt T, Doddapaneni H, Qin X, et al. Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections. BMC Med. 2021;19:255. doi:10.1101/2021.06.28. 21258780

Research paper thumbnail of Dysautonomia: An Overlooked Neurological Manifestation in a Critically ill COVID-19 Patient

The American Journal of the Medical Sciences, 2020

Research paper thumbnail of Poster: MDS-229: Assessment of Baseline Clinical and Molecular Characteristics in Indolent Chronic Myelomonocytic Leukemia

Clinical Lymphoma Myeloma and Leukemia, 2021

Research paper thumbnail of Relation of hematologic inflammatory markers and obesity in otherwise healthy participants in the National Health and Nutrition Examination Survey, 2011–2016

Baylor University Medical Center Proceedings, 2020

This study investigated the association between hematologic inflammatory markers derived from com... more This study investigated the association between hematologic inflammatory markers derived from complete blood counts and obesity. We undertook a cross-sectional study that included self-reported healthy subjects above the age of 18 years from the 2011-2016 National Health and Nutrition Examination Survey, a US population database. Study parameters included mean corpuscular volume, red cell distribution width, mean platelet volume, total platelet count, neutrophil-to-lymphocyte ratio, plateletto-lymphocyte ratio, and systemic immune-inflammation index. Body mass index was used as an index of obesity and was correlated with each hematologic inflammatory marker. Our analysis found a statistically significant association between each inflammatory parameter and higher body mass indices. We demonstrated an association between complete blood count-derived indices of inflammation and obesity, and these results provide the basis for future studies using complete blood count-derived variables and outcomes in patients with some chronic diseases.

Research paper thumbnail of Risk of kidney toxicity with carfilzomib in multiple myeloma: a meta-analysis of randomized controlled trials

Annals of Hematology, 2020

The incidence and relative risk of kidney toxicity with carfilzomib in multiple myeloma (MM) has ... more The incidence and relative risk of kidney toxicity with carfilzomib in multiple myeloma (MM) has been incompletely characterized. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing carfilzomibbased with non-carfilzomib-based regimens in MM to investigate the risk of kidney toxicity. Point estimates were pooled in the form of risk ratios (RR) with 95% confidence intervals (CI) using the random-effects model. We identified four RCTs with 2954 patients. The median duration of treatment ranged from 16.3 to 88 weeks in carfilzomib arms. The cumulative rate of kidney toxicities in the carfilzomib arms was 21.3% for all grades and 8.3% for grades 3-5 toxicities, with acute kidney injury being the predominantly reported event. Patients receiving a carfilzomib-based regimen had a significantly higher risk of total kidney toxicity compared with those in the control arms, with pooled RR of 1.79 (95% CI, 1.43-2.23, p < 0.001) and 2.29 (95% CI, 1.59-3.30; p < 0.001), for all grades and grades 3-5 toxicities, respectively. Despite adjustment for the duration of exposure in treatment arms, pooled incidence rate ratios (IRR) for kidney toxicity was significantly increased in the carfilzomib arm compared with control (pooled IRR of 1.28 for all grades and 1.66 for grades 3-5 toxicity). Subgroup analysis based on carfilzomib dose, infusion length, and treatment setting did not identify any significant subgroup effect. Kidney toxicity is an important adverse effect of carfilzomib-based regimens. Prospective studies should investigate patient-, disease-, and treatment-related risk factors for severe kidney toxicities and impact on long-term outcome.

Research paper thumbnail of Risk of Renal Toxicities With Carfilzomib In Patients With Multiple Myeloma: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Clinical Lymphoma Myeloma and Leukemia, 2019

Conclusions: VRD with weekly bortezomib and low dose lenalidomide is a very effective and rapidly... more Conclusions: VRD with weekly bortezomib and low dose lenalidomide is a very effective and rapidly acting regimen that can induce deep hematologic responses within 3 months of therapy. However, toxicity of VRD in patients with AL amyloidosis is significant, despite the use of low doses of lenalidomide.

Research paper thumbnail of Solicitation for article submission by electronic journals

Baylor University Medical Center Proceedings, 2018

The business model, editorial policies, and content quality vary significantly in online medical ... more The business model, editorial policies, and content quality vary significantly in online medical journals. Some online journals have been labeled as predatory journals because their main effort involves collecting article processing charges with little interest in content, peer review, or manuscript presentation. Some of these journals send frequent email solicitations for submissions. One author affiliated with a department of internal medicine collected all email requests for submissions to online journals over a 6month period. These emails included 210 unique journal names that covered over 40 medical fields and requested 15 different article types. Most of these journals were not listed in PubMed or the Directory of Open Access Journals. One hundred and eighty two were on Beall's list of predatory journals. The median article processing charge was $1035. Faculty and trainees at medical schools receive multiple requests for submissions, but it is difficult to determine the quality of the journal sending these requests. At a minimum, a journal should be listed in the Directory of Open Access Journals and have very clear editorial and publication policies.

Research paper thumbnail of Topical 2′-Hydroxyflavanone for Cutaneous Melanoma

Cancers, 2019

2′-hydroxyflavanone (2HF) is a dietary flavonoid with anticancer activity towardsmultiple cancers... more 2′-hydroxyflavanone (2HF) is a dietary flavonoid with anticancer activity towardsmultiple cancers. Here, we report that topically applied 2HF inhibits the growth of intradermalimplants of melanoma in immunocompetent mice. 2HF induced apoptosis and inhibited the growthof the human SK-MEL-24 as well as murine B16-F0 and B16-F10 melanoma cell lines in vitro.Apoptosis was associated with depletion of caspase-3, caspase-9, and PARP1 in B16-F0 and SKMEL-24 cells. Caspase-9 and MEKK-15 were undetected even in untreated B16-F10 cells. Signalingproteins TNFα, and phospho-PDGFR-β were depleted in all three cell lines; MEKK-15 was depletedby 2HF in SK-MEL-24 cells. 2HF enhanced sunitinib (an MEK and PDGFR-β inhibitor) and AZD2461 (a PARP1 inhibitor) cytotoxicity. 2HF also depleted the Ral-regulated, stress-responsive,antiapoptotic endocytic protein RLIP76 (RALBP1), the inhibition of which has previously beenshown to inhibit B16-F0 melanoma growth in vivo. Functional inhibition of RLIP76 was ev...

Research paper thumbnail of Depression in heart failure: Intricate relationship, pathophysiology and most updated evidence of interventions from recent clinical studies

International Journal of Cardiology, Dec 1, 2016

Heart failure (HF) is a burgeoning chronic health condition affecting more than 20 million people... more Heart failure (HF) is a burgeoning chronic health condition affecting more than 20 million people worldwide. Patients with HF have a significant (17.1%) 30-day readmission rate, which invites substantial penalty in payment to hospitals from Centers for Medicare and Medicaid Services, as per the newly introduced Hospital Readmissions Reduction Program. Depression is one of the important risk factors for readmission in HF patients. It has a significant prevalence in patients with HF and contributes to the overall poor quality of life in them. Several behavioral (smoking, obesity, lack of exercise and medication noncompliance) and pathophysiological factors (hypercortisolism, elevated inflammatory biomarkers, fibrinogen, and atherosclerosis) have been found responsible for the adverse outcome in patients with HF and concomitant depression. Hippocampal volume loss noted in patients with acute HF exacerbations may contribute to the development of depressive symptoms in them. Screening for depression in HF patients continues to be challenging due to a considerable overlap in symptoms. Published trials on the use of antidepressants and cognitive behavioral therapy (CBT) have shown variable outcomes. Newer modalities like internet-based CBT have been tried in small studies, with promising results. A recent meta-analysis observed the beneficial role of aerobic exercise training in patients with HFrEF. Future long-term prospective studies may contribute to the formulation of a detailed screening and management guideline for patients with HF and depression. Our review is aimed to summarize the intricate relationship between depression and heart failure, with respect to their epidemiology, pathophysiological aspects, and optimal management approach.

Research paper thumbnail of Risk of Atrial Fibrillation with Ibrutinib in Patients with B-Cell Malignancies: An Updated Meta-Analysis of Phase III Randomized Controlled Trials

Blood, Nov 29, 2018

Introduction: Ibrutinib is an irreversible inhibitor of Bruton&amp;amp;#39;s tyrosine kinase ... more Introduction: Ibrutinib is an irreversible inhibitor of Bruton&amp;amp;#39;s tyrosine kinase which has become an important part of the therapeutic armamentarium for B-cell malignancies. Ibrutinib has been associated with an increased incidence of atrial and ventricular arrhythmias in studies. We conducted an updated systematic review and meta-analysis of all phase III randomized controlled trials (RCT) to determine the relative risk of atrial fibrillation (AF) associated with ibrutinib use, relative risk of high grade AF (grade 3-5), and to evaluate if the estimation of risk has changed with emergence of new data since prior reports on this adverse event. Methods: We performed a systematic search of PubMed, Embase, Web of Science, Scopus, Clinical Trials.gov, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews with appropriate keywords through 07/10/18, to find all RCTs comparing ibrutinib with other agents or placebo in patients with B-cell malignancies and also reporting AF as a treatment-emergent adverse event. The search strategy, study selection, data extraction, and analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. We pooled the point estimates using random effects model of the generic inverse-variance method described by Der Simonian and Laird. Statistical analyses were performed using the Stata/SE 15.1 (StataCorp LP, College Station, TX, USA). Results: A total of 6 phase III RCTs randomizing 1811 patients (pt; 935 on ibrutinib arms and 876 in the control arms) were included in the final analysis. Four trials were conducted in pts with CLL, one in pts with Waldenstrom macroglobulinemia and the other one in pts with mantle cell lymphoma. Characteristics of these trials are shown in Table 1. In 4 RCTs ibrutinib was compared with an active agent (i.e., ofatumumab, chlorambucil, temsirolimus, and rituximab) and in the other two trials, it was compared with placebo. Ibrutinib was administered as a 1st-line therapy in the RESONATE-2 trial and both as 1st line and in refractory cases in the iNNOVATE trial. The median duration of treatment across studies with ibrutinib was 17.7 months (range 9.4-38.7 months). The pooled risk ratio (RR) for all grade atrial fibrillation was 4.27 [95% confidence interval (CI): 2.26-8.06, p&amp;amp;amp;lt;0.001, I2=0.0%, figure 1A] in patients on ibrutinib across all B-cell malignancies, as compared to patients in the control arms. The overall incidence of high-grade (grade 3-5) AF was also significantly increased in the ibrutinib arms, as compared to control [pooled RR 4.85, 95% CI: 2.02-11.63, p&amp;amp;amp;lt;0.001, I2=0.0%, figure 1B]. In subgroup analysis of trials (n=4) in pts with CLL only, ibrutinib was again associated with a statistically significant increase in risk of all grade and high-grade AF [pooled RR 4.03, 95% CI: 1.99-8.15, p&amp;amp;amp;lt;0.001, I2=0.0%, figure 2A, and pooled RR 3.83, 95% CI: 1.29-11.42, p=0.016, I2=0.0%, figure 2B, respectively]. No publication bias was observed across all the studies included in final analysis. Conclusion: In agreement with prior reports, this updated meta-analysis confirmed that ibrutinib was associated with a significantly increased risk of all grade AF in pts with B-cell malignancies (RR 4.27). Our analysis shows that the risk of high grade AF (grade3-5) is also significantly increased with ibrutinib (RR 4.85). These pts need to be closely monitored for development of AF to help improve morbidity and mortality. Disclosures Short: Takeda Oncology: Consultancy. Maiti:Celgene Corporation: Other: Research funding to the institution.