Browsing by Author "Murthy, Hemant S."

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    Age no Bar – a CIBMTR analysis of Elderly Patients undergoing Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
    (Wiley, 2020) Munshi, Pashna N.; Vesole, David; Jurczyszyn, Artur; Zaucha, Jan Maciej; St. Martin, Andrew; Davila, Omar; Agrawal, Vaibhav; Badawy, Sherif M.; Battiwalla, Minoo; Chhabra, Saurabh; Copelan, Edward; Kharfan-Dabaja, Mohamed A.; Farhadfar, Nosha; Ganguly, Siddhartha; Hashmi, Shahrukh; Krem, Maxwell M.; Lazarus, Hillard M.; Malek, Ehsan; Meehan, Kenneth; Murthy, Hemant S.; Nishihori, Taiga; Olin, Rebecca L.; Olsson, Richard F.; Schriber, Jeffrey; Seo, Sachiko; Shah, Gunjan; Solh, Melhem; Tay, Jason; Kumar, Shaji; Qazilbash, Muzaffar H.; Shah, Nina; Hari, Parameswaran N.; D'Souza, Anita; Medicine, School of Medicine
    Background: Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. Methods: The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori. Results: An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2 . On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P = .02]) compared with the reference group (those aged 60-69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2 , including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%]; P = .003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%]; P = .003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%]; P = .01]), likely representing frailty. Conclusions: The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.
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    Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes
    (Elsevier, 2021) Oran, Betül; Ahn, Kwang Woo; Fretham, Caitrin; Beitinjaneh, Amer; Bashey, Asad; Pawarode, Attaphol; Wirk, Baldeep; Scott, Bart L.; Savani, Bipin N.; Bredeson, Christopher; Weisdorf, Daniel; Marks, David I.; Rizzieri, David; Copelan, Edward; Hildebrandt, Gerhard C.; Hale, Gregory A.; Murthy, Hemant S.; Lazarus, Hillard M.; Cerny, Jan; Liesveld, Jane L.; Yared, Jean A.; Yves-Cahn, Jean; Szer, Jeffrey; Verdonck, Leo F.; Aljur, Mahmoud; van der Poel, Marjolein; Litzow, Mark; Kalaycio, Matt; Grunwald, Michael R.; Diaz, Miguel Angel; Sabloff, Mitchell; Kharfan-Dabaja, Mohamed A.; Majhail, Navneet S.; Farhadfar, Nosha; Reshef, Ran; Olsson, Richard F.; Gale, Robert Peter; Nakamura, Ryotaro; Seo, Sachiko; Chhabra, Saurabh; Hashmi, Shahrukh; Farhan, Shatha; Ganguly, Siddhartha; Nathan, Sunita; Nishihori, Taiga; Jain, Tania; Agrawal, Vaibhav; Bacher, Ulrike; Popat, Uday; Saber, Wael; Medicine, School of Medicine
    Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m2. The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.
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    Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research
    (Ferrata Storti Foundation, 2019-09-26) Lazaryan, Aleksandr; Dolan, Michelle; Zhang, Mei-Jie; Wang, Hai-Lin; Kharfan-Dabaja, Mohamed A.; Marks, David I.; Bejanyan, Nelli; Copelan, Edward; Majhail, Navneet S.; Waller, Edmund K.; Chao, Nelson; Prestidge, Tim; Nishihori, Taiga; Kebriaei, Partow; Inamoto, Yoshihiro; Hamilton, Betty; Hashmi, Shahrukh K.; Kamble, Rammurti T.; Bacher, Ulrike; Hildebrandt, Gerhard C.; Stiff, Patrick J.; McGuirk, Joseph; Aldoss, Ibrahim; Beitinjaneh, Amer M.; Muffly, Lori; Vij, Ravi; Olsson, Richard F.; Byrne, Michael; Schultz, Kirk R.; Aljurf, Mahmoud; Seftel, Matthew; Savoie, Mary Lynn; Savani, Bipin N.; Verdonck, Leo F.; Cairo, Mitchell S.; Hossain, Nasheed; Bhatt, Vijaya Raj; Frangoul, Haydar A.; Abdel-Azim, Hisham; Al Malki, Monzr; Munker, Reinhold; Rizzieri, David; Khera, Nandita; Nakamura, Ryotaro; Ringdén, Olle; van der Poel, Marjolein; Murthy, Hemant S.; Liu, Hongtao; Mori, Shahram; De Oliveira, Satiro; Bolaños-Meade, Javier; Elsawy, Mahmoud; Barba, Pere; Nathan, Sunita; George, Biju; Pawarode, Attaphol; Grunwald, Michael; Agrawal, Vaibhav; Wang, Youjin; Assal, Amer; Castillo Caro, Paul; Kuwatsuka, Yachiyo; Seo, Sachiko; Ustun, Celalettin; Politikos, Ioannis; Lazarus, Hillard M.; Saber, Wael; Sandmaier, Brenda M.; De Lima, Marcos; Litzow, Mark; Bachanova, Veronika; Weisdorf, Daniel; Acute Leukemia Committee of the CIBMTR; Medicine, School of Medicine
    Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.
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    Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report
    (SAGE, 2020-07-14) Zhou, Zheng; Nath, Rajneesh; Cerny, Jan; Wang, Hai-Lin; Zhang, Mei-Jie; Abdel-Azim, Hisham; Agrawal, Vaibhav; Ahmed, Gulrayz; Al-Homsi, A. Samer; Aljurf, Mahmoud; Alkhateeb, Hassan B.; Assal, Amer; Bacher, Ulrike; Bajel, Ashish; Bashir, Qaiser; Battiwalla, Minocher; Bhatt, Vijaya Raj; Byrne, Michael; Cahn, Jean-Yves; Cairo, Mitchell; Choe, Hannah; Copelan, Edward; Cutler, Corey; Damlaj, Moussab B.; DeFilipp, Zachariah; De Lima, Marcos; Diaz, Miguel Angel; Farhadfar, Nosha; Foran, James; Freytes, César O.; Gerds, Aaron T.; Gergis, Usama; Grunwald, Michael R.; Gul, Zartash; Hamadani, Mehdi; Hashmi, Shahrukh; Hertzberg, Mark; Hildebrandt, Gerhard C.; Hossain, Nasheed; Inamoto, Yoshihiro; Isola, Luis; Jain, Tania; Kamble, Rammurti T.; Khan, Muhammad Waqas; Kharfan-Dabaja, Mohamed A.; Kebriaei, Partow; Kekre, Natasha; Khera, Nandita; Lazarus, Hillard M.; Liesveld, Jane L.; Litzow, Mark; Liu, Hongtao; Marks, David I.; Martino, Rodrigo; Mathews, Vikram; Mishra, Asmita; Murthy, Hemant S.; Nagler, Arnon; Nakamura, Ryotaro; Nathan, Sunita; Nishihori, Taiga; Olin, Rebecca; Olsson, Richard F.; Palmisiano, Neil; Patel, Sagar S.; Patnaik, Mrinal M.; Pawarode, Attaphol; Perales, Miguel-Angel; Politikos, Ioannis; Popat, Uday; Rizzieri, David; Sandmaier, Brenda M.; Savani, Bipin N.; Seo, Sachiko; Shah, Nirav N.; Uy, Geoffrey L.; Valcárcel, David; Verdonck, Leo F.; Waller, Edmund K.; Wang, Youjin; Weisdorf, Daniel; Wirk, Baldeep; Wong, Eric; Yared, Jean A.; Saber, Wael; Medicine, School of Medicine
    There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
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    Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
    (Elsevier, 2020-08) Im, Annie; Rashidi, Armin; Wang, Tao; Hemmer, Michael; MacMillan, Margaret L.; Pidala, Joseph; Jagasia, Madan; Pavletic, Steven; Majhail, Navneet S.; Weisdorf, Daniel; Abdel-Azim, Hisham; Agrawal, Vaibhav; Al-Homsi, A. Samer; Aljurf, Mahmoud; Askar, Medhat; Auletta, Jeffery J.; Bashey, Asad; Beitinjaneh, Amer; Bhatt, Vijaya Raj; Byrne, Michael; Cahn, Jean-Yves; Cairo, Mitchell; Castillo, Paul; Cerny, Jan; Chhabra, Saurabh; Choe, Hannah; Ciurea, Stefan; Daly, Andrew; Perez, Miguel Angel Diaz; Farhadfar, Nosha; Gadalla, Shahinaz M.; Gale, Robert; Ganguly, Siddhartha; Gergis, Usama; Hanna, Rabi; Hematti, Peiman; Herzig, Roger; Hildebrandt, Gerhard C.; Lad, Deepesh P.; Lee, Catherine; Lehmann, Leslie; Lekakis, Lazaros; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Khandelwal, Pooja; Martino, Rodrigo; Murthy, Hemant S.; Nishihori, Taiga; O'Brien, Tracey A.; Olsson, Richard F.; Patel, Sagar S.; Perales, Miguel-Angel; Prestidge, Tim; Qayed, Muna; Romee, Rizwan; Schoemans, Hélène; Seo, Sachiko; Sharma, Akshay; Solh, Melhem; Strair, Roger; Teshima, Takanori; Urbano-Ispizua, Alvaro; Van der Poel, Marjolein; Vij, Ravi; Wagner, John L.; William, Basem; Wirk, Baldeep; Yared, Jean A.; Spellman, Steve R.; Arora, Mukta; Hamilton, Betty K.; Medicine, School of Medicine
    Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.