Browsing by Author "Hashmi, Shahrukh"

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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 T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation
    (Elsevier, 2019) Saad, Ayman; Lamb, Lawrence; Wang, Tao; Hemmer, Michael T.; Spellman, Stephen; Couriel, Daniel; Alousi, Amin; Pidala, Joseph; Abdel-Azim, Hisham; Agrawal, Vaibhav; Aljurf, Mahmoud; Beitinjaneh, Amer M.; Bhatt, Vijaya Raj; Buchbinder, David; Byrne, Michael; Cahn, Jean-Yves; Cairo, Mitchell; Castillo, Paul; Chhabra, Saurabh; Diaz, Miguel Angel; Farhan, Shatha; Floisand, Yngvar; Frangoul, Hadar A.; Gadalla, Shahinaz M.; Gajewski, James; Gale, Robert Peter; Gandhi, Manish; Gergis, Usama; Hamilton, Betty Ky; Hematti, Peiman; Hildebrandt, Gerhard C.; Kamble, Rammurti T.; Kanate, Abraham S.; Khandelwal, Pooja; Lazaryn, Aleksandr; MacMillan, Margaret; Marks, David I.; Martino, Rodrigo; Mehta, Parinda A.; Nishihori, Taiga; Olsson, Richard F.; Patel, Sagar S.; Qayed, Muna; Rangarajan, Hemalatha G.; Reshef, Ran; Ringden, Olle; Savani, Bipin N.; Schouten, Harry C.; Schultz, Kirk R.; Seo, Sachiko; Shaffer, Brian C.; Solh, Melhem; Teshima, Takanori; Urbano-Ispizua, Alvaro; Verdonck, Leo F.; Vij, Ravi; Waller, Edmund K.; William, Basem; Wirk, Baldeep; Yared, Jean A.; Yu, Lolie C.; Arora, Mukta; Hashmi, Shahrukh; Medicine, School of Medicine
    Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.
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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.