Browsing by Author "Grunwald, Michael R."

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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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    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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    Survival following allogeneic transplant in patients with myelofibrosis
    (American Society of Hematology, 2020-05-08) Gowin, Krisstina; Ballen, Karen; Ahn, Kwang Woo; Hu, Zhen-Huan; Ali, Haris; Arcasoy, Murat O.; Devlin, Rebecca; Coakley, Maria; Gerds, Aaron T.; Green, Michael; Gupta, Vikas; Hobbs, Gabriela; Jain, Tania; Kandarpa, Malathi; Komrokji, Rami; Kuykendall, Andrew T.; Luber, Kierstin; Masarova, Lucia; Michaelis, Laura C.; Patches, Sarah; Pariser, Ashley C.; Rampal, Raajit; Stein, Brady; Talpaz, Moshe; Verstovsek, Srdan; Wadleigh, Martha; Agrawal, Vaibhav; Aljurf, Mahmoud; Diaz, Miguel Angel; Avalos, Belinda R.; Bacher, Ulrike; Bashey, Asad; Beitinjaneh, Amer M.; Cerny, Jan; Chhabra, Saurabh; Copelan, Edward; Cutler, Corey S.; DeFilipp, Zachariah; Gadalla, Shahinaz M.; Ganguly, Siddhartha; Grunwald, Michael R.; Hashmi, Shahrukh K.; Kharfan-Dabaja, Mohamed A.; Kindwall-Keller, Tamila; Kröger, Nicolaus; Lazarus, Hillard M.; Liesveld, Jane L.; Litzow, Mark R.; Marks, David I.; Nathan, Sunita; Nishihori, Taiga; Olsson, Richard F.; Pawarod, Attaphol; Rowe, Jacob M.; Savani, Bipin N.; Savoie, Mary Lynn; Seo, Sachiko; Solh, Melhem; Tamari, Roni; Verdonck, Leo F.; Yared, Jean A.; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Scott, Bart L.; Nakamura, Ryotaro; Mesa, Ruben; Saber, Wael; Medicine, School of Medicine
    Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.