Browsing by Author "Chhabra, Saurabh"

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    Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery.
    (J Hematol Oncol, 2018-03-04) Green, Michael MB; Chao, Nelson; Chhabra, Saurabh; Corbet, Kelly; Gasparetto, Cristina; Horwitz, Ari; Li, Zhiguo; Venkata, Jagadish Kummetha; Long, Gwynn; Mims, Alice; Rizzieri, David; Sarantopoulos, Stefanie; Stuart, Robert; Sung, Anthony D; Sullivan, Keith M; Costa, Luciano; Horwitz, Mitchell; Kang, Yubin
    BACKGROUND: The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT) promotes hematopoiesis by inducing HSC proliferation. METHODS: We conducted a phase I/II trial of plerixafor on hematopoietic cell recovery following myeloablative allogeneic HSCT. Patients with hematologic malignancies receiving myeloablative conditioning were enrolled. Plerixafor 240 μg/kg was administered subcutaneously every other day beginning day +2 until day +21 or until neutrophil recovery. The primary efficacy endpoints of the study were time to absolute neutrophil count >500/μl and platelet count >20,000/μl. The cumulative incidence of neutrophil and platelet engraftment of the study cohort was compared to that of a cohort of 95 allogeneic peripheral blood stem cell transplant recipients treated during the same period of time and who received similar conditioning and graft-versus-host disease prophylaxis. RESULTS: Thirty patients received plerixafor following peripheral blood stem cell (n = 28) (PBSC) or bone marrow (n = 2) transplantation. Adverse events attributable to plerixafor were mild and indistinguishable from effects of conditioning. The kinetics of neutrophil and platelet engraftment, as demonstrated by cumulative incidence, from the 28 study subjects receiving PBSC showed faster neutrophil (p = 0.04) and platelet recovery >20 K (p = 0.04) compared to the controls. CONCLUSIONS: Our study demonstrated that plerixafor can be given safely following myeloablative HSCT. It provides proof of principle that blocking CXCR4 after HSCT enhances hematopoietic recovery. Larger, confirmatory studies in other settings are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01280955.
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    Survival following allogeneic transplant in patients with myelofibrosis.
    (Blood advances, 2020-05) 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; Angel Diaz, Miguel; 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; Pawarode, 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
    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.