Browsing by Author "Pusic, Iskra"

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    A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation.
    (Clin Cancer Res, 2016-01-15) Arai, Sally; Pidala, Joseph; Pusic, Iskra; Chai, Xiaoyu; Jaglowski, Samantha; Khera, Nandita; Palmer, Jeanne; Chen, George L; Jagasia, Madan H; Mayer, Sebastian A; Wood, William A; Green, Michael; Hyun, Teresa S; Inamoto, Yoshihiro; Storer, Barry E; Miklos, David B; Shulman, Howard M; Martin, Paul J; Sarantopoulos, Stefanie; Lee, Stephanie J; Flowers, Mary ED
    PURPOSE: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. EXPERIMENTAL DESIGN: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m(2) i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. RESULTS: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%-43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%-44%) randomized to rituximab. Six (17%; 95% CI, 7%-34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27(+)) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. CONCLUSIONS: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab.
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    Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy.
    (Transplantation and cellular therapy, 2021-08) Kharfan-Dabaja, Mohamed A; Kumar, Ambuj; Ayala, Ernesto; Aljurf, Mahmoud; Nishihori, Taiga; Marsh, Rebecca; Burroughs, Lauri M; Majhail, Navneet; Al-Homsi, A Samer; Al-Kadhimi, Zaid S; Bar, Merav; Bertaina, Alice; Boelens, Jaap J; Champlin, Richard; Chaudhury, Sonali; DeFilipp, Zachariah; Dholaria, Bhagirathbhai; El-Jawahri, Areej; Fanning, Suzanne; Fraint, Ellen; Gergis, Usama; Giralt, Sergio; Hamilton, Betty K; Hashmi, Shahrukh K; Horn, Biljana; Inamoto, Yoshihiro; Jacobsohn, David A; Jain, Tania; Johnston, Laura; Kanate, Abraham S; Kansagra, Ankit; Kassim, Adetola; Kean, Leslie S; Kitko, Carrie L; Knight-Perry, Jessica; Kurtzberg, Joanne; Liu, Hien; MacMillan, Margaret L; Mahmoudjafari, Zahra; Mielcarek, Marco; Mohty, Mohamad; Nagler, Arnon; Nemecek, Eneida; Olson, Timothy S; Oran, Betul; Perales, Miguel-Angel; Prockop, Susan E; Pulsipher, Michael A; Pusic, Iskra; Riches, Marcie L; Rodriguez, Cesar; Romee, Rizwan; Rondon, Gabriela; Saad, Ayman; Shah, Nina; Shaw, Peter J; Shenoy, Shalini; Sierra, Jorge; Talano, Julie; Verneris, Michael R; Veys, Paul; Wagner, John E; Savani, Bipin N; Hamadani, Mehdi; Carpenter, Paul A
    Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.