MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis

• Published in: Blood 2014-08, Vol.124 (7), p.1183-1191
• Main Authors: Rondelli, Damiano, Goldberg, Judith D., Isola, Luis, Price, Leah S., Shore, Tsiporah B., Boyer, Michael, Bacigalupo, Andrea, Rambaldi, Alessandro, Scarano, Marco, Klisovic, Rebecca B., Gupta, Vikas, Andreasson, Bjorn, Mascarenhas, John, Wetzler, Meir, Vannucchi, Alessandro M., Prchal, Josef T., Najfeld, Vesna, Orazi, Attilio, Weinberg, Rona S., Miller, Crystal, Barosi, Giovanni, Silverman, Lewis R., Prosperini, Giuseppe, Marchioli, Roberto, Hoffman, Ronald
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis of Variance; Antilymphocyte Serum - therapeutic use; Blood Donors; Female; Follow-Up Studies; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Histocompatibility; Humans; Janus Kinase 2 - genetics; Kaplan-Meier Estimate; Male; Melphalan - therapeutic use; Middle Aged; Mutation; Primary Myelofibrosis - genetics; Primary Myelofibrosis - therapy; Prospective Studies; Siblings; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous; Treatment Outcome; Unrelated Donors; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2014-04-572545

From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2V617F status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as #NCT00572897. •A high survival rate was seen in primary or secondary MF patients transplanted from matched related donors using the FluMel regimen.•FluMel plus ATG in HSCT from unrelated donors for MF patients is associated with an increased risk of graft failure.