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

Abstract

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 JAK2(V617F) 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.

Figure 1

Survival after AHSCT with a FluMel conditioning regimen in MF patients. Cumulative OS (A) and EFS (B) in 32 MF patients who received a transplant from a sibling donor. Median survival has not been reached, because 75% of patients were alive at last follow-up and 71% were without disease progression. Cumulative OS (C) and EFS (D) in 34 MF patients who received a transplant from an unrelated donor. Median OS and EFS in unrelated transplants are shown.

Figure 2

Diagnosis, HLA matching, JAK2^V617F, and age do not correlate with survival after AHSCT with a FluMel conditioning regimen in MF patients. OS in recipients with grafts from sibling (Sib) and unrelated (Unrel) donors based on diagnosis (PMF, ET-MF, or PV-EF) (A), HLA-matched or HLA-mismatched donor (B) (*2/32 patients in the HLA-matched Sib group received a 1-antigen-mismatched transplant from their sibling, and none of them died), presence of JAK2^V617F mutation (Jak2 pos) (C), and age < or ≥57 years (D).

Figure 3

OS in sibling (Sib) or unrelated (Unrel) transplants by age-adjusted DIPSS categories. Patients in each group were classified as low/int-1 or int-2/high risk.