Impact of Conditioning on the Outcome of Allografting in Myelofibrosis with Myeloid Metaplasia: Better Survival with Reduced Intensity Approach in Patients ≥50 Years.

Abstract We analyzed the impact of intensity of conditioning therapy on the outcomes of allogeneic blood or marrow transplantation (BMT) in patients (pts) with myelofibrosis with myeloid metaplasia (MMM). The study included 46 consecutive patients treated at 7 transplant centers between 1998 and 2005. The indications for BMT were intermediate/high risk disease (n=41) or low risk disease with constitutional symptoms (n=5). Donors were matched sibling/family donor (n=25); mismatched family donor, 2; and unrelated, 19. Twenty-three pts received conventional myeloablative (MY) conditioning: Cy/TBI (n=22); Bu/Cy (n=1), and 23 received non-myeloablative (NMA) conditioning [fludarabine (Flu)/PO or IV Bu (n=16); Flu/TBI 200cGy (n=6); others(n=1)]. Median age at BMT of the MY and NMA group was 47 (31–60) and 54 (38–74) years, respectively. NMA group had a higher proportion of pts ≥50 years (74% vs 30%, p=0.003), a longer interval from diagnosis to BMT (p=0.05) and more transplants using blood stem cells (p=0.0002). At a median follow-up of 31 (1–89) months, 8 and 16 patients were alive in MY and NMA groups, respectively. The transplant related outcomes of the two groups are summarized in the table. Serial pre and post BMT bone marrow biopsy results were available in 24 patients. Median days to resolution of fibrosis were 167 and 363 in the MY and NMA groups (p=0.16). In a multivariate analysis, after adjusting for age the survival was better for pts ≥50 years treated with NMA approach (hazard ratio 2.98, 95% CI 1.09–8.12, p=0.03). In conclusion, both MY and NMA approaches have curative potential for pts with MMM. NMA approach is particularly promising in pts ≥50 years. Table: Comparison of BMT related outcomes for MY and NMA conditioning for MMM Outcomes MY Group (95% C.I.) NMA Group (95% C.I.) P value Neutrophil engraftment (days) 21 (13–46) 18 (1–30) 0.01 Cumulative incidence of graft failure (primary and secondary) at 2-years % 30 (16–58) 23 (10–50) 0.51 Median number of hospital days (Day 0 to +100) 41 (26–85) 27 (8–58) 0.0006 Cumulative incidence of acute GvHD grade II–IV (%) 78 (62–98) 18 (7–45) 0.0002 Cumulative incidence of chronic GVHD at 2-years % 94 (79–100) 45 (27–74) 0.0009 Cumulative incidence of TRM at 2-years % 43 (27–70) 27 (14–55) 0.08 Progression free survival at 2-years % 48 (27–66) 64 (40–80) 0.11 Overall survival at 2-years % 57 (34–74) 68 (45–83) 0.08