Comparable Results of HLA Identical Sibling Donor Peripheral Blood Hematopoietic Stem Cell Transplantation after Reduced-Intensity and High-Dose TBI-Based CD34+-Positive Cell Selection Myeloablative Preparative Regimens for High-Risk Myelodysplasia or Acute Myeloid Leukemia in First Remission: Results from a Prospective Study.

We prospectively compared the efficacy of allogeneic PBSCT from an HLA-identical sibling in adults with poor-risk AML or MDS in an early disease status (AML or RAEB type 2 in first CR after chemotherapy or RAEB type 1 with poor prognosis). Poor-risk AML/MDS was defined as the presence at diagnosis of one or more of the following: poor-risk karyoype, normal karyotype with flt-3 duplications or MLL mutations, high level of MRD after consolidation (>0.1%), and, in RAEB type 1, an IPSS³Int-2. Based only on the patients’ age, the transplant protocol consisted in conditioning with cyclophosphamide-TBI and use of CD34+-selected PBSCT (CyTBI-CD34+ group, if £ 50 y.o.) or a reduced-intensity conditioning (RIC) with fludarabine and oral busulphan (FluBu-RIC, If > 50 y.o.). Between 1998 and 2005, 74 consecutive patients entered the study (35 in the CyTBI-CD34+ and 39 in the FluBu-RIC group). Both groups differed in some baseline characteristics, mainly younger age in the CyTBI-CD34+ group (median 42 vs. 59 years, p<0.01), a higher transplant comorbidity index in the FluBu-RIC group (median 0 vs. 3 points, respectively, P<0.01), a higher proportion of AML (with respect to RAEB) in CyTBI-CD34+ group (82% vs 54%, respectively, P=0.02), and a higher proportion of poor-risk karyorypes in the FluBu-RIC group (32% vs 72%, respectively, P<0.01). The median follow-up exceeds 4 years in both groups. All patients had sustained donor-engraftment by day +60, except for one lethal graft failure in the CyTBI-CD34+ group. The 4-year probability of OS was and LFS were similar in both groups (52% and 53% in the CyTBI-CD34+ group vs. 53% and 53% in the FluBu-RIC group, respectively, P>0.8 for OS and LFS). In addition, the 4-year cumulative incidence of non-relapse mortality (NRM) was 25% (95% CI 11–38%) and 22% (95% CI 5–39%), respectively (P>0.8), while the incidence of relapse was 22% (95% CI 5–39%) and 25% (95% CI 6–44%), respectively (P>0.8). In univariate analysis, the only variable that decreased OS and LFS by increasing NRM was the patient male/donor female sex combination (n=18 cases). The OS and NRM in these 18 cases were 37% and 40%, respectively, while the 56 cases with other sex combinations had much better outcomes (66% OS and 8% NRM, P=0.004 and P==0.001 for the comparison of OS and NRM, respectively). Trends were seen for improved OS and lower NRM in the CyTBI-CD34+ group in patients less than 40 years of age (P=0.1) and in patients receiving higher doses of CD34+ cells/kg in the FluBu-RIC group (P=0.1). Our single-center results suggest comparable outcomes for RIC alloPBSCT in high-risk adults with poor-risk AML and MDS in an early disease phase.