Summary:Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients o60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age 460 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status 41. The 1-year TRM in patients with 0 or 1 and 42 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (Po0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors. Allogeneic stem cell transplantation (alloSCT) is a wellestablished treatment approach for numerous hematological malignancies. However, high-dose conditioning regimens designed to both control the malignancy and to prevent graft rejection are associated with a high mortality and a high incidence of acute and long-term side effects, especially in elderly or debilitated patients. A potential way to overcome this problem is by decreasing the intensity of chemotherapy and/or radiotherapy given prior to transplantation. Several groups of investigators have developed reduced-intensity conditioning (RIC) regimens that lead to successful engraftment in patients with hematological and nonhematological malignancies, without the extrahematologic toxicities of traditional myeloablative transplants. [1][2][3][4][5][6] Based on numerous phase II trials, RIC are able to induce graft-versus-leukemia/tumor (GVL) effects with acceptable levels of extrahematologic toxicity. Thus, these attenuated regimens have been used mostly in older patients or patients with pre-existing organ dysfunction who would otherwise have a high risk of transplant-related mortality (TRM) after a myeloablative alloSCT. To date however, risk factors for TRM and their impact on overall survival (OS) after RIC transplants have not been described. We report here results of a prospective multicenter study of two RIC regimens (for myeloid and lymphoid malignancies) followed by allogeneic peripheral blood SCT (PBSCT) that is being conducted in several institutions in Spain, with special emphasis on pretransplant variables that influenced early TRM and OS.
Patients and methods
Patient selectionEligibility criteria for entry into this RIC allogeneic PBSCT program included patients with a myeloid o...