The CIBMTR score predicts survival of AML patients undergoing allogeneic transplantation with active disease after a myeloablative or reduced intensity conditioning : a retrospective analysis of the Gruppo Italiano Trapianto Di Midollo Osseo

The prognosis of acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) not in complete remission is poor, although this treatment option remains the only possible curative approach for these patients. A retrospective analysis recently published by European Group for Blood and Marrow Transplantation (EBMT) on primary refractory AML allotransplanted with unrelated donors showed that factors associated with improved survival were the following: having received fewer than three courses of induction therapy, the presence of a lower percentage of bone marrow blast infiltration at transplant and patient cytomegalovirus seropositivity. This allowed the development of a scoring system that identified four groups with survival rates ranging between 44 and 0%. However, the largest retrospective analysis on AML patients with active disease at the time of conditioning (1673 patients) has been conducted by the Center for International Blood and Marrow Transplant Research (CIBMTR), which, on five pretransplantation variables (duration of first complete remission (CR) <6 months, circulating blasts, donor other than HLA-identical sibling, Karnofsky score less than 90 and poor-risk cytogenetics), also set up a pre-HSCT score defining a 3-year overall survival (OS) ranging from 42 to 6%. Here we report outcome data obtained in Italy in a similar cohort of AML patients (523 patients) allotransplanted with active disease. The primary aim of the study was to externally validate the CIBMTR score in a multicenter, retrospective study setting, evaluating the prognostic power of the score in a wider patient population that included not only those receiving a myeloablative conditioning (MAC) but also those treated with a reduced-intensity conditioning (RIC) (as detailed in Supplementary Table 1) and those grafted with a cord blood. Twenty Italian centers belonging to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) participated in this retrospective observational study. Data were retrieved from the GITMO database, and missing data or specific queries were asked to each center. Overall, 523 patients (no one enrolled into prospective trials) from 20 GITMO centers were included in this study. Patient, disease and transplant characteristics are listed in Table 1. The median age was 47.6 (range 18–72). At time of conditioning, AML was defined as primary refractory (patients not achieving a CR after the first induction chemotherapy), MDS-related (untreated patients with >20% bone marrow blasts), untreated first relapse (patients not receiving a salvage chemotherapy before conditioning), refractory first relapse (patients not achieving a remission after a salvage chemotherapy), second or further relapse (untreated or refractory to further salvage chemotherapy). A marrow blast infiltration >25% or any level of peripheral blood (PB) blasts was found in 42%. Donors were HLA identical sibling or matched unrelated in 69%, a family or unrelated mismatched in 25% and a cord blood unit in 6%. More than 60% of patients received a MAC and 37% received a RIC program. A T-cell depletion was performed in vivo in 37% and ex vivo in 8% of patients as described elsewhere.