ALBERT

Description: Abstract 3122 The outcome of high-risk acute myeloid leukemia (AML) patients not undergoing an allogeneic transplantation is extremely poor. Therefore transplantation from haploidentical donor represents an alternative option for these patients on urgency to be transplanted. We report the results of a study on unmanipulated, G-CSF primed, haploidentical bone marrow (BM) transplantation in patients with high-risk AML lacking a suitable HLA-identical donor. Materials and methods: Between August 2005 to December 2011 58 patients (median age: 44 yrs, range 5–71) with very high-risk AML (CR1=32; CR2=16; advanced stage=10) underwent BM transplant from haploidentical donor. As pretransplant regimens, 43 patients were conditioned with a myeloablative regimen (MAC), while 15 patients received a reduced intensity conditioning (RIC). Of the 58 patients, 43 received the chemotherapy based regimen consisting of Thiotepa, i.v. Busulphan and Fludarabine (TBF MAC or RIC protocol). All 42 patients received an identical GvHD prophylaxis consisting of pretransplant ATG combined with CSA, MTX, MMF and Basiliximab, an anti-CD25 monoclonal antibody. Donors were primed with G-CSF at 4 microgr/Kg/d for 7 consecutive days. BM was harvested on day 0 and infused unmanipulated. Results: The median number of total nucleated, CD34+ and CD3+ cells infused was 7.2 (1–28)x108/kg, 2.04 (0.8–11)x106/Kg and 2.9 (0.9–6.7)x107/Kg, respectively. Five patients died early. All 53 evaluable patients engrafted at a median of 21 (13–29) days and the cumulative incidence (CI) of neutrophil engraftment was 100% at 30 days. For 53 evaluable patients, acute GVHD was absent or just grade I in 25 (47%). The 100-day CI of II-IV and III-IV grade acute GVHD was 34+/−0.4% and 12+/−0.2% respectively. Extensive chronic GVHD occurred in 4 (8%) out of 49 evaluable patients and the 2-year CI of extensive chronic GVHD was 13+/−0.4%. The 1 and 5-year CI of transplant-related mortality (TRM) was 32+/−0.4% and 34+/−0.4% respectively. The overall CI of relapse was 20+/−0.4% at 1-year and 34+/−0.7% at 5-year. The overall and disease-free survival probability was 61+/−6% and 54+/−7% at 1 year, 49+/−7% and 42+/−7% at 5 years. For patients in early stage of disease (CR1+CR2: n=48) the 1 and 3-year probability of overall survival was 70+/−7% and 58+/−8%. Conclusions: Haploidentical transplant using G-CSF primed, unmanipulated BM is correlated with high engraftment rate, low incidence of acute and chronic GVHD, acceptable TRM and favorable outcome. This approach represents a valid and feasible alternative to transplant from matched unrelated donor or cord blood for high-risk AML patients particularly on urgency to be transplanted. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 680 Cytogenetics play an essential role in determining the prognosis of patients with AML. However, there is still no validated cytogenetics grouping scheme that specifically applies to patients undergoing allogeneic stem cell transplantation, which hampers accurate prognostication and risk stratification. We studied 821 adult patients (median age 41, range 18–74) who underwent SCT between 1999 and 2004 for AML (excluding APL) in CR1 or CR2 and who were reported to the CIBMTR from centers with 〉20 patients meeting study criteria. 75% of patients received a myeloablative conditioning. 496 patients had a normal karyotype. The primary cytogenetics reports were manually reviewed for 92% of the patients with an abnormal karyotype. We compared the ability of the 6 existing grouping schemes (MRC, CALGB, EORTC/GIMEMA, SWOG/ECOG, DFCI, and Monosomal Karyotype (MK) classifications) to stratify patients, using both the Akaike Information Criterion in multivariable models and the C-statistic. Among all existing schemes, the DFCI system provided a marginally superior stratification for overall and leukemia-free survival. We also built a new classification using individual cytogenetic abnormalities in a Cox model that included other significant covariates (performance status, therapy-related disease, conditioning intensity, graft source, donor match, duration of CR1, and gender match). This CIBMTR scheme (see Table), which is similar to the DFCI scheme except for the inclusion of patients with t(8;21) in the intermediate group, could stratify patients into 3 groups with similar treatment-related mortality but significantly different overall survival, leukemia-free survival, and incidence of relapse. This scheme appeared to apply to both patients in CR1 and in CR2 (see FiguresF2). This transplant-specific scheme could be adopted for prognostication purposes and to stratify patients with karyotypic abnormalities entering transplantation clinical trials. Future studies may clarify the relative outcome of patients with t(8;21) and refine this scheme with the inclusion of molecular abnormalities. Disclosures: No relevant conflicts of interest to declare.