[1088] Impact of FLT3 Internal Tandem Duplication (FLT3/ITD) on the Outcome of HLA-Identical Sibling Hematopoietic Transplantation for Adult Acute Myeloid Leukemia (AML) in First Remission: Substantial Probability of Leukemia-Free Survival Despite Increased Relapse Risk. A Retrospective Analysis of the EBMT-ALWP. Session Type: Poster Session, Board #242-I
Salut Brunet, Myriam Labopin, Jan J. Cornelissen, Gérard Socié, Ana Paola Iori, Leo F. Verdonck, Tapani Ruutu, Alois Gratwohl, Jean-Luc Harousseau, Jorge Sierra, Vanderson Rocha On Behalf of the Acute Leukemia Working Party (ALWP) of the European Group for Blood and Marrow Transplantation (EBMT), Paris, France
The prognosis of patients with AML and FLT3 internal tandem duplication (FLT3/ITD) is poor. It is unclear whether this mutation has impact on the outcome of allogeneic stem cell transplantation (Allo-SCT) for AML. Different cooperative groups have obtained controversial results. For this reason, registry data including large numbers of patients are of interest. We analysed the predictive value of FLT3/ITD on relapse incidence (RI), non-relapse mortality (NRM) and leukemia-free survival (LFS) in patients with AML in 1st CR who underwent a myeloablative allo-SCT from HLA-identical siblings and were reported to the EBMT. The series included 682 patients, 610 negative ITD/FLT3 and 72 FLT3/ITD positive reported between 1998 and 2007 with a median follow up time of 24 and 11 months, respectively. No significant differences were observed between the two groups regarding gender, median age (38 vs 40 yrs), FAB classification, cytogenetic distribution, number of induction courses to achieve CR, interval diagnosis to transplant (134 vs 133 days), source of stem cells (PB or BM) and CMV serostatus. In contrast, patients with FLT3/ITD had higher leukocyte counts at diagnosis (14 vs 65 x109/L, p<0.0001), were transplanted with T-cell replete progenitors (78% vs 97%, p<0.0001) and more frequently a female donor to male recipient (yes: 31% vs 20%, p=0.04). Univariate (Table1) and multivariate analyses demonstrated the adverse impact of FLT3/ITD for LFS (HR 0.56, p=0.009) and relapse incidence (HR=2.9, p<0.001) but not for NRM (p=0.83). It is remarkable, however, 53% of FLT3/ITD positive patients transplanted for AML in first CR remain alive and disease-free at 2 years. Other independent prognostic factors for LFS and relapse were: T-cell depleted graft, poor cytogenetics and more than one induction course to achieve first CR. For NRM the only prognostic factor was age 
45 years (HR=1.9, p=0.004). In summary, this analysis shows an adverse impact of FLT3/ITD on transplantation outcome. Despite this finding, half of FLT3/ITD positive AML patients in first CR remain disease-free at 2 years, a proportion that seems higher than with other treatment options.Table 1. Two years outcomes of HSCT in adults patients with AML in CR1 according to the presence of FLT3/ITD.
| LFS | Relapse | NRM | |
| FLT3/ITD+ (n=70) | 53 7% | 367% | 177% |
| FLT3/ITD-(n=610) | 642% | 202% | 192% |
| P (log rank test) | P=0.06 | P<0.0001 | P=0.49 |
Abstract #1088 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Myeloid Leukemia|Flt3-ITD|Stem Cell Transplant
Disclosure: No relevant conflicts of interest to declare.
Saturday, December 8, 2007 5:30 PM
Session Info: Poster Session: Clinical Results: Allogeneic Matched Related Donor Transplantation I (5:30 p.m.-7:30 p.m.)