Impact of genetic abnormalities after allogeneic stem cell transplantation in multiple myeloma: report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC)

Background and aim: Del (13q), t (4;14) and del (17p) are wellrecognized poor prognostic genetic abnormalities in multiple myeloma after standard chemotherapy and autologous stem cell transplantation (SCT). We investigated the impact of these genetic abnormalities, detected by fluorescence in situ hybridization (FISH), on the outcome of patients who underwent allogeneic SCT, in a retrospective study of the SFGM-TC. Patients and methods: Data were collected from 15 centers for a total of 160 patients. The median age of the population at diagnostic was 52 years (range, 30-64 years). Most patients had advanced myeloma: beta2microglobuline was > to 4 mg/L in 48% and more than 90% had received at least one autologous SCT. The median time from diagnostic to allogeneic transplantation was 14 months (range, 4-175 months). Chromosomal abnormalities were found in 117 of 160 patients (73%), distributed as follows (in percent of patients analyzed for the abnormality): 61% for del (13q), 24% for t (4;14), 26% for del (17p), 24% for t (11;14) and 4% for t (14;16). Seventy three percent of patients received a reduced intensity conditioning regimen; the source of stem cells was peripheral blood in 79% of patients and 69% of donors were HLA-identical siblings. Results: With a median follow-up of 20 months, the 2-year progression, progression free survival (PFS) and overall survival (OS) were respectively 51%, 34% and 57%. One-year transplant-related mortality was 21%. Grade II to IV acute graft-versus-host disease (GvHD) was present in 34%. Limited and extensive chronic GvHD occurred respectively in 28% and 32% of evaluable patients. In univariate analysis, the del (13q), t (4;14) and del (17p) had no impact on PFS (2y PFS: 36% for del (13q) versus 32% for non-del (13q) (P=0.35); 36% for del (17p) versus 21% for non-del (17p) (P=0.89); 20% for t (4;14) versus 34% for non-t (4;14) (P=0.37)). Better PFS was associated with younger age at transplant (P=0.04), chemo sensitive disease at transplant (P=0.02) and a short delay from diagnostic to transplant (P=0.02). In multivariate analysis, the diagnosistransplant interval was the only factor associated with better PFS (P=0.017, OR: 1.6, CI 1.1-2.4). Conclusion: These data suggest no impact of genetic abnormalities after allogeneic SCT for multiple myeloma. Contrary to published data (Schilling et al., Leukemia, 2008), multiple myeloma with t (4;14) does not seem to benefit from allogeneic SCT.