Poor Outcome after Allogeneic Hematopoietic Stem Cell Transplantation for De Novo AML with Chromosome 7 Abnormalities: A Report for the ALWP of the European Group for Blood and Marrow Transplantation.
Authors: Buzyn Agnes , Labopin Myriam , Finke Jurgen , Ruutu Tapani , Ehninger G. , Verdonck Leo F. , Socie Gerard , Willemze Roelof , Indrak Karel , Russell Nigel H. , Rocha Vanderson ,   for the ALWP of the EBMT
Published: October 2019

Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many acute myeloid leukemia (AML) patients, especially those with high-risk features. However, for the latter, cure rates remain disappointing due to relapse and transplant related mortality. Since high-risk AML defines a heterogeneous group of patients, the aim of this study was to evaluate specifically the impact of chromosome 7 abnormalities on the outcome of patients transplanted for AML. From 1982 to 2005, 159 de novo AML patients were reported in the EBMT registry with a chromosome 7 abnormality. Median age was 40 years (16–67). FAB subtypes were various: 20 M0, 34 M1, 34 M2, 30 M4, 10 M5, 6 M6, 9 M7, 16 missing. Monosomy 7 was present in 86 patients (54%) either isolated (n=71) or associated to a complex karyotype (n=15), whereas 46% had partial deletion. HSCT was performed in complete remission (CR1) in 85 patients (53%) and for an advanced phase for 69 (43%) defined as either primary refractory (n=49) or progressive (n= 20). The donor was a match sibling (n=88), unrelated donor (MUD) (n=42), or mismatched UD (n=29). The conditioning regimen was myeloablative for 123 patients (77%), containing TBI for 82. Stem cell source was peripheral blood for 97 patients (61%). T cell depletion was performed for 54% of the transplants either in vivo (n=60) or in vitro (n=26). The median follow up of the cohort is 47 months. A GvHD grade II-IV occurred in 47 patients (30%) and III/IV in 28 patients (18%). Among 132 patients alive at day 100, 38% developed chronic GvHD. At time of analysis only 42 patients are alive. The main cause of death is relapse (57%). The univariate analysis shows that the probability of OS at 5 years is 43% for patients transplanted in CR as compared to 11% for advanced phase patients (p<0,0001), and is only 17% for patients with a monosomy 7 compared to 29% for patients with a partial deletion (p=0,007). The survival of patients with AML FAB subtypes M5, 6 or 7 is only 8% compared to 24% for other subtypes (p=0,03). The year of transplant, T cell depletion, type of donor, conditioning regimen, cell source, and patients age have no influence on survival. In the multivariate analysis, CR at transplant (p= 0,005) and partial deletion of chromosome 7 (p=0,02) are the only two factors associated with a better 5 years OS. In conclusion, patients with abnormalities of the chromosome 7 and specially those with monosomy 7 represent a very high risk group of AML patients after HSCT, mostly because of the relapse risk, suggesting a very poor graft-versus-leukemia (GvL) effect in this disease which does not seem to be improved by the use of an UD. Thus, new approaches attempting to decrease the relapse rate of de novo AML with chromosome 7 abnormalities after HSCT are urgently needed.