Abstract
INTRODUCTION:Monosomy 7 or deletion 7q (-7/7q-) is the most frequent high-risk cytogenetic feature reported in acute myeloid leukemia (AML) and is associated with a dismal outcome after chemotherapy alone. Allogeneic stem cell transplantation (SCT) appears to be the best consolidation strategy in these patients (pts), thereby significantly improving outcomes. Nevertheless, -7/7q- occurs frequently with other high-risk cytogenetic abnormalities such as complex karyotype (CK), monosomal karyotype (MK), monosomy 5 or deletion 5q (-5/5q-), 17p abnormalities (abn(17p)) or inversion/translocation of chromosome 3q26 (inv(3)). The presence of such abnormalities may further influence the outcomes of SCT in pts with -7/7q-. The purpose of this study was to evaluate the role of SCT in AML with -7/7q- in the context of additional cytogenetic abnormalities.
METHODS:We selected adult pts with AML and -7/7q- reported to the EBMT registry with a complete cytogenetic report. We included only first SCT from a sibling or unrelated donor (UD) performed between 2000 and 2016.
RESULTS: A total of 1109 pts were identified. Median age at SCT was 52 year-old (range, 18-76) and median follow-up was 34 months (range, 0.7-193). A diagnosis of secondary AML was reported in 213 pts (19%). At the time of SCT, 702 patients (63%) were in first remission (CR1), 58 (5%) in subsequent remission and 349 (32%) had active disease. Four hundred ninety-six pts received SCT from a sibling donor (45%). Most pts had a Karnofsky's performance status (KPS) of more than 80% at the time of SCT (93%). A myeloablative conditioning regimen was administered in 50% of the pts. In vivo T-cell depletion was part of the regimen in 56% of the pts.
The 2-year probability of leukemia-free survival (LFS) and overall survival (OS) were 30% and 36%, respectively. The 2-year probability of non-relapse mortality (NRM) was 20% and the 2-year cumulative incidence of relapse (RI) was 50%. The cumulative incidence of acute graft-versus-host disease (GvHD) was 31% and the 2-year cumulative incidence of chronic GvHD was 31%. The 2-year probability of GvHD and relapse-free survival (GRFS) was 21%. In multivariate analysis, age was not associated with any outcomes. Active disease was significantly associated with increased NRM and RI, which translated into worse LFS, OS and GRFS. Significant higher NRM was associated with UD. Secondary AML was associated with higher NRM and decreased OS. Better KPS correlated significantly with less NRM and better LFS, OS and GRFS.
To evaluate the impact of additional cytogenetic abnormalities, we have been able to sort out 5 different groups within the entire cohort. The first group included 523 pts with -7/7q- with or without CK, but without any of the following chromosomal abnormalities: MK, -5/5q-, abn(17p) or inv(3). One hundred ninety-nine pts belonged to the second group that included pts with -7/7q- within MK but without -5/5q-, abn(17p) or inv(3). The third group included 151 pts with -7/7q- in association with -5/5q- but no abn(17p) or inv(3). Group 4 included 125 pts with -7/7q- and abn(17p) but without inv(3). Finally, 111 pts had inv(3) in addition to 7/7q- and were assigned to the fifth group. NRM was similar across all groups. The 2-year probability of LFS was 39.7% for group 1, 28.5% for group 2, 22.5% for group 3, 16.4% for group 4 and 13.7% for group 5 (p<0.001) (see figure). The 2-year probabilities of OS in the 5 groups were 47.7%, 34.9%, 28.2%, 15.9% and 19.7%, respectively (p<0.001). The corresponding 2-year probability of GRFS was 29.7% for group 1, 16.6% for group 2, 14.5% for group 3, 8.1% for group 4 and 8.9% for group 5 (p<0.001). Multivariate analysis confirmed those significant differences across groups. We observed comparable results when the analysis was focused on CR1 pts.
CONCLUSIONS: SCT in AML pts with -7/7q- provides durable response in one third of the pts. Disease status at the time of transplantation remains the strongest prognostic factor for poor outcomes. The presence of -7/7q- with or without CK in the absence of MK, -5/5q-, abn(17p) or inv(3) was associated with a better survival after SCT. On the contrary, addition of MK, -5/5q-, abn(17p) or inv(3) identifies a sub-group of pts that benefits less from SCT. In these pts, future efforts should focus on prevention of relapse by therapeutic modalities like early withdrawal of immunosuppression, administration of hypomethylating agents, donor lymphocytes infusion or others.
Socié: Alexion Pharmaceuticals, Inc.: Consultancy. Mohty: Sanofi: Honoraria, Speakers Bureau.
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