Results of a large retrospective cohort study of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) compared with those with AML-not otherwise specified (AML-NOS) showed a heterogeneous range of post-transplantation outcomes in the former group. The findings from this study were published in Biology of Blood and Marrow Transplantation.
AML-MRC is a distinct AML entity according to the 2016 WHO classification system of AML. It is defined by the presence of multilineage dysplasia (MLD), and/or a history of myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN), and/or cytogenetics characteristics of MDS. Although results of previous studies have shown worse survival of patients with AML-MRC compared with those with AML-NOS, outcomes following allo-SCT, as well as disease-related factors associated with these outcomes, have not been well characterized.
In this study, clinicopathologic data for 3964 and 4091 adult patients with AML-MDC and AML-NOS, respectively, who underwent allo-SCT were obtained from the Transplant Registry Unified Management Program 2 of the Japanese Data Center for Hematopoietic Cell Transplantation. Study end points included overall survival (OS), leukemia-free survival (LFS), relapse, and nonrelapse mortality (NRM).
Patients in the AML-MRC subgroup were a median age of 56 years, were more likely to be older, male, and to have worse performance status, and less likely to have achieved a complete remission (CR) prior to transplantation compared with patients in the AML-NOS subgroup. In addition, the time period from diagnosis to transplantation was significantly shorter for patients with AML-MRC (170 days vs 234 days, P <.001).
In the AML-MRC subgroup, 22.3% had MLD solo, 27.6% had a history of MDS or MDS/MPN, and 49.8% had MDS-related cytogenetic abnormalities.
A breakdown by MDS-related cytogenetics showed 16.3%, 10.5%, 2.3%, 8.3%, 1.7%, and 0.8% of patients had disease characterized by monosomal karyotype (MK), complex karyotype (CK), isolated -5/del(5q), isolated -7/del(7q), other unbalanced abnormalities, and balanced abnormalities. Median follow-up for survivors was 45 months.
Perhaps unsurprisingly, on multivariate analysis, both OS (hazard rate [HR], 1.11; 95% CI, 1.01–1.21; P =.029) and LFS (HR, 1.17; 95% CI, 1.09–1.26; P <.001) following allo-SCT were worse, and there was a greater risk of relapse (HR, 1.22; 95% CI, 1.11–1.34; P <.001), for the cohort of patients with AML-MRC compared with those in the AML-NOS cohort.
Interestingly, however, multivariate analyses of the cytogenetic subgroups of patients in the AML-MRC subgroup showed improved OS for patients with MLD-solo compared with the AML-NOS cohort (HR, 0.81; 95% CI, 0.71–0.94; P =.005).
While no differences in OS were seen for patients with AML-MRC characterized by a history of MDS or MDS/MPN, or isolated −7/del(7q) compared with the AML-NOS cohort, each of the cytogenetic subgroups (ie, AML-MRC characterized by MK, CK, or isolated −5/del[5q]) had worse survival than patients with AML-NOS.
Based on these results, the study authors stratified the AML-MRC cohort into 3 risk groups: low risk=MLD-solo; history of MDS or MDS/MPN, isolated -7/del(7q), other unbalanced and balanced abnormalities; intermediate risk=CK group, and isolated -5/del/(5q); and high risk= MK group.
When patients with AML-MRC not in CR at the time of allo-SCT (approximately 50% of the AML-MRC cohort) were stratified according to this risk system, 3-year OS rates were 36.3%, 25.0%, and 5.7% in low-, intermediate-, and high-risk groups, respectively (P <.001).
“Taken together, urgent allo-SCT should be considered in fit patients with intermediate- or high-risk AML-MRC who have achieved CR. In contrast, the outcomes were modest or even dismal in intermediate- or high-risk patients not in CR at transplantation, suggesting the minimal beneficial effect of allo-SCT in these patients. Therefore, indication for allo-SCT in
those patients should be carefully reviewed,” the authors wrote.
Other factors shown to be independently associated with worse survival in patients with AML-MRC following allo-SCT were older age, poor performance status, and at least 5% blast percentage in peripheral blood. Interestingly, in the AML-MRC cohort, grade 1/2 acute graft-versus-host-disease (aGVHD) was associated with improved survival, whereas the OS of those developing grade 3/4 aGVHD was worse, compared with those who did not develop aGVHD.
Some of the study limitations identified by the authors included the absence of data on genetic mutations that could have the potential to refine disease defined as MRD-solo, possibilities for selection bias, and gaps in data related to treatments administered prior to and following allo-SCT.
In summarizing the results of their study, the authors noted that their “prognostic risk
stratification can potentially aid in elucidating the diverse transplantation outcomes in
patients with AML-MRC. Performing allo-SCT at the appropriate time while taking into
consideration the disease status, clinical condition of the patient, donor source, and
controlling aGVHD can potentially improve outcomes in patients with AML-MRC.”
Harada K, Konuma T, Machida S, et al. Risk stratification and prognosticators of acute myeloid leukemia with myelodysplasia-related changes patients undergoing allogeneic stem cell transplantation: a retrospective study of the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation [published online May 2, 2019]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2019.04.025