Risk Stratification and Prognosticators of Acute Myeloid Leukemia with Myelodysplasia-Related Changes in 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

Abstract

Although the prognosis of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is worse than that of AML not otherwise specified (AML-NOS), transplantation outcomes and prognosticators of AML-MRC patients undergoing allogeneic stem cell transplantation (allo-SCT) remain unclear. Transplantation outcomes of AML-MRC (n = 4091) were compared with those of AML-NOS (n = 3964) in patients who underwent allo-SCT between 2003 and 2016 using a nationwide registration database. The 3-year overall survival (OS; 35.5% versus 50.6%) was lower and the relapse (42.3% versus 32.1%) and nonrelapse mortality (26.3% versus 22.0%) rates were higher in the AML-MRC group than in the AML-NOS group. Based on the hierarchical AML-MRC classification, myelodysplasia as the sole criterion was associated with better OS compared with AML-NOS, whereas monosomal or complex karyotype and ¡5/del(5q) were associated with poor OS. A history of myelodysplastic syndrome and ¡7/del(7q) did not affect OS. Accordingly, AML-MRC with complex karyotype or ¡5/del(5q) and that with monosomal karyotype were classified as intermediate and high risks, respectively, whereas the remaining cases were classified as low risk. The 3-year OS rates were 50.7%, 36.9%, and 13.8% in the low-, intermediate-, and high-risk groups, respectively (P < .001). Risk classification, older age, and low performance status score were significant risk factors for survival in AML-MRC, independently of the disease status. Grades I to II acute graftversus-host disease significantly reduced the 3-year relapse (24.7% versus 31.6%), leading to better survival (hazard ratio, .64). Our prognostic risk stratification can potentially aid in elucidating the diverse transplantation outcomes in patients with AML-MRC.

Impact of pretransplant measurable residual disease on the outcome of allogeneic hematopoietic cell transplantation in adult monosomal karyotype AML

“…Several studies have indicated that adults with MK AML are essentially non-curable with conventional chemotherapies. 8,9,12,13,17,20 Although some of the reported outcomes with allogeneic HCT seemed better than what was observed with other post-remission therapies, the recurrent notion that relapse rates are very high and survival estimates short after transplantation [10][11][12]14,15,[18][19][20][21][22] may have decreased enthusiasm to expose patients to the risks associated with allografting. The findings from our large retrospective single-institution study confirm that adults with intermediate-or adverse-risk AML and MK have worse post-HCT outcomes than corresponding patients without MK AML, with the 3-year cumulative incidence of relapse approaching 60% in our cohort of MK AML patients (as compared to less than 30% for the non-MK AML patients).…”

“…[9][10][11][12][13][14][15][16][17][18][19][20][21] While results with allogeneic HCT appear better than with non-HCT post-remission therapies, several studies -including one from our institution -have reported poor post-HCT outcomes for adults with MK AML. [10][11][12]14,15,[18][19][20][21][22] Based on these data, it is now generally accepted that having MK AML is an important adverse prognostic factor for patients undergoing allogeneic HCT. However, to what degree these outcomes are accounted for by the presence of measurable ('minimal') residual disease (MRD) before HCT is unknown.…”

“… 8 Numerous studies have subsequently confirmed this association. 9 – 21 While results with allogeneic HCT appear better than with non-HCT post-remission therapies, several studies – including one from our institution – have reported poor post-HCT outcomes for adults with MK AML. 10 – 12 , 14 , 15 , 18 – 22 …”

Hematopoietic cell transplantation in adults with acute myeloid leukemia: A review of the results from various nationwide registry studies in Japan

“…Given the obvious prognostic impact of this disease subtype, patients with AML-MRC were further classified into three risk groups: a high-risk group including those with a monosomal karyotype, an intermediate-risk group including those with a complex karyotype and isolated -5⊘del(5q) , and a lowrisk group made up of the remaining patients. The 3-year OS probabilities after allogeneic HCT were 14%, 37%, and 51% for high-, intermediate-, and low-risk patients, respectively 14 . Given that the effectiveness of adding induction chemotherapy before allogeneic HCT for patients with AML-MLD remains uncertain, some patients proceed directly to allogeneic HCT without receiving induction chemotherapy.…”

Effect of MT2A on apoptosis and proliferation in HL60 cells

“…However, the AML patients with an unfavorable prognosis, extraordinarily complex karyotypes consisted of -5/del(5q), -7/del(7q), and 11q23, have become an international consensus [7]. Traditionally, AML patients are mainly treated with cytarabine/anthracycline ("7+3") combined with Gituzumab intensive chemotherapy protocols [8], and azacarbine/decitabine/venetoclax combined with hypomethylated chemotherapy drugs or low-intensity chemotherapy with low dose cytarabine [9].…”