Survival Following Relapse in Children with Acute Myeloid Leukemia: A Report from AML-BFM and COG

Abstract

Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM 29 ± 4%, COG 25 ± 2%) predicted diminished survival. In the BFM dataset, there was no difference in OS for patients who had a complete remission with full hematopoietic recovery (CR) following post-relapse re-induction compared to those with partial neutrophil and platelet recovery (CRp and CRi) only (52 ± 7% vs. 63 ± 10%, p = 0.39). Among 90 patients alive at last follow-up, 87 had received a post-relapse hematopoietic stem cell transplant (HSCT). OS for patients with post-relapse HSCT was 54 ± 4%. In conclusion, initial high-risk features and early relapse remain prognostic. Response assessment with full hematopoietic recovery following initial relapse therapy does not predict survival. These data indicate the need for post-relapse risk stratification in future studies of relapse therapies.

Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium

“…Despite progress in the treatment of pediatric acute myeloid leukemia (AML), outcomes remain sub‐optimal with 5‐year overall survival around 70% 1 . The primary treatment challenge is chemotherapy resistance which results in relapse in about 1/3 of patients and <40% survival at 5 years 2–5 . In addition, 10%–20% of patients are refractory to upfront therapy with even worse 3–5‐year survival ranging from 6%–19% 3,6 .…”

Impact of KMT2A Rearrangement and CSPG4 Expression in Pediatric Acute Myeloid Leukemia

“…As previously described, KMT2A-r was strongly associated with monocytic morphology, especially with the FAB subtype M5 [20]. As risk group stratification is strongly based on molecular genetics as well as on therapy response, it was not surprising that the distribution of risk groups correlated with the distribution of KMT2A fusion partner genes [25]. Nevertheless, some differences in risk group stratification and distri-…”

“…As previously described, KMT2A -r was strongly associated with monocytic morphology, especially with the FAB subtype M5 [ 20 ]. As risk group stratification is strongly based on molecular genetics as well as on therapy response, it was not surprising that the distribution of risk groups correlated with the distribution of KMT2A fusion partner genes [ 25 ]. Nevertheless, some differences in risk group stratification and distribution of KMT2A subgroups are due to the availability of newer methods with higher sensitivity (TruSight RNA Fusion Panel) which allowed the retrospective identification of KMT2A translocation partner genes, which would have resulted in a different risk group stratification and, thus, different treatment.…”

Pediatric Acute Myeloid Leukemia—Past, Present, and Future

“…In case of relapse, all patients indicate alloHSCT in the 2nd CR. Although the prognostic characteristics of relapsed AML are impaired, the survival rate has been maintained or improved [56,57].…”