Relative impact of residual cytogenetic abnormalities and flow cytometric measurable residual disease on outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia

Abstract

Measurable residual disease (MRD) before hematopoietic cell transplantation (HCT) is an independent established prognostic factor in patients with acute myeloid leukemia (AML). Several methods exist to evaluate the presence of residual leukemia cells, but how these are used best in combination is unclear. To examine how residual cytogenetic abnormalities and MRD testing by multiparameter flow cytometry (MFC) may refine risk assessment before HCT, we analyzed 506 adults with cytogenetically abnormal AML who underwent both routine karyotyping and MFC MRD testing before receiving a first allograft while in morphologic remission. Testing for residual cytogenetic abnormalities and MFC MRD identified four groups of patients with differential relapse-free survival (RFS, hazard ratio [HR]=1.63 for Cytoabnormal/MFCnegative [P=0.01, n=63], HR=3.24 for Cytonormal/MFCpositive [P

Contribution of measurable residual disease status to prediction accuracy of relapse and survival in adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation

“…In univariate analyses, pre-HCT MRD status was the strongest (albeit poor) 2). Inclusion of pre-HCT cytogenetic data (normalized vs. not normalized for patients presenting with abnormal karyotypes), which we very recently found to provide complementary information to flow cytometric MRD data despite its low sensitivity, 10 improved models only minimally, yielding Cstatistics of 0.66, 0.63, and 0.63 for relapse, RFS, and OS. The prediction accuracy could be further improved when information from pre-HCT MRD testing was included (C-statistics of 0.70, 0.66, and 0.65 for relapse, RFS, and OS; C-statistics using ELN cut-off: 0.70, 0.67, 0.65).…”

Relative prognostic value of flow cytometric measurable residual disease before allogeneic hematopoietic cell transplantation for adults with MDS/AML or AML

“…The methodology of the MFC MRD assay has remained essentially unchanged throughout the study period, with any level of MRD considered positive, consistent with prior analyses and the performance characteristics of the assay. [3][4][5][6][7][8][9]15,[27][28][29]…”

“…14 For example, in the context of allografting, we previously showed combined consideration of MFC-based MRD and residual cytogenetics distinguishes four groups of AML patients with different post-HCT outcomes. 15 Because of the increasing recognition that some myelodysplastic neoplasms (MDS) share disease features and clinical outcomes with AML, 16 the hematopathological criteria to separate MDS from AML have changed over time and, most recently, have softened. [17][18][19] Specifically, while some disease entities with recurrent genetic abnormalities are now defined as AML, even in cases with less than 20% blasts, [17][18][19] a new category encompassing cases with 10%-19% blasts as "MDS/AML" has been introduced in the 2022 International Consensus Classification (ICC) to recognize the diagnostic continuum between MDS and AML.…”

The present and future of measurable residual disease testing in acute myeloid leukemia

“…This may include genetic context (Table 1) but also risk group 11 and allogeneic transplantation status. 12,22,23 Finally, in addition to the assay itself, a key ingredient in sensitivity is supplying the assay with an appropriate input. Typically, cells are obtained from bone marrow or peripheral blood samples, or fluids/tissues of other organs.…”

“…This may include genetic context ( Table 1 ) but also risk group 11 and allogeneic transplantation status. 12 , 22 , 23 …”