Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML

• Published in: Bone marrow transplantation (Basingstoke) Vol. 48; no. 11; pp. 1415 - 1420
• Main Authors: Ustun, C, Wiseman, A C, DeFor, T E, Yohe, S, Linden, M A, Oran, B, Burke, M, Warlick, E, Miller, J S, Weisdorf, D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2013; Nature Publishing Group
• Subjects: 692/699/67/1990/283/1897; 692/700/565/545/576/1955; Acute myeloid leukemia; Adult; Aged; Bone marrow; Cancer regression; Cell Biology; Cohort Studies; Conditioning; Confidence intervals; Criteria; Female; Flow cytometry; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Heterogeneity; Humans; Immunophenotyping; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute - surgery; Leukemia, Myeloid, Acute - therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm, Residual - surgery; Neoplasm, Residual - therapy; original-article; Patients; Prognosis; Public Health; Retrospective Studies; Stem cell transplantation; Stem Cells; Survival; Testing; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous; Treatment Outcome; Young Adult; AML; reduced-intensity conditioning regimen; minimal residual disease; relapse; allogeneic hematopoietic cell transplantation; CR
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2013.124

Reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) can cure patients with AML in CR. However, relapse after RIC allo-HCT may indicate heterogeneity in the stringency of CR. Strict definition of CR requires no evidence of leukemia by both morphologic and flow cytometric criteria. We re-evaluated 85 AML patients receiving RIC allo-HCT in CR to test if a strict definition of CR had direct implications for the outcome. These patients had leukemia immunophenotype documented at diagnosis and analyzed at allo-HCT. Eight (9.4%) had persistent leukemia by flow cytometric criteria at allo-HCT. The patients with immunophenotypic persistent leukemia had a significantly increased relapse (hazard ratio (HR): 3.7; 95% confidence interval (CI): 1.3–10.3, P =0.01) and decreased survival (HR: 2.9; 95% CI: 1.3–6.4, P <0.01) versus 77 patients in CR by both morphology and flow cytometry. However, the pre-allo-HCT bone marrow (BM) blast count (that is, 0–4%) was not significantly associated with risks of relapse or survival. These data indicate the presence of leukemic cells, but not the BM blast count affects survival. A strict morphologic and clinical lab flow cytometric definition of CR predicts outcomes after RIC allo-HCT, and therefore is critical to achieve at transplantation.