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

Abstract

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 ¼ 0.01) and decreased survival (HR: 2.9; 95% CI: 1.3-6.4, Po0.01) 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. Keywords: allogeneic hematopoietic cell transplantation; reduced-intensity conditioning regimen; AML; relapse; minimal residual disease; CR INTRODUCTIONAllogeneic hematopoietic SCT (allo-HCT) remains the most effective treatment for most patients with AML. 1 The two main mechanisms by which allo-HCT can cure AML are through the immunologically based GVL effect and leukemic cell cytoreduction by HCT conditioning. 2-5 Reduced-intensity conditioning (RIC) was introduced to allo-HCT more than a decade ago for patients who are older, had significant co-morbid conditions or poorer performance status. [6][7][8] The anti-neoplastic potency of these RIC HCT regimens relies primarily on the GVL effect rather than ablating all residual leukemic disease. 9 It is clear that patients with active leukemia had more relapse and worse OS after allo-HCT regardless of donor type or patient age. [10][11][12][13][14][15] Following allo-HCT, 40-60% of AML patients in CR1 enjoy long-term OS, whereas o20% of refractory or relapsed AML patients survive. 1,11 Yet even for allo-HCT during CR, relapse remains the most frequent complication of allo-HCT. 16 As relapse has been reported more frequently after RIC allo-HCT compared with myeloablative conditioning (MAC) allo-HCT in patients with AML, this suggests heterogeneity in the interpretation of a CR, which may be more important after RIC allo-HCT. [17][18][19][20][21][22][23] The CR definition updated in 2003 24 clearly requires no evidence of leukemia by flow cytometry in addition to the morphologic remission as reported: 'The presence of a unique phenotype (by flow cytometry) identical to what was found in the pretreatment specimen (for example, CD34, CD7 coexpression) should be viewed ...

Pre-transplant MRD predicts outcome following reduced-intensity and myeloablative allogeneic hemopoietic SCT in AML

“…[20][21][22] In our study, the adverse OS in the MRD-positive patients was solely due to a higher risk of relapse in this group, with no demonstrable difference in NRM. Unlike other studies we only included patients in a CR by all other methodology in the analysis.…”

“…A recently published study by Ustun et al 22 indicates that this association may be extended to the recipients of RIC allografts, but with very few patients in their MRDpositive group, these results warrant verification.…”

Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival

“…Infectious prophylaxis, other supportive care measures, and GVHD prophylaxis have been described. 24, 26, 27 …”

Novel disease burden assessment predicts allogeneic transplantation outcomes in myelodysplastic syndrome

“…10–12 Equine anti-thymocyte globulin (15 mg/kg twice daily × 3 days) was provided to patients who had not received multiagent chemotherapy within 3 months of HCT for unrelated donor/umbilical cord blood or 6 months for matched-related donor. Treatment regimens were reviewed and approved by the University of Minnesota institutional review board and all participating subjects provided informed consent before proceeding to transplant.…”