<p>Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly offered as a consolidation strategy for older/infirm patients with acute myeloid leukemia (AML). Fludarabine/melphalan (Flu/Mel) conditioning is associated with effective disease control but results in significant toxicity and non-relapse mortality (NRM) when combined with calcineurin-inhibitors plus methotrexate or mycophenolate mofetil. Flu/Mel with alternative graft-versus-host disease (GVHD) prophylaxis may be better tolerated and result in superior outcomes in patients with AML. In this single-center retrospective analysis, we analyzed long-term outcomes of patients with AML (n = 342) who underwent allo-HCT with Flu/Mel conditioning and tacrolimus/sirolimus (Tac/Sir)-based GVHD prophylaxis from 2008-2019 at City of Hope. Patient median age was 63 years (range: 23–78), with 37% having high-very high Disease Risk Index (DRI) and 42% with HCT-Comorbidity Index (CI) ≥ 3. Five-year overall survival (OS: primary objective) was 55% (95% CI: 49–61%) among all patients and 70% (95% CI: 55–81%) in patients ≥70 years old. Only presence of active disease correlated with lower 5-year OS on multivariate analysis (HR = 1.95; p &lt; .001). Five-year NRM was 24% (95% CI: 19–29%) among all patients and 21% (95% CI: 11–34%) in those ≥70 years old. In conclusion, Flu/Mel conditioning with Tac/Sir GVHD prophylaxis is associated with favorable OS and acceptable NRM, even in older/infirm patients with AML.</p><p></p>

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Long-term survival outcomes of allo-HCT in AML with fludarabine/melphalan conditioning and tacrolimus/sirolimus GVHD prophylaxis

  • Amandeep Salhotra,
  • Dongyun Yang,
  • Monzr M. Al Malki,
  • Sally Mokhtari,
  • Diana Knobler,
  • Vaibhav Agarwal,
  • Karamjeet Sandhu,
  • Gabriel Park,
  • Ahmed Aribi,
  • Haris Ali,
  • Ibrahim Aldoss,
  • Salman Otoukesh,
  • Shukaib Arslan,
  • Brian Ball,
  • Paul Koller,
  • Idoroenyi Amanam,
  • Hoda Pourhassan,
  • Amanda Blackmon,
  • Pamela Becker,
  • Vinod Pullarkat,
  • Andrew S. Artz,
  • Eileen Smith,
  • Guido Marcucci,
  • Stephen Forman,
  • Anthony Stein,
  • Ryotaro Nakamura

摘要

Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly offered as a consolidation strategy for older/infirm patients with acute myeloid leukemia (AML). Fludarabine/melphalan (Flu/Mel) conditioning is associated with effective disease control but results in significant toxicity and non-relapse mortality (NRM) when combined with calcineurin-inhibitors plus methotrexate or mycophenolate mofetil. Flu/Mel with alternative graft-versus-host disease (GVHD) prophylaxis may be better tolerated and result in superior outcomes in patients with AML. In this single-center retrospective analysis, we analyzed long-term outcomes of patients with AML (n = 342) who underwent allo-HCT with Flu/Mel conditioning and tacrolimus/sirolimus (Tac/Sir)-based GVHD prophylaxis from 2008-2019 at City of Hope. Patient median age was 63 years (range: 23–78), with 37% having high-very high Disease Risk Index (DRI) and 42% with HCT-Comorbidity Index (CI) ≥ 3. Five-year overall survival (OS: primary objective) was 55% (95% CI: 49–61%) among all patients and 70% (95% CI: 55–81%) in patients ≥70 years old. Only presence of active disease correlated with lower 5-year OS on multivariate analysis (HR = 1.95; p < .001). Five-year NRM was 24% (95% CI: 19–29%) among all patients and 21% (95% CI: 11–34%) in those ≥70 years old. In conclusion, Flu/Mel conditioning with Tac/Sir GVHD prophylaxis is associated with favorable OS and acceptable NRM, even in older/infirm patients with AML.