1. Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated Donor Using Tacrolimus/Sirolimus-based GvHD Prophylaxis: Impact of HLA Mismatch.
- Author
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Al Malki MM, Gendzekhadze K, Yang D, Mokhtari S, Parker P, Karanes C, Palmer J, Snyder D, Forman SJ, Nademanee A, and Nakamura R
- Subjects
- Chronic Disease, Disease-Free Survival, Female, Follow-Up Studies, Graft vs Host Disease epidemiology, Hematologic Neoplasms therapy, Histocompatibility Testing methods, Humans, Immunosuppressive Agents therapeutic use, Incidence, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Rate trends, Transplantation Conditioning, Transplantation, Homologous, United States epidemiology, Forecasting, Graft vs Host Disease prevention & control, HLA Antigens immunology, Hematopoietic Stem Cell Transplantation adverse effects, Sirolimus therapeutic use, Tacrolimus therapeutic use, Unrelated Donors
- Abstract
Background: While tacrolimus and sirolimus (T/S)-based graft-versus-host disease (GvHD) prophylaxis has been effective in preventing acute GvHD post hematopoietic cell transplantation (HCT), its efficacy and long-term outcome in matched (MUD) and mismatched unrelated donor (mMUD) setting is not well defined., Methods: Herein, we evaluated a consecutive case-series of 482 patients who underwent unrelated donor HCT (2005-2013) with T/S-based GvHD prophylaxis., Results: With a median follow-up of 6.2 years (range = 2.4-11.3), the 5-year overall survival (OS) and relapse/progression-free survival were 47.5% (95% confidence interval [CI]: 43.0-52.0) and 43.6% (95% CI: 39.1-48.1), respectively; and the 5-year cumulative incidence of nonrelapse mortality (NRM) and relapse were 24.9%, and 31.5%, respectively. In this cohort, mMUD was associated with worse OS (39.0% versus 50.7% at 5 y; P = 0.034), primarily due to greater risk of NRM (33.5% versus 21.7%; P = 0.038). While rates of relapse, acute (II-IV or III-IV) or chronic GvHD (limited or extensive) were not different, death caused by chronic GvHD (20.8% versus 12.8%; P = 0.022) and infection (33.0% versus 18.1%; P < 0.01) were significantly greater in mMUD. In multivariable analysis, high-risk disease (hazard ratio [HR] = 2.21, 95% CI: 1.16-4.23; P < 0.01) and mMUD (HR = 1.55, 95% CI: 1.15-2.08; P = 0.004) were independent predictive factors for OS., Conclusions: T/S-based GvHD prophylaxis is an effective and acceptable GvHD prophylactic regimen. However, survival after mMUD remained poor, possibly related to the severity of chronic GvHD.
- Published
- 2020
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