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Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide.

Authors :
McCurdy, Shannon R.
Kanakry, Christopher G.
Tsai, Hua-Ling
Gojo, Ivana
Smith, B. Douglas
Gladstone, Douglas E.
Bolaños-Meade, Javier
Borrello, Ivan
Matsui, William H.
Swinnen, Lode J.
Huff, Carol Ann
Brodsky, Robert A.
Ambinder, Richard F.
Fuchs, Ephraim J.
Rosner, Gary L.
Jones, Richard J.
Luznik, Leo
Source :
Biology of Blood & Marrow Transplantation. Jun2019, Vol. 25 Issue 6, p1128-1135. 8p.
Publication Year :
2019

Abstract

• Grade II acute graft-versus-host disease is associated with improved overall and progression-free survival after HLA-matched BMT with post-transplant cyclophosphamide. • Grade II acute graft-versus-host disease is associated with decreased relapse, but no difference in nonrelapse mortality when using post-transplant cyclophosphamide. Post-transplant cyclophosphamide (PTCy) can be used as the sole immunosuppression after myeloablative conditioning (MAC) for HLA-matched bone marrow transplantation (BMT). However, the effects of graft-versus-host disease (GVHD) with this platform are undefined. We retrospectively analyzed 298 consecutive adult patients with hematologic malignancies who engrafted after MAC HLA-matched sibling donor (MSD; n = 187) or HLA-matched unrelated donor (MUD; n = 111) T-cell–replete BMT with PTCy 50 mg/kg on days +3 and +4. After MSD and MUD BMT, 35% and 57% of patients, respectively, developed grade II acute GVHD (aGVHD) by 100 days, 11% and 14% grade III to IV aGVHD by 100 days, and 9% and 16% chronic GVHD (cGVHD) by 1 year. In landmark analyses at 100 days after HLA-matched BMT, 4-year overall survival (OS) and progression-free survival (PFS) were 57% (95% confidence interval [CI],.49 to.67) and 40% (95% CI,.31 to.51) in patients without grades II to IV aGVHD, and 68% (95% CI,.59 to.78) and 54% (95% CI,.44 to.65) in patients with grade II aGVHD. In adjusted time-dependent multivariable analyses, grade II aGVHD was associated with improved OS (hazard ratio,.58; 95% CI,.37 to.89; P =.01) and PFS (hazard ratio,.50; 95% CI,.34 to.74; P <.001) after HLA-matched BMT with PTCy. The ability of PTCy to limit grades III to IV aGVHD and cGVHD while maintaining grade II aGVHD may contribute to its effectiveness, and further attempts to reduce aGVHD may be detrimental. Landmark Analyses: Effects of Grade II Acute Graft-Versus-Host Disease on Overall and Progression-Free Survival* *curves were truncated at 8-years after bone marrow transplantation OS, overall survival; No aGVHD Gr 2-4, patients without grade 2-4 acute graft-versus-host disease; aGVHD Gr 2, patients with grade II acute graft-versus-host disease; No., number; PSF, progression-free survival; Relp, relapse; NRM, nonrelapse mortality. Graphical Abstract Legend: A) In patients who were alive at day 100 after HLA-matched bone marrow transplantation with post-transplant cyclophosphamide, the probabilities of overall survival (OS) were compared. OS was higher in patients who had developed maximal grade II acute graft-versus-host disease (Grade II Acute GVHD; OS, dark blue line) when compared with patients who had not developed grade II-IV acute graft-versus-host disease (no GVHD; OS, orange line). B) In patients who were alive and who had not relapsed at day 100 after HLA-matched bone marrow transplantation with post-transplant cyclophosphamide, the probabilities of progression-free survival (PFS) were compared. PFS was higher in patients who had developed maximal grade II acute graft-versus-host disease (Grade II Acute GVHD; PFS, dark blue line) when compared with patients who had not developed grade II-IV acute graft-versus-host disease (no GVHD; PFS, orange line). Image, graphical abstract [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10838791
Volume :
25
Issue :
6
Database :
Academic Search Index
Journal :
Biology of Blood & Marrow Transplantation
Publication Type :
Academic Journal
Accession number :
136878970
Full Text :
https://doi.org/10.1016/j.bbmt.2018.12.767