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

Shannon R. McCurdy, Christopher G. Kanakry, Hua Ling Tsai, Ivana Gojo, B. Douglas Smith, Douglas E. Gladstone, Javier Bolaños-Meade, Ivan Borrello, William Matsui, Lode J. Swinnen, Carol Ann Huff, Robert A. Brodsky, Richard F. Ambinder, Ephraim J. Fuchs, Gary L. Rosner, Richard J. Jones, Leo Luznik

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1128-1135
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2019

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Graft vs Host Disease
Bone Marrow Transplantation
Cyclophosphamide
Confidence Intervals
Transplants
Survival
Disease-Free Survival
Unrelated Donors
Aptitude
Hematologic Neoplasms
Immunosuppression
Siblings
Tissue Donors

Keywords

  • Graft-versus-host disease
  • Myeloablative HLA-matched bone marrow transplantation
  • Post-transplant cyclophosphamide

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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. / McCurdy, Shannon R.; Kanakry, Christopher G.; Tsai, Hua Ling; Gojo, Ivana; Smith, B. Douglas; Gladstone, Douglas E.; Bolaños-Meade, Javier; Borrello, Ivan; Matsui, William; Swinnen, Lode J.; Huff, Carol Ann; Brodsky, Robert A.; Ambinder, Richard F.; Fuchs, Ephraim J.; Rosner, Gary L.; Jones, Richard J.; Luznik, Leo.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 6, 01.06.2019, p. 1128-1135.

Research output: Contribution to journalArticle

McCurdy, SR, Kanakry, CG, Tsai, HL, Gojo, I, Smith, BD, Gladstone, DE, Bolaños-Meade, J, Borrello, I, Matsui, W, Swinnen, LJ, Huff, CA, Brodsky, RA, Ambinder, RF, Fuchs, EJ, Rosner, GL, Jones, RJ & Luznik, L 2019, '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', Biology of Blood and Marrow Transplantation, vol. 25, no. 6, pp. 1128-1135. https://doi.org/10.1016/j.bbmt.2018.12.767
McCurdy, Shannon R. ; Kanakry, Christopher G. ; Tsai, Hua Ling ; Gojo, Ivana ; Smith, B. Douglas ; Gladstone, Douglas E. ; Bolaños-Meade, Javier ; Borrello, Ivan ; Matsui, William ; Swinnen, Lode J. ; Huff, Carol Ann ; Brodsky, Robert A. ; Ambinder, Richard F. ; Fuchs, Ephraim J. ; Rosner, Gary L. ; Jones, Richard J. ; Luznik, Leo. / 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. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 6. pp. 1128-1135.
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abstract = "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.",
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