Prophylaxis with Sirolimus and Tacrolimus ± Antithymocyte Globulin Reduces the Risk of Acute Graft-versus-Host Disease without an Overall Survival Benefit Following Allogeneic Stem Cell Transplantation

Lindsay L. Rosenbeck, Patrick J. Kiel, Iftekhar Kalsekar, Craig Vargo, John Baute, Cheryl K. Sullivan, Lisa Wood, Sahar Abdelqader, Jennifer Schwartz, Shivani Srivastava, Rafat Abonour, Michael Robertson, Robert Nelson, Kenneth Cornetta, Christopher A. Fausel, Sherif Farag

Research output: Contribution to journalArticle

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Abstract

Methotrexate (MTX) is a standard agent used in combination with calcineurin inhibitors for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic cell (HCT) transplantation. We retrospectively compared the incidence of acute GVHD (aGVHD), transplant-related morbidity, and mortality in patients given sirolimus/tacrolimus ± antithymocyte globulin (ATG) versus MTX/tacrolimus or cyclosporine and allogeneic transplantation for hematologic malignancies. Between January 1, 2005, and April 30, 2009, 106 consecutive patients received peripheral blood HCT or bone marrow grafts after 1 of 6 myeloablative conditioning regimens. The incidence of grade II-IV aGVHD was 18.6% in patients who received sirolimus/tacrolimus compared to 48.9% who received MTX (P = .001). The incidence of grade III-IV aGVHD was 5% and 17% (P = .045), respectively. There was no difference in overall survival (OS) between the groups (P = .160). Chronic GVHD (cGVHD) occurred in 40.4% who received sirolimus and 41.9% receiving MTX (P = .89). The incidence of thrombotic microangiopathy or interstitial pneumonitis was not significantly different between groups. The reduction in the risk of severe aGVHD was offset by an increased (20% versus 4%, P = .015) incidence of and mortality from sinusoidal obstructive syndrome (SOS). Sirolimus/tacrolimus appears to reduce the incidence of aGVHD after conventional allotransplantion compared to MTX-calcineurin inhibitor prophylaxis; however, this did not improve survival.

Original languageEnglish
Pages (from-to)916-922
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume17
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Antilymphocyte Serum
Stem Cell Transplantation
Tacrolimus
Graft vs Host Disease
Sirolimus
Methotrexate
Survival
Incidence
Thrombotic Microangiopathies
Transplants
Mortality
Cell Transplantation
Interstitial Lung Diseases
Homologous Transplantation
Hematologic Neoplasms
Risk Reduction Behavior
Cyclosporine
Bone Marrow
Morbidity

Keywords

  • Graft-versus-host disease
  • Sinusoidal obstructive syndrome
  • Sirolimus
  • Stem cell transplant
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

Prophylaxis with Sirolimus and Tacrolimus ± Antithymocyte Globulin Reduces the Risk of Acute Graft-versus-Host Disease without an Overall Survival Benefit Following Allogeneic Stem Cell Transplantation. / Rosenbeck, Lindsay L.; Kiel, Patrick J.; Kalsekar, Iftekhar; Vargo, Craig; Baute, John; Sullivan, Cheryl K.; Wood, Lisa; Abdelqader, Sahar; Schwartz, Jennifer; Srivastava, Shivani; Abonour, Rafat; Robertson, Michael; Nelson, Robert; Cornetta, Kenneth; Fausel, Christopher A.; Farag, Sherif.

In: Biology of Blood and Marrow Transplantation, Vol. 17, No. 6, 06.2011, p. 916-922.

Research output: Contribution to journalArticle

Rosenbeck, Lindsay L. ; Kiel, Patrick J. ; Kalsekar, Iftekhar ; Vargo, Craig ; Baute, John ; Sullivan, Cheryl K. ; Wood, Lisa ; Abdelqader, Sahar ; Schwartz, Jennifer ; Srivastava, Shivani ; Abonour, Rafat ; Robertson, Michael ; Nelson, Robert ; Cornetta, Kenneth ; Fausel, Christopher A. ; Farag, Sherif. / Prophylaxis with Sirolimus and Tacrolimus ± Antithymocyte Globulin Reduces the Risk of Acute Graft-versus-Host Disease without an Overall Survival Benefit Following Allogeneic Stem Cell Transplantation. In: Biology of Blood and Marrow Transplantation. 2011 ; Vol. 17, No. 6. pp. 916-922.
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