Sirolimus and tacrolimus as immune prophylaxis compared to cyclosporine with or without methotrexate in patients undergoing allogeneic haematopoietic stem cell transplantation for non-malignant disorders
- 2 October 2011
- journal article
- research article
- Published by Wiley in European Journal of Haematology
- Vol. 87 (6), 503-509
- https://doi.org/10.1111/j.1600-0609.2011.01685.x
Abstract
For prevention of graft-versus-host disease (GVHD), treatment of 24 haematopoietic stem cell transplantation (HSCT) patients with sirolimus and tacrolimus was compared to treatment of matched controls with cyclosporine-based regimens. The patients mainly had non-malignant disorders. Two-thirds of the donors were unrelated, and bone marrow was the most common source of stem cells. Rejection occurred in four patients in the sirolimus group and three in the control group. Donor chimerism for CD3, CD19 and CD33 was similar in the two groups. The cumulative incidence of grade II acute GVHD was 22% in the sirolimus patients and 17% in the controls (P = 0.78). No patients developed acute GVHD of grades IIIIV. The cumulative incidence of chronic GVHD was 25% and 37% in the two groups, respectively (P = 0.40). Two patients in the sirolimus group developed EpsteinBarr virus lymphoma, and none in the controls. Side effects and toxicity were similar in the two groups. There was no transplant-related mortality at 5 yr in the sirolimus group, as opposed to 8% in the controls (P = 0.47). Survival at 5 yr was 95% and 92%. Thus, sirolimus combined with tacrolimus is a promising immunosuppressive regimen in HSCT, also for non-malignancies, and its efficacy should be confirmed in prospective clinical trials.Keywords
This publication has 30 references indexed in Scilit:
- Sirolimus immunosuppression for graft-versus-host disease prophylaxis and therapy: an updateCurrent Opinion in Hematology, 2010
- Mucositis after Allogeneic Hematopoietic Stem Cell Transplantation: A Cohort Study of Methotrexate- and Non-Methotrexate-Containing Graft-versus-Host Disease Prophylaxis RegimensTransplantation and Cellular Therapy, 2005
- Structure of S6 Kinase 1 Determines whether Raptor-mTOR or Rictor-mTOR Phosphorylates Its Hydrophobic Motif SitePublished by Elsevier BV ,2005
- A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. Ii. Survival, function, and protocol compliance at 1 yearTransplantation, 2004
- Rapamycin inhibits IL-4—induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivoBlood, 2003
- A prospective randomized multicenter study of tacrolimus in combination with sirolimus in renal-transplant recipientsTransplantation, 2003
- Superior T-cell suppression by rapamycin and FK506 over rapamycin and cyclosporine A because of abrogated cytotoxic T-lymphocyte induction, impaired memory responses, and persistent apoptosisTransplantation, 2003
- Rapamycin specifically interferes with GM-CSF signaling in human dendritic cells, leading to apoptosis via increased p27KIP1 expressionBlood, 2003
- Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantationBone Marrow Transplantation, 2001
- SIROLIMUS (RAPAMYCIN)-BASED THERAPY IN HUMAN RENAL TRANSPLANTATIONTransplantation, 1999