Document Detail


Rapamycin for refractory acute graft-versus-host disease.
MedLine Citation:
PMID:  19898203     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Rapamycin, an inhibitor of mammalian target of rapamycin kinase, is a potent immunosuppressive drug that also displays antineoplastic properties and expands regulatory T cells. Steroid-refractory acute graft-versus-host disease (GVHD) remains a significant cause of mortality after allogeneic stem-cell transplantation and therapeutic options are not codified. We retrospectively evaluated the role of rapamycin in this setting. METHODS: In this retrospective single-center study, 22 patients were identified, from October 2004 to February 2008, as having received rapamycin for acute GVHD refractory to one or more lines of treatment. We analyzed the efficacy and tolerance of rapamycin and the outcome of these 22 patients in this setting. RESULTS: Rapamycin resulted in a rapid and sustained complete remission of GVHD in 72% of heavily pretreated patients. Cytopenias were frequent but did not require treatment interruption. Thrombotic microangiopathy developed in 36% of patients when rapamycin was associated with calcineurin inhibitors and frequently resolved after interruption of one or both drugs. At a median follow-up of 13 months, overall survival was 41%. Previous treatment with high-dose steroid pulses was associated with a worse outcome (survival 12% vs. 69%). The major cause of death was infectious complications (77%). CONCLUSION: Despite a small and heterogeneous population of patients, these results are encouraging and provide a rationale for prospective studies that use rapamycin in steroid-refractory acute GVHD as a second- or third-line agent.
Authors:
David Ghez; Marie Th??r??se Rubio; Natacha Maillard; Felipe Suarez; Marie-Olivia Chandesris; Richard Delarue; B??n??dicte Deau-Fischer; Bruno Varet; Olivier Hermine; Agn??s Buzyn
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  88     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-09     Completed Date:  2010-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1081-7     Citation Subset:  IM    
Affiliation:
Adult Hematology Department, H??pital Necker-Enfants Malades, Paris, France. david.ghez@nck.aphp.fr
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Bacterial Infections / epidemiology
Graft vs Host Disease / drug therapy*,  epidemiology,  immunology
Hematopoietic Stem Cell Transplantation / methods*,  mortality
Humans
Immunosuppressive Agents / adverse effects,  therapeutic use*
Leukemia / immunology,  mortality,  surgery*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology,  surgery
Middle Aged
Retrospective Studies
Sirolimus / adverse effects,  therapeutic use*
Survival Rate
Survivors
Transplantation, Homologous
Treatment Outcome
Young Adult
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 53123-88-9/Sirolimus

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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