Rapamycin for refractory acute graft-versus-host disease.
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%).


CONCLUSIONS
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.
Ghez
David
D
Adult Hematology Department, Hôpital Necker-Enfants Malades, Paris, France. david.ghez@nck.aphp.fr
Rubio
Marie Thérèse
MT
Maillard
Natacha
N
Suarez
Felipe
F
Chandesris
Marie-Olivia
MO
Delarue
Richard
R
Deau-Fischer
Bénédicte
B
Varet
Bruno
B
Hermine
Olivier
O
Buzyn
Agnès
A
D000293:Adolescent; D000328:Adult; D001424:Bacterial Infections / Q000453:epidemiology; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000601:surgery; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D017741:Survivors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
D007166:Immunosuppressive Agents; D020123:Sirolimus