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.
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: J Labrador; L López-Corral; O López-Godino; L Vázquez; M Cabrero-Calvo; R Pérez-López; M Díez-Campelo; F Sánchez-Guijo; E Pérez-López; C Guerrero; I Alberca; M C Del Cañizo; J A Pérez-Simón; J R González-Porras; D Caballero Journal: Bone Marrow Transplant Date: 2014-02-24 Impact factor: 5.483
Authors: Paul J Martin; Yoshihiro Inamoto; Mary E D Flowers; Paul A Carpenter Journal: Biol Blood Marrow Transplant Date: 2012-04-14 Impact factor: 5.742
Authors: R Zeiser; A Burchert; C Lengerke; M Verbeek; K Maas-Bauer; S K Metzelder; S Spoerl; M Ditschkowski; M Ecsedi; K Sockel; F Ayuk; S Ajib; F S de Fontbrune; I-K Na; L Penter; U Holtick; D Wolf; E Schuler; E Meyer; P Apostolova; H Bertz; R Marks; M Lübbert; R Wäsch; C Scheid; F Stölzel; R Ordemann; G Bug; G Kobbe; R Negrin; M Brune; A Spyridonidis; A Schmitt-Gräff; W van der Velden; G Huls; S Mielke; G U Grigoleit; J Kuball; R Flynn; G Ihorst; J Du; B R Blazar; R Arnold; N Kröger; J Passweg; J Halter; G Socié; D Beelen; C Peschel; A Neubauer; J Finke; J Duyster; N von Bubnoff Journal: Leukemia Date: 2015-07-31 Impact factor: 11.528
Authors: Virginia Escamilla Gómez; Valentín García-Gutiérrez; Lucía López Corral; Irene García Cadenas; Ariadna Pérez Martínez; Francisco J Márquez Malaver; Teresa Caballero-Velázquez; Pedro A González Sierra; María C Viguria Alegría; Ingrid M Parra Salinas; Cristina Calderón Cabrera; Marta González Vicent; Nancy Rodríguez Torres; Rocío Parody Porras; Christelle Ferra Coll; Guillermo Orti; David Valcárcel Ferreiras; Rafael De la Cámara LLanzá; Paula Molés; Kyra Velázquez-Kennedy; María João Mende; Dolores Caballero Barrigón; Estefanía Pérez; Rodrigo Martino Bofarull; Silvanna Saavedra Gerosa; Jorge Sierra; Marc Poch; María T Zudaire Ripa; Miguel A Díaz Pérez; Blanca Molina Angulo; Isabel Sánchez Ortega; Jaime Sanz Caballer; Juan Montoro Gómez; Ildefonso Espigado Tocino; José A Pérez-Simón Journal: Bone Marrow Transplant Date: 2019-11-07 Impact factor: 5.483