title: Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in Allo-SCT for leukemia patients with high relapse risk: an observational cohort study.
abstract: Certain leukemias have a high relapse risk even after allo-SCT, and GVHD prophylaxis with calcineurin inhibitors (CNIs) may interfere with a possible GVL effect. Therefore, we replaced CYA by sirolimus in patients with high relapse risk. In contrast to CNIs, sirolimus promotes the generation of regulatory T-cells and has potent antineoplastic activity. Sirolimus has been used in combination with CNI for GVHD prophylaxis in hematopoietic SCT. However, no CNI-free prophylactic regimen with sirolimus has been evaluated so far. Within the FLAMSA-RIC protocol, 15 patients received GVHD prophylaxis with sirolimus and mycophenolate mofetil (MMF). The underlying diagnoses were relapsed or refractory T-ALL (n=3), AML with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) or mixed-lineage leukemia-partial tandem duplication (MLL-PTD; n=10; 5 with refractory disease) and CML in refractory myeloid blast crisis (n=2). All evaluable patients (n=14) were engrafted. Grades II-IV acute GVHD occurred in 21% and chronic GVHD in 30% of patients. Non-relapse mortality rate was 14%. No thrombotic microangiopathy or sinusoidal obstruction syndrome was observed. Three patients with FLT3-ITD+ AML relapsed after a median of 112 days. At a median follow-up of 10 months after transplantation, 10 patients are alive and in complete remission. In conclusion, sirolimus-based GVHD prophylactic regimens deserve further investigation.
authors.affiliation: Centre for Bone Marrow and Blood Stem Cell Transplantation, Deutsche Klinik für Diagnostik, Wiesbaden, Germany. schleuning.kmt@dkd-wiesbaden.de
authors.forename: M
authors.initials: M
authors.lastname: Schleuning
authors.forename: D
authors.initials: D
authors.lastname: Judith
authors.forename: Z
authors.initials: Z
authors.lastname: Jedlickova
authors.forename: T
authors.initials: T
authors.lastname: Stübig
authors.forename: M
authors.initials: M
authors.lastname: Heshmat
authors.forename: H
authors.initials: H
authors.lastname: Baurmann
authors.forename: R
authors.initials: R
authors.lastname: Schwerdtfeger
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007938:Leukemia / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011292:Premedication / Q000379:methods; D016879:Salvage Therapy / Q000379:methods; D020123:Sirolimus / Q000008:administration & dosage*; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus