Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

• Published in: Bone marrow transplantation (Basingstoke) Vol. 49; no. 5; pp. 684 - 690
• Main Authors: LABRADOR, J, LOPEZ-CORRAL, L, ALBERCA, I, DEL CANIZO, M. C, PEREZ-SIMON, J. A, GONZALEZ-PORRAS, J. R, CABALLERO, D, LOPEZ-GODINO, O, VAZQUEZ, L, CABRERO-CALVO, M, PEREZ-LOPEZ, R, DIEZ-CAMPELO, M, SANCHEZ-GUIJO, F, PEREZ-LOPEZ, E, GUERRERO, C
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.2014
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood circulation disorders; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Calcineurin; Calcineurin inhibitors; Care and treatment; Disease prevention; Dosage and administration; Drug Therapy, Combination; Female; Graft versus host reaction; Graft vs Host Disease - drug therapy; Graft vs Host Disease - epidemiology; Graft vs Host Disease - prevention & control; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - statistics & numerical data; Hematopoietic stem cells; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - blood; Incidence; Male; Medical sciences; Methotrexate - administration & dosage; Methotrexate - blood; Middle Aged; Multivariate Analysis; Physiological aspects; Prognosis; Prophylaxis; Rapamycin; Retrospective Studies; Risk analysis; Risk Factors; Risk groups; Serum levels; Sirolimus - administration & dosage; Sirolimus - blood; Stem cell transplantation; Stem cells; Tacrolimus; Tacrolimus - administration & dosage; Tacrolimus - blood; Thrombotic Microangiopathies - epidemiology; Thrombotic Microangiopathies - etiology; Thrombotic microangiopathy; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Homologous; Young Adult; Antineoplastic agent; Calcineurin inhibitor; Sirolimus; Stem cell; Hematopoietic cell; Homograft; Cardiovascular disease; Epidemiology; Thrombohemolytic microangiopathy; Macrocycle; Vascular disease; Prevention; Allogeneic hematopoietic stem cell transplantation; allo-SCT; Graft; Protein synthesis inhibitor; Immunopathology; Graft versus host disease; risk factors; Hematology; Lactone; Recipient; Macrolide; transplant-associated thrombotic microangiopathy; Immunomodulator; Antibiotic; Tacrolimus; Risk factor; Immunosuppressive agent
• DOI: 10.1038/bmt.2014.17
• ISSN: 0268-3369

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.