Risk Factors for Thrombotic Microangiopathy in Allogeneic Hematopoietic Stem Cell Recipients Receiving GVHD Prophylaxis with Tacrolimus Plus MTX or Sirolimus

Overview

Journal Bone Marrow Transplant

Specialty General Surgery

Date 2014 Feb 26

PMID 24566710

Citations 20

Authors

J Labrador

L Lopez-Corral

O Lopez-Godino

L Vazquez

M Cabrero-Calvo

R Perez-Lopez

M Diez-Campelo

F Sanchez-Guijo

E Perez-Lopez

C Guerrero

I Alberca

M C Del Canizo

J A Perez-Simon

J R Gonzalez-Porras

D Caballero

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Incidence, risk factors, and outcomes of transplant-associated thrombotic microangiopathy in pediatric patients after allogeneic hematopoietic cell transplantation: a single-institution prospective study.

Yoon S, Kang S, Kim H, Choi E, Im H, Koh K Bone Marrow Transplant. 2025; .

PMID: 39815034 DOI: 10.1038/s41409-024-02506-w.

Development and implementation of evidence-based, nurse-leading early warning model and healthcare quality improvement project for transplant-associated thrombotic microangiopathy: a mixed-methods, before-and-after study.

Zhou X, Ye Y, Jin A, Pan Z, Xu Z, Ding S BMC Nurs. 2024; 23(1):535.

PMID: 39113009 PMC: 11304727. DOI: 10.1186/s12912-024-02093-7.

Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation....

Schoettler M, Carreras E, Cho B, Dandoy C, Ho V, Jodele S Transplant Cell Ther. 2022; 29(3):151-163.

PMID: 36442770 PMC: 10119629. DOI: 10.1016/j.jtct.2022.11.015.

The Addition of Sirolimus to GVHD Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Efficacy and Safety.

Chen X, Sun H, Cassady K, Yang S, Chen T, Wang L Front Oncol. 2021; 11:683263.

PMID: 34568015 PMC: 8458935. DOI: 10.3389/fonc.2021.683263.

A prognostic model (BATAP) with external validation for patients with transplant-associated thrombotic microangiopathy.

Zhao P, Wu Y, He Y, Chong S, Qu Q, Deng R Blood Adv. 2021; 5(24):5479-5489.

PMID: 34507352 PMC: 8714708. DOI: 10.1182/bloodadvances.2021004530.

References

Kojouri K, George J . Thrombotic microangiopathy following allogeneic hematopoietic stem cell transplantation. Curr Opin Oncol. 2007; 19(2):148-54. DOI: 10.1097/CCO.0b013e3280148a2f. View

Ho V, Cutler C, Carter S, Martin P, Adams R, Horowitz M . Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005; 11(8):571-5. DOI: 10.1016/j.bbmt.2005.06.001. View

Carreras E, Diaz-Ricart M . The role of the endothelium in the short-term complications of hematopoietic SCT. Bone Marrow Transplant. 2011; 46(12):1495-502. DOI: 10.1038/bmt.2011.65. View

Ghez D, Rubio M, Maillard N, Suarez F, Chandesris M, Delarue R . Rapamycin for refractory acute graft-versus-host disease. Transplantation. 2009; 88(9):1081-7. DOI: 10.1097/TP.0b013e3181ba0a13. View

Cho B, Yahng S, Lee S, Eom K, Kim Y, Kim H . Validation of recently proposed consensus criteria for thrombotic microangiopathy after allogeneic hematopoietic stem-cell transplantation. Transplantation. 2010; 90(8):918-26. DOI: 10.1097/TP.0b013e3181f24e8d. View

Worel N, Greinix H, Leitner G, Mitterbauer M, Rabitsch W, Rosenmayr A . ABO-incompatible allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning: close association with transplant-associated microangiopathy. Transfus Apher Sci. 2007; 36(3):297-304. DOI: 10.1016/j.transci.2007.03.004. View

Khaled S, Palmer J, Stiller T, Senitzer D, Maegawa R, Rodriguez R . A phase II study of sirolimus, tacrolimus and rabbit anti-thymocyte globulin as GVHD prophylaxis after unrelated-donor PBSC transplant. Bone Marrow Transplant. 2012; 48(2):278-83. PMC: 3566319. DOI: 10.1038/bmt.2012.175. View

Willems E, Baron F, Seidel L, Frere P, Fillet G, Beguin Y . Comparison of thrombotic microangiopathy after allogeneic hematopoietic cell transplantation with high-dose or nonmyeloablative conditioning. Bone Marrow Transplant. 2009; 45(4):689-93. DOI: 10.1038/bmt.2009.230. View

Nester C, Thomas C . Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated?. Hematology Am Soc Hematol Educ Program. 2012; 2012:617-25. DOI: 10.1182/asheducation-2012.1.617. View

10.

Nakamae H, Yamane T, Hasegawa T, Nakamae M, Terada Y, Hagihara K . Risk factor analysis for thrombotic microangiopathy after reduced-intensity or myeloablative allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2006; 81(7):525-31. DOI: 10.1002/ajh.20648. View

11.

Pidala J, Kim J, Jim H, Kharfan-Dabaja M, Nishihori T, Fernandez H . A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation. Haematologica. 2012; 97(12):1882-9. PMC: 3590095. DOI: 10.3324/haematol.2012.067140. View

12.

Cutler C, Henry N, Magee C, Li S, Kim H, Alyea E . Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005; 11(7):551-7. DOI: 10.1016/j.bbmt.2005.04.007. View

13.

Shimoni A, Yeshurun M, Hardan I, Avigdor A, Ben-Bassat I, Nagler A . Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reduced-intensity conditioning: The incidence is not reduced. Biol Blood Marrow Transplant. 2004; 10(7):484-93. DOI: 10.1016/j.bbmt.2004.03.002. View

14.

Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T . Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer. 2009; 115(20):4715-26. DOI: 10.1002/cncr.24531. View

15.

Sarkodee-Adoo C, Sotirescu D, Sensenbrenner L, Rapoport A, Cottler-Fox M, Tricot G . Thrombotic microangiopathy in blood and marrow transplant patients receiving tacrolimus or cyclosporine A. Transfusion. 2003; 43(1):78-84. DOI: 10.1046/j.1537-2995.2003.00282.x. View

16.

Siami K, Kojouri K, Swisher K, Selby G, George J, Laszik Z . Thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation: an autopsy study. Transplantation. 2008; 85(1):22-8. DOI: 10.1097/01.tp.0000297998.33418.7e. View

17.

Oberic L, Buffet M, Schwarzinger M, Veyradier A, Clabault K, Malot S . Cancer awareness in atypical thrombotic microangiopathies. Oncologist. 2009; 14(8):769-79. DOI: 10.1634/theoncologist.2009-0067. View

18.

Rodriguez R, Nakamura R, Palmer J, Parker P, Shayani S, Nademanee A . A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens. Blood. 2009; 115(5):1098-105. PMC: 2817636. DOI: 10.1182/blood-2009-03-207563. View

19.

Changsirikulchai S, Myerson D, Guthrie K, McDonald G, Alpers C, Hingorani S . Renal thrombotic microangiopathy after hematopoietic cell transplant: role of GVHD in pathogenesis. Clin J Am Soc Nephrol. 2009; 4(2):345-53. PMC: 2637592. DOI: 10.2215/CJN.02070508. View

20.

Ringden O, Remberger M, Dahllof G, Garming-Legert K, Karlsson H, Svenberg P . Sirolimus and tacrolimus as immune prophylaxis compared to cyclosporine with or without methotrexate in patients undergoing allogeneic haematopoietic stem cell transplantation for non-malignant disorders. Eur J Haematol. 2012; 87(6):503-9. DOI: 10.1111/j.1600-0609.2011.01685.x. View