title: Transplant-associated thrombotic microangiopathy in pediatric patients treated with sirolimus and tacrolimus.
abstract: BACKGROUND
  Transplant-associated thrombotic microangiopathy (TMA) syndromes are reported to occur with increased frequency in transplant patients treated with siroliumus combined with a calcineurin inhibitor. We performed a retrospective study of all pediatric transplant patients at City of Hope who were administered combined tacrolimus/sirolimus (TAC/SIR) to determine the occurrence of TMA.
  
  
  METHODS
  This analysis includes 41 consecutive patients between the ages of 2 and 20 (median age 9.1) who received an allogeneic hematopoietic stem cell transplant from any source and also received TAC/SIR for prevention or treatment of GVHD. Of those 41 patients, 20 received TAC/SIR as GVHD prohpylaxis and were designated the preventative group (PG), while 21 received TAC/SIR as treatment for GVHD and were designated the therapy group (TG). TMA occurrence in both groups was documented from day -1 of transplant to day 60 for the PG, and until 30 days after last dose for the TG. TMA was defined according to 2005 consensus criteria.
  
  
  RESULTS
  Five of twenty patients in the PG, and five of twenty one in the TG, experienced TMA, with an overall rate of 23.8% for the population. All ten patients with TMA showed elevated levels of TAC, SIR or both and nine of ten suffered from organ injury due to regimen-related toxicity or GVHD.
  
  
  CONCLUSIONS
  Physicians should exercise caution in the use of TAC/SIR in pediatric patients due to a high rate of TMA. It is not recommended for heavily pre-treated patients and peak levels of TAC/SIR must be very carefully controlled.
authors.affiliation: Department of Pediatrics, City of Hope, Duarte, CA 91010, USA. jrosenthal@coh.org
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenthal
authors.forename: Anna
authors.initials: A
authors.lastname: Pawlowska
authors.forename: Ellen
authors.initials: E
authors.lastname: Bolotin
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cervantes
authors.forename: Sean
authors.initials: S
authors.lastname: Maroongroge
authors.forename: Sandra H
authors.initials: SH
authors.lastname: Thomas
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*; D057049:Thrombotic Microangiopathies / Q000453:epidemiology* / Q000209:etiology*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus