Background: Chronic graft versus host disease (cGVHD) is an important complication and a cause of mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, new immunosuppressants such as tacrolimus (FK506) and mycophenolate mofetil (MMF) have been available and shown positive curative effects in cGVHD patients. This study was undertaken to analyze the clinical characteristics and risk factors of cGVHD after allogeneic hematopoietic stem cell transplantation and to assess the therapeutic effectiveness of methylprednisolone (MP) and MMF in combination with FK506 or cyclosporine A (CSA) in the immunosuppressive treatment of pediatric cGVHD.

Methods: In 40 patients who received allo-HSCT and engrafted, 25 were treated with umbilical cord blood transplantation (UCBT) and the remaining 15 with peripheral stem cell transplantation (PBSCT). GVHD prophylaxis employed CSA, MP and MMF. Treatment regimen consisted of MP, MMF and FK506 in one group, and MMF and CSA in the other.

Results: Eleven of the 40 engrafted patients (27.5%) developed cGVHD. The cGVHD morbidity was 20% among UCBT patients (5 of 25) and 40% among PBSCT patients (6 of 15). Eight patients presented the continuation of acute GVHD. One patient fully recovered after combined use of CSA and MMF, and 10 patients were given 1 “triple therapy” including MP, MMF and FK506, with an overall response rate of 100%. Three patients died of cytomegalovirus (CMV)-induced interstitial pneumonia, septicemia, and fungi pneumonia, respectively, giving a mortality rate of 27.3%. Seven patients showed an even-free survival (EFS) of more than 3 years, another patient has so far been surviving 29 months at writing. Hepatotoxicity, nephrotoxicity, hypertension, articular capsulitis and cardiac arrhythmia were side-effects most frequently observed. Infection was identified as the main complication and the major cause of death.

Conclusions: The incidence of cGVHD is higher after PBSCT than after UCBT, and the presence of acute GVHD is an important risk factor for subsequent cGVHD. A combination of MP, MMF and FK506 or CSA is safe and effective in the treatment of cGVHD in pediatric patients.