Treatment of severe life-threatening graft-versus-host disease by autologous peripheral blood stem cell transplantation using a nonmyeloablative preconditioning regimen.

Graft-versus-host disease (GVHD) is the major obstacle to successful allogeneic stem cell transplantation (SCT). Although novel immunosuppressants, including tacrolimus (FK506), have been introduced clinically, the probability of grade II-IV acute GVHD is still relatively high, at 32-33 % in related SCT 1, 2 and 34-56 % in unrelated SCT. 3, 4 Furthermore, a significant proportion of patients prove refractory to all treatments for GVHD. On the other hand, clinical trials have shown early remission of refractory autoimmune disorders after autologous or allogeneic SCT.5 GVHD is considered to be a pathological state caused by abnormally activated donor lympho-cytes. Therefore, re-transplantation with cryopreserved host-derived hematopoietic stem cells may improve refractory GVHD by destroying the abnormal lympho-cytes. We report here a case of successful control of refractory, life-threatening GVHD using autologous peripheral blood stem cell transplantation (autoPBSCT). In December 2000, a 38-year old man was diagnosed as having acute myeloid leukemia (FAB-M5b), and underwent autoPBSCT in May 2001 in the first complete remission (CR). However, the patient had hematologic relapse 6 months after autoPBSCT. After receiving salvage chemotherapy, the patient achieved a second CR, and was transferred to our hospital to undergo allogene-ic SCT, because the second CR was not considered likely to be permanent. He had no HLA-identical related or unrelated donors. He had no siblings, and his parents were too old and his child was too small to donate bone marrow (BM). Therefore, we decided to perform allo-geneic SCT from his HLA-2-antigen-mismatched cousin. Institutional review board approval was obtained for the treatment protocol, and written informed consent was obtained from the patient and the donor. The transplant procedure was performed as previously described. 6 The conditioning regimen consisted of flu-darabine 30 mg/m 2 days –10 to –7, cyclophosphamide 60 mg/kg on days –5 to –4, and fractionated total body irradiation (10 Gy in four fractions on days –3 and-2). GVHD prophylaxis consisted of continuous intravenous infusion of FK506 0.03 mg/kg/day from day –2, methotrexate 10 mg/m 2 on day 1 and 7 mg/m 2 on day 3, methylprednisolone (mPSL) 2 mg/kg from day 1, and oral mycophenolate mofetil (MMF) 15 mg/kg/day daily from day 5. The patient received marrow without any manipulation. Hematopoietic reconstitution was rapid, with absolute neutrophil count >0.5x10 9 /L on day 11, and platelet count >20x10 9 /L on day 18. However, the patient began to develop diarrhea and skin rash on days 19 and 24, respectively, …