From May 2003, 13 patients with refractory hematological malignancies received HLA haploidentical hematopoietic stem cell transplantations in out BMT center.
13 patients, including 9 male and 4 female, are with an average age of 31.4 years (range, 15 to 46). Among them, 4 cases were of accelerated phase of CML, 1 blast phase of CML, 1 polyleptic ANLL-M3, 1 ANLL-M2, 2 ANLL M4, 1 ANLL M6, 2 NHL, and 1 MDS-RA. Of the 13 donors, 8 were the mothers of the recipients, 4 were the siblings, and the rest was the son. All the donors were HLA haploidentical matched to the patients.
4 patients were conditioned with CY/TBI/Ara-C regimen, (Ara-C 3. 0g/m2, q12h, ×3 d; CTX45 mg/kg×2 d; TBI 5 Gy ×2 d, ATG5 mg/kg ×4 d)). 8 patients were conditioned with improved BU/CY regimen, (BU 4 mg/kg ×3 d, CTX 1. 8 g/m 2 ×2 d, Ara-C 2 g/m 2 × 1 d, Me-CCNU 250 mg/m 2 ×1 d, ATG5 mg/kg ×4 d) and 1 patient of MDS-RA was conditioned with nonmyeloablative regimen (Fludarabine 30 mg/m2/d × 5d, CTX 30 mg/kg/d x 2d, TBI 300 cGy d1.
G-CSF was given to the donors at 250 mg /day for a continuous 5~7 days. On the 4th~8th day, their bone marrow was collected under epidural anesthesia. In the simple bone marrow transplantation, the amount of the bone marrow collected was 15~20 ml/kg recipient b.w. And BMT associated with HSCT was given to 9 of the patients. The average parameter of the mononuclear cells re-infused was 8.84×108/kg; while the CD34+ cells was 2.67×106/kg.
The treatments of CsA, MTX, MMF, ATG, and anti-CD25 monoclonal antibody were given as prophylaxis for GVHD. All the 13 patients received standard supportive care, and got hematopoietic reconstitution. The mean time of engraftment with neutrophil count more than 1.0 x 109/L was 15 days and platelet count more than 20 x 109/L was 21 days. All the patients was tested with STR-PCR, and showed a genotype the same as the donor’s.
5 of the 13 patients suffered grade I~II acute GVHD. 1 patient suffered grade III dermo-GVHD 30 days after transplantation. The CMV-DNA of 3 patients turned out positive after the transplantation, 2 patients suffered grade I~II hemorrhagic cystitis. There were totally 2 deaths, one of which who was in the IV phase of NHL died due to recurrent disease after the transplantation, the other suffered graft rejection on the 28 day of the hematopoietic reconstitution, which complicated with centrum infection after the second transplantation.
11 recipients got CR after transplantation. 1 patient of the accelerated phase of CML relapsed on the +70 day and 1 M3 patient relapsed 18 months after transplantation, both of them died after ineffective therapy. One patient of accelerated phase of CML relapsed genetically 1 year after the transplantation, and then got remission after the administration of Glivec. Full donor-type engraftment was sustained successfully in these 8 recipients. The patients were followed up until June 2005, with a median follow-up time of 18 months (range, 12 to 25 months).
Our initial results show that the conditioning regimens, either with or without radiotherapy, are able to transplant the haploidentical hematopoietic stem cell without first T lymphocytes depletion. If ATG, mycophenolate mofetil and anti-CD25 monoclonal antibody, etc. are applied, the incidence of severe aGVHD will be decreased. 8 of the 13 patients survived for more than one year after transplantation. It shows favorable short-term curative effects.