[Successful engraftment of T-cell undepleted haploidentical transplants by donor primed with G-CSF and additional use of ATG and MMF for recipients].
Seventeen patients and their family donors HLA 2 - 3 antigen mismatched of 2 - 3 loci were enrolled in the study of haploidentical transplants from February 1999 to March 2001. Among patients with leukemia, most patients were classified as high risk. Eleven patients with ALL were all in more than second remission but one was in relapse. Patients with AML were one in CR1, one in CR2 while 4 patients with CML were two in CP and two in AP. The male-to-female ratio was 14:3 and the median age was 15 (range from 8 to 35). Conditioning regimens included Ara-C 3.0 g/m(2), 2 times per day x 3 d, on day 7, 6 and 5 pre-transplantation, CTX 45 mg/(kg per d) x 2 d on day 5 and 4 pretransplantation. TBI with 1000 cGy by 2 fractions on day 2 and 1 pretransplantation. The fresh and unmanipulated marrow was infused on day 0. Donors were received G-CSF (Lenograstim) at 3 - 4 microg/(kg per d) x 7 d. The BM cells were collected on eighth day. In GVHD prophylaxis, CSA, MTX, ATG (Antithymocyte globulin, Rabbit Fresenius S) and MMF (mycophenolate mofetic) were used in different periods. The dose of CSA was 1.5 mg/(kg per d) on day 7 to 1 pretransplantation, then 3 mg/(kg per d) from day 1 pretransplantation. MTX was 15 mg/m(2) on day 1 and 10 mg/m(2) on day 3, 6 and 11 posttransplantation. ATG was administered day 4 to 1 pretransplantation at 5 mg/(kg per d) and MMF dose was 1.0 g/d from day 7 posttransplantation. All patients established successful engraftment after initial transplantation. The median days of neutrophil exceeding 0.5 x 10(9)/L and platelet exceeding 20 x 10(9)/L were 18 (range 13 - 23) and 20 (range 16 - 32) days, respectively. Patients were monitored up to day 100 for the sign of aGVHD. The established grades II to IV aGVHD occurred in 5 out of 17 patients (29.4%). Eleven patients were surviving at a median follow-up of 13 months (range 3 - 27 months). Six out of the 17 patients died those 3 of them died of severe aGVHD, 2 of infection and 1 of leukemia relapse. Severe regimen-related toxicities were not experienced in all patients. The median follow-up period was 13 (range 3 - 27) months. Eleven patients were alive in disease-free situation with a Karnofsky performance status of 100%. This could be caused by the low overall incidence of aGVHD as a result of BM primed with G-CSF. The four-agent of immunosuppressive combined prophylaxis against GVHD in different periods may be highly effective.
Chen
Hui-Ren
HR
Research Centre for Hematology, The General Hospital of Air Force, Beijing 100036, China.
Ji
Shu-Quan
SQ
Yan
Hong-Min
HM
Wang
Heng-Xiang
HX
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006239:Haplotypes; D006410:Hematopoiesis; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008212:Lymphocyte Depletion; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D009173:Mycophenolic Acid