Haploidentical transplantation for acute lymphoblastic leukemia in childhood.
Haploidentical transplantation in childhood acute lymphoblastic leukemia (ALL) is a promising option for children lacking a suitable donor. We have updated our series of patients with ALL and report the results. Additionally, we reviewed the literature and try to embed our own experiences in the published results. We performed HLA-mismatched stem cell transplantations with megadoses of purified positively selected mobilized peripheral blood CD34+ progenitor cells (PBPC) from adult donors in 27 children with acute lymphoblastic leukemia (ALL) in first (CR1 n = 7), second (CR2 n = 10), or third (CR3 n = 4) complete remission, and in refractory state (NR n = 6). The patients received a mean number of 19.1+/-11.3 x 10(6)/kg purified CD34+ and a mean number of 15.5+/-24.2 x 10(3)/kg CD3+ T-cells. No additional graft-versus-host disease (GVHD) prophylaxis was used, except as short-term CSA in the first 3 patients. The myeloablative treatment was based on busulfan in 12 and on TBI in 14 patients. One patient was grafted with a non-myeloablative approach. Engraftment was rapid in 26 patients, with two patients suffering from a rejection. These two and one patient with initial non-engraftment had been successfully regrafted. The probability of survival of the total group is 0.34+/-0.09; the 12 patients transplanted in remission showed a probability of survival of 0.44+/-0.11. None of the patients transplanted in non-remission survived. There was no statistical difference in survival for patients with a 1, 2 or 3 antigen mismatched donor (out of 6 HLA antigens) or for patients in 1st, 2nd or 3rd remission. Causes of death were relapses in 10 patients, veno-occlusive disease (VOD) in 1, multi-organ failure (MOF) in 2 and infections in 4 patients. 3/24 evaluable patients without any additional GVHD-prophylaxis developed grade 1 or 2 GVHD. Ten patients were treated with additional donor lymphocyte infusion (DLI), from which 4 developed a maximum grade 3 GVHD. We conclude that the HLA barrier can be overcome by transplantation of megadoses of highly purified CD34+ PBPC and GVHD can effectively be prevented. This approach offers a promising treatment option for patients with acute lymphoblastic leukemia needing urgently transplantation but lacking a suitable donor.
Klingebiel
Thomas
T
Klinik für Kinderheilkunde III, Zentrum für Kinderheilkunde und Jugendmedizin der Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany. thomas.klingebiel@kgu.de
Handgretinger
Rupert
R
Lang
Peter
P
Bader
Peter
P
Niethammer
Dietrich
D
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D001782:Blood Donors; D017252:CD3 Complex; D002648:Child; D002675:Child, Preschool; D005260:Female; D006410:Hematopoiesis; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D013601:T-Lymphocytes; D019172:Transplantation Conditioning; D016896:Treatment Outcome
D018952:Antigens, CD34; D017252:CD3 Complex