Comparison of outcome of allogeneic bone marrow transplantation with and without granulocyte colony-stimulating factor (lenograstim) donor-marrow priming in patients with chronic myelogenous leukemia.
To investigate the effect of granulocyte colony-stimulating factor (G-CSF) donor-marrow priming on hematopoietic recovery and clinical outcome after allogeneic hematopoietic stem cell transplantation, we compared HILA-matched related marrow transplantation with and without G-CSF donor priming in a prospective randomized study for a homogeneous group of chronic myelogenous leukemia (CML) patients. Fifty patients (aged 12-41 years) with CML were enrolled in the study. Thirty-two patients (study group) received the marrow grafts primed with G-CSF at 3 to 4 micro/kg per day for 7 days prior to the marrow harvest, and 18 patients (control group) received the marrow grafts without G-CSF priming. All patients received the same graft-versus-host disease (GVHD) prophylaxis (cyclosporine A and methotrexate) and postgraft G-CSF treatment, 3 to 4 micro/kg daily until the absolute neutrophil counts (ANCs) were >10(9)/L. The primary end points were engraftment and incidence of acute GVHD. The secondary end points were the incidence of chronic GVHD, relapse, and overall disease-free survival. The study and control groups were comparable for age, sex, donor selections, conditioning regimens, and disease status. The median times to both neutrophil and platelet engraftment (ANC > 0.5 x 10(9)/L; platelets > 20 x 10(9)/L) were significantly faster in the study group than in the control group, at 15 versus 21 days (P < .001) and 17.5 versus 24 days (P < .001), respectively. G-CSF donor printing yielded significantly higher numbers of total nuclear cells in the marrow grafts compared to the numbers in the control grafts (7.2 versus 2.9 x 10(8)/kg, P < .001). Similar results were seen for CD34+ (6.1versus 2.7 x 10(6)/kg, P < .001) and colony-forming unit-granulocyte/macrophage (CFU-GM) cells (68 versus 16 x 10(4)/kg, P < .001). The incidence of grades II to IV acute GVHD was surprisingly low in the study group: only 2 (6.3%) of 32 transplantation patients in the study group developed grade II acute GVHD, limited to the skin, whereas 5 (27.8%) of 18 patients in the control group developed grades II to IV acute GVHD (P = .032). G-CSF priming did not change the total numbers of CD3+ cells in the marrow grafts but lowered CD4+ cells and increased CD8+ cells, resulting in a significant reduction of CD4:CD8 ratio (P = .018). Six patients in the study group developed chronic GVHD either during or after cyclosporine taper. There were no significant differences in chronic GVHD (24% versus 33.3%), relapse rates (12.5% versus 11.1%), and overall survival rates (78.1% versus 66.7%, P = .32) between the study and control groups during a median follow-up period of 24 months (range, 6-50 months). There was, however, a trend in favor of improved chronic GVHD and disease-free survival in the study group. We conclude that G-CSF donor-marrow priming accelerates both neutrophil and platelet engraftment and is associated with a very low incidence of grades II to IV acute GVHD in CML patients after HLA-matched sibling marrow transplantation.
Ji
Shu-Quan
SQ
Research Center for Hematology, Air Force General Hospital, Beijing, People's Republic of China. jishuquan@263.net
Chen
Hui-Ren
HR
Wang
Hang-Xiang
HX
Yan
Hong-Ming
HM
Pan
Shi-Ping
SP
Xun
Chang-Qing
CQ
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D000078224:Lenograstim; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim