G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion:: an excellent alternative for high-risk leukemia

被引:37
作者
Ji, SQ [1 ]
Chen, HR
Wang, HX
Yan, HM
Zhu, L
Liu, J
Xue, M
Xun, CQ
机构
[1] Gen Hosp Air Force, Hematol Res Ctr, PLA, Beijing 100036, Peoples R China
[2] Univ Kentucky, Dept Med, Div Hematol Oncol, Lexington, KY 40506 USA
[3] Univ Kentucky, Dept Med, Stem Cell Transplant Program, Lexington, KY 40506 USA
关键词
G-CSF; GVHD; engraftment; haploidentical bone marrow transplantation;
D O I
10.1038/sj.bmt.1703769
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versus-graft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 mug/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34(+) and CFU-GM cells, reduced total lymphocytes and reversed the CD4(+)/CD8(+) ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60+/-7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.
引用
收藏
页码:861 / 866
页数:6
相关论文
共 29 条
[1]   EFFECT OF HLA COMPATIBILITY ON ENGRAFTMENT OF BONE-MARROW TRANSPLANTS IN PATIENTS WITH LEUKEMIA OR LYMPHOMA [J].
ANASETTI, C ;
AMOS, D ;
BEATTY, PG ;
APPELBAUM, FR ;
BENSINGER, W ;
BUCKNER, CD ;
CLIFT, R ;
DONEY, K ;
MARTIN, PJ ;
MICKELSON, E ;
NISPEROS, B ;
OQUIGLEY, J ;
RAMBERG, R ;
SANDERS, JE ;
STEWART, P ;
STORB, R ;
SULLIVAN, KM ;
WITHERSPOON, RP ;
THOMAS, ED ;
HANSEN, JA .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 320 (04) :197-204
[2]  
ANTIN JH, 1992, BLOOD, V80, P2964
[3]   Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients [J].
Basara, N ;
Blau, WI ;
Kiehl, MG ;
Schmetzer, B ;
Bischoff, M ;
Kirsten, D ;
Günzelmann, S ;
Fauser, AA .
CLINICAL TRANSPLANTATION, 2000, 14 (02) :121-126
[4]   MARROW TRANSPLANTATION FROM RELATED DONORS OTHER THAN HLA-IDENTICAL SIBLINGS [J].
BEATTY, PG ;
CLIFT, RA ;
MICKELSON, EM ;
NISPEROS, BB ;
FLOURNOY, N ;
MARTIN, PJ ;
SANDERS, JE ;
STEWART, P ;
BUCKNER, CD ;
STORB, R ;
THOMAS, ED ;
HANSEN, JA .
NEW ENGLAND JOURNAL OF MEDICINE, 1985, 313 (13) :765-771
[5]   Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: A retrospective comparison with marrow transplantation [J].
Bensinger, WI ;
Clift, R ;
Martin, P ;
Appelbaum, FR ;
Demirer, T ;
Gooley, T ;
Lilleby, K ;
Rowley, S ;
Sanders, J ;
Storb, R ;
Buckner, CD .
BLOOD, 1996, 88 (07) :2794-2800
[6]   Bone marrow mobilized with granulocyte colony-stimulating factor in related allogeneic transplant recipients: A study of 29 patients [J].
Couban, S ;
Messner, HA ;
Andreou, P ;
Egan, B ;
Price, S ;
Tinker, L ;
Meharchand, J ;
Forrest, DL ;
Lipton, J .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2000, 6 (4A) :422-427
[7]  
DEEG HJ, 1991, BONE MARROW TRANSPL, V7, P193
[8]  
Durrant ST, 1999, BLOOD, V94, p608A
[9]   Pathogenesis of acute graft-versus-host disease: Cytokines and cellular effectors [J].
Ferrara, JLM .
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH, 2000, 9 (03) :299-306
[10]   BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE - INCREASED RISK FOR RELAPSE ASSOCIATED WITH T-CELL DEPLETION [J].
GOLDMAN, JM ;
GALE, RP ;
HOROWITZ, MM ;
BIGGS, JC ;
CHAMPLIN, RE ;
GLUCKMAN, E ;
HOFFMANN, RG ;
JACOBSEN, SJ ;
MARMONT, AM ;
MCGLAVE, PB ;
MESSNER, HA ;
RIMM, AA ;
ROZMAN, C ;
SPECK, B ;
TURA, S ;
WEINER, RS ;
BORTIN, MM .
ANNALS OF INTERNAL MEDICINE, 1988, 108 (06) :806-814