Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation.
OBJECTIVE
Matched unrelated bone marrow transplantation (BMT) for patients with hematological malignancies is associated with a high incidence of transplant-related complications due to high doses of chemoradiotherapy administered pre-BMT to ensure engraftment. The aim of this study was to investigate the feasibility of low-intensity conditioning for BMT from matched unrelated donors.


METHODS
Sixteen patients with hematologic malignancies underwent non-T-cell-depleted BMT following a low-intensity conditioning regimen consisting of fludarabine monophosphate 30 mg/m(2)/day for 6 days, busulfan 4 mg/kg/day for 2 days, anti-T lymphocyte globulin 10 mg/kg/day for 4 days. Seven of the patients suffered from chronic myelogenous leukemia, four from acute lymphoblastic leukemia, four from acute myelogenous leukemia, and one from Ki-1 non-Hodgkin's lymphoma. Three of the patients had secondary leukemia and two were post-autologous BMT (ABMT). All patients were transplanted from fully matched unrelated donors.


RESULTS
Fifteen of the 16 patients had 100% donor chimerism; no graft rejection was observed. None of the patients developed >Grade II veno-occlusive disease, sepsis, multiorgan failure, or renal or pulmonary toxicity. Four patients died posttransplant; one of thrombocytopenia and severe hemorrhagic cystitis, one of central nervous system toxicity, one of Grade IV graft-vs-host disease, and one following relapse (9 months post-BMT). Survival and disease-free survival at 36 months are 75% (95% confidence interval 46-90%) and 60% (95% confidence interval 30-80%), respectively.


CONCLUSIONS
These results indicate that low-intensity conditioning is sufficient to ensure stable engraftment of bone marrow grafts in a matched unrelated setting.
Department of Bone Marrow Transplantation, Hadassah University Hospital, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel. nagler@hadassah.org.il
A
A
Nagler
M
M
Aker
R
R
Or
E
E
Naparstek
G
G
Varadi
C
C
Brautbar
S
S
Slavin
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D002066:Busulfan / Q000008:administration & dosage*; D002452:Cell Count; D002648:Child; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006648:Histocompatibility; D006801:Humans; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D015993:Life Tables; D017728:Lymphoma, Large-Cell, Anaplastic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016019:Survival Analysis; D013601:T-Lymphocytes; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D000961:Antilymphocyte Serum; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine