Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen.
A nonmyeloablative conditioning regimen was investigated in 47 patients with hematological malignancy receiving allogeneic progenitor cells from matched, unrelated donors. The median patient age was 44 years. The majority of patients had high-risk features, including having failed a prior transplantation (29 individuals). Twenty of the transplants were mismatched for HLA class I and/or class II alleles. Recipient conditioning consisted of 20 mg CAMPATH-1H on days -8 to -4, 30 mg/m(2) fludarabine on days -7 to -3, and 140 mg/m(2) melphalan on day -2. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine A alone. Primary graft failure occurred in only 2 of 44 evaluable patients (4.5%). Chimerism studies in 34 patients indicated that the majority (85.3%) attained initial full donor chimerism. Only 3 patients developed grade III to IV acute GVHD, and no patients have yet developed chronic extensive GVHD. The estimated probability of nonrelapse mortality at day 100 was 14.9% (95% confidence interval [CI], 4.7%-25.1%). With a median follow-up of 344 days (range, 79-830), overall and progression-free survivals at 1 year were 75.5% (95% CI, 62.8%-88.2%) and 61.5% (95% CI, 46.1%-76.8%), respectively. In summary, a nonmyeloablative regimen incorporating in vivo CAMPATH-1H is effective in promoting durable engraftment in most patients and in reducing the risk of severe GVHD following matched unrelated donor transplantation.
Chakraverty
Ronjon
R
Department of Haematology, University College Hospital, 98 Chenies Mews, London WC1E 6HX, United Kingdom.
Peggs
Karl
K
Chopra
Rajesh
R
Milligan
Donald W
DW
Kottaridis
Panagiotis D
PD
Verfuerth
Stephanie
S
Geary
Johanne
J
Thuraisundaram
Dharsha
D
Branson
Kate
K
Chakrabarti
Suparno
S
Mahendra
Premini
P
Craddock
Charles
C
Parker
Anne
A
Hunter
Ann
A
Hale
Geoff
G
Waldmann
Herman
H
Williams
Catherine D
CD
Yong
Kwee
K
Linch
David C
DC
Goldstone
Anthony H
AH
Mackinnon
Stephen
S
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality*; D006801:Humans; D007239:Infections / Q000209:etiology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D016019:Survival Analysis; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan