Long-term outcomes of alemtuzumab-based reduced-intensity conditioned hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myelogenous leukemia secondary to myelodysplastic syndrome.
Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a potential cure for patients with myelodysplastic syndrome (MDS) who are ineligible for standard-intensity regimens. Previously published data from our institution suggest excellent outcomes at 1 yr using a uniform fludarabine, busulfan, and alemtuzumab-based regimen. Here we report long-term follow-up of 192 patients with MDS and acute myelogenous leukemia (AML) secondary to MDS (MDS-AML) transplanted with this protocol, using sibling (n = 45) or matched unrelated (n = 147) donors. The median age of the cohort was 57 yr (range, 21 to 72 yr), and median follow-up was 4.5 yr (range, 0.1 to 10.6 yr). The 5-yr overall survival (OS), event-free survival, and nonrelapse mortality were 44%, 33%, and 26% respectively. The incidence of de novo chronic graft-versus-host disease (GVHD) was low at 19%, illustrating the efficacy of alemtuzumab for GVHD prophylaxis. Conversely, the 5-yr relapse rate was 51%. For younger patients (age <50 yr), the 5-yr OS and relapse rates were 58% and 39%, respectively. On multivariate analysis, advanced age predicted significantly worse outcomes, with patients age >60 yr having a 5-yr OS of 15% and relapse rate of 66%. Patients receiving preemptive donor lymphocyte infusions had an impressive 5-yr OS of 67%, suggesting that this protocol may lend itself to the incorporation of immunotherapeutic strategies. Overall, these data demonstrate good 5-yr OS for patients with MDS and MDS-AML undergoing alemtuzumab-based RIC-HSCT. The low rate of chronic GVHD is encouraging, and comparative studies with other RIC protocols are warranted.
Department of Haematological Medicine, King's College Hospital, London, UK.
Victoria T
VT
Potter
Department of Haematological Medicine, King's College Hospital, London, UK.
Pramila
P
Krishnamurthy
Department of Haematological Medicine, King's College Hospital, London, UK.
Linda D
LD
Barber
Department of Haematological Medicine, King's College Hospital, London, UK.
Ziyi
Z
Lim
Department of Haematological Medicine, King's College Hospital, London, UK.
Michelle
M
Kenyon
Department of Haematological Medicine, King's College Hospital, London, UK.
Robin M
RM
Ireland
Department of Haematological Medicine, King's College Hospital, London, UK.
Hugues
H
de Lavallade
Department of Statistics, King's College, London, UK.
Abdel
A
Dhouri
Department of Haematological Medicine, King's College Hospital, London, UK.
Judith C W
JC
Marsh
Department of Haematological Medicine, King's College Hospital, London, UK.
Robert
R
Marcus
Department of Haematological Medicine, King's College Hospital, London, UK.
Stephen
S
Devereux
Department of Haematological Medicine, King's College Hospital, London, UK.
Aloysius
A
Ho
Department of Haematological Medicine, King's College Hospital, London, UK.
Antonio
A
Pagliuca
Department of Haematological Medicine, King's College Hospital, London, UK. Electronic address: ghulam.mufti@kcl.ac.uk.
Ghulam J
GJ
Mufti
D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
D061067:Antibodies, Monoclonal, Humanized; D019653:Myeloablative Agonists; D000074323:Alemtuzumab
Acute myelogenous leukemia; Alemtuzumab; Myelodysplastic syndrome; Reduced intensity; Transplantatiom