Allogeneic marrow transplantation for myelodysplastic syndrome with advanced disease morphology: a phase II study of busulfan, cyclophosphamide, and total-body irradiation and analysis of prognostic factors.
OBJECTIVE
To determine if an intensive preparative regimen of busulfan (BU), cyclophosphamide (CY), and total-body irradiation (TBI) could improve outcome after marrow transplantation for advanced morphology myelodysplasia (refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEB-T], and chronic myelomonocytic leukemia [CMML]) compared with that obtained with conventional CY/TBI and to analyze prognostic factors for transplantation for myelodysplasia.


METHODS
A phase II study was conducted of 31 patients (median age, 41 years) treated with BU (7 mg/kg), CY (50 mg/kg), TBI (12 Gy), and human leukocyte antigen (HLA)-matched (n = 23) or -mismatched (n = 2) related or unrelated donor (n = 6) marrow transplantation. Results were compared with 44 historical control patients treated with CY (120 mg/kg) and TBI.


RESULTS
The 3-year actuarial disease-free survival (DFS) rate was similar for the BU/CY/TBI group and the CY/TBI group (23% v 30%, P = .6), but there were trends toward lower relapse rates (28% v 54%, P = .27) and higher nonrelapse mortality rates (68% v 36%, P = .12) among the current patients compared with historical controls. Multivariate analysis showed that a normal karyotype pretransplant and the use of methotrexate as part of posttransplant immunosuppression were associated with improved survival and reduced nonrelapse mortality. Univariate analysis showed significant differences in relapse rates based on marrow source (57% for HLA genotypically matched marrow v 18% for all others, P = .04) and on disease morphology (66% for RAEB-T v 38% for RAEB and CMML, P = .05).


CONCLUSIONS
Patients with advanced morphology myelodysplasia tolerated the intensified BU/CY/TBI preparative regimen and reduced posttransplant immunosuppression poorly. Novel transplant procedures are needed to reduce relapse rates without increasing nonrelapse mortality rates. In addition, transplantation before progression to RAEB-T, if possible, may reduce the risk of relapse.
Anderson
J E
JE
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Appelbaum
F R
FR
Schoch
G
G
Gooley
T
T
Anasetti
C
C
Bensinger
W I
WI
Bryant
E
E
Buckner
C D
CD
Chauncey
T
T
Clift
R A
RA
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007239:Infections / Q000209:etiology; D007621:Karyotyping; D008727:Methotrexate / Q000008:administration & dosage; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012008:Recurrence; D012044:Regression Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D016572:Cyclosporine; D003520:Cyclophosphamide; D002066:Busulfan; D008775:Methylprednisolone; D008727:Methotrexate