Survival improvement of poor-prognosis AML/MDS patients by maintenance treatment with low-dose chemotherapy and differentiating agents.
We evaluated a maintenance, post-remission treatment with low-dose chemotherapy plus differentiating agents on poor-prognosis acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients ineligible to allografting. Patients had either age over 60 and/or secondary AML, therapy-related AML, previous relapse, high-risk MDS. Forty-five patients received the maintenance therapy based on two alternated schedules: (a) 6-thioguanine + 13-cis retinoic acid + dihydroxylated vitamin D3 and (b) low-dose cytarabine + 6-mercaptopurine + all-trans retinoic acid + dihydroxylated vitamin D3. We compared their outcome, at a median follow-up of 52 months, to that of a matched population of 49 patients who stopped treatments after consolidation. Maintenance group had a lower relapse incidence (70.3 vs. 86.4 % at 5 years p = 0.007) and a longer disease-free survival (median 21.2 vs. 8.7 months, p = 0.017). The relapse reduction improved overall survival: median 40.4 months (35.9 % at 5 years) for maintenance group vs. 15.8 (14.2 % at 5 years) for controls (p = 0.005). At multivariate Cox analysis, both cytogenetic and maintenance therapies resulted independent outcome predictors for overall survival. Maintenance treatment also reduced minimal residual disease (detected by WT1 and CBFβ-MYH11) in five of eight evaluable patients. The present results suggest that our strategy of maintenance therapy might improve the outcome of poor-risk AML/MDS patients.
Section of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Turin, via Genova, 3, 10126, Turin, Italy, dario.ferrero@unito.it.
Dario
D
Ferrero
Elena
E
Crisà
Filippo
F
Marmont
Ernesta
E
Audisio
Chiara
C
Frairia
Valentina
V
Giai
Tiziana
T
Gatti
Moreno
M
Festuccia
Benedetto
B
Bruno
Ludovica
L
Riera
Roberto
R
Passera
Mario
M
Boccadoro
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D018365:Neoplasm, Residual; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction; D012306:Risk; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D018943:Anthracyclines; D003561:Cytarabine; D005047:Etoposide; D019772:Topotecan; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine