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Blood Sep 2001In an attempt to improve induction chemotherapy for older patients with acute myeloid leukemia (AML),1314 patients were randomized to 1 of 3 induction treatments for 2... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
In an attempt to improve induction chemotherapy for older patients with acute myeloid leukemia (AML),1314 patients were randomized to 1 of 3 induction treatments for 2 courses of DAT (daunorubicin, cytarabine, and thioguanine) 3 + 10, ADE (daunorubicin, cytarabine, and etoposide) 10 + 3 + 5, or MAC (mitoxantrone-cytarabine). The remission rate in the DAT arm was significantly better than ADE (62% vs 50%; P =.002) or MAC (62% vs 55%; P =.04). This benefit was seen in patients younger and older than 70 years. There were no differences between the induction schedules with respect to overall survival at 5 years (12% vs 8% vs 10%). A total of 226 patients were randomized to receive granulocyte colony-stimulating factor (G-CSF) or placebo as supportive care from day 8 after the end of treatment course 1. The remission rate or survival were not improved by G-CSF, although the median number of days to recover neutrophils to 1.0 x 10(9)/L was reduced by 5 days. Patients who entered remission (n = 371) were randomized to stop after a third course (DAT 2 + 7) or after 6 courses, ie, a subsequent COAP (cyclophosphamide, vincristine, cytarabine, and prednisolone), DAT 2 + 5, and COAP. The relapse risk (81% vs 73%), disease-free survival (16% vs 23%), and overall survival at 5 years (23% vs 22%) did not differ between the 3-course or 6-course arms. In addition to a treatment duration randomization, 362 patients were randomized to receive 12-month maintenance treatment with low-dose interferon, but no benefit was seen with respect to relapse risk, disease-free survival, or overall survival.
Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Daunorubicin; Disease-Free Survival; Drug Administration Schedule; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunologic Factors; Interferon-alpha; Lenograstim; Leukemia, Myeloid; Male; Middle Aged; Mitoxantrone; Prednisone; Recombinant Proteins; Remission Induction; Survival Analysis; Thioguanine; Treatment Outcome; United Kingdom; Vincristine
PubMed: 11520775
DOI: 10.1182/blood.v98.5.1302 -
Anales de Pediatria (Barcelona, Spain :... Sep 2006Conventional prognostic factors for relapse in patients with acute lymphoblastic leukemia (ALL) are the main basis of risk-stratified treatments.
BACKGROUND
Conventional prognostic factors for relapse in patients with acute lymphoblastic leukemia (ALL) are the main basis of risk-stratified treatments.
OBJECTIVES
To analyze conventional risk factors for relapse and design a predictive model for relapse in our series, after 20 years of experience in treating ALL.
PATIENTS AND METHOD
We performed a multivariate analysis of conventional prognostic factors in the treatment of ALL in our unit and compared them with the risk groups in the Berlin-Frankfurt-Münster (BFM-ALL) treatment protocols.
RESULTS
Between 1984 and 2004, 232 children were diagnosed with ALL and treated according to the different versions of the BFM protocols (BFM83, BFM86, BFM90 and BFM95) at the Hospital Niño Jesús, Madrid, Spain. The event-free survival for all patients was 79.4 % (95 % CI: 72.7-85.4). Overall survival among patients who relapsed was 10.72 % (95 % CI: 6-27.3). The only significant prognostic factor for relapse identified by multivariate analysis was leukocyte [white blood cell (WBC)] count higher than 80,000/ml at diagnosis (hazard ratio [HR]: 4.63; 95 % CI: 1.61-13.3; p 5 0,004). The sensitivity and specificity of WBC in predicting relapses were 31.4 % and 87.5 %, respectively. The sensitivity and specificity of BFM risk group stratification in predicting relapses were 25 and 85.9 respectively.
CONCLUSIONS
A leukocyte count at diagnosis higher than 80,000/ml and BFM risk-stratified treatment have insufficient sensitivity and specificity to identify relapses.
Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Etoposide; Female; Humans; Infant; Male; Mercaptopurine; Methotrexate; Multivariate Analysis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prednisone; Prognosis; Recurrence; Risk Factors; Survival Rate; Time Factors; Vincristine
PubMed: 16956497
DOI: 10.1157/13092154 -
Blood Sep 2001Acute myeloid leukemia (AML) in older adults carries a poor prognosis, and the optimum treatment remains to be determined. In younger patients, treatment stratification... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial.
Acute myeloid leukemia (AML) in older adults carries a poor prognosis, and the optimum treatment remains to be determined. In younger patients, treatment stratification is frequently based upon diagnostic karyotype, which was the most important prognostic factor in the UK Medical Research Council (MRC) AML10 trial. Considered here is whether karyotype is also predictive in older adults; this is done by studying 1065 cases from MRC AML11 (median age, 66 years). Three prognostic groups were distinguished on the basis of response to induction therapy and overall survival (OS). Those with t(15;17), t(8;21), or inv(16) composed the favorable risk group. Overall, these abnormalities predicted a superior complete remission (CR) rate (72%), reflecting relatively low levels of resistant disease (RD) (8%), and lower relapse risk (RR) (56%) associated with superior OS (34% at 5 years). Normal karyotype (CR, 63%; RD, 17%; RR, 78%; OS, 15%) and other noncomplex abnormalities (CR, 53%; RD, 32%; RR, 85%; OS, 10%) composed the intermediate group; while complex karyotype predicted an extremely poor prognosis (CR, 26%; RD, 56%; RR, 91%; OS, 2%). Combining MRC AML10 and AML11 (n = 2677) revealed that the most favorable changes were rarer in older patients (younger than 55 years, 24%; 55 years or older, 7%), while complex abnormalities were more common (6% vs 13%). This study suggests that hierarchical cytogenetic classification identifies biologically distinct subsets of AML that are represented in all age groups. Furthermore, it highlights the importance of karyotype as a critical independent determinant of outcome in older patients with AML, providing a potential framework for stratified treatment approaches.
Topics: Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Cyclophosphamide; Cytarabine; Daunorubicin; Disease-Free Survival; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Immunologic Factors; Interferon-alpha; Karyotyping; Lenograstim; Leukemia, Myeloid; Life Tables; Male; Middle Aged; Predictive Value of Tests; Prednisone; Prognosis; Recombinant Proteins; Remission Induction; Survival Analysis; Thioguanine; Treatment Outcome; United Kingdom; Vincristine
PubMed: 11520776
DOI: 10.1182/blood.v98.5.1312 -
Blood Dec 2006
Comparative Study
Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Disease-Free Survival; Etoposide; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Remission Induction; Retrospective Studies; Risk Factors; Survival Rate; Treatment Outcome
PubMed: 17114571
DOI: 10.1182/blood-2006-06-032680