Hematologic Cancer
Hematologic Cancer
Asou N, Adachi K, Tamura J, et al
J Clin Oncol 16(1):78-85, 1998
The authors conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia and analyzed the prognostic factors for predicting complete remission, event-free survival, and disease-free survival. All patients received ATRA until complete remission. If patients had an initial leukocyte count >3.0 × 10/L, they received daunorubicin and behenoyl cytarabine. During therapy, if patients showed blast and promyelocyte counts greater than 1.0 × 10/L, they received additional daunorubicin and behenoyl cytarabine. After achieving complete remission, patients received 3 courses of consolidation and 6 courses of maintenance/intensification chemotherapy. Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved complete remission. Multivariate analysis showed that no or minor purpura at diagnosis (P =.0046) and age <30 years ( P =.0076) were favorable factors for achievement of complete remission. Predicted 4-year overall survival and event-free survival rates were 74% and 54%, respectively, and the 4-year predicted disease-free survival rate for 173 complete-remission patients was 62%. Multivariate analysis showed that age less than 30 years (P =.0003) and initial leukocyte count less than 10 × 10/L ( P =.0296) were prognostic factors for longer event-free survival, and initial leukocyte count <10.0 × 10/L was a sole significant prognostic factor for longer disease-free survival (P =.0001). Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for acute promyelocytic leukemia treated with ATRA followed by intensive chemotherapy.
Survival of Acute Promyelocytic Leukemia Treated With ATRA
Editorial Commment by Hussain I.Saba, MD
The multicenter study by Asou and colleagues indicates that at the time of diagnosis, 3 important parameters correlate well with prognosis of M3 acute promyelocytic leukemia. These include patient's age, absence of bleeding diathesis, and the initial leukocyte count. In this study, convincing data have been presented in the area of assessing the prognosis of patients with promyelocytic leukemia. These data seem to be supported by findings from other recently reported studies.
In a study from Lyons, France, Thomas and colleagues (Blood 10[suppl P]:172a, 1995) have found that age and performance status are important predictors in achievement of complete response in acute promyelocytic leukemia, with a decreased rate of complete response attributed to older age. Poor prognostic factors for survival in this French study were age >=50 at diagnosis (P =.004), World Health Organization performance status >1 (P <.001), initial platelet level <50G/L (P =.02), absence of HEUR (P =.003), high serum LDH level (P =.03), hyperuricemia (P <.0001), and an initial finding of disseminated intravascoagulation (P =.0003).
In another study, age has been implicated as the prognostic parameter for early hemorrhagic death in acute promyelocytic leukemia: The British Study reported by Taylor and associates, of 134 patients from the Royal Victoria Infirmary (Blood 85[suppl 1]:784a, 1995), found the actual survival at 5 years in the age group younger than 25 years was 78%, as compared with 29% in age group older than 25 years. In younger patients, only 9% died with hemorrhagic disease, as compared with 28% in the older age group (P =.028). Other factors in assessment of prognosis of acute promyelocytic leukemia in relation to survival have included the influence of the chromosomal abnormalities in addition to 15;17 translocation.
In a study by Hiorns and colleagues (Br J Haematol 96(2):314-321, 1997), 39% of patients (21/54) had additional chromosomal abnormalities at presentation. The presence of additional chromosomal abnormalities had an adverse effect on prognosis, independent of other prognostic indicators.
In a recent ECOG study, data were analyzed in 172 patients with acute promyelocytic leukemia treated with all- trans retinoic acid and chemotherapy, similar to the Japanese study (M.S. Tallman, personal communication). The analysis appears to show no correlation of age or initial WBC count with the prognosis of acute promyelocytic leukemia. Nor has any relation to prognosis been found for M3 patients with base breakpoint location on the M3 gene. In view of these studies, it appears that more data would be useful to precisely define the prognostic significance of age, initial white cell count, and chromosomal changes in patients with acute promyelocytic leukemia.
Asou N, Adachi K, Tamura J, et al
J Clin Oncol 16(1):78-85, 1998
The authors conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia and analyzed the prognostic factors for predicting complete remission, event-free survival, and disease-free survival. All patients received ATRA until complete remission. If patients had an initial leukocyte count >3.0 × 10/L, they received daunorubicin and behenoyl cytarabine. During therapy, if patients showed blast and promyelocyte counts greater than 1.0 × 10/L, they received additional daunorubicin and behenoyl cytarabine. After achieving complete remission, patients received 3 courses of consolidation and 6 courses of maintenance/intensification chemotherapy. Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved complete remission. Multivariate analysis showed that no or minor purpura at diagnosis (P =.0046) and age <30 years ( P =.0076) were favorable factors for achievement of complete remission. Predicted 4-year overall survival and event-free survival rates were 74% and 54%, respectively, and the 4-year predicted disease-free survival rate for 173 complete-remission patients was 62%. Multivariate analysis showed that age less than 30 years (P =.0003) and initial leukocyte count less than 10 × 10/L ( P =.0296) were prognostic factors for longer event-free survival, and initial leukocyte count <10.0 × 10/L was a sole significant prognostic factor for longer disease-free survival (P =.0001). Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for acute promyelocytic leukemia treated with ATRA followed by intensive chemotherapy.
Survival of Acute Promyelocytic Leukemia Treated With ATRA
Editorial Commment by Hussain I.Saba, MD
The multicenter study by Asou and colleagues indicates that at the time of diagnosis, 3 important parameters correlate well with prognosis of M3 acute promyelocytic leukemia. These include patient's age, absence of bleeding diathesis, and the initial leukocyte count. In this study, convincing data have been presented in the area of assessing the prognosis of patients with promyelocytic leukemia. These data seem to be supported by findings from other recently reported studies.
In a study from Lyons, France, Thomas and colleagues (Blood 10[suppl P]:172a, 1995) have found that age and performance status are important predictors in achievement of complete response in acute promyelocytic leukemia, with a decreased rate of complete response attributed to older age. Poor prognostic factors for survival in this French study were age >=50 at diagnosis (P =.004), World Health Organization performance status >1 (P <.001), initial platelet level <50G/L (P =.02), absence of HEUR (P =.003), high serum LDH level (P =.03), hyperuricemia (P <.0001), and an initial finding of disseminated intravascoagulation (P =.0003).
In another study, age has been implicated as the prognostic parameter for early hemorrhagic death in acute promyelocytic leukemia: The British Study reported by Taylor and associates, of 134 patients from the Royal Victoria Infirmary (Blood 85[suppl 1]:784a, 1995), found the actual survival at 5 years in the age group younger than 25 years was 78%, as compared with 29% in age group older than 25 years. In younger patients, only 9% died with hemorrhagic disease, as compared with 28% in the older age group (P =.028). Other factors in assessment of prognosis of acute promyelocytic leukemia in relation to survival have included the influence of the chromosomal abnormalities in addition to 15;17 translocation.
In a study by Hiorns and colleagues (Br J Haematol 96(2):314-321, 1997), 39% of patients (21/54) had additional chromosomal abnormalities at presentation. The presence of additional chromosomal abnormalities had an adverse effect on prognosis, independent of other prognostic indicators.
In a recent ECOG study, data were analyzed in 172 patients with acute promyelocytic leukemia treated with all- trans retinoic acid and chemotherapy, similar to the Japanese study (M.S. Tallman, personal communication). The analysis appears to show no correlation of age or initial WBC count with the prognosis of acute promyelocytic leukemia. Nor has any relation to prognosis been found for M3 patients with base breakpoint location on the M3 gene. In view of these studies, it appears that more data would be useful to precisely define the prognostic significance of age, initial white cell count, and chromosomal changes in patients with acute promyelocytic leukemia.
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