pirarubicin and Down-Syndrome

On the basis of results of previous Japanese trials for myeloid leukemia in Down syndrome (ML-DS), the efficacy of risk-oriented therapy was evaluated in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-D05 study.. All patients received induction chemotherapy that consisted of pirarubicin, intermediate-dose cytarabine, and etoposide. Patients who achieved complete remission (CR) after initial induction therapy were stratified to the standard risk (SR) group and received four courses of reduced-dose intensification therapy. Patients who did not achieve CR were stratified to the high risk (HR) group and received intensified therapy that consisted of continuous or high-dose cytarabine.. A total of 72 patients were eligible and evaluated. One patient died of sepsis during initial induction therapy. Sixty-nine patients were stratified to SR and two patients to HR. No therapy-related deaths were observed during intensification therapy. The 3-year event-free and overall survival rates were 83.3% ± 4.4% and 87.5% ± 3.9%, respectively. Age at diagnosis less than 2 years was a significant favorable prognostic factor for risk of relapse (P = 0.009).. The attempt of risk-oriented prospective study for ML-DS was unsuccessful, but despite the dose reduction of chemotherapeutic agents, the overall outcome was good, and further dose reduction might be possible for specific subgroups.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Disease-Free Survival; Down Syndrome; Doxorubicin; Etoposide; Female; Humans; Induction Chemotherapy; Infant; Japan; Kaplan-Meier Estimate; Leukemia, Myeloid; Male; Prospective Studies

The aim of the JCCLSG AML 9805 Down study was to evaluate the effect of continuous and high-dose cytarabine combined chemotherapy on the survival outcome of acute myeloid leukemia (AML) with Down syndrome (DS).. From May 1998 to December 2006, DS patients with newly diagnosed AML were enrolled. Remission induction therapy consisted of two courses of pirarubicin, vincristine, and continuous-dose cytarabine (AVC1). The patients who achieved complete remission (CR) after two courses of AVC1 were subsequently treated with mitoxantrone and continuous-dose cytarabine (MC), etoposide and high-dose cytarabine (EC) and pirarubicin, vincristine, and continuous-dose cytarabine (AVC2).. Twenty-four patients were enrolled. All patients were younger than 4 years and diagnosed as having acute megakaryoblastic leukemia. Twenty-one patients achieved CR. Three patients died during remission induction therapy due to serious infection. No toxic deaths were observed during remission. All but one patient maintained CR without serious complications. The 5-year overall and event-free survivals were 87.5%  ± 6.8% and 83.1%  ± 7.7%, respectively.. Continuous and high-dose cytarabine combined chemotherapy with reduced intensity would be effective in DS children with AML.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Disease-Free Survival; Down Syndrome; Doxorubicin; Female; Humans; Infant; Infant, Newborn; Japan; Leukemia, Myeloid, Acute; Male; Mitoxantrone; Survival Rate; Vincristine

Various methods of intensive chemotherapy have contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long-term results of the two consecutive trials of Tokyo Children's Cancer Study Group (TCCSG), incorporating repetitive use of high-dose cytarabine (HD-Ara-C) based combination chemotherapy in post-remission phase.. A total of 216 eligible children with newly diagnosed AML were treated in the two consecutive multi-center trials of TCCSG, M91-13 and M96-14, from August 1991 to September 1998. In M91-13 trial, patients received eight courses of intensive post-remission chemotherapy, including six HD-Ara-C containing courses, after remission-induction therapy. Autologous hematopoietic stem cell transplantation (HSCT) could be selected by physician's choice, and allogeneic HSCT was allocated if donor was available. In M96-14 trial, the last two HD-Ara-C courses were omitted from the chemotherapy arm.. The remission-induction rate was 88.8% and probability of 5-year Overall survival (OS) and event-free survival (EFS) were 62% (56-69% with 95% Confidence intervals (CIs)) and 56% (49-62%), respectively. Treatment-related mortality (TRM) was 7.8%. Among patients without Down syndrome (DS) or acute promyelocytic leukemia (APL), the presence of t(8;21) or inv(16) was a significant good prognostic factor both in the univariate and multivariate analyses. Children with DS (N = 10) and APL (N = 14) also showed a good survival exceeding 70% in 5 years.. These results suggest that repetitive use of HD-Ara-C was effective and safe for childhood AML. However, further optimization of AML therapy is required.

Topics: Acute Disease; Adolescent; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Down Syndrome; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Hydrocortisone; Infant; Infections; Japan; Kaplan-Meier Estimate; Leukemia, Myeloid; Male; Methotrexate; Mitoxantrone; Remission Induction; Survival Analysis; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Tretinoin; Vincristine

To evaluate a less intensive chemotherapeutic regimen specifically designed for patients with Down syndrome (DS) and acute myeloid leukemia (AML), and to determine the prognostic factors for event-free survival.. Seventy-two patients with AML-DS were treated with remission induction chemotherapy consisting of pirarubicin (25 mg/m2/d for 2 days), cytarabine (100 mg/m2/d for 7 days), and etoposide (150 mg/m2/d for 3 days). Patients received four courses of intensification therapy of the same regimen. Prophylaxis for CNS leukemia was not included.. All but two patients were younger than 4 years, and 67 of the 72 patients (93%) were diagnosed as acute megakaryoblastic leukemia (AMKL). Seventy of the 72 patients (97.2%) achieved a complete remission (CR), and the estimated 4-year event-free survival (EFS) rate was 83% +/- 9%. Nine patients relapsed, and one died as a result of pneumonia during CR. Multivariate analysis revealed that the presence of monosomy 7 was a greater risk factor of adverse outcome (odds ratio = 5.67; P = .027).. A less intensive chemotherapeutic regimen produces excellent outcomes in standard-risk AML-DS patient. Risk-oriented therapy should be considered for future trials in AML-DS.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Disease-Free Survival; Down Syndrome; Doxorubicin; Etoposide; Female; Humans; Infant; Leukemia, Megakaryoblastic, Acute; Male; Prospective Studies; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Disease-Free Survival; Down Syndrome; Doxorubicin; Female; Humans; Infant; Infant, Newborn; Japan; Leukemia, Myeloid, Acute; Male; Mitoxantrone; Survival Rate; Vincristine