Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group

Abstract

CCG-2961 incorporated 3 new agents, idarubicin, fludarabine and interleukin-2, into a phase 3 AML trial using intensivetiming remission induction/consolidation and related donor marrow transplantation or high-dose cytarabine intensification. Among 901 patients under age 21 years, 5-year survival was 52%, and event-free survival was 42%. Survival improved from 44% between 1996 and 1998 to 58% between 2000 and 2002 (P ‫؍‬ .005), and treatment-related mortality declined from 19% to 12% (P ‫؍‬ .025). Partial replacement of daunomycin with idarubicin in the 5-drug induction combination achieved a remission rate of 88%, similar to historical controls. Postremission survival was 56% in patients randomized to either 5-drug reinduction or fludarabine/ cytarabine/idarubicin. For patients with or without a related donor, respective 5-year disease-free survival was 61% and 50% (P ‫؍‬ .021); respective survival was 68% and 62% (P ‫؍‬ .425). Donor availability conferred no benefit on those with inv(16) or t(8;21) cytogenetics. After cytarabine intensification, patients randomized to interleukin-2 or none experienced similar outcomes. Factors predictive of inferior survival were age more than 16 years, non-white ethnicity, absence of related donor, obesity, white blood cell count more than 100 000 ؋ 10 9 /L, ؊7/7q؊, ؊5/5q؊, and/or complex karyo- IntroductionIn the past 2 decades, cooperative group trials in pediatric acute myeloid leukemia (AML) have increased overall 5-year survival (OS) from approximately 30% to more than 50%. [1][2][3][4][5][6] Intensification of dose, increased number of days of conventional induction chemotherapy, matched related donor bone marrow transplantation (MRD BMT) in first remission, and risk stratification of treatment have all contributed to this progress. Risk stratification typically classifies as favorable those patients with Down syndrome or with AML characterized by t(8;21), t(15;17), or inv(16) cytogenetic abnormalities and rapid early response to induction therapy. Unfavorable features include high white blood cell count, Ϫ7/7qϪ, Ϫ5/5qϪ, or complex cytogenetics, and slow or no early response. [7][8][9][10][11] The emerging consensus is that patients with favorable AML do not benefit from MRD BMT in first remission. 2,12 Since 1986, the Children's Cancer Group (CCG) explored a strategy to treat newly diagnosed AML using intensively timed 5-drug combination chemotherapy consisting of dexamethasone, cytarabine, thioguanine, etoposide, and rubidomycin (daunomycin) (DCTER) for remission induction followed by BMT for patients with matched related donors or intensively timed high-dose cytarabine/asparaginase (HidAC) after remission therapy for patients without related donors. [13][14][15] Intensive timing involves administration of the second cycle of 5 drugs on day 10 regardless of remission status or blood counts. In the previous phase 3 trial, CCG-2891, intensively timed DCTER achieved an event-free survival (EFS) of 41% and OS of 49% at 5 years.This manuscript describes the successor phase...

A comparison of the outcomes of children with acute myelogenous leukemia in either first or second complete remission (CR1 vs CR2) following allogeneic hematopoietic stem cell transplantation at a single transplant center

“…18 Furthermore, a recently published study conducted by the same group, CCG 2961, again demonstrated significantly better diseasefree survival for children with AML receiving related donor HSCT in CR1, vs chemotherapy only (60 vs 50%; P ¼ 0.02). 19 In our study, the 3-year TRM was 11% in our CR1 HSCT recipients. This relatively low TRM could be explained by the fact that most of our CR1 patients received matched related donor cells and had better organ function and less infectious complications compared with CR2 patients.…”

Costo efectividad de los tratamientos de consolidación para la leucemia mieloide aguda en pacientes pediátricos, estratificados en riesgo alto, dentro del sistema de salud colombiano

“…En cuanto a los resultados clínicos, las conclusiones de esta evaluación serían válidas incluso con un esquema diferente al BFM, pues la razón por la que no hay consenso sobre cuál de los protocolos de quimioterapia debe emplearse es, precisamente, que en los ensayos clínicos aleatorios no se reporta superioridad significativa de ninguno frente a los demás en términos de la supervivencia libre de enfermedad o en la global (25,28,29). El principal elemento diferenciador de los esquemas de quimioterapia es su costo, factor que quedó cubierto con el análisis de sensibilidad, lo que permitió concluir que la razón de costoefectividad del trasplante no era sensible al costo de la quimioterapia, por lo que los resultados se mantendrían para cualquiera de los esquemas de quimioterapia actualmente empleados en la consolidación de la leucemia mieloide aguda.…”

Low dose interleukin‐2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission

“…Moreover, recently presented results of CALGB trial 19808 in which patients under age 60 with untreated AML were randomized to receive IL-2 or observation after intensive post-remission therapy suggested a trend for a threeyear disease-free (56% 'v' 45%, P 5 0.11) and overall (68% 'v' 61%, P 5 0.09) survival benefit for those randomized to immunotherapy [49]. Although these studies suggest that post-remission immunotherapy could have a role in younger AML patients, randomized trials of IL-2 in the post-autograft setting in adults [50] and post-chemotherapy setting in children [51] each failed to demonstrate superiority of the experimental arm.…”