Outcome for children with relapsed acute myeloid leukaemia following initial therapy in the Medical Research Council (MRC) AML 10 trial

Abstract

children with acute myeloid leukaemia (AML) were treated in the MRC AML 10 trial. Three risk groups were identified based on cytogenetics and response to treatment. One hundred and twenty-five children relapsed -103 in the bone marrow only, 12 in the bone marrow combined with other sites, and six had isolated extramedullary relapses (site was not known in four cases). Eighty-seven children received further combination chemotherapy, one all-trans retinoic acid for acute promyelocytic leukaemia, and one a matched unrelated donor allograft in relapse, and 61 achieved a second remission. One patient with no details on reinduction therapy also achieved second remission. Treatment in second remission varied -44 children received a BMT (22 autografts, 12 matched unrelated donor allografts, 10 family donor allografts), and 17 were treated with chemotherapy alone. The overall survival rate for all children (treated and untreated) was 24% at 3 years, with a disease-free survival of 44% for those achieving a second remission. Length of first remission was the most important factor affecting response rates -children with a first remission of less than 1 year fared poorly (second remission rate 36%, 3 year survival 11%), whereas those with longer first remissions had a higher response rate (second remission rate 75%, 3 year survival 49%, P Ͻ 0.0001).

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

“…Comparable observations have been reported by other groups: A 3-year OS rate of 24% after relapse was reported for treated and untreated pediatric patients from the MRC (Medical Research Council) AML10 trial. 6 The 5-year OS was 34% in 146 patients from the NOPHO (Nordic Society for Pediatric Hematology and Oncology) studies 9 and 33% in 106 patients treated within the French LAME (Leucémie Aiguë Myéloblas-tique Enfant) 89/91 protocol. 3 Data from the St Jude institutional trials showed a 5-year OS of 23% in 160 relapse patients.…”

“…Survival after recurrence was poor so far, ranging from 21 to 33%. [3][4][5][6] The duration of first complete remission (CR1) has been reported to be the major prognostic factor in relapse with a 5-year survival of only 10% in early relapse defined as relapse occurring within 12 months after diagnosis. 5 French-American-British (FAB) subtypes as well as cytogenetics and intensity of first-line treatment including allogeneic stem cell transplantation (allo-SCT) are well recognized as additional prognostic factors in the relapse setting.…”

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

“…[4][5][6] To improve the treatment outcome of these patients; high-dose chemo/ radiotherapy combined with allogeneic HSCT has been undertaken. Data from series of children transplanted for AML in CR2 are limited.…”

“…[1][2][3] Although CR2 may be achieved in the majority of these children with chemotherapy alone, long-term survival is limited to 8-33%. [4][5][6] While most would recommend allogeneic hematopoietic stem cell transplant (HSCT) as therapy for relapsed AML, the role of HSCT is less certain for children with AML in CR1. 1,2,7 With the excellent results of chemotherapy and the known risks and long-term side effects of HSCT, the decision to proceed with HSCT in CR1 remains controversial.…”

Impaired Long-Term Expansion and Self-Renewal Potential of Pediatric Acute Myeloid Leukemia–Initiating Cells By PTK787/ZK 222584

“…Despite an initial complete remission rate of 90%, 30% to 40% of the pediatric patients with AML relapse, and the 5-year overall survival rate is approximately 60% (1)(2)(3). Therefore, certain leukemic cells have to be resistant to current treatment strategies, and persist after therapy.…”