High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation

Abstract

Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were identified among 1041 consecutively enrolled patients as high risk (HR) based on clinical features or high MRD. The HR cohort received the AIEOP-BFM (Associazione Italiana di Ematologia ed Oncologia Pediatrica (Italy)-Berlin-Frankfurt-Münster ALL Study Group) 2000 ALL Protocol I, then three novel HR chemotherapy blocks, followed by allogeneic transplant or chemotherapy. Of the 111 HR patients, 91 began HR treatment blocks, while 79 completed the protocol. There were 3 remission failures, 12 relapses, 7 toxic deaths in remission and 10 patients who changed protocol due to toxicity or clinician/parent preference. For the 111 HR patients, 5-year event-free survival (EFS) was 66.8% (±5.5) and overall survival (OS) was 75.6% (±4.3). The 30 patients treated as HR solely on the basis of high MRD levels had a 5-year EFS of 63% (±9.4%). All patients experienced grade 3 or 4 toxicities during HR block therapy. Although cure rates were improved compared with previous studies, high treatment toxicity suggested that novel agents are needed to achieve further improvement.

Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: an international collaborative study

“…However, the increased treatment-related toxicity associated with high-risk regimens may limit the final clinical benefit. 42 Alternatively, patients may be offered an extension of maintenance therapy, especially since many of the relapses were shown to occur within two years after completion of contemporary chemotherapy regimens in the Dutch Childhood Oncology Group (DCOG) ALL-10 protocol. 4 For this reason, the DCOG decided to extend the maintenance therapy for IKZF1-deleted cases stratified as medium-risk with an extra year of treatment in the current DCOG ALL-11 protocol.…”

Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study

“…25 A study contemporary to AIEOP-BFM ALL 2000, which used the same stratification criteria, has been published recently. 26 In that study, however, different postinduction/consolidation HR chemotherapy blocks were used and indications for MUD HSCT were broader, resulting in about 50% of HR patients undergoing HSCT (compared with 25% of patients in our study). Crucial for these patients might be the identification of an effective consolidation disease control with MRD level reduction before HSCT.…”

A pre-clinical model of resistance to induction therapy in pediatric acute lymphoblastic leukemia

“…9 Specifically, although T-cell ALL (T-ALL) represents only 10–15% of all pediatric ALL, it constitutes up to 48% of high-risk patients. 9,10 Moreover, patients who relapse early in the bone marrow (BM; within 18–24 months), as is the case for the majority of T-ALL relapses, experience a dismal outcome. 9,11 Relapsed ALL is thus a leading cause of cancer-related deaths in children.…”