Postinduction Treatment for Childhood Acute Lymphoblastic Leukemia Subgroups
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
T-cell Acute Lymphoblastic Leukemia
Historically, patients with T-cell acute lymphoblastic leukemia (ALL) have had a worse prognosis than children with precursor B-cell ALL. With current treatment regimens, outcomes for children with T-cell ALL are now approaching those achieved for children with precursor B-cell ALL. For example, the 5-year event-free survival (EFS) for children with T-cell ALL treated on the Dana-Farber Cancer Institute (DFCI) Consortium ALL protocols was 75% compared with 84% for children with precursor B-cell ALL.[1]
Protocols of the former Pediatric Oncology Group (POG) treated children with T-cell ALL distinctly from children with B-lineage ALL. The POG-9404 protocol for patients with T-cell ALL was designed to evaluate the role of high-dose methotrexate and the role of the cardioprotectant dexrazoxane. The multiagent chemotherapy backbone for this protocol was based on the DFCI 87-001 regimen. Results of an interim analysis of the POG protocol led investigators to conclude that the addition of high-dose methotrexate to the DFCI-based chemotherapy regimen results in significantly improved EFS, due in large measure to a decrease in the rate of central nervous system (CNS) relapse.[2] This POG study was the first clinical trial to provide convincing evidence that high-dose methotrexate can improve outcome for children with T-cell ALL. High-dose asparaginase and doxorubicin were also important components of this regimen.[1,2]
Protocols of the former Children's Cancer Group (CCG) treated children with T-cell ALL on the same treatment regimens as children with precursor B-cell ALL, basing protocol and treatment assignment on the patients' clinical characteristics (e.g., age and white blood cell count [WBC]) and the disease response to initial therapy. Most children with T-cell ALL meet National Cancer Institute (NCI) high-risk criteria. Results from CCG-1961 showed that an augmented Berlin-Frankfurt-Munster (BFM) regimen with a single delayed intensification course produced the best results for patients with morphologic rapid response to initial induction therapy.[3] Almost 60% of events in this group, however, were isolated CNS relapses. Overall results from POG-9404 and CCG-1961 were similar, though POG-9404 used cranial radiation for every patient while CCG-1961 used cranial radiation only for patients with slow morphologic response.[4,2] Among children with NCI standard-risk T-cell ALL, the EFS for children treated on CCG-1952 and CCG-1991 studies was inferior to the EFS for children treated on the POG-9404 study.[5]
In the Children's Oncology Group (COG), children with T-cell ALL are no longer treated on the same protocols as children with precursor B-cell ALL. All patients with T-cell ALL are considered high risk regardless of age and WBC count. Pilot studies from this group have demonstrated the feasibility of incorporating nelarabine (a nucleoside analog with demonstrated activity in patients with relapsed and refractory T-cell lymphoblastic disease) [6,7] in the context of a BFM backbone for patients with newly diagnosed T-cell ALL; efficacy will be evaluated in the current trial.[8]
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