Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Postinduction Treatment for Specific ALL Subgroups
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) ALL Consortium protocols was 75% compared with 84% for children with precursor B-cell ALL.
Protocols of the former Pediatric Oncology Group (POG) treated children with T-cell ALL differently 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. The multiagent chemotherapy regimen for this protocol was based on the DFCI-87001 regimen.
Results of the POG-9404 study indicated that the addition of high-dose methotrexate to the DFCI-based chemotherapy regimen resulted in significantly improved EFS in patients with T-cell ALL (10-year EFS, 78% for those randomly assigned to high-dose methotrexate versus 68% for those randomly assigned to therapy without high-dose methotrexate, P = .05).
High-dose methotrexate was associated with a lower incidence of relapses involving the central nervous system (CNS). This POG study was the first clinical trial to provide evidence that high-dose methotrexate can improve outcome for children with T-cell ALL. High-dose asparaginase, doxorubicin, and prophylactic cranial irradiation were also important components of this regimen.[1,4]
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 [WBC] count) 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-Münster (BFM) regimen with a single delayed intensification course produced the best results for patients with morphologic rapid response to initial induction therapy (estimated 5-year EFS 83%). Almost 60% of events in this group, however, were isolated CNS relapses.
Overall results from POG-9404 and CCG-1961 were similar, although POG-9404 used cranial radiation for every patient, while CCG-1961 used cranial radiation only for patients with slow morphologic response.[6,4]
Among children with NCI standard-risk T-cell ALL, the EFS for those treated on CCG-1952 and COG-1991 studies was inferior to the EFS for those treated on the POG-9404 study.
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. Pilot studies from the COG have demonstrated the feasibility of incorporating nelarabine (a nucleoside analog with demonstrated activity in patients with relapsed and refractory T-cell lymphoblastic disease) [8,9] in the context of a BFM regimen for patients with newly diagnosed T-cell ALL. The pilot study showed a 5-year EFS rate of 73% for all patients receiving nelarabine and 69% for those patients with a slow early response.
The role of prophylactic cranial radiation in the treatment of T-cell ALL is controversial. Some groups, such as St. Jude Children's Research Hospital (SJCRH) and the Dutch Childhood Oncology Group (DCOG), do not use cranial radiation in first-line treatment of ALL, while other groups, such as DFCI, COG, and BFM, use radiation for the majority of patients with T-cell ALL.