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Consolidation/intensification therapy
Source: Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 21, 2025 · Captured 2026-09-09.
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Once CR has been achieved, systemic treatment in conjunction with CNS-directed therapy follows. The intensity of the postinduction chemotherapy varies considerably depending on risk group assignment, but all patients receive some form of intensification after the achievement of CR and before beginning maintenance therapy.
The most commonly used intensification schema is the BFM backbone. This therapeutic backbone, first introduced by the BFM clinical trials group, includes the following:[1]
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An initial consolidation (referred to as induction IB) immediately after the initial induction phase. This phase includes intrathecal therapy, cyclophosphamide, low-dose cytarabine, and mercaptopurine.An interim maintenance phase, which includes intrathecal therapy and four doses of high-dose methotrexate (typically 5 g/m2) with leucovorin rescue.
Reinduction (or delayed intensification), which typically includes agents and schedules similar to those used during the induction and initial consolidation phases.
Maintenance, typically consisting of daily mercaptopurine (6-MP), weekly low-dose methotrexate, and sometimes, intermittent administration of vincristine and a corticosteroid, as well as continued intrathecal therapy.
This backbone has been adopted by many groups, including the COG. Variation of this backbone includes the following:
Intensification for higher-risk patients by including additional doses of vincristine and pegaspargase, as well as repeated interim maintenance and delayed intensification phases.[56,57]
The use of escalating doses of methotrexate (starting at a dose of 100 mg/m2) without leucovorin rescue instead of or in addition to high-dose methotrexate during interim maintenance phases.
Elimination or truncation of some of the phases for lower-risk patients to minimize acute and long-term toxicity.
Other clinical trial groups utilize a different therapeutic backbone during postinduction treatment phases, as follows:
DFCI: The DFCI ALL Consortium protocols include 30 weeks of pegaspargase therapy beginning at week 7 of therapy, given in conjunction with maintenance regimen (vincristine/dexamethasone pulses, weekly low-dose methotrexate, daily mercaptopurine).[3] These protocols also do not include a delayed intensification phase, but high-risk patients receive additional doses of doxorubicin (instead of low-dose methotrexate) during the first six months of postinduction therapy.
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NOPHO: The NOPHO also emphasizes the use of pegaspargase during consolidation and intensification. In the ALL2008 trial, all patients received five doses of pegaspargase given every other week after induction. Patients then received an additional ten doses at 2-week intervals or three doses at 6-week intervals. Both regimens produced equally excellent survival rates, with reduced toxicity in the three-dose regimen.[58]
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SJCRH: SJCRH follows a BFM backbone but augments the reinduction and maintenance phases for some patients by including intensified dosing of pegaspargase, frequent vincristine/corticosteroid pulses, and rotating drug pairs during maintenance (mercaptopurine/methotrexate, cyclophosphamide/cytarabine, dexamethasone/vincristine).[59]
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