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Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Postinduction Treatment for Childhood ALL

Standard Postinduction Treatment Options for Childhood ALL

Standard treatment options for consolidation/intensification and maintenance therapy include the following:

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  1. Chemotherapy.

Central nervous system (CNS)-directed therapy is provided during premaintenance chemotherapy by all groups. Some protocols (Children's Oncology Group [COG], St. Jude Children's Research Hospital [SJCRH], and Dana-Farber Cancer Institute [DFCI]) provide ongoing intrathecal chemotherapy during maintenance, while others (Berlin-Frankfurt-Münster [BFM]) do not. (Refer to the CNS-directed Therapy for Childhood Acute Lymphoblastic Leukemia section of this summary for specific information about CNS therapy to prevent CNS relapse in children with acute lymphoblastic leukemia [ALL] who are receiving postinduction therapy.)

Consolidation/intensification therapy

Once complete remission (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]

  1. An initial consolidation (sometimes referred to as "Induction IB") immediately after the initial induction phase. This phase includes cyclophosphamide, low-dose cytarabine, and a thiopurine (mercaptopurine or thioguanine).
  2. An interim maintenance phase, which includes multiple doses of either intermediate-dose or high-dose methotrexate (1-5 g/m2) with leucovorin rescue or escalating doses of methotrexate (starting dose 100 mg/m2) without leucovorin rescue.
  3. Reinduction (or delayed intensification), which typically includes the same agents used during the induction and initial consolidation phases.
  4. Maintenance, typically consisting of mercaptopurine, low-dose methotrexate, and sometimes, vincristine/steroid pulses.

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 interim maintenance and/or reinduction phases and administering additional agents during some phases (e.g., vincristine and L-asparaginase added to 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:

  • Pediatric Oncology Group (POG): Protocols conducted by the former POG included intensification with high-dose antimetabolite therapy (e.g., multiple doses of intermediate-dose or high-dose methotrexate with leucovorin rescue), but no reinduction/delayed intensification phase.[2]
  • DFCI: The DFCI ALL Consortium protocols include 20 to 30 weeks of L-asparaginase beginning at week 7 of therapy, given in conjunction with maintenance regimen (vincristine/dexamethasone pulses, low-dose methotrexate, nightly mercaptopurine).[3] These protocols also do not include a delayed intensification phase, but high-risk patients do receive additional doses of doxorubicin (instead of methotrexate) during intensification.
  • SJCRH: SJCRH follows a BFM-backbone but intensifies maintenance for some patients using rotating drug pairs.[4]
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