Postinduction Treatment for Childhood ALL
In high-risk patients, a number of different approaches have been used with comparable efficacy.[7,19]; [Level of evidence: 2Di] Treatment for high-risk patients generally is more intensive than that for standard-risk patients and typically includes higher cumulative doses of multiple agents, including anthracyclines and/or alkylating agents. Higher doses of these agents increase the risk of both short- and long-term toxicities, and many clinical trials have focused on reducing the side effects of these intensified regimens.
Evidence (intensification for high-risk ALL):
- In a DFCI ALL Consortium trial, children with high-risk ALL were randomly assigned to receive doxorubicin alone (30 mg/m2 /dose to a cumulative dose of 300 mg/m2) or the same dose of doxorubicin with dexrazoxane during the induction and intensification phases of multiagent chemotherapy. [20,21]
- The use of the cardioprotectant dexrazoxane prior to doxorubicin resulted in better left ventricular fractional shortening and improved end-systolic dimension Z-scores without any adverse effect on EFS or increase in second malignancy risk compared with the use of doxorubicin alone 5 years posttreatment.
- A greater long-term protective effect was noted in girls compared with boys.
- The former CCG developed an augmented BFM treatment regimen featuring repeated courses of escalating-dose IV methotrexate (without leucovorin rescue) given with vincristine and L-asparaginase during interim maintenance and additional vincristine/L-asparaginase pulses during initial consolidation and delayed intensification. Augmented therapy also included a second interim maintenance and delayed intensification phase.
- In the CCG-1882 trial, National Cancer Institute (NCI) high-risk patients with slow early response (M3 marrow on day 7 of induction) were randomly assigned to receive either standard- or augmented-BFM therapy.
- The augmented therapy regimen in the CCG-1882 trial produced a significantly better EFS than did standard CCG modified BFM therapy.
- In an Italian study, investigators showed that two applications of delayed intensification therapy (protocol II) significantly improved outcome for patients with a poor response to a prednisone prophase.
- The CCG-1961 study used a 2 × 2 factorial design to compare both standard- versus augmented-intensity therapies and therapies of standard duration (one interim maintenance and delayed intensification phase) versus increased duration (two interim maintenance and delayed intensification phases) among rapid early responders.
- Augmented therapy was associated with an improvement in EFS; there was no benefit associated with the administration of the second interim maintenance and delayed intensification phases.[Level of evidence: 1iiA]
- There was a significant incidence of osteonecrosis of bone in teenaged patients who received the augmented-BFM regimen.