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

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Evidence (maintenance therapy):

  1. In a meta-analysis of randomized trials comparing thiopurines, 6-thioguanine (6-TG) did not improve the overall EFS, although particular subgroups may benefit from its use.[34] The use of continuous 6-TG instead of 6-mercaptopurine (6-MP) during the maintenance phase is associated with an increased risk of hepatic complications, including veno-occlusive disease and portal hypertension.[35,36,37,38,39] Because of the increased toxicity of 6-TG, 6-MP remains the standard drug of choice.

Other approaches to maintenance therapy include the following:

  • The Brazilian Childhood Cooperative group reported a variation in approach to maintenance therapy.[40][Level of evidence: 1A] In a cohort comprising mostly lower-risk children, standard oral versus intermittent IV dosing of methotrexate (weekly vs. every 3 weeks) and 6-MP (daily vs. 10 days on and 11 days off) were compared. Intermittently dosed medications were given at higher doses overall than were standard dosed medications. In addition, boys on the protocol received only 2 years of therapy.
    • A significant survival advantage was noted in boys receiving intermittent dosing, while the outcome in girls was equivalent. Because of differences in risk classification and OS rates slightly lower than reported by other groups, it is difficult to know whether the benefits this approach offered to boys would apply in other settings.
  • Treatment protocols from the SJCRH previously included an intensified maintenance phase that consisted of rotating pairs of agents, including cyclophosphamide and epipodophyllotoxins, along with more standard maintenance agents.[6]
    • A randomized study from Argentina demonstrated no benefit from this intensified approach compared with a more standard maintenance regimen for patients who receive induction and consolidation phases based on a BFM backbone.[41]
    • The intensified maintenance with rotating pairs of agents has also been associated with more episodes of febrile neutropenia [41] and a higher risk of secondary acute myelogenous leukemia,[42] and is no longer used in upfront therapy.[41]

Vincristine/corticosteroid pulses

Pulses of vincristine and corticosteroid are often added to the standard maintenance backbone, although the benefit of these pulses within the context of intensive, multiagent regimens remains controversial.

Evidence (vincristine/corticosteroid pulses):

  1. A CCG randomized trial conducted in the 1980s demonstrated improved outcome in patients receiving monthly vincristine/prednisone pulses.[43] A meta-analysis combining data from six clinical trials from the same treatment era showed an EFS advantage for vincristine/prednisone pulses.[44,45]
  2. A systematic review of the impact of vincristine plus steroid pulses from more recent clinical trials raised the question of whether such pulses are of value in current ALL treatment, which includes more intensive early therapy.[45]
  3. In a multicenter randomized trial in children with intermediate-risk ALL being treated on a BFM regimen, there was no benefit associated with the addition of six pulses of vincristine/dexamethasone during the continuation phase, although the pulses were administered less frequently than in other trials in which a benefit had been demonstrated.[46]
  4. A small multicenter trial of average-risk patients demonstrated superior EFS in patients receiving vincristine plus corticosteroid pulses. In this study, there was no difference in outcome based on type of steroid (prednisone vs. dexamethasone).[47][Level of evidence: 1iiA]
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WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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