Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Postinduction Treatment for Childhood ALL
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):
- A CCG randomized trial conducted in the 1980s demonstrated improved outcome in patients receiving monthly vincristine/prednisone pulses. A meta-analysis combining data from six clinical trials from the same treatment era showed an EFS advantage for vincristine/prednisone pulses.[48,49]
- 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.
- 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.
- 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).[Level of evidence: 1iiA]
For regimens that include vincristine/steroid pulses, a number of studies have addressed which steroid (dexamethasone or prednisone) should be used. From these studies, it appears that dexamethasone is associated with superior EFS, but also may lead to a greater frequency of steroid-associated complications, including bone toxicity and infections, especially in older children and adolescents. Dexamethasone has not been associated with an increased frequency of these complications in younger patients.[13,52,53,54,55]
Evidence (dexamethasone vs. prednisone):
- In a CCG study, dexamethasone was compared with prednisone for children aged 1 to younger than 10 years with lower-risk ALL.[13,52]
- Patients randomly assigned to receive dexamethasone had significantly fewer CNS relapses and a significantly better EFS rate.
- In a Medical Research Council trial, dexamethasone was compared with prednisolone during induction and maintenance therapies in both standard-risk and high-risk patients.
- The EFS and incidence of both CNS and non-CNS relapses improved with the use of dexamethasone.
- Dexamethasone was associated with an increased risk of steroid-associated toxicities, including behavioral problems, myopathy, and osteopenia.
- In a DFCI ALL Consortium trial, patients were randomly assigned to receive either dexamethasone or prednisone during all postinduction treatment phases.
- Dexamethasone was associated with a superior EFS, but also with a higher frequency of infections (primarily episodes of bacteremia) and, in patients aged 10 years or older, an increased incidence of osteonecrosis and fracture.