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Treatment of Recurrent Childhood ALL


In some European clinical trial groups, orchiectomy of the involved testicle is performed instead of radiation. Biopsy of the other testicle is performed at the time of relapse to determine if additional local control (surgical removal or radiation) is to be performed. While there are limited clinical data concerning outcome without the use of radiation therapy or orchiectomy, the use of chemotherapy (e.g., high-dose methotrexate) that may be able to achieve antileukemic levels in the testes is being tested in clinical trials.

Evidence (chemotherapy and radiation therapy):

  1. Dutch investigators treated five boys with a late testicular relapse with high-dose methotrexate during induction (12 g/m2) and at regular intervals during the remainder of therapy (6 g/m2) without testicular radiation. All five boys were long-term survivors.[90]
  2. A study that looked at testicular biopsy at the end of frontline therapy failed to demonstrate a survival benefit for patients with early detection of occult disease.[91]
  3. In a small series of boys who had an isolated testicular relapse after a SCT for a prior systemic relapse of ALL, five of seven boys had extended EFS without a second SCT.[76][Level of evidence: 3iA]

Treatment Options Under Clinical Evaluation for Recurrent Childhood ALL

Treatment options under clinical evaluation include the following:

COG trials for ALL in first relapse

The COG has divided patients with first relapse into three risk categories as outlined in Table 4. Clinical trials in some risk categories are available.

Table 4. Children's Oncology Group ALL Relapse Risk Stratification for B-Precursor ALLa

Isolated CNS or Testicular RelapseBone Marrow or Combined Relapse
ALL = acute lymphoblastic leukemia; CNS = central nervous system.
a All relapsed T-cell ALL is considered high risk.
<18 months from diagnosisIntermediate riskHigh risk
18–36 months from diagnosisLow riskHigh risk
>36 months from diagnosisLow riskIntermediate risk
  1. COG-AALL0433 (Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell ALL [high-dose vincristine arm closed to accrual as of September 2010]): Patients with intermediate-risk relapse are eligible for this study. Patients will receive a chemotherapy regimen similar to POG studies, POG-9061 and POG-9412, which have been shown to be efficacious in the isolated relapse setting and well tolerated. Intensification of vincristine is being studied in a randomized fashion. For patients with a matched sibling, the choice of bone marrow transplant or chemotherapy is left to the discretion of the treating physician and/or family. The vincristine randomization has been closed for patients younger than 10 years at diagnosis due to increased toxicity in the higher-dose vincristine arm.
  2. COG-AALL07P1 (Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed ALL or Lymphoblastic Lymphoma): Patients with marrow relapse of T-cell ALL and early marrow relapse (<36 months) of B-precursor ALL are eligible for this study. This is a phase II pilot study to determine the feasibility and safety of adding bortezomib to intensive reinduction chemotherapy. Bortezomib is a proteasome inhibitor that has been shown to sensitize leukemic cells to apoptosis induced by chemotherapy.

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