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

Approximately 3% of patients have detectable central nervous system (CNS) involvement by conventional criteria at diagnosis (cerebrospinal fluid [CSF] specimen with ≥5 white blood cell [WBC]/μL with lymphoblasts and/or the presence of cranial nerve palsies). However, unless specific therapy is directed toward the CNS, the majority of children will eventually develop overt CNS leukemia. Therefore, all children with acute lymphoblastic leukemia (ALL) should receive systemic combination chemotherapy together with some form of CNS prophylaxis.

Because the CNS is a sanctuary site (i.e., an anatomic space that is poorly penetrated by many of the systemically administered chemotherapy agents typically used to treat ALL), specific CNS-directed therapies must be instituted early in treatment to eliminate clinically evident CNS disease at diagnosis and to prevent CNS relapse in all patients. Historically, survival rates for children with ALL improved dramatically after CNS-directed therapies were added to treatment regimens.

Standard treatment options for CNS-directed therapy include the following:

  1. Intrathecal chemotherapy.
  2. CNS-directed systemic chemotherapy.
  3. Cranial radiation.

All of these treatment modalities have a role in the treatment and prevention of CNS leukemia. The combination of intrathecal chemotherapy plus CNS-directed systemic chemotherapy is standard; cranial radiation is reserved for selective situations.[1]

The type of CNS-therapy that is used is based on a patient's risk of CNS-relapse, with higher-risk patients receiving more intensive treatments. Data suggest that the following groups of patients are at increased risk of CNS relapse:

  • Patients with five or more WBC/µL and blasts in the CSF (CNS3), obtained at diagnosis.
  • Patients with blasts in the CSF but fewer than 5 WBC/µL (CNS2) may be at increased risk of CNS relapse,[2] although this risk appears to be nearly fully abrogated if they receive more doses of intrathecal chemotherapy, especially during the induction phase.[3]
  • Patients with T-cell ALL, especially those with high presenting peripheral blood leukocyte counts.
  • Patients who have a traumatic lumbar puncture showing blasts at the time of diagnosis may have an increased risk of CNS relapse. These patients receive more intensive CNS-directed therapy on some treatment protocols.[3,4]

CNS-directed treatment regimens for newly diagnosed childhood ALL are presented in Table 2:

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