CNS involvement at diagnosis

The presence or absence of CNS leukemia at diagnosis has prognostic significance in both patients with B-ALL and T-ALL. Patients who have a nontraumatic diagnostic lumbar puncture may be placed into one of three categories according to the number of WBC/µL and the presence or absence of blasts on cytospin as follows:

Children with B-ALL or T-ALL who present with CNS3 disease at diagnosis are at a higher risk of treatment failure (both within the CNS and systemically) than patients who are classified as CNS1 or CNS2.[47-49] The prognostic implication of CNS2 status at diagnosis may differ between patients with B-ALL and T-ALL. Some studies have reported increased risk of CNS relapse and/or inferior EFS in patients with B-ALL and CNS2 status at diagnosis, compared with patients with CNS1 status,[50,51] while other studies have not.[47,52-54] In an analysis of 2,164 patients with T-ALL treated in two consecutive COG trials, there was no difference in EFS, DFS, or cumulative incidence of relapse between patients with CNS1 and CNS2 status.[49]

A traumatic lumbar puncture (≥10 erythrocytes/µL) that includes blasts at diagnosis has also been associated with increased risk of CNS relapse and overall poorer outcome in some studies,[47,53,55] but not others.[51,52,56] Patients with CNS2, CNS3, or traumatic lumbar puncture have a higher frequency of unfavorable prognostic characteristics than those with CNS1, including significantly higher WBC counts at diagnosis, older age at diagnosis, an increased frequency of the T-ALL phenotype, and KMT2A gene rearrangements.[47,52,53]

Most clinical trial groups have approached the treatment of CNS2 and traumatic lumbar puncture patients by using more intensive therapy, primarily additional doses of intrathecal therapy during induction.[47,57,58]; [52][Level of evidence B4]; [59][Level of evidence A1]

To determine whether a patient with a traumatic lumbar puncture (with blasts) should be treated as CNS3, the COG uses an algorithm relating the WBC and red blood cell counts in the spinal fluid and the peripheral blood.[60]