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Risk-based Treatment Assignment

    continued...

    WBC count at diagnosis

    A WBC count of 50,000/µL is generally used as an operational cut point between better and poorer prognosis,[1] although the relationship between WBC count and prognosis is a continuous rather than a step function. Patients with B-precursor ALL and high WBC counts at diagnosis have an increased risk of treatment failure compared with patients with low initial WBC counts.

    The median WBC count at diagnosis is much higher for T-cell ALL (>50,000/µL) than for B-precursor ALL (<10,000/µL), and there is no consistent effect of WBC count at diagnosis on prognosis for T-cell ALL.[6,25,26,27,28,29,30,31] One factor that might explain the lack of prognostic effect for WBC count at diagnosis may be the very poor outcome observed for T-cell ALL with the early T-cell precursor phenotype, as patients with this subtype appear to have lower WBC count at diagnosis (median <50,000/µL) than do other T-cell ALL patients.[32]

    CNS involvement at diagnosis

    The presence or absence of CNS leukemia at diagnosis has prognostic significance. 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:

    • CNS1: Cerebrospinal fluid (CSF) that is cytospin negative for blasts regardless of WBC count.
    • CNS2: CSF with fewer than 5 WBC/µL and cytospin positive for blasts.
    • CNS3 (CNS disease): CSF with 5 or more WBC/µL and cytospin positive for blasts.

    Children with ALL who present with CNS disease (CNS3) 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.[33] The adverse prognostic significance associated with CNS2 status, if any, may be overcome by the application of more intensive intrathecal therapy, especially during the induction phase.[33,34]; [35][Level of evidence: 2A]

    A traumatic lumbar puncture (≥10 erythrocytes/µL) that includes blasts at diagnosis appears to be associated with increased risk of CNS relapse and indicates an overall poorer outcome.[33,36] 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.[37]

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