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Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of Recurrent Childhood ALL

Prognostic Factors in Recurrent Childhood ALL

The prognosis for a child with acute lymphoblastic leukemia (ALL) whose disease recurs depends on the following factors: [1,2,3,4,5,6,7,8,9,10,11,12,13]; [14][Level of evidence: 3iiDi]

  • Patient characteristics (e.g., age and peripheral blast count at time of relapse).
  • Time from diagnosis to relapse.
  • Site of relapse.
  • Cytogenetics.
  • Immunophenotype.

Patient characteristics

Age 10 years and older at diagnosis has been reported as an independent predictor of poor outcome.[13]

The Berlin-Frankfurt-Münster group has also reported that high peripheral blast counts (>10,000/μL) at the time of relapse were associated with inferior outcomes in patients with late marrow relapses.[10]

Time from diagnosis to relapse

For patients with relapsed B-precursor ALL, early relapses fare worse than later relapses, and marrow relapses fare worse than isolated extramedullary relapses. For instance, survival rates after marrow relapse range from less than 20% for patients with marrow relapses occurring within 18 months from diagnosis to 40% to 50% for those whose relapses occur more than 36 months from diagnosis.[5,13]

For patients with isolated central nervous system (CNS) relapses, the overall survival (OS) rates for early relapse (<18 months from diagnosis) are 40% to 50% and 75% to 80% for those with late relapses (>18 months from diagnosis).[13,15] No evidence exists that early detection of relapse by frequent surveillance (complete blood counts or bone marrow tests) in off-therapy patients improves outcome.[16]

Site of relapse

Patients who have combined marrow/extramedullary relapses fare better than those who have isolated marrow relapses.[5,13]

Patients with marrow relapses who have persistent morphologic disease at the end of the first month of reinduction therapy have an extremely poor prognosis, even if they subsequently achieve a second complete remission (CR2).[17][Level of evidence: 2Di]; [18][Level of evidence: 3iiiA]


TP53 alterations (mutations and/or copy number alterations) are observed in approximately 11% of patients with ALL at first relapse and have been associated with inferior reinduction failure rate (38.5% TP53 alteration vs. 12.5% TP53 wild-type) and event-free survival (EFS) (9% TP53 alteration vs. 49% TP53 wild-type), of which approximately one-half are newly observed at time of relapse.[19]


Immunophenotype is an important prognostic factor at relapse. Patients with T-cell ALL who experience a marrow relapse (isolated or combined) at any time during treatment or posttreatment have a very poor prognosis.[5]

Other factors

Other prognostic factors for recurrent ALL include the following:

  1. The Children's Oncology Group (COG) reported that risk group classification at the time of initial diagnosis was prognostically significant after relapse; patients who met National Cancer Institute (NCI) standard-risk criteria at initial diagnosis fared better after relapse than did NCI high-risk patients.[13]
  2. Several studies have demonstrated that minimal residual disease (MRD) levels after the achievement of CR2 are of prognostic significance in relapsed ALL.[17,20,21,22]; [23][Level of evidence: 3iiiDi] High levels of MRD at the end of reinduction and at later time points have been correlated with an extremely high risk of subsequent relapse.

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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