Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Pediatric Treatment Editorial Board uses a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
Prognostic Factors in Recurrent ALL
The prognosis for a child with acute lymphoblastic leukemia (ALL) whose disease recurs depends on the time from diagnosis to relapse and site of relapse, as well as cytogenetics and immunophenotype.[1,2,3,4,5,6,7,8,9,10,11,12,13]; [Level of evidence: 3iiDi] 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 are 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.
Patients who have combined marrow/extramedullary relapses fare better than those with isolated marrow relapses.[5,13] The Berlin-Frankfurt-Muenster (BFM) group has also reported that high peripheral blast counts at the time of relapse (>10,000/?L) were associated with inferior outcomes in patients with late marrow relapses. 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. Age older than 10 years has also been reported as an independent predictor of poor outcome.
Immunophenotype is an important prognostic factor at relapse. Patients with T-cell ALL who experience a marrow relapse (isolated or combined) at any point during treatment or posttreatment have a very poor prognosis.
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 remission (CR2).[Level of evidence: 2Di] Several studies have demonstrated that minimal residual disease (MRD) levels after the achievement of CR2 are of prognostic significance in relapsed ALL.[17,18,19,20]; [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.