Induction failure in acute lymphoblastic leukemia of childhood

Abstract

BACKGROUND Although it is widely accepted that failure to achieve complete remission (CR) portends a poor prognosis in childhood acute lymphoblastic leukemia (ALL), there is variability in the precise definition of induction failure and, to the authors' knowledge, few published data exist regarding the outcome of patients who are slow to achieve CR. METHODS Between 1987–1995, 774 children with ALL were treated on 2 consecutive protocols and were evaluable to assess the time required to attain CR. The authors compared presenting characteristics and outcomes of patients based on their remission status after 1 month of induction chemotherapy: CR (n = 656), protracted hypoplasia (low peripheral blood counts and/or hypocellular marrow) (n = 95), and persistent leukemia (M2 or M3 bone marrow and/or evidence of extramedullary leukemia) (n = 23). The median follow‐up was 5.2 years. RESULTS Presenting features that predicted persistent leukemia included a leukocyte count > 100,000/mm3 and T‐cell phenotype. Approximately 91% of patients with persistent leukemia and 100% with protracted hypoplasia eventually achieved CR. The 5‐year event free survival (EFS) (95% confidence intervals [95% CI] in parentheses) for patients with persistent leukemia after 1 month was 16% (95% CI, 0%, 31%), which was significantly worse (P < 0.001) than that for those who achieved CR within 1 month (5‐year EFS, 82%; 95% CI, 79%, 86%) and that for those with protracted hypoplasia (5‐year EFS, 79%; 95% CI, 70%, 87%). For patients with persistent leukemia, there was no significant difference in survival based on bone marrow status (M2 or M3) after 1 month or on the number of induction cycles received before achieving CR. CONCLUSIONS Patients with persistent leukemia at the end of 1 month of therapy have a dismal prognosis, regardless of when they subsequently achieve CR. More intensive and/or novel therapies should be considered for this subset of patients. Cancer 1999;85:1395–404. © 1999 American Cancer Society.

Outcome of Childhood Acute Lymphoblastic Leukaemia after Induction Therapy --- Three-Year Experience in a Tertiary Care Hospital in Bangladesh

“…According to a study by Silverman et al 16 , failure of induction therapy is a relatively rare event occurring in fewer than 5% of children with ALL treated with current r egimens, but in our study the failure of induction therapy was 4% which is similar.…”

Myths and Lessons from the Adult/Pediatric Interface in Acute Lymphoblastic Leukemia

“…Although the time to attain a complete remission was not of prognostic importance in at least one adult trial, 12 we found that in childhood ALL, the time to enter a complete remission had significant implications, and the difference between a complete remission in 1 month or 2 months was a matter of life or death for the majority of slow responders. 15 …”

Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981–1995)

“…Details of therapy have been previously published, 3,4,9,10 and are summarized in Table 2. In general, each protocol consisted of five phases of therapy: investigational window, remission induction, CNS treatment, intensification, and continuation.…”

“…We have previously reported the poor prognosis of patients with persistent leukemia at the end of 1 month of therapy and have altered our definition of induction failure to include such patients. 10 Others have reported on the prognostic significance of more sensitive early response measures, including marrow response after 7-14 days of multi-agent remission induction, 39 peripheral blast counts after 1 week of corticosteroids, 26 and minimal residual disease levels during and at the completion of remission induction therapy. 40,41 We are currently investigating early response and minimal residual disease measures within the context of DFCI ALL consortium protocols.…”