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Therapeutic trial for infant acute lymphoblastic leukemia: the Pediatric Oncology Group experience (POG 8493)
L S Frankel1, J Ochs, J J Shuster
1Scott and White Memorial Hospital, Temple, Texas 76508, U.S.A.
Insights
A new therapy for infant acute lymphocytic leukemia (ALL) showed a modest improvement in event-free survival. Further research is needed for better treatment outcomes in this vulnerable population.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- Infants under one year with acute lymphocytic leukemia (ALL) have a poor prognosis despite advances in treatment for older children.
- Infant ALL presents unique challenges, including higher rates of central nervous system (CNS) leukemia, elevated white blood cell counts, and specific lymphoblast characteristics.
Purpose of the Study:
- To evaluate a novel therapeutic approach specifically designed for infants diagnosed with acute lymphocytic leukemia (ALL).
- To assess the efficacy and outcomes of a tailored chemotherapy regimen in a cohort of infant ALL patients.
Main Methods:
- Eighty-two infants under one year with ALL were enrolled in Pediatric Oncology Group (POG) protocol 8493.
- Treatment involved intensive chemotherapy, including cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP), with consolidation and continuation phases, and intrathecal therapy, avoiding radiotherapy.
- Key patient characteristics at diagnosis, such as CNS leukemia, white blood cell count, immunophenotype, and cytogenetic abnormalities (e.g., 11q23 translocation), were analyzed.
Main Results:
- A complete remission rate of 93% (76 out of 82 infants) was achieved.
- The actuarial event-free survival at 4 years was 28%, with a relapse rate of 66% (50 out of 76 infants in remission).
- Infants diagnosed at older ages (>274 days) demonstrated a better outcome compared to younger infants (<274 days).
Conclusions:
- The implemented therapy resulted in a modest improvement in outcomes for infant ALL compared to historical data from POG trials.
- Despite improvements, current treatment strategies remain insufficient, highlighting the urgent need for more effective therapies for infants with ALL.
Purpose:
Despite improved event-free survival of older children with acute lymphocytic leukemia (ALL), infants <1 year of age continue to have a very poor prognosis. A new therapy designed specifically for infants with ALL was initiated.
Patients And Methods:
From 1984 until 1990, 82 eligible infants <1 year of age were entered on a Pediatric Oncology Group (POG) protocol 8493 for infant ALL. Compared to older patients, infants at diagnosis had more overt CNS leukemia (26%), higher initial WBC count (56% >50,000/microl), and a higher likelihood of CD-10 (CALLA) negative lymphoblasts (55%). A translocation involving chromosome 11 at band q23 was detected in 27 of 64 cytogenetically informative cases. Treatment was based upon two institutional pilot studies utilizing chemotherapy doses based upon body weight. Important components included remission induction with cyclophosphamide (Ctx), vincristine (Vcr), cytosine arabinoside (Ara-C), and prednisone (Pred) (COAP); consolidation therapy with teniposide (VM-26) and Ara-C; and continuation therapy with alternating pulses of COAP with VM-26/Ara-C separated by a methotrexate (Mtx) and 6-mercaptopurine (6-MP) backbone plus CNS therapy consisting of standard triple intrathecal therapy (TIT) (Mtx/hydrocortisone/Ara-C), which avoided the use of radiotherapy in this population.
Results:
Seventy-six infants achieved a complete remission (93%). Fifty patients have relapsed: 35 isolated marrow relapses, five isolated CNS relapses, eight combined marrow and CNS relapses, and two other relapses. Actuarial event-free survival was 28% (SE = 5%) at 4 years. Infants >274 days (9 months) at diagnosis had a better outcome than those <274 days.
Conclusions:
This study represents a modest outcome improvement in comparison to previous experience with ALL for infants treated on POG trials. More effective therapy is still needed for infants with ALL.