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The use of intermediate dose methotrexate in increased risk childhood acute lymphoblastic leukemia. A comparison of
Insights
Intermediate dose methotrexate (IDM) improved remission duration in high-risk acute lymphoblastic leukemia (ALL) patients but did not reduce central nervous system (CNS) relapse rates. Further research is needed to optimize CNS-directed therapies for these patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Pharmacology
Background:
- High-risk acute lymphoblastic leukemia (ALL) requires intensive therapy to improve outcomes.
- Central nervous system (CNS) prophylaxis is crucial to prevent relapse.
- Avoiding cranial irradiation is desirable to minimize long-term sequelae.
Purpose of the Study:
- To evaluate the efficacy of intermediate dose methotrexate (IDM) for CNS prophylaxis and systemic intensification in high-risk ALL patients.
- To assess the impact of IDM on remission duration and CNS relapse rates.
- To compare two treatment protocols with varying intensities of IDM and intrathecal chemotherapy.
Main Methods:
- A cohort of 41 high-risk ALL patients received treatment between 1974 and 1978.
- Two consecutive protocols were used: IDM X 3 (three courses of IDM) and IDM X 6 (six courses of IDM).
- Both protocols included intrathecal methotrexate (IT MTX), with IDM X 6 also receiving triple IT chemotherapy.
Main Results:
- The cumulative remission rate was significantly higher with IDM X 6 (57%) compared to IDM X 3 (30%) (P=0.046).
- The cumulative incidence of primary CNS relapse was 36.4% for IDM X 3 and 29.9% for IDM X 6 (P=0.44).
- More intensive therapy improved remission duration but did not significantly decrease CNS relapse incidence.
Conclusions:
- Intermediate dose methotrexate (IDM) and intensive intrathecal chemotherapy can improve remission duration in high-risk ALL.
- The current IDM regimens did not significantly reduce the incidence of primary CNS relapse.
- Further optimization of CNS-directed therapy is necessary for high-risk ALL patients to prevent relapse and long-term sequelae.
Abstract:
Between January 1974 and November 1978, 41 consecutive increased risk (age less than 24 months or less than 120 months, or leukocyte count greater than 30,000/mm3) patients with acute lymphoblastic leukemia (ALL) were entered on two consecutive treatment protocols which employed intermediate dose methotrexate (IDM). IDM was employed for central nervous system prophylaxis and systemic intensification. It was anticipated that the avoidance of prophylactic cranial irradiation would result in a lower incidence of longterm central nervous system sequelae. Twenty-two children and adolescents were entered on the first study (IDM X 3) which employed three courses of IDM (500 mg/m2) and six doses of intrathecal (IT) methotrexate (MTX). Nineteen children and adolescents were entered on the second study (IDM X 6) which employed six courses of IDM (3-500 mg/m2 and 3-1500 mg/m2), six doses of IT MTX and three additional doses of triple IT chemotherapy (MTX, cytosine arabinoside, and hydrocortisone or dexamethasone). The cumulative percentage of patients who remained in continuous complete remission was 30% for IDM X 3 and 57% for IDM X 6. This difference was statistically significant (P = 0.046; and BM + CNS, I-using IDM X 6. The cumulative incidence of primary CNS relapse was 36.4% for IDM X 3 and 29.9% for IDM X 6. This difference was not statistically significant (P = 0.44). The use of more intensive therapy with IDM and triple IT chemotherapy did improve the duration of continuous, complete remission but did not decrease the incidence of primary CNS relapse in increased risk patients.