Intensive Alternating Drug Pairs After Remission Induction for Treatment of Infants With Acute Lymphoblastic Leukemia

Abstract

Although early intensive rotating therapy is tolerable, the relapse-free survival rate remains poor for infants treated with the schedule on this protocol.

A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial

“…The use of alternating myelosuppressive combination chemotherapy early in the post-induction period was tested in the POG 8398 pilot protocol. 13 Significant but tolerable toxicity was encountered. Drug combinations were selected for their antileukemic effects in relapsed disease and for their relative non-cross-resistance as suggested by the Goldie-Coldman hypothesis.…”

“…13,17 Treatment regimens are listed in infusion and continued every 6 h for five doses or until plasma MTX was Ͻ0.1 mol/l. All courses of chemotherapy during intensification began when the absolute neutrophil count was у500/ l and platelet count was у100 000/ l. If courses of DNR/AC or VM-26/AC resulted in prolonged neutropenia (Ͻ500/ l for Ͼ24 days), each myelosuppressive drug was reduced by 25% for the next course.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20] Increased toxicity was also noted with the aggressive use of myelosuppressive agents. 9,13,14,16,18,[19][20][21][22] However, preliminary results from POG 8698 suggested that early intensification with the less toxic combination of intermediate-dose methotrexate (MTX) and mercaptopurine (MP) might be as effective as the more myelosuppressive combinations used in another POG pilot study (POG 8398) for HR-ALL. 13,17 In 1991, the POG opened a group-wide randomized phase III clinical trial (POG 9006) to treat children with HR-ALL.…”

“…9,13,14,16,18,[19][20][21][22] However, preliminary results from POG 8698 suggested that early intensification with the less toxic combination of intermediate-dose methotrexate (MTX) and mercaptopurine (MP) might be as effective as the more myelosuppressive combinations used in another POG pilot study (POG 8398) for HR-ALL. 13,17 In 1991, the POG opened a group-wide randomized phase III clinical trial (POG 9006) to treat children with HR-ALL. The primary objectives of this randomized trial were to compare the efficacy and toxicity of regimen A: 12 early intensive courses of antimetabolite-based chemotherapy (intermediatedose MTX/MP) vs regimen B: 12 early intensive courses of alternating myelosuppressive, non-cross-resistant combination chemotherapy with MTX/MP as per the Goldie-Coldman hypothesis.…”

Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement

“…Virtually all infants with ALL achieve complete remission but many patients relapse, often within 1 year after diagnosis (reviewed in 1,[2][3][4].…”