Salvage therapy for relapsed or refractory childhood acute lymphocytic leukemia by alternative administration a lymphoid- and myeloid-directed chemotherapeutic regimen consisting of dual modulation of ARA-C, hydroxyurea, and etoposide

• Published in: Leukemia research Vol. 21; no. 9; pp. 811 - 815
• Main Authors: Higashigawa, Masamune, Hori, Hiroki, Hirayama, Masahiro, Kawasaki, Hajime, Ido, Masaru, Azuma, Eiichi, Sakurai, Minoru
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.1997; Elsevier Science
• Subjects: 6MP, 6-mercaptopurine; ALL, acute lymphocytic leukemia; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ara-C, cytarabine; Asparaginase - administration & dosage; Asparaginase - adverse effects; Asparaginase - pharmacology; biochemical modulation; Biological and medical sciences; BMT, bone marrow transplantation; Bone Marrow Transplantation; Chemotherapy; Child; Combined Modality Therapy; CR, complete remission; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Cyclophosphamide - pharmacology; Cytarabine - administration & dosage; Cytarabine - adverse effects; Cytarabine - pharmacology; dCDP, deoxycytidine diphosphate; dCK, deoxycytidine kinase; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Dexamethasone - pharmacology; Drug Administration Schedule; Drug Evaluation; Etoposide - administration & dosage; Etoposide - adverse effects; Etoposide - pharmacology; Female; Fever - etiology; G-CSF, granulocyte colony-stimulating factor; Gastrointestinal Diseases - chemically induced; GM-CSF, granulocyte-macrophage colony-stimulating factor; HU, hydroxyurea; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - adverse effects; Hydrocortisone - pharmacology; Hydroxyurea - administration & dosage; Hydroxyurea - adverse effects; Hydroxyurea - pharmacology; IL-3, interleukin 3; Leucovorin - administration & dosage; Leucovorin - adverse effects; Leucovorin - pharmacology; Male; Medical sciences; Methotrexate - administration & dosage; Methotrexate - adverse effects; Methotrexate - pharmacology; Mitoxantrone - administration & dosage; Mitoxantrone - adverse effects; Mitoxantrone - pharmacology; MLL, mixed lineage leukemia; MTX, methotrexate; Pharmacology. Drug treatments; Pilot Projects; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Recurrence; Remission Induction; RR, ribonucleotide reductase; Salvage Therapy; Treatment Outcome; HU, hydroxyurea; RR, ribonucleotide reductase; ara-C, cytarabine; dCDP, deoxycytidine diphosphate; biochemical modulation; 6MP, 6-mercaptopurine; bone marrow transplantation; dCK, deoxycytidine kinase; BMT, bone marrow transplantation; IL-3, interleukin 3; Chemotherapy; MTX, methotrexate; CR, complete remission; G-CSF, granulocyte colony-stimulating factor; MLL, mixed lineage leukemia; GM-CSF, granulocyte-macrophage colony-stimulating factor; ALL, acute lymphocytic leukemia; Antineoplastic agent; Lymphoid cell; Relapse; Hydroxycarbamide; Administration schedule; Cell surface; Isomerases; Cytarabine; Lymphoproliferative syndrome; Targeted drug; Acute lymphocytic leukemia; Antimitotic; Pyrimidine nucleoside; Negative therapeutic reaction; Human; DNA topoisomerase (ATP-hydrolysing); Drug combination; Enzyme; Acute; Etoposide; Enzyme inhibitor; Malignant hemopathy; Myeloid cell; Antigen; Podophyllotoxine derivatives; Treatment
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/S0145-2126(97)00068-4

Risk-directed chemotherapeutic regimens in recent use have improved the prognosis of children with acute lymphocytic leukemia (ALL). However, many patients relapse during or shortly after cessation of the initial continuation chemotherapy. Since achievement of a second complete remission (CR) is the initial step in successful retreatment effort, it is important to develop salvage protocols for children with relapsed or refractory ALL. In the present study, we developed a new salvage protocol (MLL-93) and applied the concept of dual chemical modulation of cytarabine, hydroxyurea, and etoposide with the alternative administration of high doses of myeloid- and lymphoid-directed agents. We also planned to perform allogeneic bone marrow transplantation (BMT) following a CR if patients had HLA-identical donor(s). The six patients treated with the MLL-93 protocol achieved a second CR. One patient in CR died of interstitial pneumonia after an unrelated allogeneic BMT. The other five patients have been in CR for 12–41 months. We suggest that the concepts of alternative administration of lymphoid- and myeloid-directed drugs and biochemical modulation are useful in the treatment of children with relapsed or refractory ALL.