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.
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 patients 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.
Higashigawa
M
M
Department of Pediatrics, Mie University School of Medicine, Japan.
Hori
H
H
Hirayama
M
M
Kawasaki
H
H
Ido
M
M
Azuma
E
E
Sakurai
M
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D016026:Bone Marrow Transplantation; D002648:Child; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D005334:Fever / Q000209:etiology; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D016896:Treatment Outcome
D003561:Cytarabine; D005047:Etoposide; D003907:Dexamethasone; D003520:Cyclophosphamide; D008942:Mitoxantrone; D001215:Asparaginase; D002955:Leucovorin; D006854:Hydrocortisone; D006918:Hydroxyurea; D008727:Methotrexate