title: Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia.
abstract: Relapsed acute lymphoblastic leukemia (ALL) usually carries a dire prognosis. We evaluated the effectiveness and long-term complications of intensive rotational combination chemotherapy for late hematologic relapse (median, 16 months after elective cessation of therapy) among 34 children and young adults (ages 4 to 23 years). Concurrent central nervous system (CNS) relapse was present in 3 cases and testicular relapse in 4. Secondary therapy comprised an intensive five-drug reinduction (6 weeks) followed by continuation treatment with four drug pairs, rotated weekly in 4-week cycles over 120 weeks. Intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine) was given three times during reinduction and every 8 weeks during continuation. Treatment was electively discontinued at week 120 in the absence of detectable disease. Thirty-three patients (97%) attained a second complete remission. At a median follow-up of 9.3 years (range, 4.5 to 11.4), estimates of 5-year second event-free and overall survival (+/- SE) are 65% +/- 8% and 79% +/- 7%, respectively. Eleven patients had a second relapse (9 marrow, 2 testicular) and one developed secondary myeloid leukemia. There have been no CNS relapses or deaths in remission. Treatment was well-tolerated and was given largely on an outpatient basis. Late effects are primarily endocrinologic; one child had a second malignant solid tumor (presumed related to initial radiation therapy) that was treated successfully. Intensive treatment with alternating non-cross-resistant drug pairs for late hematologic relapses of ALL is effective and well-tolerated, and produces results similar to those achieved in patients with newly diagnosed ALL. Event-free survival compares favorably with reports of other relapse regimens, including those incorporating bone marrow transplantation.
authors.affiliation: Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: G K
authors.initials: GK
authors.lastname: Rivera
authors.forename: M M
authors.initials: MM
authors.lastname: Hudson
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: E
authors.initials: E
authors.lastname: Benaim
authors.forename: R C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: W M
authors.initials: WM
authors.lastname: Crist
authors.forename: C H
authors.initials: CH
authors.lastname: Pui
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006130:Growth Disorders / Q000209:etiology; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D017254:Leukemic Infiltration; D015993:Life Tables; D008297:Male; D008578:Meninges / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage; D016609:Neoplasms, Second Primary / Q000209:etiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012074:Remission Induction; D016879:Salvage Therapy; D016019:Survival Analysis; D015996:Survival Rate; D013713:Teniposide / Q000008:administration & dosage; D013737:Testis / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014750:Vincristine; D013713:Teniposide; D001215:Asparaginase; D011241:Prednisone; D006854:Hydrocortisone; D008727:Methotrexate