Novel multiagent chemotherapy for bone marrow relapse of pediatric acute lymphoblastic leukemia

Med Pediatr Oncol. 2000 May;34(5):313-8. doi: 10.1002/(sici)1096-911x(200005)34:5<313::aid-mpo1>3.0.co;2-q.

Abstract

Background: Despite improvements in the treatment of pediatric acute lymphoblastic leukemia, approximately one in five patients will develop recurrent disease. The majority of these patients do not survive. This limited institution study sought to improve event-free survival (EFS) by intensification of chemotherapy.

Procedure: Twenty-one patients with either an isolated marrow (n = 16) or a combined marrow and central nervous system relapse (n = 5) received treatment according to Children's Hospital of Philadelphia protocol CHP-540. Six patients had an initial remission of <36 months, and five patients had relapsed within 1 year of completion of phase III therapy. Induction and reinduction therapy consisted of idarubicin, vincristine, dexamethasone, asparaginase, and triple intrathecal chemotherapy. Consolidation and reconsolidation therapy employed high-dose cytarabine, etoposide, and asparaginase given in a sequential manner. Maintenance therapy included courses of high- or low-dose cytarabine followed by sequential etoposide and asparaginase pulse, moderate-dose methotrexate with delayed leukovorin rescue, and vincristine/dexamethasone pulses. Therapy continued for 2 years from the start of interim maintenance in the 16 patients who did not receive a bone marrow transplant (BMT). Two patients underwent an HLA-identical sibling BMT specified by protocol. Four received a nonprotocol-prescribed alternative donor BMT.

Results: The complete remission induction rate was 95%. With a median follow-up from date of relapse of 49 months in survivors, the actuarial EFS based on intent to treat is 75%. There were three toxic deaths in patients in CR and two deaths from relapse.

Conclusions: This regimen is toxic but effective and deserves study in a larger setting.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III

MeSH terms

  • Adolescent
  • Antibiotics, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Bone Marrow / drug effects*
  • Bone Marrow Transplantation
  • Central Nervous System Neoplasms / drug therapy
  • Child
  • Child, Preschool
  • Cytarabine / administration & dosage
  • Dexamethasone / administration & dosage
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Idarubicin / administration & dosage
  • Infant
  • Injections, Spinal
  • Male
  • Neoplasm Recurrence, Local / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Remission Induction
  • Vincristine / administration & dosage

Substances

  • Antibiotics, Antineoplastic
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Antineoplastic Agents, Phytogenic
  • Cytarabine
  • Vincristine
  • Etoposide
  • Dexamethasone
  • Asparaginase
  • Idarubicin