Lomustine, cytarabine, cyclophosphamide, etoposide - An effective conditioning regimen in autologous hematopoietic stem cell transplant for primary refractory or relapsed lymphoma: Analysis of toxicity, long-term outcome, and prognostic factors

J Cancer Res Ther. 2018 Jul-Sep;14(5):926-933. doi: 10.4103/0973-1482.181183.

Abstract

Background: High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the treatment of choice for patients with relapsed and refractory (RR) lymphoma. We analyzed toxicity and long-term outcome with lomustine, cytarabine, cyclophosphamide, etoposide (LACE) conditioning in patients with primary refractory or relapsed lymphoma undergoing autologous transplant.

Materials and methods: One-hundred patients with primary refractory (23), chemotherapy sensitive relapse (74) or RR (3) Hodgkin lymphoma (HL - 70 patients), and non-HL (NHL - 30 patients) underwent HSCT with LACE (lomustine 200 mg/m 2 day-7, etoposide 1000 mg/m 2 day-7, cytarabine 2000 mg/m 2 day-6 to day-5, and cyclophosphamide 1800 mg/m 2 day-4 to day-2) conditioning between November 2007 and December 2013. At transplant, 68 patients were in complete remission (CR), 29 in partial remission, 2 had stable disease, and 1 had progressive disease. Patients were followed up for development of transplant-related toxicities and long-term survival outcome.

Results: The incidence of grades 3-4 oral mucositis and grades 3-4 diarrhea was 8% and 4%, respectively. Median days to myeloid and platelet engraftment were 10 and 13. Transplant-related mortality was 7%. At median follow-up of 3 years, probability of overall survival (OS) and progression-free survival (PFS) at 3 years was 70% and 58% in entire cohort, 78% and 62% in HL and 51% and 46% in NHL subgroup, respectively. International Prognostic Score (IPS) >2 at relapse prognosticated for poor OS (P = 0.002) and PFS (P < 0.001) in HL subgroup. Positron emission tomography positivity pretransplant (HL subgroup) and at day + 100 (NHL subgroup) predicted for poor survival.

Conclusion: We conclude that LACE is effective and well-tolerated conditioning regimen. IPS at relapse is the most important prognostic factor in HL transplant.

Keywords: Conditioning regimen; Hodgkin lymphoma; hematopoietic stem cell transplantation; non-Hodgkin lymphoma; prognostic factors.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Hodgkin Disease / pathology
  • Hodgkin Disease / therapy
  • Humans
  • Lomustine / administration & dosage
  • Lymphoma / pathology
  • Lymphoma / therapy*
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / therapy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Prognosis*
  • Recurrence
  • Remission Induction
  • Transplantation Conditioning
  • Transplantation, Autologous
  • Young Adult

Substances

  • Cytarabine
  • Etoposide
  • Lomustine
  • Cyclophosphamide