Effect of the dose per body weight of conditioning chemotherapy on severity of mucositis and risk of relapse after autologous haematopoietic stem cell transplantation in relapsed diffuse large B cell lymphoma

Br J Haematol. 2008 Oct;143(2):268-73. doi: 10.1111/j.1365-2141.2008.07342.x. Epub 2008 Aug 10.

Abstract

High-dose chemotherapy and haematopoietic stem cell (HSC) transplantation is considered standard therapy in patients with chemosensitive relapsed diffuse large B cell lymphoma (DLBCL). BCNU (carmustine), etoposide, cytarabine and melphalan (BEAM) is a widely used standard DLBCL conditioning regimen. The practice of basing chemotherapy doses on body surface area (BSA) is empirical and the best biometric parameter to dose chemotherapy is unknown. Weight-based dosing has been suggested to better predict toxicity of the conditioning regimen. We correlated the dose/weight ratio with toxicity and overall outcome in a uniform cohort of 80 consecutive patients receiving HSC transplant for relapsed DLBCL at Mayo Clinic, Rochester, MN following BSA-dosed BEAM conditioning chemotherapy. Melphalan dose was used as surrogate for the entire regimen. Median age at the time of transplant was 62 (26-77) years; 65% were males. The median melphalan dose was 3.2 mg/kg (range 2.2-4.5). Patients who received >3.6 mg/kg of melphalan were more likely to have grade 3 or 4 mucositis (44.4% vs. 9.8%, P = 0.001) and prolonged hospitalization (median 13 vs. 7 d; P = 0.04). Dose/weight ratio did not correlate with cumulative incidence of relapse (P = 0.3) or survival (P = 0.8). Transplant physicians should consider limiting the dose of BEAM to the equivalent of 3.6 mg/kg of melphalan.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Body Weight
  • Carmustine / administration & dosage
  • Carmustine / adverse effects
  • Chi-Square Distribution
  • Cohort Studies
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Length of Stay
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / surgery
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Melphalan / therapeutic use
  • Middle Aged
  • Mucositis / chemically induced
  • Recurrence
  • Risk
  • Statistics, Nonparametric
  • Transplantation Conditioning / adverse effects*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Cytarabine
  • Etoposide
  • Melphalan
  • Carmustine

Supplementary concepts

  • BEAM regimen