Intravenous busulfan plus melphalan is a highly effective, well-tolerated preparative regimen for autologous stem cell transplantation in patients with advanced lymphoid malignancies

Biol Blood Marrow Transplant. 2011 Mar;17(3):412-20. doi: 10.1016/j.bbmt.2010.07.016. Epub 2010 Jul 30.

Abstract

We investigated the administration of intravenous (i.v.) busulfan (Bu) combined with melphalan (Mel) in patients with advanced lymphoid malignancies undergoing autologous stem cell transplantation. Bu 130 mg/m(2) was infused daily for 4 days, either as a fixed dose per body surface area (BSA), or to target an average daily area under the curve of 5000 μmol-min, determined by a test dose of i.v. Bu at 32 mg/m(2) given 48 hours prior to the high-dose regimen, followed by a rest day, followed by 2 daily doses of Mel at 70 mg/m(2). Stem cells were infused the following day. Eighty patients had i.v. Bu delivered per test dose guidance. The median daily systemic Bu exposure was 4867 μmol-min. One hundred two patients (Hodgkin lymphoma n = 49, non-Hodgkin lymphoma n = 12, multiple myeloma = 41) with a median age of 44 years (range: 19-65 years) were treated. The 2-year overall survival and progression-free survival rates were 85% and 57%, respectively, for patients with Hodgkin lymphoma, 67% and 64%, respectively, for patients with non-Hodgkin lymphoma, and 82% and 42%, respectively, for patients with multiple myeloma. The regimen was very well tolerated with treatment-related mortality at 100 days, 1 year, and 2 years of 1%, 3%, and 3%, respectively. Intravenous Bu-Mel was well tolerated. Disease control wa encouraging, and should be explored in larger phase II studies.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / pharmacokinetics
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Busulfan / pharmacokinetics
  • Busulfan / therapeutic use*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / therapy
  • Humans
  • Infusions, Intravenous
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / therapy
  • Lymphoproliferative Disorders / drug therapy
  • Lymphoproliferative Disorders / therapy*
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Melphalan / therapeutic use*
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / therapy
  • Severity of Illness Index
  • Survival Analysis
  • Transplantation Conditioning / adverse effects*
  • Transplantation, Autologous
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Busulfan
  • Melphalan