Effect of chemotherapy with alkylating agents on the yield of CD34+ cells in patients with multiple myeloma. Results of the Spanish Myeloma Group (GEM) Study

Haematologica. 2006 May;91(5):621-7. Epub 2006 Apr 19.

Abstract

Background and objectives: Although alkylating agents are clearly beneficial in multiple myeloma (MM), their deleterious effect on bone marrow hematopoietic progenitor cells usually precludes their use as front-line therapy in patients scheduled to undergo autologous stem cell transplantation (ASCT). We analyzed the impact of first-line chemotherapy with alkylating agents on stem cell collection in MM patients.

Design and methods: Seven hundred and eighty-nine patients included in the Spanish multicenter protocol GEM-2000 underwent mobilization therapy after four courses of alternating VBMCP/VBAD chemotherapy.

Results: The mobilization regimens consisted of standard or high-dose granulocyte colony-stimulating factor (G-CSF) in 551 (70%) patients, and chemotherapy and G-CSF in 206 (26%) patients. The CD34+ cell yield was lower than 4x10(6)/kg in 388 patients (49%), and equal or greater than 4x10(6)/kg in 401 patients (51%). Multivariate analysis indicated that advanced age (p<0.0001) and longer interval between diagnosis and mobilization (p=0.012) were the two variables associated with a lower CD34+ cell yield. Significant differences in CD34+ cell yield were not observed between the mobilization regimens. Of the 789 patients included in the protocol, 726 (92%) underwent the planned ASCT, whereas 25 (3%) patients did not because of the low number of CD34+ cells collected. Following ASCT, 0.5x10(9) neutrophils/L could be recovered after 11 days (median time; range, 5-71 days) and 20x10(9) platelets/L could be recovered after 12 days (median time; range, 6-69 days).

Interpretation and conclusions: A short-course of therapy with alkylating agents according to the GEM-2000 protocol was associated with an appropriate CD34+ cell collection, and allowed the planned ASCT to be performed in the majority of MM patients.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antigens, CD34 / analysis
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Blood Cell Count
  • Carmustine / administration & dosage
  • Carmustine / pharmacology
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacology
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology
  • Drug Administration Schedule
  • Female
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cell Mobilization*
  • Humans
  • Male
  • Melphalan / administration & dosage
  • Melphalan / pharmacology
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / surgery
  • Peripheral Blood Stem Cell Transplantation*
  • Prednisone / administration & dosage
  • Prednisone / pharmacology
  • Transplantation Conditioning
  • Transplantation, Autologous
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / pharmacology

Substances

  • Antigens, CD34
  • Antineoplastic Agents, Alkylating
  • Granulocyte Colony-Stimulating Factor
  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Melphalan
  • Carmustine
  • Prednisone

Supplementary concepts

  • M-2 protocol
  • VBAD protocol