High-dose melphalan with G-CSF-stimulated whole blood rescue followed by stem cell harvesting and busulphan/cyclophosphamide with autologous stem cell transplantation in multiple myeloma

Bone Marrow Transplant. 2001 May;27(9):925-31. doi: 10.1038/sj.bmt.1703013.

Abstract

In 90 consecutive patients with multiple myeloma, we investigated the feasibility of administering a tandem high-dose therapy regimen, using whole blood for rescue after the first and leucapheresis harvested between the two high doses, for rescue after the second high dose. After 5 days of G-CSF 1 litre of whole blood (WB) was obtained, left undisturbed at 4 degrees C and reinfused 24 h after HDM (140 mg/m(2)). Patients not in progression after 3-6 months were again mobilised, leucapheresed and treated with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg (Bu/Cy) and reinfusion. In 90 patients, WB contained a mean (range) of 0.57 (0.02-3.22) x 10(6)/kg CD34(+) cells. Recovery after HDM was in 13 days for granulocytes and in 18 days for platelets, with 11 patients not recovering within 3 months. There were three toxic deaths. Sixty-six patients qualified for harvesting after HDM. In the first 11, marrow was harvested. The subsequent 55 patients were mobilised and in 45 the preset minimum of 1.5 x 10(6) CD34(+) cells was obtained. Forty-nine patients actually received Bu/Cy. Recovery after Bu/Cy and marrow reinfusion was in 35 days for granulocytes and 20 days for platelets, with two of five patients not recovering after 3 months. After Bu/Cy and leucapheresis reinfusion, recovery was in 17 days for granulocytes and in 34 days for platelets. Nine patients did not recover within 3 months. There were four toxic deaths. The median overall survival from diagnosis for patients receiving HDM was 49 months and for patients also receiving Bu/Cy, 84 months. We conclude that WB rescue after HDM followed by leucapheresis and a second transplant is feasible in the majority of patients. Better mobilisation techniques are required to increase the number of patients who can receive the second transplant.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Alkylating / toxicity
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Blood Transfusion, Autologous / methods*
  • Busulfan / administration & dosage
  • Busulfan / toxicity
  • Cohort Studies
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / toxicity
  • Female
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Hematopoietic Stem Cell Transplantation / standards
  • Humans
  • Leukapheresis / methods*
  • Male
  • Melphalan / administration & dosage*
  • Melphalan / toxicity
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Transplantation, Autologous / methods
  • Transplantation, Autologous / mortality
  • Transplantation, Autologous / standards
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide
  • Busulfan
  • Melphalan