Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma

R. Abraham, C. Chen, R. Tsang, D. Simpson, C. Murray, M. Davidson, J. Meharchand, D. M. Sutton, R. M. Crump, A. Keating, Alexander Keith Stewart

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Randomized trials conducted by the Intergroupe Francaise du Myelome (IFM) demonstrate that the use of high-dose chemotherapy (HDCT) and stem cell transplantation (SCT) improves event-free (EFS) and overall survival (OS) in younger patients with multiple myeloma (MM). Nevertheless, current HDCT regimens remain inadequate as all patients ultimately relapse following SCT. In an attempt to improve the OS of MM patients post-SCT we used an escalated HDCT regimen incorporating both intensified melphalan (160 mg/m2) and fractionated total body irradiation (12 Gy) to maximize the dose response of myeloma cells to these agents and included infusional etoposide 60 mg/kg in an attempt to eradicate clonal B cells potentially contributing to the myeloma clone. One hundred patients with MM received this intensified SCT regimen. The 100-day treatment-related mortality was 12 predominantly reflecting the development of interstitial pneumonitis (IP) in 28 of patients of whom 7/28 (25) died. The predicted 5-year OS and EFS following the diagnosis of MM were 60 and 35, respectively. The median OS from the time of transplant is 41 months and the median EFS is 28 months. More than two prior chemotherapy regimens, previous radiation therapy (RT) and the presence of an abnormal karyotype involving chromosomes 11 or 13 were significantly predictive of poor outcome. Interferon maintenance was not associated with improved outcome. Intensification of the HDCT regimen utilizing etoposide together with escalated melphalan and TBI increases morbidity and mortality without increasing OS beyond that reported with less toxic regimens.

Original languageEnglish (US)
Pages (from-to)1291-1297
Number of pages7
JournalBone Marrow Transplantation
Volume24
Issue number12
StatePublished - 1999
Externally publishedYes

Fingerprint

Multiple Myeloma
Stem Cell Transplantation
Stem Cells
Transplants
Drug Therapy
Survival
Mortality
Melphalan
Etoposide
Abnormal Karyotype
Therapeutics
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 11
Whole-Body Irradiation
Poisons
Interstitial Lung Diseases
Interferons
B-Lymphocytes
Radiotherapy
Clone Cells

Keywords

  • Autologous
  • Myeloma
  • Radiation
  • Stem cell
  • Transplant

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma. / Abraham, R.; Chen, C.; Tsang, R.; Simpson, D.; Murray, C.; Davidson, M.; Meharchand, J.; Sutton, D. M.; Crump, R. M.; Keating, A.; Stewart, Alexander Keith.

In: Bone Marrow Transplantation, Vol. 24, No. 12, 1999, p. 1291-1297.

Research output: Contribution to journalArticle

Abraham, R, Chen, C, Tsang, R, Simpson, D, Murray, C, Davidson, M, Meharchand, J, Sutton, DM, Crump, RM, Keating, A & Stewart, AK 1999, 'Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma', Bone Marrow Transplantation, vol. 24, no. 12, pp. 1291-1297.
Abraham, R. ; Chen, C. ; Tsang, R. ; Simpson, D. ; Murray, C. ; Davidson, M. ; Meharchand, J. ; Sutton, D. M. ; Crump, R. M. ; Keating, A. ; Stewart, Alexander Keith. / Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma. In: Bone Marrow Transplantation. 1999 ; Vol. 24, No. 12. pp. 1291-1297.
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