Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogeneic tandem transplantation in patients with multiple myeloma

Biol Blood Marrow Transplant. 2013 Mar;19(3):398-404. doi: 10.1016/j.bbmt.2012.10.008. Epub 2012 Oct 16.

Abstract

Within a prospective protocol, the incidence and impact of achievement of molecular remission (mCR) and high-risk cytogenetics was investigated in 73 patients with multiple myeloma (MM) after autologous (auto)-allogeneic (allo) tandem stem cell transplantation (SCT). After induction chemotherapy, patients received melphalan 200 mg/m(2) before undergoing auto-SCT, followed 3 months later by melphalan 140 mg/m(2) and fludarabine 180 mg/m(2) before allo-SCT. Sixteen patients had high-risk cytogenetic features, defined by positive FISH for del(17p13) and/or t(4;14). Overall, 66% of the patients achieved CR or near-CR, and 41% achieved mCR, which was sustained negative (at least 4 consecutive samples negative) in 15 patients (21%), with no significant difference in incidence between the patients with high-risk cytogenetics and others (P = .70). After a median follow-up of 6 years, overall 5-year progression-free survival was 29%, with no significant difference between del 17p13/t(4;14)-harboring patients and others (24% versus 30%; P = .70). The 5-year progression-free survival differed substantially according to the achieved remission: 17% for partial remission, 41% for CR, 57% for mCR, and 85% for sustained mCR. These results suggest that auto-allo tandem SCT may overcome the negative prognostic effect of del(17p13) and/or t(4;14) and that achievement of molecular remission resulted in long-term freedom from disease.

Trial registration: ClinicalTrials.gov NCT00781170.

MeSH terms

  • Adult
  • Cytogenetic Analysis
  • Disease-Free Survival
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Melphalan / pharmacology
  • Melphalan / therapeutic use
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • Myeloablative Agonists / pharmacology
  • Myeloablative Agonists / therapeutic use
  • Prognosis
  • Prospective Studies
  • Remission Induction / methods*
  • Translocation, Genetic*
  • Transplantation Conditioning*
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Treatment Outcome
  • Vidarabine / analogs & derivatives
  • Vidarabine / pharmacology
  • Vidarabine / therapeutic use

Substances

  • Myeloablative Agonists
  • Vidarabine
  • fludarabine
  • Melphalan

Associated data

  • ClinicalTrials.gov/NCT00781170