title: Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells.
abstract: OBJECTIVE
  To describe molecular monitoring of minimal residual disease in patients with myeloma who have achieved complete remission (CR) after autologous or allogeneic transplantation of hematopoietic cells.
  
  
  METHODS
  Clonal markers based upon the rearrangement of immunoglobulin heavy-chain genes were generated for each patient and used for polymerase chain reaction (PCR) detection of residual myeloma cells. Fifty-one patients entered the program and 36 achieved CR. After transplantation, molecular monitoring was performed on 29 patients (15 autologous and 14 allogeneic transplants) who had molecular markers.
  
  
  RESULTS
  Our data show that molecular remissions are rarely achieved (7%) with high-dose chemotherapy followed by single or double autografting. In addition, virtually all peripheral blood progenitor cell and bone marrow samples contained residual myeloma cells, even when sample collection was scheduled after repeated courses of high-dose chemotherapy. All patients autografted with PCR-positive cells remain positive, and eight of 15 have relapsed. Two patients were autografted with PCR-negative cells: one is in clinical and molecular remission, and one relapsed 25 months after the transplant. In the allografting setting, a higher proportion of patients (50%) achieved molecular remission; there were two relapses, one in the PCR-positive group and one in the PCR-negative group.
  
  
  CONCLUSIONS
  This is the first large study of molecular remissions in myeloma patients to use a PCR-based approach utilizing patient-specific tumor markers. The sizeable fraction of patients who achieved molecular remission after allografting with peripheral blood progenitor cells represents a promising finding in an incurable disease.
authors.affiliation: Dipartimento di Medicina ed Oncologia Sperimentale, Azienda Ospedaliera San Giovanni Battista-Divisione Universitaria di Ematologia, Torino, Italy. paolo.corradini@hsr.it
authors.forename: P
authors.initials: P
authors.lastname: Corradini
authors.forename: C
authors.initials: C
authors.lastname: Voena
authors.forename: C
authors.initials: C
authors.lastname: Tarella
authors.forename: M
authors.initials: M
authors.lastname: Astolfi
authors.forename: M
authors.initials: M
authors.lastname: Ladetto
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
authors.forename: M T
authors.initials: MT
authors.lastname: Van Lint
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: M
authors.initials: M
authors.lastname: Musso
authors.forename: I
authors.initials: I
authors.lastname: Majolino
authors.forename: M
authors.initials: M
authors.lastname: Boccadoro
authors.forename: A
authors.initials: A
authors.lastname: Pileri
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D015321:Gene Rearrangement; D005819:Genetic Markers; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D012074:Remission Induction; D017422:Sequence Analysis, DNA; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D007135:Immunoglobulin Variable Region