Bone marrow mammaglobin expression as a marker of graft-versus-tumor effect after reduced-intensity allografting for advanced breast cancer

Bone Marrow Transplant. 2006 Feb;37(3):311-5. doi: 10.1038/sj.bmt.1705248.

Abstract

We assessed mammaglobin (MMG) gene expression in bone marrow (BM) aspirates from patients with advanced breast cancer who had received a reduced-intensity conditioning and stem cell allografting, in order to detect a graft-versus-tumor effect on micrometastatic disease. Nine patients received a reduced-intensity conditioning with fludarabine, cyclophosphamide, and thiotepa, followed by peripheral blood allografting from HLA-identical sibling donors. Nested RT-PCR analysis with sequence-specific primers for MMG was carried out on a monthly basis on BM samples. Three patients had MMG-positive BM, four patients had MMG-negative BM before allografting, and two were undetermined. In two patients, a clinical response after allografting (partial remission) occurred concurrently with the clearance of MMG expression, at a median of 6 months after allografting, following immune manipulation. In two patients, a prolonged stable disease and negative MMG expression occurred after day +360 from allografting. In two patients, progression of the disease was associated with MMG RT-PCR changing from negative to positive. In one case, a disease response occurring after donor lymphocyte infusion and grade II acute GVHD was heralded by negativization of MMG expression. Although preliminary, these data suggest that a graft-versus-breast cancer effect is detectable on micrometastatic BM disease.

MeSH terms

  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology
  • Bone Marrow Neoplasms / metabolism*
  • Bone Marrow Neoplasms / pathology
  • Bone Marrow Neoplasms / secondary
  • Bone Marrow Neoplasms / therapy
  • Bone Marrow Transplantation
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cyclophosphamide / administration & dosage
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Graft Survival
  • Graft vs Tumor Effect*
  • Humans
  • Mammaglobin A
  • Middle Aged
  • Myeloablative Agonists / administration & dosage
  • Neoplasm Proteins / biosynthesis*
  • Predictive Value of Tests
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Thiotepa / administration & dosage
  • Transplantation Conditioning / methods
  • Transplantation, Homologous
  • Uteroglobin / biosynthesis*
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Biomarkers, Tumor
  • Mammaglobin A
  • Myeloablative Agonists
  • Neoplasm Proteins
  • SCGB2A2 protein, human
  • Cyclophosphamide
  • Thiotepa
  • Uteroglobin
  • Vidarabine
  • fludarabine