Bone marrow mammaglobin expression as a marker of graft-versus-tumor effect after reduced-intensity allografting for advanced breast cancer.
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.
Bregni
M
M
Division of Hematology-Bone Marrow Transplantation, Department of Oncology, Hematology-Bone Marrow Transplantation Unit, and Blood Bank--Tissue Typing Laboratory, Istituto Scientifico H San Raffaele, Milan, Italy. marco.bregni@hsr.it
Fleischhauer
K
K
Bernardi
M
M
Pescarollo
A
A
Guggiari
E
E
Lunghi
F
F
Deola
S
S
Scaramuzza
S
S
Re
F
F
Setola
E
E
Monari
M
M
Mazzi
B
B
Servida
P
P
Corradini
P
P
Peccatori
J
J
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D019046:Bone Marrow Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary / Q000628:therapy; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006085:Graft Survival; D020350:Graft vs Tumor Effect; D006801:Humans; D060785:Mammaglobin A; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013852:Thiotepa / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014598:Uteroglobin / Q000096:biosynthesis*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D014408:Biomarkers, Tumor; D060785:Mammaglobin A; D019653:Myeloablative Agonists; D009363:Neoplasm Proteins; C556448:SCGB2A2 protein, human; D003520:Cyclophosphamide; D013852:Thiotepa; D014598:Uteroglobin; D014740:Vidarabine; C024352:fludarabine