The role of molecular monitoring in autotransplantation for non-Hodgkin's lymphoma.
Seventy-two patients with non-Hodgkin's lymphoma were evaluated for the presence of molecular markers (IgH, bcl-1, bcl-2 rearrangement) on bone marrow, at diagnosis and after PBSCT, and on harvests in order to find a possible predictive role of minimal residual disease on treatment outcome. At diagnosis, 41 (59%) out of 69 available bone marrows showed molecular involvement. Fifty-six percent of leukaphereses were involved, mainly indolent lymphoma (P = 0.001) or advanced disease (P = 0.01). Ex vivo purging cleared only one stem collection out of 31 PCR-positive leukaphereses. Aggressive lymphomas showed both a longer overall survival (OS) (P = 0.03) and relapse-free survival RFS (P = 0.02) when transplanted with unpurged stem cells, whereas indolent NHL survival was not influenced by ex vivo purging. Twenty out of 26 samples taken during follow-up had bone marrow involvement at diagnosis. Of these, 15 cleared their bone marrow; both OS and RFS were significantly longer in the PCR-negative cases (P = 0.05 and P = 0.005). At 1 year after PBSCT, 75% of patients were PCR negative, with 50% molecular remissions; the relapse rate was 55% for patients still PCR positive vs 29% for those who were PCR negative. Thus, after high-dose chemotherapy, close molecular monitoring of MRD using qualitative PCR techniques seems to represent a reliable prognostic indicator.
Galimberti
S
S
Department of Oncology, Transplant and Advances in Medicine - Section of Hematology, University of Pisa, Italy.
Marasca
R
R
Caracciolo
F
F
Fazzi
R
R
Papineschi
F
F
Benedetti
E
E
Guerrini
F
F
Morabito
F
F
Oliva
E
E
Di Renzo
N
N
Federico
M
M
Petrini
M
M
Torelli
G
G
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001853:Bone Marrow / Q000737:chemistry*; D016465:Bone Marrow Purging; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000032:analysis* / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D019254:Genes, bcl-2; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis* / Q000235:genetics; D007937:Leukapheresis; D015993:Life Tables; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone