High molecular response rate and clinical correlation in patients with follicular lymphoma treated with cyclophosphamide-vincristine-prednisone plus interferon alpha 2b.
OBJECTIVE
The role of molecular monitoring of minimal residual disease (MRD) in low-grade non-Hodgkin's lymphoma is controversial. We have performed a prospective study of the molecular behavior of 35 patients with follicular non-Hodgkin's lymphoma who received cyclophosphamide-vincristine-prednisone chemotherapy in conjunction with IFN-alpha 2b.


METHODS
Bcl-2 and clonal immunoglobulin heavy chain (IgH) gene rearrangements were assayed at diagnosis by PCR in lymph node and bone marrow (BM) and sequentially after treatment.


RESULTS
Molecular markers were detected in BM of 29 (83%) patients at diagnosis: Bcl-2 rearrangement in 20 patients (90% major breakpoint and 10% minor cluster) and clonal IgH rearrangement in 9 of 15 patients negative for Bcl-2. Molecular and clinical response was noted in 25 (86%) patients after induction treatment. Progression-free survival at 5 years was 78.1 +/- 8%. A correlation between clinical and molecular response was found in 24 patients with molecular markers in BM at diagnosis and >2 years of follow-up: 94% of patients with undetectable MRD showed continuous clinical remission, whereas 50% of patients who reverted back to positive molecular markers relapsed (P < 0.05).


CONCLUSIONS
The rate of molecular response is high in patients treated with cyclophosphamide-vincristine-prednisone and IFN and MRD sequential analysis is useful for disease surveillance.
Fernández-Ruiz
Elena
E
Unidad de Biología Molecular, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain. rarranzs@aehh.org
Cabrerizo
María
M
Ortega
Mara
M
Blas
Carlos
C
Llamas
Pilar
P
Santos-Roncero
Matilde
M
Nieto
Santiago
S
Acevedo
Agustín
A
Pérez
Guillermo
G
Nicolás
Concepción
C
Fernández-Rañada
José María
JM
Arranz
Reyes
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000008:administration & dosage*; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage*
D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone