Intensive conventional-dose chemotherapy for stage IV low-grade lymphoma: high remission rates and reversion to negative of peripheral blood bcl-2 rearrangement.
BACKGROUND
Advanced-stage low-grade lymphoma is characterized by initial responsiveness to many conventional therapies but ultimate relapse. Intensive therapy approaches with non-cross-resistant regimens have not been extensively explored. The polymerase chain reaction (PCR) can be used to monitor for the presence of cells with rearrangement of bcl-2, and provides a sensitive and stringent parameter of disease activity and treatment response that may have clinical utility.


METHODS
From 1988 to 1992, 138 evaluable patients were treated with 3 sequential chemotherapy regimens, as well as with interferon alfa 2b (IFN) in combination with corticosteroids. Nineteen patients had serial PCR monitoring for bcl-2 rearrangement.


RESULTS
Among a subset of 58 patients who had an initial phase of IFN plus prednisone, the response rate was 59%, mostly partial remissions (PR). With the chemotherapy program, 65% have achieved complete remission to date, and 30% PR. By PCR analysis, 13 of 19 tested achieved negative status ('molecular remission'), a much higher frequency of molecular remission than has been seen with standard therapies, and these molecular remissions appear to correlate with a lower likelihood of relapse.


CONCLUSIONS
Intensive conventional-dose chemotherapy can achieve high rates of remission, even when monitored by the stringent PCR technique.
McLaughlin
P
P
Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston.
Hagemeister
F B
FB
Swan
F
F
Cabanillas
F
F
Romaguera
J
J
Rodriguez
M A
MA
Lee
M S
MS
Pate
O
O
Sarris
A
A
Younes
A
A
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015993:Life Tables; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D012074:Remission Induction; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D003561:Cytarabine; D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D002945:Cisplatin; D011241:Prednisone; D008775:Methylprednisolone