Clearing of cells bearing the bcl-2 [t(14;18)] translocation from blood and marrow of patients treated with rituximab alone or in combination with CHOP chemotherapy.

Abstract

PURPOSE:

Patients who were PCR-positive for B-cell leukemia-lymphoma 2 (bcl-2) gene rearrangement [t(14;18)] were evaluated for responses to rituximab alone or combined with CHOP.

PATIENTS AND METHODS:

Patients had relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (IWF: A-D). The single-agent trial used 375 mg/m2 weekly x 4; combination therapy included six cycles of CHOP and six 375 mg/m2 infusions of rituximab. Bcl-2 analyses of bone marrow (BM) and peripheral blood (PB) samples at base-line and following therapy were performed using a PCR assay.

RESULTS:

In the single-agent trial, of 70 patients whose peripheral blood (PB) was bcl-2 positive at baseline, 36 became bcl-2-negative, 13 remained positive, and 21 varied between positive and negative. The overall response rates (ORRs) were 72%, 31%, and 57%, respectively. Twelve of twenty-two patients with repeat bone marrow (BM) samples were bcl-2-negative three months post-treatment. Of 18 patients in the combination trial, 8 were bcl-2 positive in PB and/or BM. All of seven patients positive in PB at baseline and six of seven patients positive in BM were negative at the end of therapy; all patients responded to treatment (100% ORR).

CONCLUSIONS:

Rituximab, alone or combined with CHOP, eradicated bcl-2 positive cells from PB and BM in over half of the patients treated and was associated with a high overall clinical response rate. The impact on disease-free and overall survival awaits long-term follow up.

• Authors: M S Czuczman, A J Grillo-López, P McLaughlin, C A White, M Saleh, L Gordon, A F LoBuglio, J Rosenberg, B Alkuzweny, D Maloney
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 12 Issue 1 Pg. 109-14 (Jan 2001) ISSN: 0923-7534 [Print] England
• PMID: 11249036 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adult
• Aged
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Bone Marrow Cells
• Chromosomes, Human, Pair 14 (genetics)
• Chromosomes, Human, Pair 18 (genetics)
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Female
• Genes, bcl-2 (genetics)
• Hodgkin Disease (drug therapy, genetics)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Neoplastic Cells, Circulating
• Prednisone (administration & dosage)
• Rituximab
• Translocation, Genetic (genetics)
• Vincristine (administration & dosage)