Pentostatin Combined with Cyclophosphamide, and Rituximab Induces High Response Rates in Patients with Untreated Indolent B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4722-4722
Author(s):  
Felipe Samaniego ◽  
Luis E. Fayad ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Maria Alma Rodriguez ◽  
...  

Abstract The addition of rituximab to combination chemotherapy has improved treatment outcomes of indolent lymphomas. Combination therapy with purine analogs, akylating agents, and monoclonal antibodies is a promising approach for treating indolent B-cell lymphoma. Nucleoside analog-based regimens selectively target lymphoid cells, making them attractive drugs for lymphoid cancers. Pentostatin is a nucleoside analog that compared with other nucleoside analogs appears to have less bone marrow cell toxicity. The combination of pentostatin, cyclophosphamide, and rituximab (PCR) is an effective regimen for relapsed chronic lymphocytic leukemia and relapsed indolent B-cell lymphoma. In this study, we examined the efficacy of pentostatin, cyclophosphamide, and rituximab for the treatment of B-cell lymphoma. Pentostatin (4 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) were given on day 1 of a 21-day cycle with restaging after every 3 cycles. Patients received prophylaxis with acyclovir 400 mg/po bid and trimethoprim-sulfamethoxazole 3 times per week. Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), was stained for ZAP70 staining and immunoglobulin heavy chain gene mutations. At the time of abstract submission, 29 patients are eligible for response and toxicity. There were 12 patients with follicular lymphoma, 13 with SLL/CLL, and 4 with mucosa-associated lymphoid tissue (MALT), and the median age was 63 years. This regimen was used as first-line therapy for 26 patients and second-line therapy in 3 patients. We observed an overall response of 27 out of 29 (93%), CR/CRu in 19 out of 29 (65%), PR in 8 out of 29 (27%), and mixed response in 2 out of 29 (7%). The main toxicities were nausea and vomiting. No prolonged pancytopenia or myelodysplasia were observed. The correlation of ZAP70 and immunoglobulin heavy chain gene mutations with response is ongoing. Our preliminary data demonstrate that PCR therapy is an effective regimen in previously untreated indolent lymphoma.

Cell ◽  
1986 ◽  
Vol 44 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Michael L. Cleary ◽  
Timothy C. Meeker ◽  
Shoshana Levy ◽  
Elizabeth Lee ◽  
Martha Trela ◽  
...  

2008 ◽  
Vol 14 (10) ◽  
pp. 3002-3010 ◽  
Author(s):  
Shotaro Nakamura ◽  
Hongtao Ye ◽  
Chris M. Bacon ◽  
Alison Goatly ◽  
Hongxiang Liu ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4282-4282
Author(s):  
Ritsuro Suzuki ◽  
Shigeo Nakamura ◽  
Masao Seto

Abstract Background: Several oncogenes, such as cyclin D1, BCL2, BCL6, and c-Myc have been identified to be translocated with immunoglobulin gene In B-cell lymphomas. These genes are overexpressed by the promoter/enhancer activity of immunoglobulin genes, and play important roles in lymphomagenesis. We investigated a translocation partner of immunoglobulin heavy chain gene in a case of diffuse large B-cell lymphoma (DLBCL) with t(1;14)(p33;q32) translocation. Materials and methods: The patient is a 58-year-old female with stage 3AE gastric DLBCL with t(1;14)(p33;q32) translocation. High molecular weight DNA was extracted from resected specimens. Long distance inversed PCR was performed to identify the breakpoint of translocation partner. Cloned fragments were sequenced and the sequence was searched in the database. RT-PCR and 5′- and 3′-RACE (rapid amplification of cDNA end), and were performed to identify the full length of cDNA which is overexpressed as a result of translocation. Results: The breakpoint was located in the 1p34 region. An EST located 20kb downstream from the breakpoint was overexpressed. This EST was not expressed in normal lymphocyte and most of the lymphoma samples and cell lines without t(1;14)(p33;q32). No other known genes including ESTs and hypothetical genes within 1Mb from the breakpoint was overexpressed. Therefore, we concluded that a gene including this EST is the target of t(1;14)(p33;q32) translocation. 5′- and 3′-RACE and RT-PCR revealed that a non-coding RNA without open reading frame of 20kb length was overexpressed. Several palindrome-like sequences existed in the non-coding RNA, but the expression of short length (17–25mer) RNA sequence was not detected. Conclusion: We identified a previously unrecognized type of translocation partner activated by immunoglobulin heavy chain gene in t(1;14)(p33;q32) translocation. Although the intimate mechanism is not clarified, the cloned novel non-coding RNA plays a role in lymphomagenesis.


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