Interleukin 10 gene promoter polymorphism and risk of diffuse large B cell lymphoma [DLBCL]

Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin's lymphoma [NHL], this work was designed to study the impact of IL-10 [-1082 G/A; rs!800896 and -819 C/T; rs!800871] gene promoter polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma [DLBCL]; the major type of NHL. To the best of our knowledge, this study is the first one that examines IL-10 promoter polymorphism in DLBCL in Egyptians. Genotyping polymorphism is performed using sequence-specific primers polymerase chain reaction [SSP-PCR] in 100 Egyptian DLBCL patients and 119 normal controls. Circulating plasma levels of IL-10 were measured using Enzyme-linked immunosorbent assay [ELISA]. Insignificant change in IL-10 [-1082 and -819] genotypes was recorded. Although A allele is slightly decreased in DLBCL patients, it did not reach statistical significance. GT haplotype was significantly elevated [P < 0.05] in NHL patients. A significant linkage disequilibrium between the -1082 and 819 SNPs with D' = 0.596 and r[2] = 0.1032 [P < 0.001] was demonstrated. Significantly increased plasma IL-10 [P < 0.01] was found which is positively correlated [r = 0.307; P < 0.01] with the disease Taken together, our findings demonstrated that IL-10 promoter gene polymorphism [-1082 and -819] may not have an influence on the clinical outcome of DLBCL, especially in terms of overall secretion level. Further investigations of other cytokine gene polymorphisms will lead to a better understanding of the disease's biological background

phase II study of high-dose celecoxib and metronomic [low-dose] cyclophosphamide and methotrexate in patients with relapsed and refractory lymphoma

Relapsed, histologically aggressive non-Hodgkin lymphoma [NHL] has a poor prognosis; relapsed patients who do not respond to second line therapy or are unfit for BMT have a worse prognosis. Angiogenesis is increased in aggressive NHL and could be targeted by selective cyclooxygenase-2 inhibition and metronomic chemotherapy. We assessed the toxicity of metronomic chemotherapy and the response and progression-free survival in patients with relapsed/refractory diffuse large B-cell lymphoma [DLBCL]. We prospectively studied 41 patients with a diagnosis of relapsed and/or refractory DLBCL who may have received any number of preceding therapies [as long as one included an anthracycline] and were not candidates for bone marrow transplantation. They received oral cyclophosphamide [50 mg every day], oral methotrexate [2.5 mg 4 times/week] and high-dose oral celecoxib [400 mg twice daily] until there was disease progression or unacceptable toxicity. All 41 patients [median age, 56 years] were evaluable for toxicity and response, with a median follow up of 9.1 months [range, 4-35 months]. At relapse, 51.2% had a high international prognostic index. The treatment protocol was well tolerated with no major toxicities. The most common toxicities were fatigue [61%], nausea [22%], neutropenia [1 9.5%], and anemia [22%]. In 31.7% there was a partial response and 48.8% had stable disease. Progression-free survival was 12 months. The median response duration was 10 months. We conclude that metronomic chemotherapy can be used for patients with relapsed and or refractory DLBCL with reasonable outcome and acceptable toxicity. Standard approaches such as hematopoietic stem cell transplantation and chemoimmunotherapy combinations should be explored prior to a decision on metronomic chemotherapy

Management of soft tissue sarcoma of extremities in adults

Soft-tissue sarcomas [STS] are a group of rare malignant tumors, many of which arise in the limbs. To review the results of managements of STS of extremities in adults treated in the period between December 1997 till December 2000, in Oncology Unit Menufia University Hospital [MUH]. Sixteen adult patients had STS in their extremities. Seven males and 9 females with a mean age of 45.3 years. Variables studied were; clinical presentation and its duration, tumor characteristics [site, size, pathological type and grade, lymph node status], treatment given, and its outcome, as well as the disease free survival [DFS]. The most common type of presentation was a painless mass for 5 months +/- 2. Most sarcomas were located in the lower extremity [81%]; all the patients underwent conservative surgical excision except one underwent disarticulation. Eight patients had adjuvant radiotherapy and 5 patients had chemotherapy. The commonest histopathology found was liposarcomas [7 cases, 43%], followed by fibrosarcoma [4 cases, 18%], and 50% of patients had high-grade tumours. The tumour size, type, and grade were independent risk factors for poorer disease free survival. The disease free survival for all patients, for 5 years was 81.25%. With limb salvage surgery and radiotherapy delivery, local control of STS in the extremity has become feasible. Other modalities, as hormonal treatment and immunetherapy should be further studied to optimize the outcome and improve DFS