Rituximab in the therapy of stage III and IV follicular lymphoma: Results of the REFLECT 1 study of the Serbian Lymphoma Group.

PURPOSE: Follicular lymphoma (FL) is an indolent lymphoma that responds well to rituximab+chemotherapy. We evaluated the prognosis and efficacy of immunochemotherapy in patients with previously untreated, advanced FL. METHODS: REFLECT 1 is a multicentre, prospective study of 99 patients with previously untreated FL stage III-IV. All patients were treated with rituximab+chemotherapy x 6 cycles, plus 2 cycles of rituximab monotherapy. Clinical assessment was performed at baseline, after completion of the first 6 cycles of therapy and every 3 months from the end of immunochemotherapy to the end of the study period. RESULTS: Eighty-nine out of 99 patients with complete documentation were included. Complete remission (CR) was achieved in 61.6%, partial remission (PR) in 11.6% and progressive disease (PD) in 24.4% of the patients. Time to progression (TTP) and overall survival (OS) after the 1st, 2nd and 3rd year were 89.9, 72.7, 57.8%, and 94.2, 92,6 and 92.6%, respectively. The probability of achieving CR was significantly lower in the high risk group according to Follicular Lymphoma Prognostic Index (FLIPI) score. Expression of CD43 antigen had a significant impact on the probability of 2-year TTP and OS, and ECOG performance status had a significant impact on OS. CONCLUSIONS: Treatment with rituximab plus chemotherapy is effective in advanced stages of FL. Significant prognostic factors are FLIPI score for induction therapy outcome, CD43 antigen expression for OS and TTP and ECOG performance status for OS.

High dose chemotherapy with stem cell support in the treatment of testicular cancer.

Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease.

Concurrent chronic lymphocytic leukemia and merkel cell carcinoma in primary skin tumor and metastatic lymph node.

Association between chronic lymphocytic leukemia and other malignancies has been known for a long time. This epidemiological phenomenon is explained by immunosuppression caused by disease itself or by the applied therapy. Merkel cell carcinoma is a rare malignant tumor of the skin of neuroendocrine origin diagnosed almost exclusively in immunocompromised host. We presented an unique case of coexisting infiltration of chronic lymphocytic leukemia cells within primary cutaneous Merkel cell carcinoma and metastatic lymph node in young HIV-negative female patient.

Comparison of prognostic impact of absolute lymphocyte count, absolute monocyte count, absolute lymphocyte count/absolute monocyte count prognostic score and ratio in patients with diffuse large B cell lymphoma.

BACKGROUND: The combination of absolute lymphocyte count (ALC) and absolute monocyte count (AMC) at diagnosis has prognostic relevance in patients with diffuse large B cell lymphoma (DLBCL). AIMS: The present study was designed to investigate the prognostic significance of ALC and AMC and to determine whether ALC/AMC ratio or ALC/AMC prognostic score is better predictor of outcome in DLBCL. METHODS: We retrospectively analyzed the prognostic significance of ALC and AMC, ALC/AMC ratio and ALC/AMC prognostic score at diagnosis in 222 DLBCL patients treated with R-CHOP. RESULTS: ROC analysis showed that optimal cut-off values of AMC and ALC/AMC ratio with the best sensitivity and specificity were 0.59×10(9)/L and 2.8, respectively. Cut-off of ALC was determined according to the literature data (1×10(9)/L). Low ALC, high AMC, low ALC/AMC ratio and high ALC/AMC prognostic score were in significant association with lower rate of therapy response and survival. In contrast, these parameters were not in significant correlation with relapse rate. The patients with low ALC, "high" AMC, low ALC/AMC ratio and high ALC/AMC prognostic score at diagnosis had significantly shorter EFS and OS. In multivariate analysis all tested parameters (ALC, AMC, ALC/AMC prognostic score and ALC/AMC ratio) are independent risk factors along with "bulky" disease and IPI. CONCLUSION: All tested parameters (ALC, AMC, ALC/AMC score and ALC/AMC ratio) may be useful prognostic factors in DLBCL patients. ALC/AMC score has a slight advantage as it allows the classification of patients into three prognostic groups. Further studies are needed to determine which of these parameters has the highest predictive value.

[Metastases of unknown origin--principles of diagnosis and treatment].

DEFINITION: Cancer of unknown primary (CUP) origin refers to patients who present with histologicaly confirmed metastatic cancer in whom a detailed medical history, complete physical examination, including pelvic and rectal examination, full blood count and biochemistry, urinalysis and stool occult blood testing, hisinpathological review oJ biopsy speimens with the use of immunohistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mammography, fail to identify the primary site. EPIDEMIOLOGY OF CUP: The cancer of unknown primary accounts for 3%-5% of all human cancers. DIAGNOSIS OF CUP: The standard diagnostic procedure for the majority of patients includes histopathologic review of biopsy specimens with the use of immunoltistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mamography, fail to identify the abdomen and pelvis. The four common histologic diagnoses are: adenocarcinoma (70%), poorly differentiated carcinoma (20%), squamous carcinoma (10%), and poorly differentiated neoplasms (5%). PROGNOSIS OF CUP: The prognosis for most patients with unknown primary tumors is poor, with survival often less than 6 months from diagnosis. THERAPY OF CUP: Based on clinical and pathologic features, approximately 40% of patients can be categorized within subsets for which specific treatment has been defined. Empiric therapy is an option for the remaining 60% of patients. CONCLUSION: Metastatic tumors of unknown origin have a unique clinical presentation due to a specific biology. Insight into the molecular biology of unknown primary tumors will be essential for the development of more effective treatments.