Search

We report a case of a 61-year-old man with a history of CREST syndrome (calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) who presented for evaluation of thrombocytopenia. He had evident cervical adenopathy and lymph node biopsy showed small lymphocytic lymphoma (SLL) with evident systemic adenopathy and bone marrow involvement. The patient achieved a complete remission with FCR (fludarabine/cyclophosphamide/rituximab) chemotherapy. About 30 cases of lymphomas are reported in the literature in association with systemic sclerosis. To our knowledge, there are no reports of a small lymphocytic lymphoma (SLL) in association with limited cutaneous systemic sclerosis with classic features of the CREST syndrome.

Importance of the Field: Follicular lymphoma (FL) is a subgroup of B-cell Non-Hodgkin's lymphomas (NHL) that account for 15 - 30% of all lymphomas. I-131 tositumomab is a radiommunoconjugate of (131)I and the anti-CD20 monoclonal antibody tositumomab. It is one of two available radioimmunoconjugates for the treatment of recurrent, refractory, or transformed FL., Areas Covered in This Review: This review describes the clinical pharmacology of I-131 tositumomab, dosing and administration guidelines, and the key clinical trials providing evidence of its efficacy and safety in patients with FL, transformed, or other aggressive B-NHL, in combination with chemotherapy, or its incorporation in transplant conditioning regimens. This review also covers safety and regulatory concerns regarding the use of I-131 tositumomab., What the Reader Will Gain: This review critically appraises the clinical trials behind approval of I-131 tositumomab as a second-line agent for FL and also outlines the data supporting its use in the upfront setting., Take Home Message: I-131 tositumomab is a safe and effective option for patients with recurrent, refractory, or transformed FL and carries promise in the upfront treatment of FL, aggressive B-NHL, and as a transplant conditioning regimen.

I report a case of functional hyposplenism in a patient with history, and typical radiological findings, of asbestos-related lung disease and presenting with recurrent pneumococcal pneumonia. Functional hyposplenism is not rare and is suspected in cases of recurrent pneumococcal pneumonia and/or sepsis. The two most time-honored diseases associated with hyposplenism are celiac disease and sickle cell anemia. No cases of functional hyposplenism associating pleural and/or parenchymal lung diseases secondary to asbestos exposure have been reported to date. Asbestos bodies were reported in the spleen, and multiple other extra-pulmonary organs, yet their significance remains uncertain. Asbestos exposure may be associated with the development of functional hyposplenism and, subsequently, an increased risk of invasive pneumococcal disease.

Objective: Curcumin, a natural compound derived from tumeric, has been shown to induce apoptosis in the leukemic cell line K562 and other cancer cell lines. However, it is unknown whether curcumin also has an inhibitory effect on BCR-ABL-expressing B-lymphoid cells. We tested whether curcumin has an inhibitory effect on BCR-ABL B-cell acute lymphoblastic leukemia (B-ALL) in vitro and in vivo., Methods: Pre-B cells isolated from B6 mice expressing wild-type BCR-ABL (B6p210) and T315I mutant (B6T315I) were cultured in serial concentration of curcumin. Cultured cells were analyzed by automated cell counter, flow cytometry, western blotting, and transcription factor arrays. B-ALL was induced by transplantation of MSCV-GFP-p210 transduced donor marrow in lethally irradiated Balb/c mice. Diseased mice were treated with placebo or curcumin until death of the mice. Diseased mice were analyzed by flow cytometric and histopathological analyses., Results: Curcumin inhibited the proliferation of B6p210 and B6T315I cells at concentration as low as 10 muM and induced apoptosis of the cells at concentrations of 30 muM. Using western blots and transcription factors arrays, we showed that curcumin decreased NF-kappaB levels and increased p53 levels. Curcumin decreased c-Abl levels in cells expressing the wild, but not the mutant, BCR-ABL oncogene. Curcumin treatment resulted in a statistically significant improved survival in diseased mice along with decreasing white blood and GFP cell counts., Conclusions: Curcumin is effective against leukemic cells expressing p210 BCR-ABL and T315I BCR-ABL and holds promise in treating BCR-ABL-induced B-ALL.

In the first part of this review, we described the physiological basis of splenic function and hypofunction. We also described the wide spectrum of diseases that can result in functional hyposplenism. In the second part of this review, we will be discussing the clinical picture, including complications, diagnostic methods, and management of hyposplenism.

Hyposplenism is not a rare condition and can complicate a remarkable number of illnesses. The two most time-honored diseases associated with the development of hyposplenism are sickle cell anemia and celiac disease. Hyposplenism is relatively easy to recognize by typical changes observed on the peripheral blood smear; including Howell-Jolly bodies, monocytosis, lymphocytosis, and increased platelet counts. Diagnosis can be confirmed by pitted RBC counts or 99Tc-labelled radiocolloid scan of the spleen; wherever available. Diagnosis needs to be made promptly to institute pneumococcal vaccination in a timely fashion and to recognize and treat bacterial infections promptly and aggressively because of the tendency of hyposplenic subject to develop fatal invasive disease. Overwhelming pneumococcal sepsis accounts for the major mortality cases in hyposplenic subjects; however severe infections with other encapsulated bacteria and protozoa have been reported. Hyposplenic individuals may also be at a higher risk for vascular, autoimmune and thrombotic diseases and they may have a higher risk of developing solid tumors. The commonly used pneumococcal polysaccharide vaccine is ineffective in asplenic subjects, because it requires the presence of IgM memory B cells, and should be given before splenectomy. In splenectomized, and functionally hyposplenic subjects, the pneumococcal conjugate vaccine is more effective, because it utilizes a T cell dependent mechanism, and should be the preferred vaccine in these circumstances.

Objective: The study was designed to answer the question whether a particular (slow/fast) acetylator phenotype is a risk for malignant lymphoma patients. Differences in acetylator phenotypes were previously described in urinary bladder and colorectal carcinoma patients compared to controls. Addressing this issue may help understanding the possible role of xenobiotics' metabolism in the pathogenesis of malignant lymphomas. Caffeine is currently preferred as a metabolic probe due to its noninvasiveness., Design: Case-control study., Setting: Hematology/oncology inpatient unit and outpatient clinic, Ain Shams University Hospitals, Cairo, Egypt: a tertiary care academic medical institution., Participants: Urine samples were collected 4 h after the oral administration of a caffeine-containing beverage to 83 patients with malignant lymphomas and 92 control subjects. Diagnosis of lymphoma was ascertained histopathologically. Controls were matched in terms of age, sex and residence (urban/rural)., Measurements: To define the acetylation phenotype, the nanomolar ratio of the urinary concentrations of the caffeine metabolites: acetylamino-6-amino-3-methyluracil and 1-methylxanthine (AAMU/1X) was calculated for every study subject., Results: An excess of fast acetylators was shown in the malignant lymphoma group compared to the control. The odds ratio for malignant lymphoma associated with fast acetylation was 1.304 (95% CI, 0.709-2.398; p = 0.439). Paradoxically, an excess of the slow acetylator phenotype was observed in patients with low-grade non-Hodgkin lymphoma (n = 25) compared to other subjects of the lymphoma group. The odds ratio for low-grade lymphoma associated with slow acetylation was 4.00 (95% CI, 1.316-12.155; p = 0.014)., Conclusions: Owing to the small sample size, the association between the acetylator phenotype and malignant lymphomas could not be excluded. However, the study suggests that, compared to other types of lymphoma, low-grade non-Hodgkin lymphoma would be associated with slow acetylator phenotype.