Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.     

Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

Ventilation/perfusion (V/Q) scanning in contemporary patients with pulmonary embolism: utilization rates and predictors of use in a multinational study

Journal of Thrombosis and Thrombolysis - Ventilation/perfusion (V/Q) imaging and computed tomography pulmonary angiography (CTPA) are common tools for acute pulmonary embolism (PE) diagnosis....     

High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.     

Prothrombin A19911G and G20210A polymorphisms' role in thrombosis

The prothrombin G20210A polymorphism, which correlates with the plasmatic prothombin levels, is the second genetic risk factor for deep venous thrombosis (DVT), although its prothrombotic role is mild. Recently, the prothrombin A19911G polymorphism, also associated with slight variations of the prothrombin level, has been suggested to modulate the thrombotic risk of the G20210A polymorphism in a preliminary study including few patients and controls. Our study evaluated the effect of the A19911G polymorphism in the arterial and venous thrombotic risk of the prothrombin 20210G/A genotype, analysing 204 consecutive DVT patients and 204 matched controls. Moreover, we analysed 213 carriers of the 20210G/A genotype (152 with DVT, 26 with arterial thrombosis and 35 healthy subjects) and 10 homozygous 20210 A/A carriers. We developed a simple method to simultaneously determine the genotype of both polymorphisms. In accordance with our case/control study, the A19911G polymorphism did not play a significant role in the development of DVT. Analysis of 120 20210 A alleles demonstrated a complete linkage disequilibrium with the 19911 A allele. These polymorphisms (alone or combined) did not modify the risk of arterial thrombosis. However, the 19911A/G genotype slightly increased the risk of developing DVT in carriers of the 20210G/A genotype (OR 3.34 vs 5.86), supporting that the prothrombin 19911 polymorphism could modulate the risk of the G20210A polymorphism in developing DVT.     

Fetal liver cells produce both fetal and adult erythrocytes in semiallogeneic radiation chimeras: possible influence of adult environment

Two kinds of erythrocytes are released in the blood of irradiated adult hybrid mice grafted with parental fetal liver cells: fetal antigen- bearing erythrocytes (Ft+ cells) and adult-type Ft- erythrocytes. Both are of parental origin, as determined by immune lysis using histocompatibility alloantigens. The latter cells make up all the recipient's red blood cells 2 mo after receipt of the graft, Ft+ cells then being no longer detected. The transient duality of erythropoiesis in irradiated adults grafted with fetal liver cells has been confirmed by studying the kinetics of CFU-E populations, as characterized by their ability to give rise to Ft+ or Ft- erythrocytes. The results are discussed in terms of environmental factors that influenc erythroid differentiation.     

Assessment of aldehyde dehydrogenase in viable cells

Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations.