Hypertriglyceridemia: apheretic treatment.

Patients with extremely high triglyceride levels and associated lipemia are at high risk for acute pancreatitis. Two factors can increase triglyceride-rich lipoproteins; one is overproduction and other is a defect in clearance. Either mechanism can cause hypertriglyceridemia and both may exist simultaneously. Causes can be either primary or secondary. Plasmapheresis is efficacious for severe Hypertriglyceridemia in patients who have not responded to previous therapies. We have treated 15 cases of hypertriglyceridemia complicating the course of patients receiving Cyclosporin A after bone marrow transplantation. Five patients were treated with plasmapheresis, the other ten with cascade filtration. The removal rate for triglycerides was 58.0% for patients treated by cascade filtration and 63.5% for patients treated by plasmapheresis. The removal rates for triglycerides were low possibly as a consequence of early saturation of the filter.

Hypercholesterolemia and LDL apheresis.

Several trials have assessed the link between low-density lipoprotein cholesterol (LDL) and the development of coronary heart disease (CHD). LDL apheresis provides an effective role in treating patients with familial hypercholesterolemia (FH) and in preventing the progression of coronary artery disease (CAD). Five different techniques of LDL apheresis are in current use: immunoadsorption (IMA), dextran sulphate-cellulose adsorption (DSA), heparin extracorporeal LDL precipitation system (HELP), double filtration plasmapheresis (DFPP) or lipidfiltration and direct adsorption of lipoprotein using hemoperfusion (DALI). All methods are efficient,but their cost restricts LDL apheresis to the treatment of FH. Indications could include other diseases, but controlled trials are still lacking.

Cord blood (CB) stem cells for wound repair. Preliminary report of 2 cases.

In 2 patients, to promote skin wound/lesion repair we used fibrin-platelet glue combined with HLA compatible (2 mismatches accepted) buffy coats containing CD 34+ cord blood cells. The fibrin platelet glue was prepared with autologous apheresis platelets and cryoprecipitate. The original product was divided into 3 and 4 aliquots respectively for a correspondent number of applications. At each application, the margins of the lesion were infiltrated with 3 ml of cord blood buffy coat, containing 30 x 10(3) CD 34+ cells. No graft versus tissue reaction was seen in our patients in a follow-up of 3-7 months. The level of improvement, scored arbitrarily from 0 to 4, was 3 and 4, respectively. Our conclusion is that the use of cord blood cells along with fibrin platelet glue is of clinical interest.

Cytogenetic clonality in chronic myelomonocytic leukemia studied with fluorescence in situ hybridization.

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome (MDS) subtype, characterized by monocytosis, dysgranulocytosis and a low number of blast cells in the peripheral blood (PB). The clonal nature of MDS has been demonstrated by various techniques: the stem cell involved initially is capable of myeloid and lymphoid differentiation. Fluorescent in situ hybridization (FISH) is a technique which can be utilized without any pretreatment on whole interphase cells. In this study leukocytes of PB Wright-stained smears from four CMML patients with trisomy 8 (three cases) and 9 (one case) have been analyzed by FISH. Utilizing a probe for the centromere of chromosome 8 and for the heterochromatic region of chromosome 9, we observed the cells involved by trisomy. In each of the four cases neutrophils, eosinophils, basophils and monocytes may show trisomy 8 or 9, whereas lymphocytes resulted disomic. The comparison between leukocytes morphology and genotype suggests that the supernumerary chromosome does not influence cellular differentiation and maturation. We conclude that FISH analysis of PB leukocytes of patients with CMML is informative when studying the clonality of the disease. Chromosomal abnormalities seem to involve a hematopoietic cell committed to myeloid but not lymphoid differentiation. Trisomies 8 and 9 seem to confer some proliferative advantage without influencing the morphologic characteristics of leukocytes. Other causes will be investigated to explain dysmorphisms of neutrophils and monocytes typical of this disease.

Trisomy 8 detection in Ph+ CML patients using conventional cytogenetic and interphase fluorescence in situ hybridization techniques.

We examined bone marrow (BM) cells from 6 Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) patients in advanced phase of the disease using conventional cytogenetic techniques and fluorescence in situ hybridization (FISH) for detection of an extra chromosome 8. All patients showed mosaicism for trisomy 8 as a secondary chromosome abnormality. For FISH, we used the D8Z5 probe specific for the centromeric region of chromosome 8 and analyzed 300 interphase nuclei and a variable number of mitoses for each patient. The percentages of metaphases carrying trisomy 8 were similar with both techniques, whereas the percentage of interphase nuclei showing three hybridization spots indicative of trisomy 8 was significantly lower than that in metaphases. This finding suggests that cells with a supernumerary chromosome 8 may have a cell cycle time shorter than that of disomic cells.

Cytogenetic analysis in essential thrombocythemia at diagnosis and at transformation. A 12-year study.

Between 1979 and 1988, 86 patients with clinical and laboratory findings consistent with essential thrombocythemia (ET) were karyotyped at diagnosis. Four patients showed a Philadelphia chromosome and underwent myeloid blastic crisis 2.5-4.5 years later, strongly suggesting a diagnosis of chronic myeloid leukemia. A partial deletion of 13q was seen in another case evolving to leukemia a few months later. Five cases, with normal karyotypes at diagnosis, developed acute transformation after more than 5 years of chronic phase. Four of them showed unusual clonal karyotype abnormalities involving different chromosomal regions. The numerical abnormalities found were trisomy 22 in one case, and trisomy 8 and 19 in another, while structural changes included partial deletion of 5p, partial deletion of 6q, pericentric inversion of chromosome 12, and partial deletion of 20q. These abnormalities have not been previously reported in ET. This investigation confirms the absence of a specific cytogenetic marker for ET, and the infrequent transformation to acute leukemia, often with chromosomal clonal disorders.