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The case-control study was conducted in Belgrade (Yugoslavia) during the period 1994-1998. The objective of the study was to investigate factors related to the occurrence of multiple myeloma (MM). The study group consisted of 100 newly diagnosed MM patients and the same number of matched hospital controls. In the analysis conditional univariate and multivariate logistic regression were applied. According to multivariate analysis the following factors were significantly related to MM: smoking > or =25 cigarettes per day (Odds ratio--OR=6.7, 95% confidence interval--95% CI=1.3-34.3); having more than two brothers (OR=2.7, 95% CI=1.3-5.3), rheumatoid arthritis in personal history (OR=4.2, 95% CI=1.2-14.8), and frequent (4-7 times per week vs. lower frequency) consumption of yogurt (OR=3.1, 95% CI=1.6-6.0) and vegetables (OR=0.4, 95% CI=0.1-1.0).

Background: The aim of this work was to estimate the significance of a dynamic study performed during the first 20 minutes after autologous (111)In-oxinate-platelets injection in patients with chronic immune thrombocytopenic purpura (ITP). Two hypotheses were tested: a) dynamic study indicates the place of platelet sequestration; b) dynamic study reflects the quality of platelet separation and labelling procedure., Material and Methods: Thirty-nine persons were investigated: 25 with shortened platelet life span (ITP), and 14 with normal platelet life span (6 healthy subjects and eight patients with myelodysplastic syndrome--MDS). Platelet blood count on the day of platelet labelling, general yield of platelet labelling (GYL), differential yield of platelet labelling (DYL), platelet life span, dynamic study with initial platelet accumulation in the liver (IPAL), sequential static study for determining the platelet sequestration index (SI) and platelet sequestration site (SS) were investigated., Results: Two types of labelled platelet kinetics were determined in both groups of patients: IPAL < 20% and IPAL > 20%. A statistically significant difference in GYL and DYL was noted between the patients with IPAL < 20% and IPAL > 20%. No significant difference was registered in platelet blood count, life span, SS and SI between the two groups of patients. Both yields of platelet labelling were higher in the group with IPAL < 20%. There was no correlation between IPAL and platelet SI, or between IPAL and platelet SS., Conclusions: Dynamic study with (111)In-platelets cannot predict platelet sequestration site in ITP patients, but it is a useful and sensitive method of platelet labelling procedure quality control.

A 71-year-old woman presented with malaise, skin bruising, epistaxis, and gingival bleeding of recent and prompt onset. There was no adenopathy. The liver and spleen were not enlarged. Bone marrow aspirate showed a polymorphous infiltration with lymphocytes (22%), typical Marschalko plasma cells (16%), plasmacytoid lymphocytes (29%), lymphoblasts (8%), and immunoblasts (13%). The immunoblasts morphologically resembled lymphosarcoma cells with a frequent "clover-leaf" appearance. An IgM paraprotein concentration in serum was 38.5 g/L. The bone marrow histopathology confirmed the presence of heterogenous cell infiltration, with 30% of the population being comprised of lymphoblasts and immunoblasts. In order to differentiate a polymorphous variant of Waldenström macroglobulinemia (WM) from the more common small cell lymphocytic lymphoma (SLL) in anaplastic metamorphosis, flow cytometric studies were performed on marrow specimens. A typically bright surface IgM (lambda) was demonstrated with a less bright CD38. Further immunophenotype was HLA-DR+, CD19+, CD20+ and CD10-, CD22-, T-Ag- and kappa light chain- expression. This corroborated the diagnosis of an extremely rare, polymorphous variant of WM. The marrow cytogenetics disclosed 50% (10/20) pathologic metaphases 48,X,dup(X)(p21p22),der(2), +5,del(6)(q11q21), +12,inv(16)(p13q22), del(17) (p12), and 50% normal metaphases. The patient was treated with a LOPP protocol. She failed to respond and died 5 months after the diagnosis with myocardial and renal insufficiency complicating a pronounced pancytopenia in the peripheral blood.

The relationship between the extent of bone marrow reticulin and collagen fibrosis and the concentration of granulocytic (CFU-GM), erythroid (BFU-E) and megakaryocyte (CFU-Mk) progenitor cells in the peripheral blood of patients with primary agnogenic myeloid metaplasia (AMM) and secondary myelofibrosis (sMF) has not been definitively correlated. We studied 23 patients with established diagnosis of AMM and 12 patients with sMF for the extent of reticulin and collagen bone marrow fibrosis and for the spontaneous colony (sCFU-GM, sBFU-E and sCFU-Mk) formation. The control group consisted of 11 healthy volunteers. Trephine biopsy of the posterior iliac crest was performed in all individuals studied to determine the type and degree of reticulin and collagen fibrosis. Gomori's silver impregnation technique was used. sCFU-GM, sBFU-E and sCFU-Mk colony formation was related positively to spleen size, the white blood cell counts and the degree of collagen fibrosis in AMM (p < 0.01). Stimulated CFU-GM were also significantly correlated with the degree of bone marrow reticulin and collagen fibrosis. There was no correlation between the extent of peripheral blood progenitor concentration and the degree of bone marrow reticulin or collagen fibrosis in sMF and in control individuals. In conclusion, the extent of bone marrow fibrosis is significantly correlated with the peripheral blood progenitor colony formation in AMM but not in sMF.

A case of primary nonsecretory plasmacytoma of the spleen is reported. On laparotomy and splenectomy a 920 g spleen was removed, measuring 16 x 14 x 6 cm. The cut surface of the entire spleen showed that the tumour occupied most of the splenic tissue. A bone marrow aspirate and trephine, skeletal survey showed no signs of myeloma. Biopsy of the liver and regional lymph nodes was normal. Immunocytochemistry of the splenic tumour showed positivity for pan-B and plasma cell markers. After splenectomy the patient was treated with chemotherapy according to protocol VBCMP (M2).

Between February 1992 and November 1996 we treated 30 newly diagnosed acute promyelocytic leukaemia (APL) patients either with oral all-trans-retinoic acid (ATRA) alone (45 mg m-2) or with a simultaneous combination of ATRA (45 mg m-2), daunorubicin (DNR, 50 mg/m-2 for 3 days) and cytosine arabinoside (ARA-C, 200 mg m-2 for 7 days). There were 15 patients in each group. Patients with a white blood cell count < 5 x 10(9)/l at diagnosis received only ATRA as an induction therapy. Patients with initial white blood cell count > 5 x 10(9)/l received a combination of ATRA, DNR and ARA-C as an induction therapy. Within the first 20 days of induction, there were two early deaths in the group of patients receiving only ATRA, and six early deaths in the group of patients treated with a combination of ATRA and chemotherapy. Ten out of 13 patients (76.9%) receiving ATRA only achieved complete remission (CR) whereas seven out of nine patients (77.8%) receiving ATRA with chemotherapy achieved CR. Initial median peripheral white blood cell counts were significantly lower in the group of patients treated with ATRA alone (2.3 x 10(9)/l) than in the group of patients receiving ATRA and chemotherapy (14.0 x 10(9)/l). Morphological evidence of differentiation was noted in all patients entering CR. Patients in both groups who achieved CR received one course of standard '3 + 7' chemotherapy (DNR 45 mg m-2, 1-3 days, ARA-C 200 mg m-2, 1-7 days) followed by two courses of standard '2 + 5' chemotherapy (DNR 50 mg m-2 1-2 days, ARA-C 200 mg m-2 1-5 days) as a consolidation therapy. Patients not achieving remission (three out of 13 in the ATRA group and two out of nine in ATRA+chemotherapy group) did not respond to salvage chemotherapy and all died within 3 months of diagnosis. Only one out of 10 patients (10%) in CR, treated with ATRA is in relapse after 18 months. In patients treated with ATRA alone two out of 10 (20%) survived 58 months following diagnosis whereas in the ATRA+chemotherapy group one out of seven has already survived their 58th month since diagnosis. Four out of eight patients with an early death died of retinoic acid syndrome. Other toxicities due to ATRA were minimal (cheilitis, xerosis, dermatitis, diarrhoea, liver damage or pseudotumor cerebri).

By application of morphological and ultrastructural methods for identification of apoptosis, we analyzed the incidence of morphologically evident apoptosis in the bone marrow of 30 patients with myelodysplastic syndrome (MDS), and in the bone marrow of 12 healthy individuals. According to FAB classification, out of 30 patients, eight (26.6%) had refractory anemia, three (10%) had refractory anemia with ringed sideroblasts, 14 (46.6%) had refractory anemia with excess of blasts and two (6.8%) had refractory anemia with excess of blasts in transformation. Three patients (10%) had chronic myelomonocytic leukemia. Cells in apoptosis were examined on semithin slides and expressed as the apoptotic index (AI) (percent counted on at least 1000 cells). An overall increase in apoptosis in patients with MDS was found (median AI in patients vs controls, 3.13% vs 1.05%, P < 0.01 by Mann-Whitney U test). Also, negative correlation between AI and white blood cell count was found (linear r= -0.53, or Spearman rank R= -0.52, both P < 0.01). In patients with evident karyotype changes AI was not higher than in patients with normal karyotype. This suggests that discrete alterations in apoptosis are present even in karyotypically 'normal' clones. Our results strongly support the hypothesis that apoptosis has a role in ineffective hematopoiesis and may be a mechanism responsible for the paradox of hypercellular bone marrow and peripheral blood pancytopenia in MDS.

Within a period from March 1983 to November 1988, 93 newly diagnosed patients with multiple myeloma, 47 men and 46 women aged from 41 to 80 years were treated with protocol VBCMP-M2. A response was achieved in 30 (60%) patients in stage II and 22 (51%) in stage III, the overall response rate being 56%. 41% of all patients entered plateau phase, more frequently in stage II (46%) than in stage III (37%) patients. The median survival of all patients was 35 months. Comparing these groups of patients with other series from the literature, we were not able to demonstrate any advantage of this multidrug combination over other combinations or even melphalan and prednisone alone.

Tuberculosis of the liver is rare even in areas where tuberculosis is widespread. Isolated tuberculosis of the liver is extremely rare. It usually presents as a nodular - pseudo-tumorous form. Tuberculosis of the bile ducts is even less frequent. A 37 year old woman with nodular - pseudotumorous form of tuberculosis of the liver is presented. The diagnosis was established after surgical biopsy and histology. It may be caused by the bovine type of the bacillus. The patient had an excellent response to tuberculostatic drugs. Tuberculosis of the liver must be taken into account in the differential diagnosis of the liver masses.