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Purpose: Myelofibrosis is a common, poor-prognosis feature of myelodysplastic syndromes (MDS). The aim of this work was to evaluate quantitatively the extent of the juxtatrabecular fibrosis in primary MDS and in secondary myelodysplasias, along with the presence of immature precursor cells in anomalous position, that is, the displacement of granulopoiesis from the paratrabecular area to central positions., Patients and Methods: Twenty-seven bone marrow samples were examined: 9 from primary MDS, 9 from secondary myelodysplasias, and 9 normal. The percentage of myeloblasts and promyelocytes with nucleoli located in the central areas was estimated, in an attempt to correlate such feature with the degree of juxtatrabecular fibrosis. The analysis of data was performed with the Kruskal-Wallis test, values of p < 0.01 being significant., Results: Sectorial juxtatrabecular fibrosis was present in all the myelodysplastic samples, ranging from 6% to 55% of the trabecular surface; the highest values found in the controls were about 3.6% (p < 0.01). Although the juxtatrabecular fibrosis figures are higher in secondary MDS, the difference is not significant with regard to the primary MDS in the number of patients studied here. The count of myeloblasts and promyelocytes with nucleoli present in the MDS was significantly greater than that of the control group. The number of promyelocytes with nucleoli was significantly higher in the primary MDS with respect to the secondary ones, whereas no significant difference was seen between the two types of MDS regarding the myeloblast count., Conclusions: The increased number of central immature precursor cells in MDS was not directly correlated with the extent of the juxtatrabecular fibrosis. Although the number of cases is small, the fact that the juxtatrabecular fibrosis was higher in the two deceased patients in the series (49% and 56%, respectively) suggests a poor-risk prognosis for such finding.

We investigated the hematological and clinical status of 145 patients with de novo myelodysplastic syndrome (MDS), 14 of whom (10%) had eosinophilia in the bone marrow (MDS-Eo). Most of these 14 patients had severe anemia. Their bone marrow cells exhibited trilineage dysplasia and some morphological abnormalities in the eosinophils, including disproportion of eosinophilic granules, basophilic granules, a ring-shaped nucleus, and vacuolation in the cytoplasm. However, these abnormalities were less prominent than those of acute myelomonocytic leukemia with eosinophilia (FAB: M4Eo). Three of the 14 MDS-Eo patients had refractory anemia (RA), seven had RA with excess of blasts (RAEB), and four had RAEB in transformation. Cytogenetic analysis revealed chromosomal abnormalities in 12 of 13 MDS-Eo patients (92%), in particular, there were major karyotypic abnormalities (MAKA) in eight patients (62%). Cytotoxic agents were not effective in the treatment of four patients after leukemic transformation occurred. These four patients died of the leukemic transformation while seven died of bone marrow failure. The other three MDS-Eo patients are still alive; two of them have already transformed to a leukemic phase. The duration of survival of these patients was significantly shorter than that of the other MDS patients. These findings suggest that bone marrow eosinophilia in MDS may be a poor prognostic factor that is strongly related to the existence of MAKA.

We describe a case characterized by the onset of bone marrow hypoplasia. After treatment with steroid and anabolic compounds, it evolved into a myelodysplastic syndrome (MDS) as demonstrated by morphological and karyotypic analysis. Despite the dysplastic nature of the disorder, a unique feature was its association with a high platelet count. The pathogenesis of the thrombocytosis could not be clearly identified. In fact, the course of the disease was complicated by severe infections that, together with therapy, could have played some role in stimulating thrombopoiesis. However, since MDS can precede or follow a chronic myeloproliferative disease, it is also possible that the platelet elevation in our patient could have been sustained by a primitive thrombocyte disorder.

A four-year-old girl presenting with fever and purpuric lesions was diagnosed with systemic vasculitis based on her clinical and laboratory findings. She also had homozygote beta thalassemia. Oral steroids were administered and during the course of her treatment she developed necrotizing lesions on her extremities along with severe myalgia and an autoimmune refractory anemia. Autoantibodies against the Rh antigen causing a persistent hemolysis of her erythrocytes were detected in her serum. Since no improvement in her skin lesions and autoimmune hemolytic anemia was achieved with bolus methylprednisolone therapy and cyclophosphamide, plasma exchange was performed. After three sessions of plasma exchange, her immune complex and autoantibody levels gradually declined and a remission in her clinical and laboratory findings was achieved. We suggest the use of plasma exchange along with conventional therapy for similar cases with ongoing immunologic injury.

Background: Treatment of myelodysplastic syndromes (MDSs) remains unsatisfactory. A limited number of reports provide contradictory information on whether danazol, a synthetic androgen, may be useful in patients with MDS., Methods: Between 1984 and 1992, 76 patients were treated with danazol (Danatrol, Winthrop) in an open nonrandomized study. Clinical status, blood counts, differential marrow cell counts, transfusion requirements, and liver enzymes were monitored at 3-month intervals during and 6 months after discontinuation of therapy. The authors present the retrospective analysis of this cohort of patients., Results: This study shows a limited usefulness of danazol in patients with MDS. Blood counts were not significantly changed during danazol administration; neither were transfusion requirements. Overall survival and the rate of leukemic transformation were not affected when compared with 50 untreated patients or with data available in the literature. An increase in platelet numbers in four patients and in hemoglobin level in one patient was observed; these patients were unremarkable and were not transfused before initial danazol therapy; therefore, changes in blood counts were of limited clinical significance. The search for subgroups of patients likely to have a favorable response was unsuccessful. Side effects of danazol were limited. In addition, this study provides information on the frequency of antiplatelet antibodies and other autoantibodies in patients with MDS., Conclusions: This study does not support a positive effect of danazol in patients with MDS during long term follow-up. Anecdotal positive evolution in a few patients cannot be formally ascribed to danazol. These results should be interpreted by comparison with previous publications that report on small numbers of patients with limited follow-up. Based on these data, the authors cannot recommend the systematic use of danazol in MDS.

A 31-year-old woman presented with fever and arthralgia. Despite treatment with antimicrobials and corticosteroids, her symptoms persisted. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia (RA) was made by pancytopenia, dysplasia, and trisomy 8. Cultures of bone marrow, blood, and gastric juice showed Mycobacterium avium-intracellulare (MAI). She was treated with antimycobacterial drugs and recombinant human G-CSF/M-CSF and showed an initial response, but spike fever recurred and pancytopenia progressed. Hepatosplenomegaly and marked retroperitoneal lymphadenopathy were revealed, indicating further dissemination of MAI. Treatment with recombinant human GM-CSF and very-low-dose cytosine arabinoside, was started but was not effective. This case showed significant reduction in peripheral blood T-lymphocytes, especially the CD4+ population, and low immunoglobulin levels. Immunodeficiency state associated with long-term steroid therapy and MDS seemed to contribute to the development of the disseminated infection with MAI.

We report a case with refractory anaemia terminating in an acute leukaemia, which showed from the very beginning an intense eosinophilia that lasted for the whole disease, and in which the eosinophilic metaphases, as documented by the 'Morphology, Antibody, Chromosome' technique, were normal. An unusual karyotypic anomaly in the setting of a myelodysplastic syndrome could only be detected in the neutrophilic series. A general approach to detect structural aberrations of specific human chromosomes in metaphase cells by chromosomal in situ suppression hybridization of DNA libraries from sorted human chromosomes has been applied for chromosomes 11, 3 and 2, in order to identify an extra copy of chromosome 2.

Two patients with colitis and refractory anaemia requiring multiple transfusions are described. In one the anaemia was detected at the onset of colitis before drug treatment; in the other it started after 21 years of treatment with sulphasalazine and during an exacerbation of colitis with perianal abscess for which he had just been started receiving prednisolone, cofluampicil and metronidazole. Glomerulonephritis developed two weeks after the onset of anaemia. These findings together with a recent report of four patients with Crohn's disease and refractory anaemia suggests that the association may be more than coincidental and may be immune mediated.

Two asymptomatic paravertebral thoracic masses occurred in a 65-year-old patient with isolated macrocytosis. The largest one measured 8 cm and was surgically resected with a presumptive diagnosis of schwannoma. This thoracic mass was hemorrhagic, encapsulated, and composed of fat and hematopoietic tissue. While extramedullary hematopoietic tumors usually occur in patients with severe chronic hemolytic anemia, our report suggests that such lesions must be considered in the differential diagnosis of posterior mediastinal mass in patients without clinical evident anemia.

Four months after the diagnosis of refractory anemia, a 60-year-old patient developed acute leukemia with blast cells that were poorly differentiated by morphology and clearly myeloid by immunophenotyping. Cytogenetic analysis performed at leukemization showed trisomy 13. An extra copy of chromosome 13 has already been reported in a few cases of acute leukemia and myelodysplastic syndrome.

The authors report an unusual case of myelodysplastic syndrome (MDS) associated with relapsing polychondritis (RP), which developed at almost the same time as MDS. The initial diagnosis was MDS, refractory anemia (RA) subtype, according to the FAB classification. Symptoms of RP were apparently controlled by oral administration of prednisolone (PSL), although MDS was not. Within 1 month after the diagnosis, monocytosis and thrombocytopenia without excess of blasts became prominent and transformation from RA to chronic myelomonocytic leukemia (CMML) was recognized. Combination chemotherapy including daunorubicin (DNR) and cytosine arabinoside (ara-c) did not subdue the progressive monocytosis and thrombocytopenia. Finally, the patient died of pulmonary hemorrhage 3 months after the onset of the disease. The prognosis of MDS may be poorly influenced by association with RP.

The study describes progression of refractory anaemia with ring sideroblasts (RARS) of 3 years' duration to B-acute lymphoblastic leukaemia (ALL). Development of ALL in this patient was preceded by the deterioration of dyserythropoiesis, leukopenia and an increase of blasts in the bone marrow. Our case may represent an additional evidence to the hypothesis that a primary pathogenetic lesion in myelodysplastic syndrome occurs at the level of the pluripotent stem cell.

At transformation of refractory anemia with ring sideroblasts to acute nonlymphocytic leukemia (ANLL) the bone marrow cells of a 75-year-old woman showed three different karyotypes, i.e., 46,XX,46,XX,t(1;3)(p36;q21) and 46,XX,t(1;3)(p36;q21),t(14;17)(q32;q21). She received no antileukemic therapy, and 1 year later, all her bone marrow cells were t(1;3)(p36;q21),t(14;17)(q32;q21). In association with the onset and first 11 months of ANLL, the platelet count increased 10-fold to a peak of 750 x 10(9)/L, providing further evidence that the t(1;3)(p36;q21) translocation causes stimulation of thrombopoiesis. Six months after transformation, her red cells showed reduced expression of A and Leb antigens. Serum alpha-n-3-acetylgalactosaminyl transferase (blood group A transferase) and red cell adenylate kinase were both reduced. The genes for both these substances are at 9q34, which suggests an abnormality here, although cytogenetically chromosome 9 appeared normal. This is the first case with t(1;3)(p36;q21) to show concurrent loss of red cell antigens and the first report detailing the course of untreated ANLL with t(1;3)(p36;q21).

The paper deals with the progression of idiopathic refractory sideroblastic anaemia (IRSA) and its transformation to acute B lymphoblastic leukaemia (ALL). Attention is paid to haematological changes prior to leukaemia development. Acute leukaemia was best expressed in this patient by severe deterioration of dyserythropoiesis, leukopenia, and by an increase of blasts in the bone marrow over 5%. Our patient is an additional evidence to the hypothesis of the common lymphohematopoietic progenitor.

A 46-year-old man diagnosed as refractory anemia was hospitalized because of high fever and extensive erythema with ulceration in the femoral region. His peripheral blood examination showed marked leukocytosis (WBC 31,500/microliter:neutrophilic 90%) and anemia (Hb 8.6 g/dl. In spite of administration of antibiotics, the cutaneous ulcer rapidly extended to the right thigh and became necrotic. The bacterial culture of the cutaneous lesion showed no growth and a skin biopsy showed infiltration of neutrophils in the dermis. He became afebrile and his cutaneous lesion improved after administration of corticosteroid. When the dose of corticosteroid was decreased, cutaneous erythema and nodules appeared at other sites repeatedly, and disappeared after the dose of corticosteroid was increased. The cutaneous lesions had characteristics of both Sweet's syndrome and pyoderma gangrenosum. Moreover, the patient had immunological abnormalities and decreased neutrophilic functions (chemotaxis and O2- generation). Thus, it was suggested that the cutaneous lesions of this patient could be diagnosed as "neutrophilic dermatosis of MDS", and corticosteroid was recognized to be very effective in treating these skin lesions.

On the example of a 66-year-old man the authors describe the atypical course of myelodysplastic syndrome of the type of refractory anaemia with dominating thrombocytopenia, manifested by massive haemorrhage, mostly into the digestive tract. In view of the increasing number of patients with this diagnosis, the authors attempted to elaborate the approximate costs of treatment of the condition in a medical department.

A case of acquired haemoglobin H (HbH) disease with underlying myelodysplastic syndrome in the form of acquired idiopathic sideroblastic anaemia is reported. Family studies and subsequent drop in HbH percentage strongly supported the acquired nature of the defect.

Sarcoidosis has been observed in association with numerous blood dyscrasias including lymphoma, leukemia, and multiple myeloma. This report describes a patient with sarcoidosis and a refractory anemia whose bone marrow karyotype showed deletion of the long arm of chromosome 5, consistent with a myelodysplastic syndrome. Concurrent sarcoidosis and myelodysplasia may relate to the continued availability of cytokines as a consequence of repeated macrophage, T-cell, and B-cell interactions, with evolution to the 5q- abnormality. This association may merit specific attention in the future approach to the diagnostic evaluation in certain patients with sarcoidosis.

We present a patient with refractory anemia (RA) who developed Sweet's syndrome during the treatment of recombinant human granulocyte colony-stimulating factor (rhG-CSF). A 30-year-old man was admitted to the hospital for evaluation of anemia. He was diagnosed as MDS (RA). As a phase II study in MDS, rhG-CSF therapy was begun. Fever associated with cutaneous lesion developed over the left shoulder. Antibiotics showed no effects. Skin biopsy revealed Sweet's syndrome. This skin lesion disappeared thoroughly with discontinuance of G-CSF and administration of prednisolone. To examine whether Sweet's syndrome was related to the G-CSF therapy, we analyzed the effect of G-CSF on the function of patient's neutrophils. However, the function of patient's neutrophils was not activated by G-CSF administration.

In 27 patients initially diagnosed as refractory anaemia (RA) or RA with sideroblasts (RA-S) according to the FAB-classification a number of clinical, morphological and cytogenetic parameters were correlated for prognostic significance. From these correlations it emerged that severe cytopenia is centrally positioned with regard to clinical course in RA and RA-S. Positive correlations were found to initial diagnosis, clonal cytogenetic abnormalities, progression to RA with an excess of blasts (RAEB) or acute myeloid leukaemia (AML), the percentage of bone marrow blast cells and prolonged half life for radioactively labeled iron. The degree of peripheral blood granulocytopenia, alone, was correlated to bone marrow hypoplasia. Moreover, the frequency of abnormal karyotypes was inversely correlated to bone marrow cellularity and proportional to the frequency of bone marrow blast cells. From these relationships it may be proposed that chromosome abnormalities are associated with prolonged blast cell generation times and inhibition of blast cell maturation resulting in reduced marrow cellularity and blast cell accumulation, and, in the peripheral blood, falling percentages of neutrophil granulocytes. With the blast cell accumulation the bone marrow cellularity again becomes hyperplastic and the preleukaemic condition is transformed into RAEB or AML.

We present four patients with acute nonlymphocytic leukemia, one M2 and three M4 French-American-British (FAB) types and one patient with refractory anemia with excess of blasts in transformation who at diagnosis had trisomy of chromosome 4 as the primary karyotypic anomaly. This chromosome anomaly probably defines a previously undescribed subset of acute nonlymphoid leukemias. Hematologic characteristics commonly found in these patients were dysplastic features of all bone marrow lineages, suggesting that trisomy 4-associated disorders involve the early myeloid hematopoietic stem cell.

A case of iron deposition in the labial accessory salivary glands associated with prominent xerostomy and xerophtalmy is reported. Suffering from a myelodysplastic syndrome with refractory anaemia, this patient received multiple transfusions over the past 7 years. A transfusional haemosiderosis gradually developed. Histopathologic examination of accessory salivary glands demonstrated haemosiderin deposition in the serous alveoli and in the epithelial cells of intercalated and interlobular ducts. A relationship between the iron deposition in the salivary glands and the development of the sicca syndrome is suggested. The literature related to iron deposition in salivary glands and sicca syndrome is reviewed.

We report 2 patients with idiopathic refractory sideroblastic anemia who developed chronic myelomonocytic leukemia 1 to 5 yr later. This observation supports the decision of the FAB cooperative group to include both conditions in the category of myelodysplastic syndrome.

We report a case of 5q- syndrome that progressed to acute nonlymphocytic leukemia after 9 years of clinically and morphologically stable disease. The transition from the chronic to the leukemic phase was characterized by the appearance of an additional cytogenetic anomaly [inv(2)] in the cell carrying the 5q-, together with the expansion of a clone showing an apparently normal karyotype.

A 69-year-old man was diagnosed as having refractory anemia (RA), accompanied by pancytopenia of two years' duration, myelodysplasia in all three cell lines, abnormal karyotype of 46, XY, 20q--in bone marrow cells, and positive antinuclear and DNA antibody tests. One year after his first visit, he developed arthritis and maculopapular erythematous rashes. The histologic features of the skin lesions were similar to those of in discoid lupus erythematosus. He was diagnosed as having systemic lupus erythematosus supervening refractory anemia.

The association between leukemic transformation and various features recorded at presentation in patients with refractory anemia with excess of blasts and with or without ringed sideroblasts was analyzed in 255 patients using the proportional hazard model. Features associated with higher transformation rates were: higher values of blasts in peripheral blood or bone marrow; serum haptoglobin; vitamin B12; megakaryocytes in bone marrow; morphological abnormalities in granulo- or megakaryocyte series; male sex; circulating megakaryocytes in peripheral blood; older age; and lower ringed sideroblast proportion. Multivariate analysis was also performed using the following predictor variables: presence or absence of refractory anemia with excess of blasts; sex; abnormal granules in granulocytes; age; and mononuclear large megakaryocytes. Patients were divided arbitrarily into low (hazard ratio, less than 0.45), intermediate (hazard ratio, 0.45-1.85) and high (hazard ratio, greater than 1.85) risk groups. The cumulative leukemia-free rates in the low and intermediate risk groups showed long plateau phases at 95 and 71%, respectively, while in the high risk group, the rate was 10% at 5 years. For clinical purposes, the low risk group should be considered to have nonpreleukemia and the high risk group to have preleukemia.