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We report the case of a 71-year-old man with chronic myelomonocytic leukemia who developed cardiogenic shock twice due to a stenosis of the left main trunk of the coronary artery. We performed coronary artery bypass grafting to the left anterior descending artery with the left internal thoracic artery without using a cardiopulmonary bypass. The patient had no infection, leukemic transformation, or cardiac event after the surgery. Off-pump coronary artery bypass grafting is safe and useful for high risk patients, such as those with leukemia.

This report describes the case of an 8-month-old infant with a diagnosis of juvenile myelomonocytic leukemia (JMML) and type 1 neurofibromatosis that presented progression to B lineage acute lymphoid leukemia (ALL). The same rearrangement of gene T-cell receptor gamma (TCR gamma) was detected upon diagnosis of JMML and ALL, suggesting that both neoplasias may have evolved from the same clone. Our results support the theory that JMML may derive from pluripotential cells and that the occurrence of monosomy of chromosome 7 within a clone of cells having an aberrant neurofibromatosis type 1 (NF1) gene may be the cause of JMML and acute leukemia.

A 3-year-old boy was referred for treatment of chronic myelomonocytic leukemia. Radiological examination revealed a generalized increase in bone density, harlequin face, Erlenmeyer flask deformity of the metaphysial regions and pathological fractures, findings which are characteristic of osteopetrosis.

The most common myeloid malignancy seen in children with neurofibromatosis type 1 (NF-1) is juvenile myelomonocytic leukemia (JMML), a myeloproliferative disease. The vast majority of these children have inherited the neurocutaneous disease from an affected mother; boys are more often affected than girls. We present the rare finding of a 7-year-old girl with NF-1 who developed JMML. She inherited her NF-1 from the father. At the time of her initial presentation, clonogenic assays of bone marrow mononuclear cells did not show the spontaneous growth of granulocyte-macrophage colony-forming units or hypersensitivity to granulocyte-macrophage colony-stimulating factor that is characteristic of this disorder. After 1 month, repeat evaluations of the patient's clinical and laboratory test results became fully consistent with those for a diagnosis of JMML. This illustrates the stepwise evolution of this myeloproliferative disorder in NF-1 and the importance of close follow-up and reassessment of these patients. Our case is only the second report of JMML in a girl who inherited NF-1 from her father.

A 33-year-old woman developed a bullous PG precursing a chronic myelomonocytic leukemia (CMML) complicated by life-threatening, disseminated, intravascular coagulation after administration of systemic corticosteroids in combination with immunosuppressant and antibiotic agents. Although the association between PG and leukemia, as well as the coincidence of disseminated intravascular coagulation (DIC) and leukemia, is well known, a premonitoring effect of PG in combination with DIC preceding the diagnosis of chronic myelomonocytic leukemia in the same patient has not been reported recently.

The c-kit mutation Asp-816-->Val is detectable not only in neoplastic mast cells (MCs) in patients with systemic mastocytosis (SM) but also in most associated hematologic non-MC lineage disease (AHNMD). In order to prove a monoclonal disease evolution we investigated DNA of pooled microdissected single cells for the presence of the mutation in a patient with SM and concomitant chronic myelomonocytic leukemia (CMML). LightCycler melting curve analysis and direct sequencing of nested polymerase chain reaction (PCR) products revealed the c-kit mutation in tryptase-positive MC and in leukemic CD15-positive cells in bone marrow infiltrates, but not in colonic epithelial cells, thus, suggesting a monoclonal evolution of SM and concurrent CMML on the basis of a somatic mutation in a common hematologic progenitor.

Autoimmune paraneoplastic syndromes are commonly encountered in patients with myelodysplastic syndromes (MDS). A review of case reports and small series suggest as many as 10% of MDS patients may experience various autoimmune syndromes. Clinical manifestations of such phenomena may include an acute systemic vasculitic syndrome, skin vasculitis, fever, arthritis, pulmonary infiltrates, peripheral polyneuropathy, inflammatory bowel disease, glomerulonephritis, and even classical connective tissue disorders, such as relapsing polychondritis. On the other hand, asymptomatic immunologic abnormalities have also been reported in these patients. These autoimmune manifestations frequently respond to immunosuppressive agents including steroids and occasional hematologic responses to steroid therapy have also been reported. We report five patients with history of MDS who manifested different spectrums of autoimmune phenomena including: pyoderma gangrenosum (PG), vasculitis, Coombs negative hemolytic anemia, idiopathic thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy (CIDP). We also review the incidence, nature, course and response to therapy of these manifestations and discuss potential pathogenic mechanisms.

Purpose: To describe a case of peripheral keratitis in a patient with an acute exacerbation of chronic myelomonocytic leukemia (CMML)., Method: Case report and review of the literature., Results: This is the second reported case of peripheral keratitis in a patient with CMML. The previously reported patient presented with peripheral keratitis that led to the diagnosis of leukemia. Our patient had an established diagnosis of CMML, and peripheral keratitis occurred during an acute exacerbation of his chronic leukemia. The keratitis resolved with topical corticosteroids in our patient., Conclusion: Leukemia should be included in the differential diagnosis of peripheral keratitis. Elevated white blood cell count with abnormal differential in a patient with peripheral keratitis may help to establish a diagnosis of leukemia or identify an acute exacerbation of chronic leukemia.

We present the case of a patient diagnosed as having presumed idiopathic thrombocytopenic purpura (ITP) who subsequently developed chronic myelomonocytic leukaemia (CMML) after an interval of 16 months. A variety of peripheral cytopenias are commonly seen in myelodysplastic disorders (MDS), and autoimmune phenomena, including secondary ITP, are well described, especially in cases of CMML. We would advocate evaluation for possible MDS/CMML by morphological examination of the peripheral blood/bone marrow in adult patients presenting with isolated thrombocytopenia, especially if there is subsequent development of additional peripheral cytopenias, monocytosis or hepatosplenomegaly.

A variety of systemic autoimmune disorders have been reported in patients with myelodysplastic and myeloproliferative syndromes. A possible association with polymyalgia rheumatica and giant cell arteritis has also been recognised. We report another case of polymyalgia rheumatica and one of giant cell arteritis associated with a myelodysplastic syndrome and the two first cases of giant cell arteritis associated with essential thrombocytaemia and chronic myelomonocytic leukaemia, respectively. It seems that there is a relationship between these entities, but the nature of this association is still unknown.

We present the course of three patients suffering from chronic myelomonocytic leukemia (CMML), who presented with a markedly increase of their WBC (>200 G/l). All patients were started on chemotherapy consisting of ARA-C given as continuous infusion. Due to acute respiratory insufficiency, all patients were treated in the ICCU with ventilation support. Respiratory insufficiency was most likely due to pulmonary leukostasis since pulmonary infection or edema were excluded by X-ray in all patients. Therapeutic leukapheresis was therefore initiated and resulted in a dramatic improvement in one patient. Two patients died due to multiorganic failure despite effective leukocyte depletion (>40%) and maximum supportive care. At the onset of symptoms, two patients had markedly elevated serum lactate levels most likely due to microcirculatory failure. Both patients died because of deteriorating sequelae of pulmonary leukostasis, however, the patient with marginally elevated serum lactate levels survived. Leukapheresis is an established therapeutic approach in patients with hyperleukocytosis and leukostasis, which improves the prognosis of high-risk patients. In our opinion, patients presenting with asymptomatic hyperleukocytosis may benefit from early leukapheresis, particularly when increasing serum lactate levels indicate the early onset of microcirculatory failure.

A 14-year-old male presenting with a short history of right subclavicular chest pain was found to have a mediastinal tumor. Hematologic investigations and bone marrow examination showed features of myelomonocytic leukemia. The mediastinal tumor was excised, but the surgery was complicated by massive hemorrhage. The patient's condition deteriorated postoperatively and he died a week later. The histology of the mediastinal tumor showed the typical features of an immature teratoma with a yolk sac tumor. A prominent infiltrate of leukemic blast cells was present within blood vessels and in close proximity to the yolk sac component. The karyotypic analysis of leukemic cells isolated and cultured from the bone marrow showed 50XXY, +8, +21, +iso G-group marker chromosome karyotype.

A 75-year-old female known to have a chronic myelomonocytic leukaemia and an acquired FXI deficiency (FXI level, 5%) related to a FXI inhibitor (38 Bethesda units) was admitted to the hospital for acute pneumonia associated with a bulky pleural effusion. A therapeutic puncture was found to be essential for the patient. But, such a procedure is a haemostatic challenge which requires adequate preparation. A first treatment composed of intravenous immunoglobulins and immunosuppressive therapy failed to eradicate the inhibitor and to restore a normal FXI level. In this context, steroids or FXI concentrates were not recommended. Thus, small doses of recombinant activated factor VII were used to achieve haemostasis. The procedure was successful, the tolerance was good and no adverse events occurred.

Purpose: Our purpose was to describe cutaneous manifestations associated with myelodysplastic syndromes., Methods: Data from seven patients with cutaneous vasculitis (four cases), neutrophilic dermatosis (one case), relapsing polychondritis (one case), and possible erythema elevatum diutinum (one case) in association with myelodysplastic syndrome (refractory anaemia RA, RA with excess of blasts--RAEB-, RAEB in transformation RAEBt, chronic myelomonocytic leukaemia--CMML-), and analysis of the literature were reviewed., Results: The cutaneous manifestations of myelodysplastic syndrome may or may not be specific, and may reveal hemopathy transformation. The cutaneous vasculitis are the most frequent and polymorphic. The relation with neutrophilic dermatosis is more specific; they are a spectrum of diseases including pyoderma gangrenosum, Sweet's syndrome, erythema elevatum diutinum (nuclear segmentation anomalies of neutrophils both in the skin and in the blood are a biological marker of the association). Relapsing polychondritis is significantly associated with myelodysplastic syndromes. Their pathogenesis are controversial., Conclusion: Early biopsy of cutaneous lesions in myelodysplastic syndromes is indicated. Analysis of blood cell count (and more bone marrow biopsy in relapsing polychondritis) is indispensable in these neutrophilic cutaneous or vasculitis diseases.

In chronic myelomonocytic leukemia (CMML) segregation of two subtypes has been suggested depending on WBC count-myelodysplastic (MD-CMML) and myeloproliferative (MP-CMML). In a retrospective analysis of 91 (60/31) previously untreated CMML patients, we compared the presenting clinical, haematological, laboratory and bone marrow features and examined the clinical impact of this reclassification. LDH values and bone marrow cellularity were significantly increased in MP-CMML. Median survival was significantly longer for patients with MD-CMML, progression rate was higher for MP-CMML. Patients with MD-CMML had longer median preleukemic duration; after transition to AML, MP-CMML patients had longer median survival. In MDS phase anemia was more common in MP-CMML and thrombocytopenia more common in MD-CMML whereas transfusion rates showed no difference. Evaluation of prognostic scoring systems for both groups confirmed that patients' characteristics and outcome could be well compared. Our data suggest that segregation into MD-CMML and MP-CMML is justified.

We report two cases of brain abscesses caused by Ramichloridium mackenziei, a neurotropic dematiaceous fungus that seems to be geographically restricted to the Middle East. One of the patients had chronic myelomonocytic leukemia but did not receive any chemotherapeutic agents. The other patient was a normal host. Both cases had a fatal outcome despite aggressive antifungal therapy and surgical intervention. Herein, we review all previously described cases in the literature, and discuss the epidemiology, mycology and histopathology of this life-threatening organism.

A 57-year-old woman consulted for a severe xanthelasma followed by a severe and complex systemic disease and died ten years later with xanthomas extended to the face and trunk. Her lipid and cholesterol levels were normal but HDL was below normal values. Diabetes as well as amyloidosis, paraproteinemia and Bence Jones protein in urine were not found. Three years after her initial consultation monocytosis appeared in most but not all of her hemograms. Soon after her spleen was palpable and became very large. She had three bone marrow biopsies showing progressive white cell hypercellularity that was considered as possibly reactive. During her long illness she had recurrent conjunctivitis and systemic complications such as arthritis, pleural and pericardial effusions, vasculitis, sudden deafness with Ménière-like vertigo, erythema nodosum and myositis that responded, at least partially, to steroid treatments though she remained corticoid dependent in order to control her more severe symptoms. Those complications were considered to be probably due to vasculitis or immune phenomena. After a long follow up it was clear that her disease was better classified as diffuse plane xanthoma (DPX) related to a myeloproliferative syndrome and vasculitis. Her final hospitalization was due to a severe esophageal moniliasis and she died a few days later. An autopsy was performed and a chronic myelomonocytic leukemia was the final diagnosis. The ultimate cause of death was a perforated acute duodenal ulcer with peritonitis. Possible relations between DPX, immunologic reactions and myelomonocytic leukemia are discussed.

Pericardial effusion is a rare but potentially life-threatening complication of chronic myelomonocytic leukemia. A case of a 70-year-old female with CMML is reported, who developed a severe pericardial effusion after an initially stable course of disease. She underwent pericardiocentesis and subsequent intracardial instillation of mitoxantrone with poor response. Subxiphoid pericardiotomy was successfully performed. Leukocytosis did not respond to hydroxyurea. Because of decreasing performance status of the patient systemic chemotherapy was not applied and the patient died within 2 weeks. A review of the literature shows that there is no effective treatment for pericardial effusion in CMML, and some common features may be noted.

Although chronic urticaria is usually idiopathic, in rare cases it may be a sign of underlying malignancy. We describe the first case of chronic urticaria associated with chronic myelomonocytic leukemia. The urticarial lesions healed successfully with etoposide, an antineoplastic agent. This case demonstrates that cases of chronic urticaria should not to be labeled as idiopathic until diligent evaluation has failed to reveal a cause.

Background/aims: The occurrence of myeloid leukaemia in patients with systemic mastocytosis is a well recognised phenomenon. However, the pathophysiological basis of such a coevolution has not been clarified. Recent data have shown that the c-kit mutation Asp 816 to Val is detectable in neoplastic mast cells in most patients with systemic mastocytosis, including those who have associated haematological disorders. The aim of this study was to study clonal disease evolution by analysing bone marrow cells from a patient with systemic mastocytosis and associated chronic myelomonocytic leukaemia (CMML) for the presence of this mutation., Methods: The DNA of microdissected bone marrow cells from a patient with systemic mastocytosis and associated CMML was analysed for the presence of the c-kit mutation Asp 816 to Val by means of HinfI digestion and direct sequencing of semi-nested polymerase chain reaction (PCR) products., Results: The two neoplasms could easily be identified and discriminated in paraffin wax embedded bone marrow sections by tryptase and chloroacetate esterase staining. A total number of 10 tryptase positive systemic mastocytosis infiltrates and 10 tryptase negative CMML infiltrates were removed by microdissection. As assessed by HinfI digestion and direct sequencing of semi-nested PCR products, the c-kit mutation Asp 816 to Val was detected in five of seven systemic mastocytosis infiltrates and four of six CMML infiltrates. By contrast, no c-kit mutation Asp 816 to Val was found in bone marrow infiltrates in patients with CMML without associated systemic mastocytosis (n = 20)., Conclusion: These data support a monoclonal evolution of systemic mastocytosis and concurrent CMML in the patient studied.

The cases of two patients with chronic myelomonocytic leukaemia associated with periarteritis nodosa-like, antineutrophil cytoplasmic antibody negative, systemic vasculitis, are reported. A 61 year old man was admitted with fever, diffuse myalgia, and abdominal pain. Blood and bone marrow examination showed chronic myelomonocytic leukaemia. Vasculitis of the gall bladder was responsible for acalculous cholecystitis. A massive spontaneous bilateral perirenal haemorrhage occurred. A 73 year old woman with chronic myelomonocytic leukaemia had been followed up for one year when unexplained fever occurred. Two months after the onset of fever, sudden abdominal pain was ascribed to spontaneous bilateral renal haematoma related to bilateral renal arterial aneurysms. Neuromuscular biopsy showed non-necrotising periarteriolar inflammation. To our knowledge, systemic vasculitis has never been reported in chronic myelomonocytic leukaemia. In our two cases a non-random association is suggested because (a) chronic myelomonocytic leukaemia is a rare myelodysplastic syndrome, (b) spontaneous bilateral perirenal haematoma is not a usual feature of periarteritis nodosa.

It has been reported that trisomy 14 is associated with myeloid malignancies, but a case with increased platelet count has also been reported. However, the clinical significance of trisomy 14 is still uncertain. We report a patient with trisomy 14 with thrombocytosis and a gradual increase in monocytosis. He was treated with hydroxyurea, cytarabine and aclarubicin in low doses and his quality of life was maintained for a period of about 1 year from blastic crisis. Hydroxyurea, cytarabine or aclarubicin in low doses may be the treatment of choice for trisomy 14 patients with respect to the patients' quality of life., (Copyright 2000 S. Karger AG, Basel)

We present a case of juvenile myelomonocytic leukemia (JMML) with ocular infiltration. A 1-month-old boy presented with myeloid precursors in peripheral blood and a white blood cell count >10x10(9)/l. His peripheral blood monocyte count was >1x10(9)/l, bone marrow blasts were <20%, and no Ph chromosome was identified. The boy also presented with hepatosplenomegaly, pallor, fever, and skin rash. We diagnosed this case as JMML, although hemoglobin F was within the normal range and no spontaneous colony growth was observed from peripheral blood mononuclear cells. Neither Epstein-Barr (EB) virus nor cytomegalovirus was detected by PCR in bone marrow aspirate or peripheral blood. The patient had several lesions into which JMML cells might have infiltrated, including skin, liver, spleen, oral cavity, right lung, sigmoid colon, and both eyes. To our knowledge, this is the first reported case of JMML with ocular involvement. Since infiltration of JMML cells into both eyes causes blindness, further consideration of the timing of bone marrow transplantation (BMT) in JMML is necessary.

A case of juvenile myelomonocytic leukemia (JMML, previously referred to as JCML) in a neonate with Noonan syndrome (NS) is described. The boy presented with bilateral congenital hydrothoraces, nonimmune hydrops, dysmorphic facies, persistent thrombocytopenia, and leukocytosis. The diagnosis of JMML was made on bone marrow cell culture studies. Review of the literature reveals an unusual preponderance of hematologic malignancies, in particular JMML, among patients with NS. Of 40 NS patients admitted to the authors' institution during a 10-year period, there were 4 (10%) with evidence of a monocytic proliferation, which resolved spontaneously. The authors postulate that patients with NS may have an increased incidence of myeloproliferative disorders, which in most cases appears to be benign but may be preleukemic or even lethal.

A 13-year-old girl developed lupus nephritis and Hashimoto thyroiditis in the chronic phase of juvenile myelomonocytic leukemia (JMML). At age 7 months, she was diagnosed as having JMML based on the hepatosplenomegaly, leukocytosis, thrombocytopenia, increased levels of fetal hemoglobin, and spontaneous in vitro growth of granulocyte-macrophage progenitors. At the onset of JMML, she had hypergammaglobulinemia, antinuclear antibodies, rheumatoid factors and anti-smooth muscle antibody. She had been placed on oral 6-mercaptopurine for about 12 years, with clinical improvement. At age 13 years, she was found to have hematuria and proteinuria. She also developed arthritis and Raynaud's phenomenon as well. She had antinuclear antibodies, rheumatoid factors, LE phenomenon, beta-1C (C3) nephritic factor (C3NeF), antithyroid antibodies, and hypocomplementemia. The renal biopsy specimens revealed a diffuse increase in the mesangial cells and matrix by light microscopy, and intense staining of IgG, Clq and C3 by immunofluorescence microscopy. The hormonal study ultimately showed decreased thyroid functions. So she was diagnosed as lupus nephritis and Hashimoto thyroiditis. The patient is the first example to show close relationship between stem cell abnormalities in JMML and development of overt autoimmune disorders.

History and Clinical Findings: The diagnosis of pyoderma gangraenosum (PG) was made in a 33-year-old woman with ulcerative (palm-sized) skin changes and pain of the lower leg that had developed over two weeks and was accompanied by fever (39 degrees C). Treatment with prednisolone and azathioprine was initiated. As soon as the medication was reduced new skin changes developed. Two months after onset of the illness she had to be hospitalized because of fever, epigastric pain on pressure and deteriorating general condition. Physical examination provided no significant further information. LABORATORY RESULTS: The differential count demonstrated leucocytosis (15.5 Gpt/l) with a marked monocytosis (25%) as well as anaemia (haemoglobin concentration 5.2 mmol/l). C-reactive protein was elevated (120.20 mg/l). Thromboplastin time was 60%, D-dimer 1000 micrograms/l, thrombin-antithrombin-III complex 9.7 micrograms/l. ADDITIONAL INVESTIGATIONS: Sonography and computed tomography of the upper abdomen revealed splenomegaly, ascites, thrombosis of the portal, splenic and superior mesenteric veins. Bone marrow puncture showed marked increase in blasts (14%) and monocytes (10%)., Treatment and Course: The findings indicated chronic myelomonocytic leukaemia with PG and the described venous thromboses. The cutaneous changes completely receded on administration of hydroxyurea (1.0 g/d). Other causes of the skin eruption were excluded. Phenprocoumon (INR between 2 and 3) was given in treatment of the thromboses., Conclusion: When PG is diagnosed, intensive search for an underlying cause must be undertaken, because of its frequent association with serious systemic disease. Only early specific treatment will improve the skin condition.

Background: Diffuse plane xanthoma (DPX) usually has been described in association with a reticuloendothelial disease. However, the incidence of an underlying disease and its relation to clinical and histopathologic features have not been previously described., Objective: We describe the clinicopathologic features of a series of patients with DPX., Methods: Eight patients with DPX were diagnosed and studied between 1987 and 1996., Results: Three of the 8 patients had a reticuloendothelial disease (benign monoclonal gammopathy in 2 and chronic myelomonocytic leukemia in 1). These 3 patients had larger cutaneous lesions and involvement of trunk and extremities. Histologic examination showed only foamy macrophages in 2 of the 8 patients. The remainder exhibited macrophages, foamy histiocytes, lymphocytes, and Touton cells., Conclusion: The incidence of underlying disease associated with DPX seems to be lower than expected. However, patients with DPX should be observed for the potential occurrence of an associated condition.

We report a 45-year-old man with monocytosis and right hemiparesis. The patient suffered from an acute myocardial infarction from which he recovered completely when he was 42 years old. One year prior to his death, he was found to have increase in monocyte count (35.5% of leukocytes) in peripheral blood and splenomegaly; he was admitted to the hematology service of our hospital. He was diagnosed as having chronic myelomonocytic leukemia after bone marrow examination. He was treated with radiation therapy with improvement in splenomegaly. In May of 1995, he had fever, anemia, and thrombocytopenia for which he needed daily blood transfusion. In November of 1995, he had an onset of weakness in his right hand, and neurologic consultation was asked for in November 27, 1995. Neurologic examination revealed a chronically ill japanese man in no acute distress. He was alert and not demented. Higher cerebral functions were intact. Cranial nerve examination revealed right facial paresis of the central type. Motor-wise, he was right hemiparetic. Generalized muscle wasting was noted apparently due to the chronic debilitating disease. Deep tendon reflexes were within normal range in the right upper extremity, but were diminished in other areas. Sensation was intact, and no meningeal signs were noted. Pertinent laboratory findings were as follows: Hb 8 g/dl, RBC 238 x 10(4)/microliter, WBC 2,900/microliter (band 1.0%, seg 18.5%, lym 28.0%, mono 44.0%, Baso 2.5%), Plt 13 x 10(4)/microliter, PT 16.6"/10.9", APTT 44.7"/35.0". CSF contained 87 mg/dl of protein, 155 mg/dl of glucose and 2 mononuclear cells/microliter. Bone marrow was slightly hypercellular with mild increase in blast forms. No chromosome abnormality was found. CT and MRI revealed a large mass in the left fronto-parietal region and the meninges showed marked thickening with enhancement after gadolinium-DTPA in MRI. The patient was treated with glycerol and steroid, but the subsequent course was complicated by a seizure, agitation, and pneumonia. He died from respiratory failure on January 13, 1996. The patient was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had chronic myelomonocytic leukemia with infiltration of leukemic cells into meninges and the parenchyme of the cerebrum. Thickening of the dura was thought to be in part a reaction to the subdural hematoma as well as to leukemic cells along the meninges. Postmortem examination revealed hypercellular bone marrow with increase in monocytic cells (more than 20%). The lungs showed pneumonia with scattered old tuberculous lesions. The heart showed an old myocardial infarction in the posterior wall of the left ventricle. The brain showed an old chronic subdural hematoma in the left fronto-temporal region and a cystic mass lesion in the left frontoparietal region. The mass was hypercellular and most of them were monocytes. The dura mater showed reactive thickening without leukemic cell infiltration. It was concluded that this patient had chronic myelomonocytic leukemia with a formation of leukemic mass in the brain. Pathologists thought that the mass was a hematogenous spread. It is rare for chronic myelomonocytic leukemia to form a mass lesion in the brain.

High-dose methylprednisolone (HDMP) which can induce--differentiation and -apoptosis of myeloid leukemic cells has been shown to be very effective in the treatment of extramedullary infiltration (EMI) of children with acute myeloblastic leukemia (AML). In the present study 2 children with chronic myelomonocytic leukemia (CMML) who had pleural effusions were given a single daily dose of oral methylprednisolone (20 mg/kg or 30 mg/kg). In addition to dramatic improvement of respiratory symptoms, pleural effusions disappeared in four days in both patients possibly due to apoptotic cell death induced by HDMP treatment. Further studies are needed to determine whether high-dose corticosteroids are also effective on the resolution of pleural effusions associated with other malignant disease.

Objective: To describe the pathologic features of two cases of myelodysplastic syndrome associated with trisomy 14 and to summarize the relevant literature., Results: In both cases, trisomy 14 was identified using conventional cytogenetic and fluorescence in situ hybridization methods. The patients were elderly men, 70 and 77 years old, who presented with anemia and thrombocytopenia. According to the French-American-British classification, case 1 was classified as refractory anemia with ringed sideroblasts, and case 2 was classified as chronic myelomonocytic leukemia. In both cases, the aspirate smears revealed obvious abnormalities in erythroid and megakaryocytic maturation, with more subtle abnormalities in myeloid maturation. The biopsy sections were hypercellular, and there was marked myeloid hyperplasia in case 2. Both patients received only supportive therapy after the diagnosis was established. Clinical follow-up was available for both patients. The patient in case 1 died 67 months after disease onset of an unrelated illness, and the patient in case 2 was alive at last follow-up, 12 months after diagnosis., Literature Review: Thirty-five cases of trisomy 14 have been previously reported in the literature, predominantly in cytogenetics journals, and the description of the pathologic findings for the majority of these cases is limited or not provided. According to published data, the majority of these cases are myelodysplastic syndromes or acute myeloid leukemias associated with myelodysplasia., Conclusions: The detection of trisomy 14 in the bone marrow strongly correlates with the presence of a myelodysplastic syndrome. The two cases of myelodysplastic syndrome associated with trisomy 14 we describe here did not exhibit characteristic morphologic findings that might suggest the presence of the cytogenetic abnormality.

Pleural effusion in 4 patients with chronic myelomonocytic leukemia (CMML) is described in this report. According to the literature, pleural effusion in CMML is a poorly understood and rare occurrence. Two of our patients presented with pleural effusion as an initial symptom while the other 2 developed it during the course of the disease. In only 1 patient was the pleural effusion due to leukemic infiltration while in the other 3 it was a reactive phenomenon. Peripheral lymphadenopathy was observed only in the former patient who died of acute leukemia. After prednisolone therapy the pleural effusions resolved in the other 3 patients.

There are increasing concerns about the potential thrombogenic risks associated with the use of factor XI concentrates. We describe the case of a 49 year-old man with chronic myelomonocytic leukaemia and severe factor XI deficiency (< 1 u/dl), in whom the use of factor XI concentrate appeared to be associated with the development of venous thromboembolic disease. Subsequent investigations revealed the presence of both the factor V Leiden abnormality and heterozygous plasminogen deficiency. This case highlights the risks associated with the use of factor XI concentrates and suggests that these risks may be further increased in patients with an inherited or acquired prothrombotic abnormality or an underlying malignancy. Prothrombotic screening of patients with severe factor XI deficiency may be indicated particularly in younger patients in whom treatment with factor XI concentrates is a possibility.

A 41-year-old patient with dermatitis herpetiformis (DH) developed steroid-resistant blebs as a sign of exacerbating DH. The skin symptoms were resolved after 2 weeks of oral administration of diaminodiphenyl sulphone (DDS). However, 3 weeks after the start of DDS, he suffered from edematous eruption on the cheeks and neck, enlargement of the pharynx, systemic lymphoadenopathy and hepatomegaly. In addition, his leukocyte count increased rapidly from 10.1 x 10(9)/l with 13% monocytes just before the start of DDS, to 24.6 x 10(9)/l with 28% monocytes. Bone marrow aspirate showed trilineage dysplasia and chronic myelomonocytic leukemia (CMML) was diagnosed. The patient died from septic shock during neutropenia following cytotoxic chemotherapy. In this case, CMML was complicated with DH and the administration of DDS accelerated the progression of CMML with the manifestations of DDS syndrome. Although DDS is a well-established drug for DH, DDS should be used with great caution when a hematological malignancy coexists.

A novel human myeloid leukaemia cell line (HNT-34) was established from the peripheral blood of a 45-year-old female patient with acute myelogenous leukaemia (AML) transformed from chronic myelomonocytic leukaemia (CMMoL) with 3q21q26 syndrome. Morphologically, the HNT-34 cells were undifferentiated blasts which were negative for myeloperoxidase. The HNT-34 cells were positive for CD4, CD13, CD33 and CD34, but negative for CD41a and CD42b. The cells actively proliferated in suspension with a doubling time of 26-27h in the absence of any growth factors. Neither proliferative advantage nor differentiation was observed with the addition of G-CSE GM-CSF, IL-3, TPO, DMSO or PMA. Cytogenetic analysis showed 46,XX. t(3;3)(q21;q26), t(9;22)(q34;q11),20q-. Molecular analysis showed expression of EVI1 gene, P210 and P190 BCR/ABL chimaeric transcripts. The chromosomal breakpoint at 3q26 of HNT-34 cell line was located to approximately 200 kb 5' of FIM3 locus and more upstream of the MDS1. which is the same region as that of somatic cell hybrid line H10C. The breakpoint at 3q21 was located within the 390 kb centromeric from the breakpoint cluster region. These results suggest that the HNT-34 cell line may be a useful tool for the elucidation of the mechanisms of leukaemogenesis which involve the 3q21q26 syndrome and Ph1 chromosome.

We report four cases of Noonan syndrome associated with chronic myelomonocytic leukemia in childhood. These children shared some hematologic features: thrombocytopenia, splenomegaly in the first months of life, occurrence of chronic myelomonocytic leukemia without abnormalities of the initial bone marrow karyotype, and, in three cases, improvement of the hematologic disease. A common pathophysiologic process in such patients is suggested.

Chronic myelomonocytic leukemia is a disease of the elderly. It tends to have a variable clinical course, as the patient's state is immunologically dysunctional. There has been reluctance to perform open cardiac procedures because of concern about early postoperative sepsis leading to death. A 84-year-old man was admitted for the management of effort angina. PTCA was performed twice. He had left nephrectomy for Grawitz tumor nine years ago and additionally, he had been diagnosed as having chronic myelomonocytic leukemia since the next year. Preoperative laboratory assessment revealed that the total white blood cell counts were 2500 with 25 per-cent of granulocytes, a hematocrit of 31.1%, and platelet counts were 10.0 x 10(4). At the night of the treatment of his granulocytopenia with injection of granulocyte stimulating factor, he complained of continuous anterior chest pain with ST depression on ECG. Emergency single CABG was performed using a saphenous vein graft under the diagnosis of impending myocardial infarction. Postoperative course was uneventful. This is the first case report of CABG in octogenarian with chronic myelomonocytic leukemia in the world.

A 53-year-old male patient was admitted to our hospital with painful splenomegaly. He was diagnosed as having chronic myelomonocytic leukemia (CMML) with leukocytosis, monocytosis, increased lysozyme concentrations in serum und urine, and lack of the Philadelphia chromosome. The clinical course of the disease was characterized by rapidly rising leukocyte counts, cutaneous infiltrates, respiratory insufficiency and neurological symptoms. Excessive hyperleukocytosis with a significant increase in monocytic cells led to microcirculatory obstruction, vascular endothelial damage and organ malfunction. This complication could not be prevented by low-dose chemotherapy with cytosine arabinoside. The patient finally died from pulmonary and cerebral hyperleukocytic syndrome.

A 32-year-old female was admitted due to splenomegaly and leukocytosis in September, 1993. The leukocyte count was 26,900/microliter with 29% monocytes (7,800/microliter). A diagnosis of the chronic phase of chronic myelomonocytic leukemia was made. On November 19, 1993, splenic arterial embolization was performed. After the embolization, the leukocyte count rapidly increased, and acute respiratory failure developed. The respiratory condition was improved by methylprednisolone (m-PRED) pulse therapy. Subsequently, the effectiveness of chemotherapy gradually decreased, and there was an increase in the leukocyte count. Respiratory failure developed again but was successfully treated with m-PRED pulse therapy in addition to aclarubicin. On July 4, 1995, splenectomy was performed. The leukocyte count rapidly increased, and acute respiratory failure again developed. She did not respond to m-PRED pulse therapy, but the respiratory condition was markedly improved by leukoplasmapheresis. The respiratory failure in this patient may be associated with capillary leak syndrome due to neutrophilia. In addition, stasis of increased monocytes in the pulmonary capillaries and their infiltration into the pulmonary parenchyma and alveoli was thought to have occurred.

We report a patient with poor-prognosis myelodysplastic syndrome (MDS) after successful treatment of lymphoma, who was given an allogeneic BMT, engrafted and achieved complete remission, but later had a relapse of his MDS with complete disappearance of donor haemopoiesis. After two episodes of CMV pneumonia and continued prophylactic use of ganciclovir thereafter, he experienced a spontaneous complete disappearance of all signs of MDS, including myelofibrosis, and a complete return to donor haemopoiesis. This case is the first one to suggest a graft-versus-leukaemia effect (GVL) in MDS patients. It depicts the complex relationship between GVL, graft-versus-host disease (GVHD) and graft rejection. It could also constitute a clinical illustration of the possible antileukaemic effect of CMV infection and its treatment with ganciclovir.