Search

Langerhans cell histiocytosis (LCH) and malignancy occurring in the same individual is unusual and has generally been the subject of isolated case reports. LCH is a rare condition in adults. Its cause is uncertain but, with the recent demonstration of clonality and its association with malignant disease, there has been a renewal of interest. We report a singular case of Letterer-Siwe disease associated with a chronic myelomonocytic leukemia developing in an elderly woman. The simultaneous occurrence of both malignant disorders supports the hypothesis of a common genetic origin.

Acquired pure red cell aplasia (PRCA) can be primary or secondary to other diseases. PRCA association with chronic myelomonocytic leukemia (CMML) is very rarely reported. Although treatment is directed to underlying cause in secondary PRCA treatment, optimal treatment in patients with CMML and PRCA is unknown, because only four case reports are available. In addition, the effect of hypomethylating agents can be detrimental due to myelosuppression, at least in the early phase of treatment. Bone marrow examination of a 66-year-old woman with severe anemia revealed PRCA and was suspicious for CMML. There was no HLA-matched sibling for bone marrow transplantation. The patient received immunosuppressive therapy with steroids and cyclosporine with temporary response in anemia; however, progressed to acute leukemia over 8 months and died. Immunosuppressive therapy in patients with CMML and PRCA should be cautiously used because it may accelerate acute leukemia transformation.

Paraneoplastic neuropathies have rarely been reported in patients with hematological malignancies. We report herein the case of a 65-year-old Japanese woman with chronic myelomonocytic leukemia (CMML) accompanying chronic inflammatory demyelinating polyneuropathy (CIDP). She had been diagnosed with refractory anemia and subsequently developed CMML with cytogenetic abnormalities including t(3;8)(q26;q24). While regenerating bone marrow following induction chemotherapy, she complained of numbness in the lower legs and then became unable to walk. Clinical and electrophysiological features were consistent with CIDP. Intravenous immunoglobulin treatment was insufficient, although corticosteroids reduced neurological symptoms. This case suggests CIDP as one of the autoimmune phenomena associated with myelodysplastic syndrome and immunosuppressive treatment represents an effective therapy.

Behçet's disease (BD) is a multisystem inflammatory vasculitis of unknown etiology and pathogenesis. Coexistence of BD along with hematological malignancies is extremely rare. We describe a patient diagnosed with BD and chronic myelomonocytic leukaemia (CMML) with trisomy 8. This case suggests that trisomy 8 may be involved in the concurrent manifestation of myelodysplastic syndrome (MDS) and BD with gastrointestinal ulcers.

A case of lipoid pneumonia with chronic myelomonocytic leukemia is reported. A 61-year-old man was autopsied after suffering from myelodysplastic syndrome (chronic myelomonocytic leukemia) for 13 years. Interstitial lesions of the lungs were suspected as infiltration of leukemia cells before the autopsy. However, blastic leukemia cells were not observed in the lung, although they were seen in the bone marrow and spleen at autopsy. Instead, an unusual amount of cholesterol deposits was observed with mucormycosis and aspergillosis in the lungs. Cholesterol deposition was observed not only in perihilar but also in subpleural regions without apparent bronchial obstruction in both lungs. It is thought that malfunction of monocytes/macrophages resulted in repeated fungal infection and storage of cholesterol caused by tissue destruction and impaired tissue repairing.

Lonafarnib is an orally bio-available farnesyltransferase inhibitor that prevents farnesylation of specific target proteins including Ras. In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300 mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response. The median age of patients was 70 years (range 44-86). There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML. Overall 16 (24%) of the patients responded with two patients achieving a complete remission and one a partial response. Responses were seen in 6/32 and 10/35 patients with MDS and CMML, respectively. Of the 19 patients who were platelet transfusion-dependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days. A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made. Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia. Lonafarnib has demonstrable activity in patients with advanced MDS and CMML.

Granuloma annulare is a dermatologic condition of unknown etiology that has been associated with systemic diseases and reported to be a paraneoplastic manifestation. Two patients with generalized granuloma annulare as an initial manifestation of chronic myelomonocytic leukemia are herein described. We suggest that chronic myelomonocytic leukemia should be added to the list of systemic diseases associated with generalized granuloma annulare.

There have been 22 reported cases of Behçet disease associated with myelodysplastic syndrome. The majority of cases belong to incomplete types of Behçet disease and the refractory anemia subtype of myelodysplastic syndrome. We describe a case of a 49-year-old woman with Behçet disease who developed myelodysplastic syndrome with abnormal karyotype-trisomy 8. This change was not due to immunosuppressive agents because her Behçet disease was not treated with these drugs before the onset of myelodysplastic syndrome. This is the first report of a case of Behçet disease with pathologic evidence associated with the chronic myelomonocytic leukemia subtype of myelodysplastic syndrome. After reviewing the past case studies, we suggest that patients with myelodysplastic syndrome and trisomy 8 might be prone to have Behçet disease. Furthermore, more intestinal ulcers but with less eye lesions and arthritis have been noted in patients of Behçet disease with myelodysplastic syndrome than in those without myelodysplastic syndrome.

Renal artery aneurysms, once thought to be rare, are diagnosed more frequently due to the increasing use of computed tomography, angiography, and other imaging to delineate pathology. The incidence is less than 1% in the general population,(1,2) and increases to 2.5% in the hypertensive population undergoing angiography.(3) Incidence approaches 10% in autopsy series.(4) Despite increasing incidence, renal artery aneurysm rupture remains uncommon. We report the case of a man with chronic myelomonocytic leukemia who suffered bilateral renal artery aneurysm rupture over the course of 1 month.

Chronic myelomonocytic leukemia (CMML) is a hematologic stem cell disorder with myelodysplastic and myeloproliferative characteristics. Extramedullary leukemic infiltration of the skin, although uncommon in CMML, has prognostic relevance. We report a unique case of a patient with CMML who clinically presented with vitiligo that was histologically diagnosed as leukemia cutis. This case underscores the necessity of early recognition of skin changes in patients with hematologic disorders and the differentiation of nonspecific skin lesions from leukemia cutis.

The intraoral occurrence of granulocytic sarcoma is extremely rare. This article describes 2 cases of granulocytic sarcoma of the gingiva in different clinical situations: one as a precursor to acute myeloid leukemia in a 50-year-old man and the other as a sign of blast crisis in a 59-year-old man with chronic myelomonocytic leukemia. Clinicians and oral surgeons should consider the possibility of tumorous lesion and systemic disease when an intractable ulcer is encountered in an oral cavity. Early diagnosis may improve prognosis and increase expectancy of survival.

A 58-year-old man was admitted with symptoms of lethargy and easy bruising for four months duration. Peripheral blood (PB) analysis revealed a white blood cell count (WBC) of 15.9 x 10(9)/l with monocytes 5.4 x 10(9)/l. Bone marrow (BM) was hypercellular with 15% blasts, monocytosis and trilineage dysplasia. Conventional cytogenetic analysis (G-banding) detected an apparently normal male karyotype (46,XY). A diagnosis of chronic myelomonocytic leukaemia (CMML) was made. After 3 years, PB analysis revealed a WBC count of 22 x 10(9)/l and a predominance of blasts. BM aspirate analysis also revealed 89% myeloid blasts and G-banding detected the emergence of an abnormal clone harbouring an extra copy of chromosomes 13 and 15. A diagnosis of disease transformation to acute myeloid leukaemia (AML) was made. Post chemotherapy BM aspirate was very hypocellular and the abnormal +13, +15 clone was still present suggesting primary refractory disease. A second course of chemotherapy was only administered for 24 hours due to complications. The abnormal +13, +15 clone was still present and it was decided that no further treatment apart from palliative care could be offered. The patient died 11 weeks later, five months after AML transformation. This is the first description of a cytogenetically normal CMML patient transforming to AML with the emergence of a unique +13, +15 double trisomy resulting in an adverse outcome.

Here, a case is presented with two rare genetic disorders, biotinidase deficiency and juvenile myelomonocytic leukemia, in a Turkish infant. This case may serve as a reminder that the diagnosis of a genetic disorder does not exclude the possibility of a second congenital but acquired disease.

Chronic myelomonocytic leukemia (CMML) is an uncommon disorder characterized by monocytosis of the peripheral blood, absence of the Philadelphia chromosome, fewer than 20% blasts, and one or more lineages showing dysplastic features. Splenomegaly is frequently seen and may be massive. A 56-year-old man with stable CMML and moderate splenomegaly presented to the emergency department with generalized abdominal pain and abrupt drop in hemoglobin. Abdominal imaging revealed splenic rupture and emergency splenectomy was undertaken, with complete recovery. Atraumatic rupture of the spleen has rarely been reported as a complication of CMML or other myelodysplastic disorders. This report should alert physicians to consider this diagnosis in patients with CMML and acute abdominal pain., ((c) 2006 Wiley-Liss, Inc.)

Background: A 75-year-old female presented with a 1 month history of non-bloody diarrhea, associated with abdominal cramping and urgency. Her medical history was notable for chronic myelomonocytic leukemia, diagnosed 6 years previously and managed expectantly by monitoring the patient's complete blood count. Over several months, the patient's symptoms progressed, which resulted in significant weight loss. The patient's course of disease was ultimately complicated by acute disseminated encephalomyelitis and death., Investigations: Physical examination, laboratory investigations, stool studies, colonoscopy with biopsies, immunohistochemistry and pathologic review of biopsy specimens., Diagnosis: Leukemic colitis., Management: Management of underlying leukemia with systemic hydroxyurea and topical colonic 5-aminosalicylic acid therapy.

A 4-year-old girl with juvenile myelomonocytic leukemia presented to the emergency room with dyspnea. Echocardiography was performed due to cardiomegaly and prominent main pulmonary artery on a chest X-ray film. On echocardiography the right ventricular pressure calculated from the velocity of tricuspid regurgitation jet was 55 mmHg with no pulmonary stenosis. Despite treatment for pulmonary hypertension and provision of respiratory support, the patient died. A postmortem lung biopsy specimen showed infiltration by tumor cells, which suggested that the pulmonary hypertension had been caused by leukemic infiltration. In conclusion, the findings suggest that leukemic infiltration into the lungs may occur in children with juvenile myelomonocytic leukemia. It should be recognized as a potentially treatable cause of pulmonary hypertension in patients with juvenile myelomonocytic leukemia.

Despite its rarity, donor cell leukemia (DCL) is a most intriguing entity. We report here the case of a 5 year-old girl with juvenile myelomonocytic leukemia and normal female karyotype who developed acute myeloblastic leukemia with a karyotype of 46, X, t(X; 7) (p21; p11.2), der(7) t(3; 7) (q13.3; q22) 5 months after peripheral blood hematopoietic stem cell transplantation from her HLA-matched sister. We performed the analysis of short tandem repeat sequence markers to DNA obtained from donor peripheral blood, patient's peripheral blood including leukemic blasts and patient's hair root. This analysis showed that the leukemic blood DNA matched the donor blood DNA and not the patient's DNA, thus confirming DCL. To our knowledge, this is the first case of DCL after peripheral blood SCT for juvenile myelomonocytic leukemia.

Intestinal adenocarcinoma is a well-known complication of inflammatory bowel disease. Hematologic malignancies, most commonly lymphoma or acute myeloid leukemia, represent a much less well-recognized complication of these disorders; these typically occur in adults with ulcerative colitis. We report a fatal case of juvenile myelomonocytic leukemia associated with monosomy 7 in a young child with a clinical history of Crohn disease. Neither the leukemia nor the cytogenetic aberration has been previously reported in a patient with inflammatory bowel disease. The aggressive disease course emphasizes the need for proper recognition and further study of this unusual complication.

Based on clinical and pathological findings, chronic myelomonocytic leukemia (CMML) differs from other myeloproliferative/myelodysplastic disorders by its hallmark, monocytosis. It is unknown whether the presence of monocytosis and the diagnosis of CMML carry a prognostic significance. The present study aimed to determine whether the survival of patients with CMML differs from that of patients with BCR/ABL-negative CML or Ph(1-), BCR/ABL-unknown CML, once other potentially prognostic variables have been accounted for. The records of 485 patients with myeloproliferative/myelodysplastic disorders [CMML, n = 304; BCR/ABL-negative CML, n = 107; Ph(1-), BCR/ABL unknown, n = 74] were analysed. Of the covariates found to be significantly (P < 0.01) associated with survival in univariate and multivariate analyses, the following remained predictive and adversely associated with survival, after accounting for the influence of other covariates: increasing age, white blood cell count, platelets, bone marrow blasts and cellularity, decreasing hemoglobin, abnormal karyotype, and diagnosis of CMML. The diagnosis of CMML is prognostically significant and independently associated with a shorter survival and a higher risk of death than BCR/ABL-negative CML or Ph(1-) BCR/ABL-unknown CML.

A unique case of a 72-year-old man with chronic myelomonocytic leukemia (CMML) who developed hepatic veno-occlusive disease (VOD) after treatment with a single dose of vincristine and standard doses of cytarabine is described. Unexpected peroneal nerve palsy suggestive of vincristine neurotoxicity occurred concurrently and pointed to vincristine as the most likely cause of the VOD. To the best of our knowledge, association between vincristine and hepatic VOD has not been previously described in chemotherapy-naive patients with CMML.

A 70-year-old woman presented for evaluation of symmetric necrotic ulcers of the lower extremities. Biopsy results revealed changes consistent with calciphylaxis. The predisposing factors in this patient included calcium supplementation, obesity, female gender, viscous blood, renal failure, and diabetes mellitus. To our knowledge, this is the first report of calciphylaxis occurring in the setting of chronic myelomonocytic leukemia. We discuss the history, clinical presentation, diagnosis, and treatment of calciphylaxis.

Extramedullary myeloid cell tumors are discrete tissue infiltrations by leukemic cells of myeloid lineage. They are more commonly associated with relapsing acute myelogenous leukemia but can occur in myeloproliferative/myelodysplastic leukemia, usually associated with disease acceleration. Although they can occur in any organ, reported testicular infiltration is rare. We describe the clinical presentation of an extramedullary myeloid cell tumor as a unilateral testicular mass in a man with known chronic myelomonocytic leukemia and its histologic diagnosis. To our knowledge, this manner of presentation is unique in this clinical context.

We report a chronic myelomonocytic leukemia (CMML) patient whose initial symptom was pleural effusion, which is extremely rare. A 61-year-old male was referred to our hospital because of leukocytosis with blasts and pleural effusion with chest pain. Bone marrow examination showed trilineage dysplasia with 14% blasts and a normal karyotype. He was diagnosed as having MDS (RAEB) and infectious pleuritis on admission. Despite administration of antibiotics, leukocytosis with monocytosis and pleural effusion progressed rapidly. His diagnosis was then changed to CMML-2 and pleural infiltration due to leukemic cells expressing CD13, CD14 and CD33. After the leukocytosis was brought under control with hydroxycarbamide, the patient's pleural effusion disappeared.

Here is reported the case of an elderly woman that, after surgical intervention, showed an important anemia, leucocytosis and thrombocytopenia. The leucocytosis was accompanied with clean increase of the monocytes. The morphological appearances, both peripheral blood and bone marrow, showed an evident overlapping of myelodysplastic and myeloproliferative picture, characterized from the presence of refractory anemia with ringed sideroblasts (RARS) and chronic myelomonocytic leukemia (CMML). The case has been reported because it is not frequent, besides, the CMML, until from the beginning of French-American-British (FAB) classification application, has raised problems of classification. Currently, the World Health Organization (WHO) has given an arrangement to the hematological picture with myelodysplastic and myeloproliferative morphological appearances, including this pathology in a new category: myelodysplastic/myeloproliferative diseases (MDS/MPD).

The article reports the case of a patient with chronic myelomonocitic leukemia whose first complaint was gingival hyperplasia.

We describe an unusual case of chronic myelomonocytic leukemia with severe eosinophilia having t(5;12)(q31;p13) with t(1;7)(q10;p10). The eosinophilic proliferation was severe in peripheral blood and bone marrow, and they revealed marked dysplastic features. We performed fluorescence in situ hybridization (FISH) and immunohistochemistry to evaluate the clonality of eosinophils. The eosinophils were stained positively to platelet-derived growth factor receptor-beta. By FISH using chromosome 1 satellite probe and chromosome 1q telomere probe, the eosinophils were proved to belong to the malignant clone., (Copyright (c) 2005 S. Karger AG, Basel.)

Objectives: Viral infections may complicate the diagnosis of juvenile myelomonocytic leukemia (JMML) in a substantial proportion of patients, but this possibility has not been tested in a prospective study. The authors therefore measured the cellular expression of the MxA protein, a reliable marker of viral infection, at diagnosis in children with JMML to estimate the prevalence of such infections., Methods: Eighteen children, aged 1 to 69 months, who met the diagnostic criteria of the International JMML Working Group were prospectively studied. MxA expression was assessed by flow cytometric analysis of peripheral blood mononuclear cells stained with an antihuman MxA antibody. All data were obtained through the MDS Committee of the Japanese Society of Pediatric Hematology., Results: Twelve patients (67%) had elevated levels of the MxA protein, with rotavirus, RS virus, or CMV infection documented in three of these patients. Although none of the patients had primary Epstein-Barr virus (EBV) infection, reactivation of the virus was strongly suspected in four children, including two with monosomy 7, each having increased levels of MxA. Southern blot analysis revealed monoclonal integration of the EBV genome into bone marrow mononuclear cells from one of these patients. There was no discernible correlation between increases in the marker protein and the presenting features or course of the disease., Conclusions: Viral infection may be present in two thirds of children with newly diagnosed JMML, but it does not constitute a basis for revising clinical management. The possibility that EBV or other viruses contribute to JMML pathogenesis by stimulating pre-exiting malignant clones warrants further investigation.

Infantile cytomegalovirus (CMV)-associated disease and juvenile myelomonocytic leukemia (JMML) frequently present with similar clinical features, and thus the differential diagnosis is often difficult. An early and definite diagnosis of these disorders is required because their therapeutic approaches are very different. The authors describe a 2-month-old Japanese girl with JMML and CMV infection. The CMV antigen was detected by immunologic staining of leukocytes using the peroxidase-labeled monoclonal antibody HRP-C7. To assess clonality, the X-chromosome inactivation pattern was evaluated using polymerase chain reaction analysis of the human androgen receptor gene with or without predigestion of chromosomal DNA with HhaI or HpaII. The patient showed evidence of monoclonal origin of mononuclear cells at diagnosis. Although CMV infection mimicking JMML has previously been reported in two patients, to the authors' knowledge this is the first report describing a firm and definitive diagnosis of JMML based on the study of X-chromosome inactivation patterns.

We described a two-year-old boy who developed a skin infiltration from JMML. Several indurated erythematous lesions were seen on his back on his first visit to our department. Edematous erythemas had repeatedly appeared on his auricles and feet for the previous six months. He had had a high fever for a month. Hepatosplenomegaly and superficial lymphadenopathy were recognized. Laboratory investigation showed leukocytosis and anemia. The diagnosis of JMML was confirmed by the findings of myeloid hyperplasia in his bone marrow and the spontaneous colony formation and GM-CSF hypersensitivity in a culture of bone marrow cells. Histopathologically, large atypical mononuclear cells were infiltrated throughout the dermis in a perivascular and interstitial distribution in a skin biopsy specimen. These cells were CD3 (-), CD20 (-), CD45 (+), CD68 (+) and myeloperoxidase (+). Bone marrow transplantation and then cord blood stem cell transplantation were performed but soon rejected. The indurated erythematous lesions appeared again soon after the relapse of JMML. There are other reported cases of JMML with skin infiltration that preceded any other manifestations of the disease. JMML cells in some patients, including our case, seem to have a great affinity for the skin, and skin biopsy aids in early detection of this disease.

A 68-year-old man with chronic myelomonocytic leukemia (CMML) was initially treated with hydroxyurea with subsequent stable disease. In the time course, he developed bilateral pleuritis accompanied by leukocytosis and spiking fever. Cytologic analysis of the pleural effusion revealed abundant mature granulocytes and monocytes. He was treated with intravenous or oral etoposide with consequent resolution of the pleuritis, indicating the pleural involvement of CMML. Three months later, he developed hepatomegaly and became febrile. One month thereafter, the CMML transformed to acute myeloid leukemia, and the patient developed massive bloody stools associated with epigastric pain and leukocytosis. A gastrofiberscopic examination showed multiple bleeding gastric ulcers. The bleeding ulcers were treated with the clipping procedure; however, the bloody stools continued. Although intravenous etoposide was effective for the leukocytosis and hepatomegaly, the treatment did not improve the bloody stools. The patient finally died of panperitonitis. The autopsy showed multiple ulcers of the transverse colon, some of which were perforated. Microscopically, the ulcerated areas were densely infiltrated with leukemic cells predominantly consisting of immature monocytes and granulocytes. This patient may be the first reported case of CMML complicated by colonic perforation due to leukemic infiltration.

Topotecan, a topoisomerase-I inhibitor is an active drug in the treatment of AML and MDS. To evaluate its toxicity and efficacy in a combination regimen with cytarabine, we conducted a clinical phase I/II trial in patients with relapsed acute myeloid leukemia (AML) or relapsed or newly diagnosed MDS RAEB, RAEB-t or CMML. Twenty-one patients (11 AML, 10 MDS/CMML) entered the study and were treated with 1.25 mg/m2 topotecan as continuous intravenous infusion daily for 5 days and cytarabine 1.0 g/m2 by infusion over 2 h daily for 5 days (TA). Cycles were repeated on day 28. The median observation time was 131 weeks (range: 36-196 weeks). A total of 37 cycles of TA were administered. In 1 patient, the dose of TA had to be reduced and in 1 patient, there was a treatment delay for the second cycle, both because of hematologic toxicity. The most frequent non-hematologic side-effect of TA was fever, which occurred in 17 patients (89%) with temperatures over 38 degrees C. None of the patients died due to any treatment-related toxicities, but 2 patients (10%) died within 1 month due to disease progression. A CR was achieved in 7 patients (33%), 3 of whom were MDS and 4 AML. A partial remission was reported in 8 patients (38%), no change of disease in 2 patients (10%) and progressive disease in 4 patients (19%). The median remission duration was 18 weeks (range 2-161 weeks) for MDS patients and 11 weeks (range 2-49 weeks) for AML patients. The time to progression for patients of 60 years and older (n = 10) was 16 weeks (range 2-49 weeks) and the survival was 32 weeks (range 2-119 weeks). TA is a feasible and efficacious chemotherapeutic combination for the treatment of MDS RAEB, RAEB-t, CMML and AML. For patients of 60 years and older, this regimen is also a safe option.

The effective treatment for juvenile myelomonocytic leukemia (JMML) patients lacking access to stem cell transplantation remains unavailable. Here, we describe a promising result obtained with novel regimen comprised of a combination of chemotherapy and differentiation therapy. Five patients diagnosed as JMML were treated with a standard regimen (cytosine arabinoside (Ara-C) 100mg/m(2) per day continuous infusion (days 0-6), etoposide 100mg/m(2) per day (days 0-4), vincristine 1.5mg/m(2) per d (day 9) and isotretinoin 75-100mg/m(2) per day (days 10-20)). All patients responded to the standard regimen. Three of the five were later treated with salvage a regimen (Ara-C 100mg/m(2) per day continuous infusion (days 0-4), etoposide 100mg/m(2) per day (days 0-4) and Ara-C 15mg/m(2) per day SC (days 6-15)) when immature myeloid cells reappeared in the peripheral blood, the spleen increased or blast crisis occurred. Immature myeloid cells disappeared again after one cycle of salvage regimen in all patients. All patients are alive now with a median follow up duration of 27 months (8-69 months). Although the number of patients enrolled was limited, the standard and salvage regimens were found to be safe and effective alternatives for JMML patients without a matched donor. These regimens also could be used safely before stem cell transplantation.

Aim: To characterize patients with mixed myeloid neoplasias with proliferation of neutrophils, platelets and eosinophils., Material and Methods: Examination and treatment results were analysed for patients with atypical myeloid leukemia (n = 4), myelodysplastic syndrome (MDS, n = 1) and thrombocytosis, MDS and eosinophilia (n = 1). The examination included morphological, histological, cytogenetic and molecular tests., Results: One patient with atypical chronic myeloid leukemia was prior diagnosed to have primarily MDS with a typical aberration of chromosome 5. Two other patients had an initial morphological picture of resistant anemia with blast excess, signs of myeloproliferation and extramedullary hemopoiesis. One and two months after the first examination they received transfusions of erythrocytic mass. Just then they were found to have splenomegaly and leukocytosis due to proliferating and maturating forms of neutrophils. The course of the disease in patients with MDS, thrombocytosis and normal karyotype and in patients with MDS, eosinophilia and combined chromosomal breaks including translocation (3;12)(q21;p13) was characterized by resistance to standard programs of polychemotherapy and transformation into acute myeloblastic leukemia., Conclusion: In some cases atypical CML is a stage of a natural course of MDS. Some MDS variants with eosinophilia and thrombocytosis should be referred to the group of mixed myeloid neoplasias.

We describe a case of Plasmodium falciparum infection in a 25-year-old male patient with a myelodysplastic syndrome, who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) in September 2003. Conditioning regimen consisted of total body irradiation (10 Gy) and cyclophosphamide 60 mg/kg for 2 days. A dose of 4 x 10(6) CD34+ cells/kg was transfused. Engraftment was well documented on day 17 post-transplantation. Spiking fevers occurred on days 19 and 21, associated with a pancytopenia, hepatosplenomegaly and neurological signs. P. falciparum parasites were found on the peripheral blood smear (parasitemia = 23%). Marrow aspiration showed P. falciparum parasites and proliferation of mature histiocytes with hemophagocytosis. Quinine 10 mg/kg i.v. three times a day for 10 consecutive days was given. The fever subsided within 3 days, and pancytopenia vanished in 14 days. Parasitemia cleared in 6 days. The patient left the unit on day 46 with no further complications. The screening of donors showed that infection was acquired from two blood units (from a single donor) given 5 days before transplantation. We report the first case of profound hemophagocytosis in immunosuppressed patient with malaria of high parasitemia after a bone marrow transplant.

Chronic myelomonocytic leukemia (CMML) is an oncohematologic disease with a mixed nature, myeloproliferative and myelodysplastic, and presenting features are usually the consequence of peripheral blood cytopenias (anemic syndrome, infections or bleeding). Specific or non-specific cutaneous involvement in patients with myelodysplastic syndromes or chronic leukemias is exceptional, and it takes place often in advanced stages of the disease, as a preample of a transformation from chronic illness to acute leukemia. Recognition and early diagnosis of the skin lesion by cutaneous biopsy, in every patient with myelodysplastic or myeloproliferative disease, have therapeutic and prognostic significance. We describe a patient who presented with a non-especific cutaneous lesion, Bazin's erhythema induratum, as initial manifestation of chronic myelomonocytic leukemia; we also comment diagnostic, therapeutic and clinical evolution aspects.

A 1-year-old girl with juvenile myelomonocytic leukemia (JMML) underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. A few months after BMT she experienced a bone marrow relapse that did not respond to withdrawal of immunosuppression. To enhance the graft-versus-leukemia (GVL) effect, she underwent peripheral stem cell transplantation (PSCT) from the same donor, using a nonmyeloablative conditioning regimen. She achieved clinical remission and developed chronic graft-versus-host disease (GVHD), which was treated with prednisone and cyclosporine A. One year after PSCT she experienced an isolated central nervous system (CNS) relapse. She was treated with intrathecal Ara-C followed by craniospinal irradiation and achieved a third clinical remission. While extramedullary relapses have been described in JMML, this is the first report of a CNS relapse. Based on this case and others in the literature, the authors suggest that newer therapies are changing the natural history of JMML. By manipulating the GVL effect it is possible to achieve a prolonged bone marrow remission, but only at the expense of unmasking the risk of late extramedullary relapse.

The major complications of myelodysplastic syndromes are related to cytopenia and evolution to acute myeloid leukemia. Bleeding episodes in MDS, although relatively uncommon, are often related to thrombocytopenia. Bleeding may be exacerbated by platelet dysfunction, which is also found frequently. Furthermore, the major hemostatic problem underlying hyperleukocytosis, as evident in patients with MDS on blast crisis, appears to be hemorrhage rather than thrombosis. Acute thromboembolism, which causes occlusion of blood supply and organ infarction, has rarely been observed in patients with MDS. Recently, we encountered an elderly female patient, who had chronic myelomonocytic leukemia with marked myelodysplasia, terminating in blast crisis and bilateral renal infarction. This complication rapidly led to oliguric acute renal failure and mortality.

The triple association of leukemia, xanthogranulomas, and type 1 neurofibromatosis was first described in 1958. Most leukemias were juvenile myelomonocytic leukemias (JMML), usually called juvenile chronic myelogenous leukemia. We describe a 22-month-old female child with neurofibromatosis 1, xanthomagranulomas, and a JMML. Her mother and her brother also had cutaneous café-au-lait spots. Our patient was treated with mercaptopurine and improved. However, 9 months later she experienced a blastic transformation. The presence of xanthomagranulomas and NF1 in a young child should alert to a possible development of JMML, especially in patients with a family history of NF1.

The syndrome of chronic myelomonocytic leukemia (CMML) includes a heterogeneous group of patients who exhibit both myelodysplastic and myeloproliferative clinicopathological features. Troublesome splenomegaly is uncommon in myelodysplastic syndrome (MDS), but when organomegaly occurs, this complication is more likely to be associated with myelodysplastic-myeloproliferative overlap syndromes such as CMML rather than "dysplasia-only" MDS types such as refractory anemia. We report a single-institution experience with splenectomy in CMML patients, including a detailed review of splenic histopathology. Twelve patients with CMML underwent splenectomy at the Mayo Clinic, primarily because of refractory thrombocytopenia and/or mechanical complications related to splenomegaly. Three of the 12 patients (25%) died as a direct result of surgery, and significant postoperative morbidity was seen in another 4 patients (33%). Thrombocytopenia improved in 4 of the 11 patients (36%) with low platelet counts before surgery. Three of the four responders had an abundance of CD68 (PGM1)-positive foamy histiocytes in the marginal zone surrounding the splenic white pulp-a pattern which can be seen in immune thrombocytopenia-and two of these three patients had thrombocytopenia out of proportion to the degree of anemia pre-operatively, suggestive of peripheral destruction of platelets. More consistent splenic pathological findings in the 12 patients included trilineage extramedullary hematopoiesis in splenic red pulp and expansion of splenic cords by a myelomonocytic infiltrate. This study underscores both the uniformity and diversity of splenic findings in CMML, highlights the potential dangers and benefits of splenectomy in this group, and suggests peripheral destruction of platelets as a mechanism contributing to thrombocytopenia in a subset of CMML patients.

Chronic myelomonocytic leukemia with eosinophilia is a recently defined rare entity frequently associated with t(5;12)(q33;p13) translocation. It usually shows a peripheral eosinophil count greater than 1500/microL. However, the literature contains a small subset of cases in which the major manifestation is bone marrow eosinophilia. We report a case similar to that subset and discuss our finding that the immature eosinophils are identical to those seen in acute myelomonocytic leukemia with abnormal bone marrow eosinophils.

Although Demodex follicularum and Demodex brevis are common permanent ectoparasites of human pilosebaceous units, their incidence on children's skin is rare. We report a new case of demodicidosis in a 22-month-old girl undergoing chemotherapy for chronic myelomonocytic leukaemia associated with xanthoma and type 1 neurofibromatosis. The eruption cleared after oral and topical metronidazole therapy. Demodicidosis should be included in the differential diagnosis of facial eruption in immunosuppressed children.