JAK2 V617F-positive essential thrombocythemia with subsequent development of immune thrombocytopenia: A case report.

RATIONALE: Although essential thrombocythemia (ET) and immune thrombocytopenia (ITP) have different etiologies, 3 previous reports have described ET development in ITP patients, all of whom were positive for the JAK2 V617F mutation. Here, we report the first published case of ITP following ET in the absence of other platelet disorders. PATIENT CONCERNS: A 70-year-old woman with a five-year history of ET with JAK2 V617F mutation treated with hydroxycarbamide for five months presented with petechiae on her limbs. DIAGNOSIS: Her platelet count was 3 × 10/L, with the immature platelet fraction being 29%. White blood cell count and hemoglobin level were normal. Bone marrow examination showed increased number of megakaryocytes, but no morphologic dysplasia in any lineage. G-band analysis revealed no abnormalities. Platelet transfusion and cessation of hydroxycarbamide did not affect the platelet count. Thrombocytopenia was unlikely to have been induced by drugs, heparin, systemic lupus erythematosus, or human immunodeficiency virus. Hence, a diagnosis of ITP was made. INTERVENTIONS: The patient received oral prednisolone combined with intravenous immunoglobulin. OUTCOMES: Her platelet count rose to 310 × 10/L and remained stable, while her steroid dose was reduced. Further blood tests revealed the presence of antibodies against Helicobacter pylori, and appropriate treatment was administered. Resumption of hydroxycarbamide did not induce thrombocytopenia. LESSONS: Although ET and ITP have different etiologies, chronic inflammation and immune deregulation underlie both and may play an important role in the progression from one to the other. Further research is warranted to understand the relationship between ET and ITP.

Invasive Pulmonary Aspergillosis in the Epidural Space in a Patient with Acute Myelogenous Leukemia with Myelodysplasia-related Changes: A Case Study and Literature Review of Vertebral Aspergillosis in Japan.

Vertebral aspergillosis is a rare infectious disease with a high mortality rate. We herein report a 70-year-old woman with acute myelogenous leukemia with myelodysplasia-related changes, nontuberculous mycobacteriosis, and bronchiectasis who presented with a fever and cough. Her clinical symptoms and laboratory test results suggested febrile neutropenia and pneumonia. However, her clinical course was further complicated by lower extremity weakness. Magnetic resonance imaging of the spine showed consolidation contiguously spreading toward the epidural space between the T4 and T5. Cytological testing of the pleural effusion revealed Aspergillus fumigatus. We also review and summarize previously reported cases of vertebral aspergillosis in Japan.

[Unidentified Inflammatory Disease Induced by Azacitidine Therapy for Myelodysplastic Syndrome].

We report a 73-year-old woman with myelodysplastic syndromes (MDS) of the refractory anemia with excess of blasts-1 subtype, which was diagnosed in April 2014 on the basis of cytopenia for two cell types. After completing 3cycles of azacitidine (AZA) therapy, the patient was admitted to our hospital based on an initial presentation of high fever. During hospitalization, the high fever and increasing inflammatory reaction persisted. We reevaluated the effect of MDS in this patient and concluded that the AZA administration was successful and the MDS was extremely stable. On medical examination and inspection, the patient had an unidentified inflammatory disease. First, we treated her with high-dose steroid pulse therapy. However, the effect of the treatment was transient. Furthermore, the effects of cyclosporin A and oral steroid therapy were poor; therefore, we initiated tocilizumab administration. Nevertheless, she died of multiorgan failure. An increasing serum IL- 6 level induced by the AZA therapy was later confirmed. Recent studies have reported the immunomodulatory effects stimulated by AZA therapy in MDS. This case is a valuable reminder that an unidentified inflammatory disease can be induced in the course of AZA therapy for MDS.

Effects of neopterin on the hematopoietic microenvironment of senescence-accelerated mice (SAM).

The pteridine neopterin (NP) is produced by monocytes and is known to be a useful marker of immunological activation, although, it remains elusive whether neopterin itself exhibits biological functions. Recently, we found that NP stimulates hematopoietic cell proliferation and differentiation by activating bone marrow stromal cell function. In order to elucidate the biological effect of NP on stromal cells, its effects on hematopoiesis was determined in the mouse model of age-related stromal impairment, senescence-accelerated mice (SAMs). An intraperitoneal administration of NP increased the number of peripheral leukocytes and CFU-GM in the bone marrow and spleen of young SAMs, however, no increase of CFU-GM in old SAMs (stromal impairment) was observed when compared with young SAMs. NP also increased the CFU-GM colony formation of bone marrow and spleen cells from young SAMs in a soft agar culture system, but it did not enhance CFU-GM colony formation of cells from old SAMs cultured in this system. Treatment with NP induced the production of hematopoietic stimulating factors, including IL-6 and GM-CSF, by bone marrow stromal cells from young SAMs but stromal cells from old SAMs did not respond to NP stimulation. Further studies will be required to clarify the mechanism by which NP stimulates the production of hematopoietic growth factors from stromal cells, the results of this study indicate that NP is a potent hematopoietic regulatory factor by activating stromal cell function(s).

Ineffective erythropoiesis in mutant mice with deficient pyruvate kinase activity.

OBJECTIVE: A deficiency of pyruvate kinase (PK) is the most common cause of hereditary nonspherocytic anemia due to glycolytic enzyme defects. Red cells are poorly deformable due to adenosine triphosphate depletion in individuals with a PK deficiency and are destroyed in the microcirculation of the reticuloendothelial system, leading to extravascular hemolysis. The pathophysiology of PK deficiency has been widely studied in PK-deficient mice (PK-1(slc)). We examined the effects of a PK deficiency on erythroid progenitor maturation using these mice. MATERIALS AND METHODS: The appearance of apoptotic cells in spleen of PK-1(slc) mice was examined by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) staining. We also assayed hematopoietic stem cell colony formation in vitro in the spleen of PK-1(slc) mice, to investigate erythropoiesis, and annexin V binding, as a measure of apoptotic cells in constitutive erythroid colonies, to evaluate the maturation of erythroid progenitors. RESULTS: The number of hematopoietic progenitors including colony-forming unit erythroids, burst-forming unit erythroids (BFU-E), colony-forming unit granulocyte-macrophages, and multilineage colony-forming units in the spleens of PK-1(slc) was remarkably increased indicating hematopoiesis, and enhanced erythropoiesis in particular. TUNEL assays identified apoptotic cells in the splenic red pulp of the PK-1(slc) mice. Two-color flow cytometry detected apoptotic cells among anti-TER119-positive cells, suggesting that apoptotic cells were of erythroid lineage. Cells undergoing apoptosis were detected in cultures of BFU-E generated from bone marrow cells of PK-1(slc) mice. CONCLUSIONS: The results in this study indicate that the metabolic disturbance in PK deficiency alters not only the survival of red cells but also the maturation of erythroid progenitors, resulting in ineffective erythropoiesis.

[Multiple myeloma of the IgD-lambda type invading CNS].

A 52-year-old woman was admitted to the gynecological department of our hospital on July 29, 2002 because of a right lower abdominal mass. She has been suffering from pain in the right leg and inguinal area for a month before coming to the hospital. She was found to have pancytopenia and high serum levels of LDH and IgD. A bone marrow examination showed 63.8% of plasma cells and serum immunoelectrophoresis showed M-protein of the IgD-lambda type. She was diagnosed as having multiple myeloma and transferred to our department. VAD therapy was started from August 22. Although the plasma cells in the bone marrow almost disappeared, the right lower abdominal mass remained and a new mass appeared on the right frontal chest wall after two courses of the treatment. Combination chemotherapy with vincristine, ranimustine, melphalan, and dexamethasone (ROAD) was started on November 1. This was followed with thalidomide and radiation therapy of the right inguinal region was added. On December 16th, she suddenly experienced speech disturbance, nausea and the disturbance of consciousness. Examination of her cerebrospinal fluid showed 368/microl mononuclear cells with 93% plasma cells. The plasma cells disappeared after the 6th intrathecal injection with MTX and prednisolone and the chemotherapy was resumed. One month later, CNS relapse was apparent followed by generalized spread of the tumor mass, and she died on March 17, 2003.