[Fatal primary influenza virus pneumonia in a patient with secondary myelofibrosis during ruxolitinib therapy].

In recent years, fatal cases of primary influenza virus pneumonia have been rare. A 67-year-old woman with secondary myelofibrosis, who had been diagnosed with polycythemia vera 25 years prior, died of primary influenza virus pneumonia. She was immunocompromised due to the underlying disease and ruxolitinib therapy, but she was not vaccinated against influenza. She might have caught the flu from an infected family member. This case reminds us of the importance of infection control measures such as preventing familial infection during ruxolitinib therapy in severely immunocompromised patients.

Monitoring twenty-six chronic myeloid leukemia patients by BCR-ABL mRNA level in bone marrow:a single hospital experience.

Chronic myeloid leukemia (CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib is effective to control the tyrosyl phosphorylation of the protein related to the cell signaling. BCR-ABL mRNA is overexpressed in the minimal residual disease (MRD), known as an early sign of relapse. Between December 2005 and June 2008, we measured BCR-ABL mRNA levels in the bone marrow (BM) from patients by quantitative real-time polymerase chain reaction (RQ-PCR) in Aomori Prefectural Central Hospital. Eighty-six samples from 26 patients were collected. Among the 26 CML patients, 11 patients (42%) were in the pretreatment group. Seven (64%) of the 11 patients achieved complete molecular response (CMR). In the post-treatment group consisting of the remaining 15 patients, 9 (60%) patients achieved CMR. The patients receiving imatinib at a dose over 300 mg per day required 13 (6-77) months [median (range)] to achieve CMR. On the other hand, the patients receiving a dose below 300 mg per day required 29.5 (11-84) months [median (range)]. When BCR-ABL mRNA was detected during the treatment course of patients with CMR, careful observation of BCR-ABL mRNA was useful for tracking the clinical course of patients. In conclusion, the BCR-ABL mRNA level was useful for monitoring the clinical course in 26 patients with CML.

WT1 mRNA level in peripheral blood is a sensitive biomarker for monitoring minimal residual disease in acute myeloid leukemia.

The Wilms' tumor gene 1 (WT1) encodes a transcription factor that is involved in normal cellular development and cell survival. WT1 mRNA is overexpressed in the minimal residual disease (MRD) of patients with hematopoietic malignancy patients, particularly acute myeloid leukemia (AML). MRD represents the condition with the low levels of leukemia cells in the bone marrow and is known as a sign of recurrence. In hematopoietic malignancies, definition of remission is based on the lack of MRD at submicroscopic level. Between December 2005 and June 2008, we started to measure WT1 mRNA levels in the peripheral blood (PB) from patients by quantitative real-time PCR in Aomori Prefectural Central Hospital. Three hundreds and eight samples from 95 patients were evaluated. The patients included AML (55 patients), acute lymphoblastic leukemia (11), myelodysplastic syndrome (20), malignant lymphoma (5), chronic myeloid leukemia (1), prostatic carcinoma (1), and leukopenia (2). Among the 55 AML patients, 21 patients were pretreated with remission induction therapy. In the clinical course of 21 patients, timely therapeutic approaches could be started for relapse by the early detection of WT1 mRNA overexpression before the morphological findings were apparent. Monitoring WT1 mRNA is helpful to identify patients at high-risk relapse. High overall survival rate (71.2%, 15/21, median: 24.6 months, range 1.1-35.6 months) was achieved in 3 years. The overall survival rate of 34 post-treatment patients was 61.7% (median: 23.5 months, range 0.13-126.5 months after treatment start). In conclusion, the WT1 mRNA level is a sensitive biomarker for monitoring MRD.

Histiocytic sarcoma of the spleen: case report of asymptomatic onset of thrombocytopenia and complex imaging features.

Histiocytic sarcoma of the spleen, in which the malignant cells display morphologic and immunophenotypic features similar to those of mature tissue histiocytes, is a rare but potentially lethal condition that can remain asymptomatic or only mildly symptomatic for a long period of time. We studied a case of histiocytic sarcoma of the spleen in an 82-year-old woman with prolonged chronic thrombocytopenia that was non-responsive to steroid therapy. Ultrasonography, computed tomography, and magnetic resonance imaging showed a characteristically enlarged spleen and liver. Palliative irradiation therapy was clinically effective; however, disease progression proved lethal. Autopsy revealed the proliferation of tumor cells within the splenic sinus and the liver sinusoids, which displayed extreme hemophagocytosis and strong expression of the histiocytic markers CD68 (KP1 and PG-M1) and CD163. The postmortem diagnosis showed histiocytic sarcoma of the spleen with liver infiltration. This and previous reports indicate that early detection (facilitated by imaging and clinical features) and management may improve patient prognosis and survival. Histiocytic sarcoma of the spleen should be considered as a differential diagnosis in therapeutically unresponsive patients with chronic thrombocytopenia.

[Methicillin-resistant Staphylococcus aureus-induced pyomyositis that emerged during recovery from drug-induced pancytopenia].

Pyomyositis is a purulent infection of skeletal muscle characterized by fever, localized muscle pain and stiffness, swelling and tenderness. Hematological disorder is one of the predisposing conditions for the development of pyomyositis. A 54-year-old man developed methicillin-resistant Staphylococcus aureus pyomyositis during drug-induced pancytopenia. Debridement of the infection foci combined with antimicrobial agents proved effective even in the advanced stage of the disease. In patients with hematological disorders, pyomyositis should be considered when evaluating local myalgia and high fever because this disease can be very difficult to identify and can become rapidly progressive under a myelosuppressive condition.

[Long-term complete remission after single therapy with gemtuzumab ozogamicin for refractory AML in an elderly patient].

Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to calicheamicin, that is rapidly internalized after binding to CD33. This is followed by intracellular release of calicheamicin, which induces double-stranded DNA breaks, cell cycle arrest, and apoptosis. So GO is a more selective agent for acute myeloid leukemia (AML), because the CD33 antigen is expressed on AML, while it is not expressed on normal hematopoietic stem cells and nonhematopoietic tissues. However, some studies indicated that this agent showed resistance to refractory AML cells via various mechanisms, and that there were no potent effects. In this study, we report a 76-year-old female with recurrent AML who responded to single therapy with GO, achieving complete remission for more than 1 year after the start of administration, although additional remission induction was impossible. The response to GO can be stratified with reference to the response to conventional chemotherapy.

Myeloid/NK cell precursor acute leukemia lost both CD13 and CD33 at first diagnosis.

It has been reported that malignancies of natural killer (NK) cell precursors, which are present in both myeloid and lymphoid antigens, are characterized by immature lymphoblastoid morphology with CD7+, CD33+ and CD56+ phenotype. Here, we report a 18-year-old man who was diagnosed with CD33- and CD13- NK cell precursor acute leukemia at first diagnosis. Following a 3-year remission state, he had a relapse as a testicular tumor and CD33+ myeloid/NK cell precursor acute leukemia after allogenic BMT. This case suggests that myeloid antigens are not necessary for diagnosis of myeloid/NK cell precursor acute leukemia.

Rituximab monotherapy as a first-line treatment for pulmonary mucosa-associated lymphoid tissue lymphoma.

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare extranodal lymphoma with a 5-year survival rate of 80-95 %. There is no standard treatment strategy for pulmonary MALT lymphoma. In the present study, we performed a retrospective evaluation of systemic rituximab monotherapy (375 mg m(-2) day(-1), 4-8 cycles) as first-line treatment in patients with pulmonary MALT lymphoma. Of the eight patients enrolled, five achieved complete response, one achieved partial response, and two showed stable disease. Median progression-free survival was 66.0 months (range 9.7-87.2 months). Treatment was well tolerated and all patients were alive during the median follow-up period of 64.0 months. Rituximab monotherapy was efficacious in patients with pulmonary MALT lymphoma, demonstrating long-term disease stabilization and symptom reduction. Larger prospective studies are warranted to further assess the efficacy of rituximab monotherapy. In conclusion, rituximab monotherapy may be considered for first-line therapy in patients with pulmonary MALT lymphoma.

[Emergence and decrement of Ph-negative clone with trisomy 8 in CML during imatinib therapy].

An increase in the presence of the Ph-negative, trisomy 8 clone has been reported in chronic myelogenous leukemia (CML) under imatinib therapy, but any impact of the clone on patient prognosis remains uncertain. We report here on a 42-year-old male with CML who received imatinib after failure of interferon-alpha therapy. A chromosomal analysis revealed 18/20 trisomy 8 in bone marrow at 10 months of imatinib administration. Continuing imatinib at 300 mg daily resulted in a decrease in the number of trisomy 8 clones as well as the disappearance of Ph clone. Furthermore, the patient's pancytopenia was gradually improved. Imatinib therapy could be continued even with the emergence of trisomy 8.

The potential of patients' peripheral blood mononuclear cells to differentiate into dendritic cells after hematopoietic stem cell transplantation.

AIMS: Although hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological disorders, there is persistent immunosuppression in both allogeneic and autologous HSCT. Dendritic cells (DCs) play key roles in the immune system. This study investigated whether the DC progenitor cells within patients' peripheral blood after HSCT have the potential to differentiate into DCs. MAIN METHODS: Twenty-eight patients were included in this study, and peripheral blood samples were basically taken before starting the conditioning regimen, on the day of transplantation (day 0), and on days +14, +28, +42, +70 and +170 after transplantation. Immature DCs (iDCs) were induced from adherent mononuclear cells by using recombinant human granulocyte-macrophage colony-stimulating factor plus interleukin-4. KEY FINDINGS: The iDCs expressed cell surface antigens such as CD40 and HLA-DR, and they had phagocytotic activity, thus showing the characteristics of iDCs. The induction of iDCs was possible from day +14 after HSCT. However, there were differences between allogeneic and autologous HSCT in the expression of CCR5 in iDCs at day +14 after transplantation. Furthermore, the up-regulation of maturation-related antigens by maturation stimuli was higher after HSCT compared with before HSCT. SIGNIFICANCE: We demonstrated that patients' peripheral blood mononuclear cells have the potential to differentiate into DCs beginning on day +14 after HSCT, although some differences exist between allogeneic and autologous HSCT and between before and after HSCT.