Yasuharu Hamano

T/NK cell type chronic active Epstein–Barr virus disease in adults: an underlying condition for Epstein–Barr virus-associated T/NK-cell lymphoma

A chronic infectious mononucleosis-like illness caused by Epstein–Barr virus (EBV) is called ‘chronic active EBV disease’, which is defined as an EBV-associated lymphoproliferative disease. This lymphoproliferative disease is rare and predominantly occurs in Japanese children. Between 1998 and 2010, seven adult-onset cases (aged 20–45 years, median 39 years) were identified, which initially presented with inflammatory diseases, including hepatitis, interstitial pneumonitis, uveitis, nephritis and hypersensitivity to mosquito bites. They showed an EBV viral load in the peripheral blood and evidence of EBV infection of T or natural killer (NK) cells. Five cases (71.4%) developed EBV-positive T/NK-cell lymphoma/leukaemia at a median of 5 years (range 1–7 years) after the diagnosis. Although l-asparaginase-containing chemotherapy was effective for the lymphomas, only allogeneic haematopoietic cell transplantation eradicated EBV-infected cells. This observation indicates that persistent EBV infection of T or NK cells defines a distinct disease entity, which provides an underlying condition for EBV-positive T/NK-cell lymphoma/leukaemia.

Central nervous system is a sanctuary site for chronic myelogenous leukaemia treated with imatinib mesylate

Imatinib mesylate (IM) is currently used as the first therapeutic choice against chronic myelogenous leukaemia (CML). Because IM poorly penetrates the blood‐brain barrier, IM‐treated CML patients may have a potential risk of central nervous system (CNS) involvement. Here we report a case with lymphoid blast crisis isolated only in CNS after bacterial meningitis, although the patient achieved and maintained complete cytogenetic response by IM therapy. It is important to consider isolated CNS blast crisis as a possible event in IM‐treated CML patients.

Thalidomide may induce interstitial pneumonia preferentially in Japanese patients

To the Editor: A 58-year-old Japanese man with multiple myeloma (immunoglobulin D-j) was admitted to our hospital due to general fatigue, renal dysfunction and an increased level of serum M-protein on June 2006. He had no history of drug allergy. The patient was treated with seven courses of VAD (vincristine, doxorubicin and dexamethasone) regimen following tandem autologous peripheral blood stem cell transplantation (auto-PBSCT). Before auto-PBSCT, the serum M-protein became undetectable and IgD level decreased to the normal range. After obtaining the informed consent of the patient and the approbation of the Institutional Review Board of our institute, we started daily 100 mg of thalidomide (Sauramide; Penn Pharmaceuticals, South Wales, UK) on March 2008 as a maintenance therapy (1, 2). On day 50 of thalidomide administration, night sweating began, and general fatigue and low-grade fever followed on day 80. Chest and abdominal X-rays showed no significant abnormalities at this point. Administration of levofloxacin and clarithromycin for 1 wk was ineffective. The symptoms gradually worsened and C-reactive protein (CRP) level elevated from 9.7 mg ⁄dL to 17.8 mg ⁄dL in a week. A computed tomography (CT) scan revealed diffuse, ground-glass opacities in both lungs on day 87 (Fig. 1A, B), although the patient showed no respiratory symptoms such as cough, sputum, and dyspnea. The pulse oximetry at room air was 97%, and blood gas analysis showed a slight decrease in bicarbonate which maybe due to slight hyperventilation (PO2 99.8 mmHg, PCO2 30.7 mmHg at room air). We suspected that thalidomide might cause the interstitial change of the lung. The agent was immediately discontinued. The persistent fever spontaneously improved in a few days, and the infiltrative shadow in the lungs improved in a week (Fig. 1C). The CRP level decreased to the normal range, and sweating and fatigue diminished. Because the patient’s condition improved rather rapidly, we failed to

Effect of dose fractionation on pulmonary complications during total body irradiation.

Total body irradiation (TBI) is an important component of conditioning regimens for Allogeneic bone marrow transplantation (BMT). Interstitial pneumonitis (IP) and other pulmonary disorders are known regimen-related complications. The incidence of IP is related to the dose rate and dose fractionation; however, there is a paucity of clinical data regarding the optimal dose fractionation. This retrospective study evaluated patients to determine the influence of dose fractionation during TBI in preparation for allogeneic BMT on the subsequent development of IP and other pulmonary complications. Fifty-six patients were treated with TBI followed by BMT at our institute. All patients received a total TBI dose of 12 Gy given in 6 fractions over 3 days or in 4 fractions over 2 days. The prevalence of unrelated donors in the 4-fraction group was higher than that in the 6-fraction group. The overall and freedom from progression rates for patients in the 4-fraction group were better than those for patients in the 6-fraction group, but the difference did not reach significance. Clinically significant lung complications occurred in 19 (10: infectious and 9: non-infectious diseases) of 33 patients in the 6-fraction group and 12 (7: infectious and 5: non-infectious diseases) of 23 in the 4-fraction group. There was no significant difference between the two groups. There was no significant difference in pulmonary complications between patients treated with a TBI dose of 12 Gy in 6 fractions over 3 days and patients treated with a TBI dose of 12 Gy in 4 fractions over 2 days.

Non-myeloablative allogenic BMT for myelodysplastic syndrome successfully controlled accompanying relapsing polychondritis

Non-myeloablative allogenic BMT for myelodysplastic syndrome successfully controlled accompanying relapsing polychondritis

Blastic plasmacytoid dendritic cell neoplasm accompanied by autoimmune hemolytic anemia achieving complete remission with hydroxyurea and steroids.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy previously known as blastic natural killer (NK) cell lymphoma or CD4+/CD56+ hematodermic neoplasm. BPDCN is currently believed to arise from plasmacytoid dendritic cell precursors. We report the first case of BPDCN achieving complete remission with hydroxyurea (HU) and steroid treatment. An 87-year-old man came to Juntendo University Hospital, Tokyo, Japan, due to bruise-like skin lesions on the trunk, thighs and upper arms (Fig. 1a). Whole body computed tomography scans disclosed

Breakthrough Exophiala dermatitidis infection during prophylactic administration of micafungin during second umbilical cord blood transplantation after graft failure

Exophiala dermatitidis infections in patients with hematological malignancies are very rare. Our patient had a blood stream infection caused by E. dermatitidis following the second umbilical cord blood transplantation (UCBT) after graft failure during the first UCBT. To our knowledge, this is the first report describing a breakthrough fungal infection caused by E. dermatitidis during the prophylactic administration of micafungin (MCFG). Therefore, MCFG‐treated patients should be monitored for breakthrough E. dermatitidis infection during hematopoietic stem cell transplantation.

Clinical benefits of bortezomib-containing regimens for newly diagnosed AL amyloidosis with severe cardiac impairment.

Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis.

Various Neurological Symptoms by Neurolymphomatosis as the Initial Presentation of Primary Testicular Lymphoma

Neurological symptoms induced by the infiltration of malignant lymphoma into the nervous systems are subsumed under the term neurolymphomatosis (NL). Here, we report the case of a 30-year-old Japanese man with primary testicular lymphoma complicated, as seen in various neurological findings, by secondary NL prior to testicular swelling. Painless right scrotal enlargement was noticed more than 1 month after the appearance of neurological complications such as right upper extremity numbness, dysarthria, facial palsy, and diplopia. Proactive investigation and biopsies of extranodal sites at high risk of central nervous system infiltration of malignant lymphoma, such as the testes, should be considered when secondary NL is suspected based on imaging findings.

A monoclonal expansion of Epstein–Barr virus-infected natural killer cells after allogeneic peripheral blood stem cell transplantation

Here, we describe a Japanese woman showing a monoclonal expansion of EBV-infected natural killer (NK) cells after receiving allogeneic peripheral blood stem cell transplantation (PBSCT). The patient initially had T-cell-type chronic active EBV disease (CAEBV) and subsequently developed liver T-cell lymphoma. L-Asparaginase-containing chemotherapy led to a favorable lymphoma response. To eradicate CAEBV and the lymphoma, she further received allogeneic PBSCT from a human leukocyte antigen-matched sibling donor. After the PBSCT, the patient presented with transient lymphocytosis of NK cells, which were infected with a monoclonal EBV strain other than previously detected ones. These NK cells seemed to have been transmitted from the healthy donor to the recipient. The patient and donor remain well in spite of carrying these NK cells. This is the first report of an asymptomatic Japanese carrier harboring monoclonal EBV-infected NK cells.