[Chronic active Epstein-Barr virus infection with multiple vascular lesions successfully treated by cord blood transplantation].

An 18-year-old woman presented with fever and liver dysfunction. Computed tomography showed lymphadenopathy, hepatosplenomegaly, and vascular lesions such as aneurysms and irregularities at multiple arteries, including coronary arteries. Based on the high copy number of Epstein-Barr virus (EBV)-DNA in the peripheral blood, EBV-infected CD4+T cells, and the proliferation of EBER-positive cells in the bone marrow, chronic active EBV infection (CAEBV) was diagnosed. Although the fever and liver dysfunction improved as a result of the initial immunosuppressive therapy and multiagent chemotherapy, EBV-DNA remained high. Moreover, she experienced repeated episodes of angina pectoris due to coronary arterial lesions. Therefore, cord blood transplantation was performed after reduced-intensity conditioning. EBV-DNA decreased quickly after initiating the conditioning and became undetectable at day 7 after the transplant. Vascular lesions did not progress after the transplant, and the patient's angina pectoris resolved. At 2.5 years after the transplant, she is alive without disease recurrence. The prognosis of CAEBV with vascular lesions is especially poor. Although the indication for allogeneic hematopoietic stem cell transplantation (HSCT) is difficult to determine in such cases, the clinical course of our case suggests that allogenic HSCT could be safely performed under appropriate management and could successfully control not only CAEBV but also vascular lesions.

Renal dysfunction and anemia associated with long-term imatinib treatment in patients with chronic myelogenous leukemia.

Knowledge of the toxicity profile of long-term treatment with imatinib is limited. In the present study, we sought to evaluate renal function and hemoglobin levels during long-term imatinib treatment. Eighty-two patients with chronic myelogenous leukemia in chronic phase who had been on imatinib for over 5 years were retrospectively analyzed. The mean estimated glomerular filtration rate (eGFR) was significantly decreased over 5 years (77 ± 17 to 62 ± 14 ml/min/1.73m², P < 0.001). Higher age and lower eGFR value at initiation of imatinib were significantly associated with development of renal dysfunction by multivariate analyses. Mean hemoglobin levels also significantly decreased over the 5-year period (12.9 ± 1.7 to 12.4 ± 1.3 g/dl, P < 0.01). The rate of decrease in eGFR correlated significantly with hemoglobin levels (correlation coefficient = - 0.249, P < 0.05). Serum erythropoietin (EPO) levels did not increase in 16 patients with both renal dysfunction and anemia (median, 31.9 mIU/ml). In patients who participated in a clinical trial of imatinib discontinuation, mean eGFR (50.0 ± 6.5 to 56.0 ± 10.2 ml/min/1.73m², P < 0.05) and hemoglobin levels (12.0 ± 1.7 to 14.0 ± 1.6 g/dl, P < 0.01) improved significantly at 1 year after discontinuation. These findings suggest that long-term imatinib results in a partially reversible continuous decline in renal function and decreased hemoglobin levels.

Invasive hepatic mucormycosis: A case report and review of the literature.

Mucormycosis generally develops under immunocompromised conditions, including hematological malignancies and solid organ or hematopoietic stem cell transplantation. Although mucormycosis usually affects the lungs and paranasal sinuses, sporadic cases of invasive mucormycosis of the liver have been reported. We hereby report a patient with myelofibrosis who developed hepatic mucormycosis diagnosed by post-mortem examination. An extensive literature review identified 13 reported cases of hepatic mucormycosis, including ours, without lung involvement. Most of the underlying diseases or conditions were hematological malignancies and solid organ transplantation. Three cases had splenic lesions and four had gastrointestinal lesions, suggesting the possibility of translocation to the liver and/or spleen from the gastrointestinal tracts. Hepatic mucormycosis should be recognized as one of the presentations of invasive mucormycosis, especially when hepatic nodules are found in immunocompromised patients such as those with hematological malignancy or recipients of solid organ transplantation.

Very Late Relapse of Acute Promyelocytic Leukemia 17 Years after Continuous Remission.

The prognosis of acute promyelocytic leukemia (APL) has been improved by the combination of all-trans retinoic acid (ATRA) with chemotherapy. Nonetheless, relapse occurs in a certain proportion of patients, mostly within three to four years after treatment. We herein report a patient treated with ATRA and chemotherapy achieving remission who relapsed approximately 17 years after the treatment. A literature review identified 5 additional reported cases of APL relapse after more than 10 years. None of them presented with generally established risk factors for relapse, such as a high leukocyte count. The potential for late relapse of APL occurring more than 10 years after treatment should be recognized.

Recurrent bacterial pneumonia due to immunoglobulin G2 subclass deficiency after allogeneic hematopoietic stem cell transplantation: Efficacy of immunoglobulin replacement.

Immunoglobulin (Ig) G2 subclass deficiency is known to be associated with recurrent bacterial respiratory infections caused by capsulated bacteria. We encountered a case of recurrent pneumonia due to Streptococcus pneumoniae after allogeneic hematopoietic stem cell transplantation (HSCT). IgG2 subclass level was specifically low, and prophylactic Ig replacement successfully prevented subsequent infections. However, the cessation of Ig replacement resulted in subsequent pneumonia. These findings suggested that IgG2 deficiency could be a cause of recurrent pneumococcal infection after allogeneic HSCT.

Allogeneic hematopoietic stem cell transplantation following treatment with brentuximab vedotin for refractory Hodgkin lymphoma.

Brentuximab vedotin (BV) is a novel agent used for the treatment of relapsed or refractory Hodgkin lymphoma. We have described two patients with refractory Hodgkin lymphoma, who were successfully treated with BV followed by allogeneic hematopoietic stem cell transplantation (HSCT). Although both patients were resistant to conventional chemotherapies, they responded to four or five doses of BV given every 3 weeks. Then, the patients underwent bone marrow transplantation from unrelated donors after reduced-intensity conditioning consisting of fludarabine and melphalan. They remained progression-free for more than 3 years after the transplantation. These findings suggest that BV could be a promising bridging therapy to curative allogeneic HSCT for relapsed or refractory Hodgkin lymphoma. Further accumulation of such cases is warranted to evaluate the efficacy and safety of BV therapy prior to allogeneic HSCT.

Hyponatremia associated with human herpesvirus-6 (HHV-6) encephalitis after allogeneic hematopoietic stem cell transplantation: A presentation different from HHV-6 myelitis.

Human herpesvirus-6 (HHV-6) encephalitis and myelitis following allogeneic hematopoietic stem cell transplantation (HSCT) is frequently life-threatening. We retrospectively evaluated the clinical significance of hyponatremia in cases of HHV-6 encephalitis/myelitis. Using an institutional database and medical records, we identified and retrospectively analyzed 16 cases of HHV-6 encephalitis and/or myelitis after allogeneic HSCT. HHV-6 encephalitis and myelitis were defined as the symptoms/signs with HHV-6-DNA in the cerebrospinal fluid. Seizure and memory disorder were defined as symptoms/signs of encephalitis, and dysesthesia and vesicorectal disorder as those of myelitis. Five patients developed encephalitis with or without myelitis, and 11 patients developed myelitis alone. Hyponatremia (median 129.1 mEq/L; range 125.9-130.1) was observed in all five patients with HHV-6 encephalitis at diagnosis, and values were significantly lower than those in patients with HHV-6 myelitis alone (median 137.6; range 134.0-142.2; P < 0.01). In three of the five patients with encephalitis, the decrease in sodium level preceded the clinical onset of encephalitis by one or two days. These results suggest that hyponatremia may be an important manifestation of HHV-6 encephalitis, but not of myelitis, and could be a useful tool for the early prediction or diagnosis of HHV-6 encephalitis.

Single-institutional retrospective analysis of Japanese patients with chronic lymphocytic leukemia.

Unlike in Western countries, chronic lymphocytic leukemia (CLL) is a rare lymphoid malignancy in Japan, and its clinical features remain to be elucidated in the Japanese population. Therefore, we retrospectively analyzed 29 Japanese CLL patients newly diagnosed at our institute. Seventeen (59%) were male, and their median age was 62 years. With a median follow-up period from diagnosis of 69 months (range, 3-170 months), 9 patients received some form of treatment for CLL. Three patients died of disease progression with or without infection (n=2) or skin cancer (n=1). Five-year overall and treatment-free survival rates were 83% (95%CI, 46-96%) and 67% (95%CI, 45-81%), respectively. Two patients received allogeneic hematopoietic stem cell transplantation for refractory disease, and both were alive without disease relapse at 53 and 110 months, respectively, after transplantation. These results suggest the clinical courses of Japanese patients with CLL to be comparable to those in Western countries. However, future studies of larger numbers of patients are needed to further elucidate the features and long-term clinical courses of CLL in the Japanese population.

Effects of calcineurin inhibitors on sodium excretion in recipients of allogeneic hematopoietic stem cell transplantation.

Calcineurin inhibitors (CIs) such as cyclosporine A (CSA) and tacrolimus often cause renal dysfunction, resulting in increased serum creatinine, hyperkalemia, and hyperuricemia. However, the effects of CIs on sodium excretion have not been fully elucidated. We retrospectively evaluated the effects of CI administration on sodium excretion in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Fifty consecutive recipients each of allogeneic HSCT receiving either CSA or tacrolimus (100 patients in total) with available data for weekly fractional excretion of sodium (FENa) for a 4-week period after transplantation were enrolled in this retrospective analysis. No significant differences in patient characteristics were observed between CSA and tacrolimus groups except for the type of donor. FENa was significantly higher at the 3rd (1.25 ± 0.80) and 4th weeks (1.53 ± 1.06) after transplantation as compared with that at the 1st week (0.93 ± 0.51; P < 0.01, P < 0.001, respectively) in the tacrolimus group, but not at any time point in the CSA group. In addition, FENa was significantly higher in the tacrolimus group than the CSA group at the 4th week (1.53 ± 1.06 vs. 1.13 ± 0.80; P < 0.05). These results suggest that tacrolimus increases sodium excretion after allogeneic HSCT, and that this effect is minimal with CSA.

[Isolated central nervous system relapse in type II enteropathy-associated T cell lymphoma].

A 75-year-old male presented with progressive lower abdominal discomfort. CT scan demonstrated hypertrophy of the intestinal wall, small bowel dilatation, and masses in the descending colon. Biopsy specimens of the jejunum and descending colon revealed widespread distribution of medium-sized atypical lymphocytes with an immunophenotype, positivity for CD3, CD8, CD56, TAI-1, granzyme B and TCRß, but negativity for CD4, CD5, CD20, CD30 and EBER-ISH. Type II enteropathy-associated T cell lymphoma (EATL; Lugano, stage IIE) was diagnosed. Subsequently, he received 6 cycles of chemotherapy with 2/3 dose CHOP and obtained complete remission. However, 18 months after the initial presentation, he presented with rapidly progressive mental deterioration. Gadolinium enhanced T1-weighted brain MR images showed multiple masses with mild heterogeneous enhancement. Brain biopsy revealed necrotic tumors composed of medium-sized atypical lymphocytes, positive for CD3, CD8, CD56, TIA-1, granzyme B and TCRß, but negative for CD4, CD20, and EBER-ISH. CT scan disclosed no evidence of systemic lymphoma relapse, indicating central nervous system relapse of EATL. Despite immediate high-dose chemotherapy with methotrexate, he died of disease progression. EATL is a rare disease with a very poor outcome, for which a validated standard treatment is still lacking. Further studies are needed to identify innovative therapies for treating EATL.

Optic nerve involvement of Waldenström's macroglobulinemia: with autopsy findings.

Waldenström's macroglobulinemia (WM) is an indolent chronic lymphoproliferative disorder within the spectrum of lymphoplasmacytic lymphoma (LPL), characterized by a proliferation of plasmacytoid lymphocytes and the production of monoclonal IgM. Although, peripheral neurologic complications commonly occurs due to hyperviscosity in WM, central nervous system (CNS) involvement is very rare. Herein, we present the case of a 67-year-old man who initially presented with progressive visual loss and was diagnosed as WM/LPL with a very aggressive clinical course. He underwent chemotherapy with high dose methotrexate (MTX) plus cytarabine (Ara-C). However, he died and findings of a subsequent autopsy revealed the presence of lymphoplasmacytoid cells in the optic nerve.