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The presence of a JAK2 V617F or JAK2 exon 12 mutation is one of the three major criteria listed for the diagnosis of polycythemia vera (PV) in the 2017 World Health Organization Classification. However, a nationwide study has not yet been conducted in Japan since the discovery of JAK2 mutations. Therefore, the Japanese Society of Hematology (JSH) retrospectively analyzed the clinical characteristics of 596 Japanese patients with PV diagnosed between April 2005 and March 2018. Among the 473 patients with complete data on JAK2 mutations available, 446 (94.3%) and 10 (2.1%) were positive for the JAK2 V617F and JAK2 exon 12 mutations, respectively. During a median follow-up of 46 months (range: 0-179 months), 47 (7.9%) deaths occurred. The major causes of death were secondary malignancies (23.4%), acute leukemia (12.8%), non-leukemic progressive disease (10.6%) and thrombotic (6.4%) and hemorrhagic complications (6.4%). Thrombotic and hemorrhagic events occurred during the clinical course in 4.0% (n = 24) and 3.5% (n = 21) of patients, respectively. These results show that the international PV prognostic score (age, venous thrombosis and leukocytosis) is applicable to Japanese patients with PV.

The main differentials in cases of sudden elevation of hepatic enzyme levels during immunochemotherapy are reactivation of hepatitis B virus or drug-induced liver injury. Here, we report a case of acute liver injury caused by hepatitis E virus (HEV) during chemotherapy for malignant lymphoma, wherein the patient was successfully treated and completed chemotherapy. A 57-year-old woman visited her local doctor because she felt light and tired. The patient underwent lower gastrointestinal endoscopy and was diagnosed with a malignant lymphoma of the small intestine (diffuse large B-cell lymphoma). The patient had a history of oral consumption of undercooked pork liver to improve anemia and was diagnosed with acute hepatitis E. Since the patient responded to chemotherapy, she was treated with single-agent ribavirin while continuing chemotherapy, resulting in a sustained virological response. Even during treatment with immunosuppressive drugs, if appropriate treatment for hepatitis E can be administered, the patient can be fully treated without interruption. The patient was able to complete chemotherapy adequately without interruption of treatment, which was a clinically beneficial result.

A 77-year-old Japanese woman with a 21-year history of seropositive, erosive rheumatoid arthritis (RA) and a 10-year history of methotrexate (MTX) therapy was admitted with malaise and mild consciousness disturbance. Laboratory data showed hypercalcemia, acute kidney injury, normocytic anaemia, and thrombocytopenia. As we first assumed drug-induced toxicity by MTX and eldecalcitol, both were discontinued and leucovorin rescue therapy and calcitonin were administered. However, her condition continued to worsen. Serum protein electrophoresis showed only a small M-peak, immunoelectrophoresis of both the serum and urine demonstrated Bence-Jones kappa (κ) type monoclonal protein without immunoglobulin heavy chain, and bone marrow examination revealed proliferation of plasma cells. We diagnosed her with Bence-Jones κ type multiple myeloma (MM) and transferred her to the department of haematology of a higher order medical institution. Conclusively, the diagnosis of immunoglobulin (Ig) D-κ type MM, a rare variant of this disorder, was determined in accordance with serum immunofixation. Several previous studies have suggested that pre-existing RA is a risk factor for MM. Although IgD MM is characterised by its clinical severity and poor prognosis compared to other subtypes, it is often misdiagnosed or mistaken as light chain type MM, as in the present case, because of the low level of IgD M-protein, resulting in delayed diagnosis. Physicians must take MM into consideration as a differential diagnosis when inactive RA patients present with inexplicable elevated calcium, renal failure, anaemia, and bone lesion symptoms and should be aware of IgD MM to establish the correct diagnosis promptly.

The JAK2V617F mutation is a driver mutation of myeloproliferative neoplasms (MPNs). V617F allele burden is considered a risk factor for complications associated with MPNs and is a predictor of prognosis. In Japan, V617F allele burden has been measured in laboratory settings using the i-densy

To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.

We conducted a large-scale, nationwide retrospective study of Japanese patients who were diagnosed with essential thrombocythemia based on the diagnostic criteria in the World Health Organization classification. We investigated clinical characteristics, survival rates, and the incidence of thrombohemorrhagic events as well as risk factors for these events. A total of 1152 patients were analyzed in the present study. Median age at diagnosis was 65 years, the median platelet count was 832 × 109/L, and the positive mutation rates of JAK2V617F, CALR, and MPL were 62.8, 25.1, and 4.1%, respectively. Compared with European and American patients, Japanese patients were more likely to have cardiovascular risk factors and less likely to have systemic symptoms including palpable splenomegaly. Thrombocytosis was identified as a risk factor for hemorrhagic events and prognosis, but not for thrombotic events. The prognostic factors and risk classifications reported in Europe and the United States were generally applicable to Japanese patients. Regarding transformations, secondary myelofibrosis progressed in a time-dependent manner, but progression to acute leukemia was low in "true" ET patients. Skin cancers were less common and gastrointestinal cancers more common as secondary malignancies in Japanese patients, suggesting ethnic differences.

Thalassemia is caused by a reduced production of one globin chain due to a quantitative imbalance between the α-globin and non-α-globin chains that make up the hemoglobin. It is classified into α- and β-thalassemia and characterized by microcytosis with polycythemia, and a Mentzer index of ≤13 aids in the diagnosis. In the genetic analysis of α-thalassemia, the Southeast Asian type was found to be the most common genetic subtype among Japanese and non-Japanese without a substantial difference. Conversely, the genetic analysis of β-thalassemia revealed differences in the types and frequencies of mutations between Japanese individuals and foreigners living in Japan, with Japanese-specific mutations such as -31 A→G (TATA box). Acquired α-thalassemia exists in exceptional cases, and cases of myelodysplastic syndrome with acquired Hemoglobin H disease have been reported as α-thalassemia myelodysplastic syndrome. Recent trials using a novel therapeutic agent, luspatercept, for transfusion-dependent β-thalassemia revealed that luspatercept safely and significantly reduces the transfusion volume.

Werner syndrome (WS) confers a high risk of the development of neoplasias, including hematological malignancies, and curative treatment for these malignancies is difficult to achieve. A 44-year-old man with myelodysplastic syndrome was admitted to our hospital. He was diagnosed with mutation-proven WS. He underwent cord blood transplantation (CBT) following fludarabine, busulfan, and melphalan administration. A chimerism analysis of his marrow blood on day 62 showed a donor pattern ＞95%, which confirmed engraftment. The patient lived for 15 months while maintaining remission of MDS without treatment-related toxicity. Our case shows that CBT can be a treatment modality for WS patients with hematological malignancies.

Cold agglutinin disease (CAD) is a rare, complement-mediated autoimmune hemolytic anemia. Patients with CAD in the United States and Europe have an increased incidence of thromboembolism (TE), but comparable information for patients in other regions is lacking. Thus, we examined TE risk for patients with CAD in Japan. Patients with CAD (at least three claims with a CAD diagnosis; Japanese Disease Code 2830009) and non-CAD controls were retrospectively identified (2008–2017) from a large hospital-based administrative claims dataset in Japan. Cohorts were compared using conditional logistic regression. We identified 344 patients with CAD (53.2% female; mean age: 66.8 years) and 3440 matched controls. Patients with CAD had higher TE rates than controls (34.9% vs. 17.9%; P

Donor cell-derived leukemia and myelodysplastic syndrome (DCL) is a rare complication in patients after allogenic stem cell transplantation (SCT). Since 1971, numerous cases of DCL have been reported, but the detailed mechanisms of DCL are still unclear. A patient with jumping translocations (JTs) of 1q in umbilical cord blood donor cell-derived myelodysplastic syndrome (MDS), which likely occurred due to genetic alterations of TET2 and ASXL1 after cord blood transplantation (CBT), was examined in this study. Previously reported DCL cases after CBT that focused on the cytogenetic and molecular characteristics of these patients and patient outcome were reviewed. A total of 30 cases of DCL after CBT were identified between 2005 and 2018. The median time from CBT to the development of DCL was 16 months. The number of patients with DCL who were diagnosed with acute myeloid leukemia (AML) and MDS was 19 and 8, respectively. JTs were frequently observed in 5 of 27 DCL patients who had cytogenetic abnormalities, including our patient. Molecular abnormalities were described in 7 of the cases, and the most frequent abnormality was an NPM1 mutation. Other gene mutations that were usually found in de novo MDS or AML were observed in JT-DCL after CBT. From these results, chromosomal abnormalities such as JTs that occur subsequent to genetic alterations were seemed an important mechanisms underlying DCL onset in patients after CBT. Further molecular analyses regarding the genetic alterations of JTs are required to understand the pathogenesis of umbilical cord blood-derived JT-DCL.

Cord blood transplantation (CBT) is associated with delayed hematopoietic recovery and graft failure. To overcome these problems, we conducted a prospective, multicenter phase II study of intrabone marrow transplantation in which patients received reduced-intensity conditioning without anti-thymocyte globulin (ATG). The primary endpoint was the probability of full donor engraftment. Forty patients with hematologic malignancies were enrolled. Cord blood (CB) cells were injected without washing into 4 iliac bone sites (2 at each hemipelvis), at which approximately 6 mL of CB was administered at one site with local anesthesia. Full donor engraftment rate was 86.8%. The cumulative incidence of neutrophil and platelet engraftment was 86.4% and 85.5%, respectively. The median time to neutrophil (>0.5 × 109 /L) and platelet (2.0 × 109 /L) recovery was 17.5 and 44 days, respectively. The probability of severe acute graft-vs-host disease (GVHD) was 47.5%. The cumulative incidence of extensive chronic GVHD was 3.0%. The probability of relapse and non-relapse mortality was 30.4% and 28.0%, respectively. The survival rate at 3 years was 45.6%, although most patients were at an advanced stage. These results suggest that our intrabone marrow-CBT procedure without using ATG improves hematopoietic recovery and decreases the incidence of chronic GVHD, but does not decrease the incidence of acute GVHD.

Primary testicular lymphoma (PTL) is a rare, extranodal lymphoma that often relapses in the contralateral testis. We evaluated outcomes in patients with any stage of PTL who had received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab chemotherapy and prophylactic radiotherapy to the contralateral testis. We retrospectively identified 15 patients (median age 66 years; range 39–81) diagnosed with diffuse large B-cell PTL in the period 2000–2014. Characteristics and outcomes of these cases were evaluated. All patients received initial orchiectomy followed by CHOP with or without rituximab. Thirteen patients received prophylactic irradiation to the contralateral testis. During follow-up (median 67 months; range 8–190), one patient died of PTL, three died of other disease, and nine were free from relapse. For stage I–II disease, 5-year progression-free and overall survival rates were 80 and 100%, respectively. For stage III–IV PTL, 5-year progression-free and overall survival rates were 50 and 72%, respectively. Notably, no patient developed contralateral testicular involvement after prophylactic irradiation. The observed outcomes suggest that the combination of (i) CHOP plus rituximab and (ii) radiotherapy for local recurrence prophylaxis is promising for both stage I–II and stage III–IV PTL.

Purpose To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan. Patients and Methods Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed. Results Patients’ median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase–containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively). Conclusion Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor.

Autoimmune hemolytic anemia (AIHA) is secondary to underlying diseases, such as autoimmune diseases and lymphoid malignancies. Recently, solid cancers have also been reported to be associated with AIHA, although there is not much information available. In this study, we retrospectively examined the correlation between AIHA and onset of malignancy in 100 patients diagnosed with AIHA based on the broad definition of AIHA at our hospital and cooperating institutions from January 1, 1995 to May 31, 2016. Malignancies were detected in 52 of the 100 patients (hematological malignancies: 39 patients; solid cancers: 22 patients; total malignancies including multiple primary malignancies: 67 patients). Of the 67 patients with malignancies, 28 were diagnosed with malignancies within 6 months of AIHA diagnosis. All patients with cold agglutinin disease (CAD) were associated with malignancies. Compared with warm AIHA, solid cancers were significantly more common among the patients with CAD. These findings emphasize the importance of investigating the malignancies upon diagnosis of AIHA.

Congenital hemolytic anemias are classified into three major categories: red cell membrane disorders, hemoglobinopathies, and red cell enzyme disorders. The membrane disorders are caused by abnormalities in erythrocyte membrane proteins and are often associated with disease-specific deformations of red blood cells. Historically, membrane disorders have been classified according to morphology. In recent years, however, comprehensive genetic analysis with next-generation sequencing has been performed in patients with hemolytic anemia for whom making an accurate diagnosis is difficult. These studies have led to the identification of new causative genes, but there have been inconsistent associations in some cases between the diagnosed disease and the patient's clinical manifestations. Thalassemia is a hemoglobinopathy caused by a quantitative abnormality of one or the other of the globin chains in hemoglobin. Most Japanese patients with thalassemia have mild forms of the disease, which is different from reports in other countries. However, with globalization, the proportion of Japanese patients with intermediate or severe anemia is increasing. Therefore, it is incumbent on hematologists in Japan to be knowledgeable regarding prenatal diagnosis of and gene therapy for thalassemia.

Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients’ fitness for steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65–75%) and 34% (95% CI, 21–47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P

Acute myeloid leukemia (AML) with BCR-ABL1 is rare and has a poor prognosis with conventional chemotherapy or ABL tyrosine kinase inhibitors (TKIs) alone. We reported a case of AML with BCR-ABL1 patient who was successfully treated with dasatinib alone; additionally, we previously reported another case of long-term remission maintained with imatinib monotherapy. These results suggested that a treatment with a novel and significantly potent TKI may be effective in AML with BCR-ABL1 patients with low tumor burden and without additional chromosome aberrations and ABL kinase domain mutations.

A 16-year-old girl presented to our hospital with diarrhea and abdominal pain. The macroscopic findings of colonoscopy revealed multiple submucosal tumors and multiple ulcers, which were localized in the sigmoid colon, and diffuse granular mucosa which extended to the total colon. The pathological diagnosis was malignant lymphoma comprising both components of diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma, because the large lymphoma cells were CD20+, CD10-, and CD5-. Furthermore, immunohistochemical analysis of colorectal biopsy samples from multiple ulcers revealed cytomegalovirus (CMV)-positive cells. The patient was diagnosed with primary colorectal lymphoma comprising both components of DLBCL and MALT lymphoma combined with CMV colitis. She received anti-viral medication and chemotherapy.

Southwestern Japan suffered its worst rains in 2018 causing floods and mudslides, claiming 225 lives and forcing millions for evacuations. Referred as “Heisei san-jū-nenshichi-gatsugōu”, the disaster was the result of incessant precipitation caused by the interaction of typhoon “Prapiroon” with the seasonal rain front "Baiu". The present epidemiological study aims to investigate disaster-induced health issues in 728 residents of Innoshima island in the Hiroshima Prefecture by comparing their clinical data in pre-disaster (2017) and disaster-hit (2018) years which was obtained from annual health screening. Comparison of data showed a significant increase in the urine protein concentration in victims following the disaster. Probing further into the household conditions, showed that a total of 59,844 households were affected with water outage during the heavy rains, which was accompanied by severe damage of sewerage pipelines with complete recovery process taking two weeks. This two weeks of the crisis forced victims to refrain from using restrooms which in turn led to infrequent urination, thereby explaining the increased urine protein concentration in victims following the disaster. The present study addresses the acute health implications caused by the water crisis and serves as a precautionary measure for disaster management council to provide enhanced aftercare services in victims in further events of natural disasters., Epidemiology; Occupational health; Public health; Quality of life; Japan heavy Rain, Water outage, Health impact, Urinary protein, Health checkup

Extremely early diagnosis of human immunodeficiency virus (HIV) infection has been considered highly important for its treatment. We conducted a performance assessment of a newly developed rapid diagnostic reagent for HIV by using a fourth-generation immunochromatographic assay (Alere HIV Combo). We used whole-blood, plasma, and serum samples obtained from 250 Japanese adults who visited the Kawasaki Medical School Hospital and underwent HIV screening tests. We also used 12 types of commercial HIV-1 sero- conversion panels and World Health Organization standard antigens. This method, which has a detection sensitivity of 100% and a specificity of 99.3%, was as accurate as the chemiluminescent immunoassay (CLIA) method. In a sensitivity test using seroconversion panels in the early phase of infection, the mean duration until positive conversion was 19.3 days. With this method having a high detection sensitivity for HIV-1p24 antigen, the results from whole-blood samples were the same as those from plasma and serum samples. Therefore, it can be considered as a useful rapid measurement method for general practice.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are members of the herpesvirus family and common causes of viral infection in humans. CMV infection of the gastrointestinal tract occurs mainly in immunocompromised individuals, on the other hand EBV infection and reactivation involving the gastrointestinal tract is very rare. A 56-year-old man was diagnosed with severe aplastic anemia and treated with antithymocyte globulin (ATG) and cyclosporine (CSP). After 2 years of ATG/CSP therapy, he suddenly started passing bloody diarrhea and developed a high fever despite CSP treatment. Endoscopic features included severe edema and multiple superficial ulcers; the patient was initially diagnosed with severe colitis resembling inflammatory bowel disease (IBD). However, his symptoms did not resolve with steroid treatment. Immunohistochemical analysis of samples obtained from a second colonoscopy showed cells positive for CMV, and in situ hybridization revealed EBV-encoded small RNA-1-positive cells. Additionally, the patient's serum was positive for C7-HRP, and both blood and colon tissues were positive for EBV DNA, which was detected using PCR analysis. We finally diagnosed the patient with colitis associated with reactivation of both CMV and EBV. The patient remains diarrhea-free after 1.5 years with scheduled globulin treatment and after cessation of immunosuppressive drug therapy. To our knowledge, this is the first reported case of an immunodeficient patient with severe hemorrhagic colitis that was associated with reactivation of both EBV and CMV, and whose endoscopic findings mimicked IBD.

We herein describe the case of a 60-year-old man with a history of Behcet's disease and myelodysplastic syndrome who received cord blood transplantation (CBT). The patient was given anti-thymocyte globulin conditioning and tacrolimus to prevent graft-versus-host disease. Two months after CBT, his blood Tac concentration measured by an antibody-conjugated magnetic immunoassay (ACMIA) was found to have increased >4-fold, even after the Tac treatment was stopped. This false response was caused by the interference of endogenous heterophilic antibodies with ACMIA. Therefore, physicians must be aware of possible false ACMIA results for patients with a history of autoimmune disease and/or treated by xenogeneic antibody therapy.

Background High sensitivity for detection of HIV-1 p24 antigen allows for early detection of primary HIV-1 infections. Objectives To evaluate the detection sensitivity and specificity of the Daina Screen® HIV Combo assay using clinical specimens in Japan where the pretest probability (prevalence) is low. Study design We screened 17,373 preoperative outpatient blood samples using 4th generation lateral flow immunochromatography Daina Screen® HIV Combo assay for simultaneously detecting anti-HIV-1/2 and HIV-1 p24 antigens. Results Of the samples tested, 24 were positive for HIV-1 p24 antigen and 49 for HIV-1/2 antibody. Of the 49 samples, 36 were WB and HIV-1 RNA negative, 10 were WB and HIV-1 RNA positive, and 3 were WB positive, HIV-1 RNA negative, and in-house HIV-1 proviral DNA positive. RT-PCR revealed that of the 24 samples that were p24 antigen positive, one sample was HIV-1 RNA positive, which was reconfirmed using an in-house HIV-1 provirus DNA assay. From the 17,300 HIV-1 p24 antigen and anti-HIV-1/2 negative samples, pools containing 10 negative samples each were tested for HIV-1 by RT-PCR; all results were negative. Conclusion The Daina Screen® HIV Combo assay had a sensitivity and specificity of 100% and 99.7%, respectively, which sufficiently detected HIV infection in the cohort.

Calreticulin (CALR) and JAK2-V617F gene mutations, which are major genetic mutations in patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET), exert different effects on the clinical features and outcomes of these diseases. We analyzed 88 and 9 patients with ET and PMF, respectively, and determined the differences in the clinical characteristics of ET patients with JAK2-V617F compared with CALR mutations. The frequency of the JAK2-V617F and CALR mutations were 64 and 22 %, respectively. Patients with CALR mutations were younger, had a lower white blood cell count, and had a lower rate of thrombotic events than patients with the JAK2 mutation. The neutrophil alkaline phosphatase (NAP) score of 16 patients with CALR mutations was significantly lower than the normal controls, which was mainly due to the high proportion of NAP-negative neutrophils. This is the first report to show an association between CALR mutations in patients with myeloproliferative neoplasms (MPN) and the NAP score. Although the mechanism is unclear, the NAP score could be a useful and reliable biochemical marker to discriminate the mutational status of MPN patients. Further investigation is warranted to determine whether these characteristics contribute to the pathogenesis of MPN and the NAP score.

Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites. Histology findings for the following were positive at varying rates, as follows: CD10 (56 %); CD30 (39 %); CD38 (87 %); MUM-1 (91 %); CD138 (79 %); EBER (91 %); and LMP-1 (18 %). There was a marked increase in patients in 2011–12, and the cases found in that period appeared to be more aggressive, showing a higher rate of advanced-stage PBL. Fourteen cases were treated with CHOP, while the others were treated with more intensive regimens, including bortezomib and hematopoietic stem cell transplantation. The overall median survival time was 15 months. A CD4 count of >100/µL at diagnosis and attaining complete remission in the first-line chemotherapy were associated with better outcomes (P = 0.027 and 0.0016, respectively). Host immune status and chemosensitivity are associated with improved prognosis in PBL.

In cord blood transplantation (CBT), the amount of time elapsing until hematological engraftment has effects on the transplantation results. Carnitine deficiency has been reported to cause erythropoietin refractory anemia in chronic hemodialysis patients and thrombocytopenia or leukopenia of cirrhosis, and carnitine supplementation can improve hematopoiesis in patients with hepatic or renal failure. Patients who receive CBT may suffer from carnitine deficiency, but no studies have investigated the carnitine status of such patients. Herein, we determined the concentration of free carnitine (FC) and investigated the correlation between FC and engraftment in patients who received CBT. Twenty-three patients who received CBT at our hospital during the period from April 2013 to January 2015 were enrolled in this study. One patient was excluded because of graft failure, such that 22 patients were ultimately evaluable. FC concentrations of the patients were sequentially monitored at 4 time points (before conditioning therapy, day 0, day 7, and day 14), basic laboratory data were collected, and their correlations with engraftment were analyzed. FC concentrations of the patients were generally low (before conditioning therapy: 33.1, day 0: 43.2, day 7: 38.3, and day 14: 37.8 μmol/l). Significant inverse correlations were observed between FC concentrations and the number of days required for neutrophil engraftment on day 0 and day 14 (before conditioning therapy: P=0.15, r=-0.33, day 0: P=0.04, r=-0.43, day 7: P=0.30, r=-0.23, and day 14: P=0.01, r=-0.55). These results suggest carnitine to be an important nutrient that promotes hematopoietic recovery after CBT.

Hemoglobin (Hb) Hiroshima is an Hb variant that travels rapidly on electrophoresis and shows a fourfold increase in oxygen affinity and a decreased Bohr effect. We encountered a 40-year-old male patient with erythremia and an undetectable HbA1c level. The presence of an abnormal hemoglobin molecule was suggested by the results of high-performance liquid chromatography analysis. Subsequent gene analysis by direct sequencing confirmed Hb Hiroshima (β146 histidine → aspartic acid). Caution should be exercised when diagnosing erythremia.

A dominantly-inherited hereditary elliptocytosis of intermediate severity was recorded in a Japanese family from Yamagata. The condition was associated with a spectrin truncated beta-chain (MW: 214 kD; 31% of total beta-spectrin), and a defect of mutant spectrin as regards tetramerization and phosphorylation. cDNA analysis revealed skipping of exon X, the third-to-last exon of the spectrin beta-gene. At the gene level, a one-base substitution (A-->G) changed position +4 of the 5' donor splice site consensus sequence of intron X. This mutation has been described before in a French kindred, defining spectrin Le Puy. Electron micrographs following quick-freeze deep-etching showed that the skeletal network was disorganized.

Transformation from follicular lymphoma (FL) to high-grade B-cell lymphoma/leukemia (BLL) has been reported in patients with additional translocations involving the c-MYC gene. The previously reported cases were related to t(8;14) and t(8;22) but not to t(2;8). Herein is reported an FL that terminated in BLL following additional t(2;8). In accordance with previous reports, increased expression of c-MYC was observed in the present case but, interestingly, BCL-2 expression was inversely decreased after the transformation. In addition, the cell-surface immunoglobulin light-chain of lymphoma cells was initially kappa type and was then gradually replaced with the lambda type after transformation. Downregulation of BCL-2 and light-chain switch have rarely been reported in previous cases of FL transformation involving c-MYC, suggesting that additional t(2;8) translocation may play a role in these events.

Because of the rarity and the morphological variations, small cell variant of anaplastic large cell lymphoma (ALCL) represents a diagnostic challenge. Herein is reported a case of leukemic type of small cell variant of ALCL, in which the diagnosis was established by a cytogenetic analysis. The patient was a 23-year-old woman who presented with fever and leukocytosis with circulatory atypical lymphoid cells. The initial differential diagnosis on bone marrow trephine biopsy sections included viral infection and peripheral T-cell lymphoma unspecified. But a cytogenetic study on bone marrow cells indicated a novel complex translocation, t(2;5;3)(p23;q35;p21), which led to confirmation of anaplastic lymphoma kinase (ALK)-positive pleomorphic small to medium-sized cells scattered in bone marrow cells, on immunohistochemistry. ALK was distributed in both nuclear and cytoplasmic regions of neoplastic cells. The patient achieved complete remission after four courses of combination chemotherapy, and received autologous peripheral stem cell transplantation (auto-PBSCT) after two additional courses of combination chemotherapy, but relapsed 2 months after auto-PBSCT in the bilateral lung. Allogeneic stem cell transplantation led to a second remission. This case demonstrates the diagnostic importance of cytogenetic study for malignant lymphoma involving bone marrow.