Human leukocyte antigen-DQ risk heterodimeric haplotypes of left ventricular dysfunction in cardiac sarcoidosis: an autoimmune view of its role.

Cardiac sarcoidosis (CS) is the scarring of heart muscles by autoimmunity, leading to heart abnormalities and patients with sarcoidosis with cardiac involvements have poor prognoses. Due to the small number of patients, it is difficult to stratify all patients of CS by human leukocyte antigen (HLA) analysis. We focused on the structure of antigen-recognizing pockets in heterodimeric HLA-class II, in addition to DNA sequences, and extracted high-affinity combinations of antigenic epitopes from candidate autoantigen proteins and HLA. Four HLA heterodimer-haplotypes (DQA1*05:03/05:05/05:06/05:08-DQB1*03:01) were identified in 10 of 68 cases. Nine of the 10 patients had low left ventricular ejection fraction (< 50%). Fourteen amino-acid sequences constituting four HLA anchor pockets encoded by the HLA haplotypes were all common, suggesting DQA1*05:0X-DQB1*03:01 exhibit one group of heterodimeric haplotypes. The heterodimeric haplotypes recognized eight epitopes from different proteins. Assuming that autoimmune mechanisms might be activated by molecular mimicry, we searched for bacterial species having peptide sequences homologous to the eight epitopes. Within the peptide epitopes form the SLC25A4 and DSG2, high-homology sequences were found in Cutibacterium acnes and Mycobacterium tuberculosis, respectively. In this study, we detected the risk heterodimeric haplotypes of ventricular dysfunction in CS by searching for high-affinity HLA-class II and antigenic epitopes from candidate cardiac proteins.

FUS-ERG induces late-onset azacitidine resistance in acute myeloid leukaemia cells.

FUS-ERG is a chimeric gene with a poor prognosis, found in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). It remains unclear whether DNA hypomethylating agents, including azacitidine (Aza), are effective in FUS-ERG-harbouring AML and how FUS-ERG induces chemoresistance. Stable Ba/F3 transfectants with FUS-ERG were repeatedly exposed to Aza for 7 days of treatment and at 21-day intervals to investigate Aza sensitivity. Stable FUS-ERG transfectants acquired resistance acquired resistance after three courses of Aza exposure. RNA sequencing (RNA-seq) was performed when Aza susceptibility began to change; genes with altered expression or transcript variants were identified. Molecular signatures of these genes were analysed using gene ontology. RNA-seq analyses identified 74 upregulated and 320 downregulated genes involved in cell motility, cytokine production, and kinase activity. Additionally, 1321 genes with altered transcript variants were identified, revealing their involvement in chromatin organisation. In a clinical case of AML with FUS-ERG, we compared whole-genome alterations between the initial MDS diagnosis and AML recurrence after Aza treatment. Genes with non-synonymous or near mutations in transcription regulatory areas (TRAs), additionally detected in AML recurrence, were collated with the gene list from RNA-seq to identify genes involved in acquiring Aza resistance in the presence of FUS-ERG. Whole-genome sequencing of clinical specimens identified 29 genes with non-synonymous mutations, including BCOR, and 48 genes located within 20 kb of 54 TRA mutations in AML recurrence. These genes were involved in chromatin organisation and included NCOR2 as an overlapping gene with RNA-seq data. Transcription regulators involved in mutated TRAs were skewed and included RCOR1 in AML recurrence. We tested the efficacy of BH3 mimetics, including venetoclax and S63845, in primary Aza-resistant AML cells treated with FUS-ERG. Primary FUS-ERG-harbouring AML cells acquiring Aza resistance affected the myeloid cell leukaemia-1 (MCL1) inhibitor S63845 but not while using venetoclax, despite no mutations in BCL2. FUS-ERG promoted Aza resistance after several treatments. The disturbance of chromatin organisation might induce this by co-repressors, including BCOR, NCOR2, and RCOR1. MCL1 inhibition could partially overcome Aza resistance in FUS-ERG-harbouring AML cells.

Cardiac involvement of diffuse large B-cell lymphoma presenting as various arrythmias.

Symptomatic cardiac involvement of malignant lymphoma is rare. Silent invasion of malignant lymphoma makes it difficult to diagnose it in the early phase of clinical course. We describe a case with cardiac involvement of diffuse large B-cell lymphoma presenting various types of arrythmias that were not diagnosed until autopsy.

Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocytic leukemia.

Significant advancements have been achieved with regard to the outcomes of acute promyelocytic leukemia (APL) patients through the introduction of all-trans retinoic acid; however, early hemorrhagic death and differentiation syndrome remain the major causes of remission induction failure in patients with APL. To investigate early death, serious hemorrhage, and differentiation syndrome during remission induction therapy in terms of incidence, risk factors, influence on outcomes, and prophylactic effects of several new anticoagulants, the results of 344 patients enrolled in the Acute Promyelocytic Leukemia 204 study conducted by the Japan Adult Leukemia Study Group were analyzed. Early death was observed in 16 patients (4.7%), of whom 14 had serious hemorrhage and 2 had differentiation syndrome. Serious hemorrhage and differentiation syndrome of grade 2 or higher were observed in 21 and 54 patients, respectively. Patients who achieved complete remission had a 7-year disease-free survival of 84.8% if they did not experience serious hemorrhage and 40.0% if they experienced serious hemorrhage during remission induction therapy (P = 0.001). Risk factor analyses showed that higher white blood cell count was associated with early death, higher white blood cell count and lower platelet count with serious hemorrhage, and leukocytosis during induction therapy and higher body surface area with differentiation syndrome. In conclusion, these results indicate that patients with such high-risk features may benefit from more intensive supportive care. The hemorrhagic risk was not relieved by the introduction of new anticoagulants. Further studies are required to establish the predictive impact of body surface area on differentiation syndrome. This trial is registered with UMIN-CTR as C000000154 on September 13, 2005.

Real-world management of infection during chemotherapy for acute leukemia in Japan: from the results of a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group.

We conducted a nationwide questionnaire-based survey in 2019 following 2001, 2007 and 2013 surveys to clarify the real-world management of infection during chemotherapy for acute leukemia in Japan. An online questionnaire was sent through SurveyMonkey® to member institutions of the Japan Adult Leukemia Study Group in June 2019. The questionnaire consisted of 52 multiple-choice questions covering prophylactic measures, screening and diagnostic tests, empirical antibiotic therapy, antifungal management, the usage of granulocyte-colony stimulating factor, and vaccinations against influenza and pneumococcus during intensive chemotherapy for acute leukemia. Questions associated with antimicrobial stewardship were also included. Usable responses were received from 163 of 218 (74.8%) institutions. Approximately, half (52.2%) of the institutes did not have infectious disease department. As antibiotic prophylaxis, fluoroquinolones (62%) were most commonly used in induction chemotherapy for acute myeloid leukemia. No prophylaxis accounted for 19% of the institutions, which has gradually increased compared to previous surveys. In empirical antibiotic therapy for febrile neutropenia, monotherapy with ß-lactam antibiotics was the most commonly used first-line therapy. De-escalation was not considered in 42.2% of the institutions. In conclusion, this study clarified the real-world management of infection during intensive chemotherapy for acute leukemia in 2019 and raised future issues in Japan.

Impact of CD56 Continuously Recognizable as Prognostic Value of Acute Promyelocytic Leukemia: Results of Multivariate Analyses in the Japan Adult Leukemia Study Group (JALSG)-APL204 Study and a Review of the Literature.

BACKGROUND: After long-term analysis of the JALSG-APL204 study we recently reported that maintenance therapy with tamibarotene was more effective than all-trans retinoic acid (ATRA) by reducing relapse in APL patients. Here, the clinical significance of other important prognostic factors was evaluated with multivariate analyses. PATIENTS AND METHODS: Newly diagnosed acute promyelocytic leukemia (APL) patients were registered with the study. Induction was composed of ATRA and chemotherapy. Patients who achieved molecular remission after consolidation were randomly assigned to maintenance with tamibarotene or ATRA. RESULTS: Of the 344 eligible patients, 319 (93%) achieved complete remission (CR). After completing consolidation, 269 patients underwent maintenance random assignment-135 to ATRA, and 134 to tamibarotene. By multivariate analysis, overexpression of CD56 in blast was an independent unfavorable prognostic factor for relapse-free survival (RFS) (p = 0.006) together with more than 10.0 × 109/L WBC counts (p = 0.001) and the ATRA arm in maintenance (p = 0.028). Of all phenotypes, CD56 was related most clearly to an unfavorable prognosis. The CR rate, mortality rate during induction and overall survival of CD56+ APL were not significantly different compared with CD56- APL. CD56 is continuously an independent unfavorable prognostic factor for RFS in APL patients treated with ATRA and chemotherapy followed by ATRA or tamibarotene maintenance therapy.

Survival of a case of Bacillus cereus meningitis with brain abscess presenting as immune reconstitution syndrome after febrile neutropenia - a case report and literature review.

BACKGROUND: Bacillus cereus sometimes causes central nervous system infection, especially in compromised hosts. In cases of meningitis arising during neutropenia, CSF abnormalities tend to be subtle and can be easily overlooked, and mortality rate is high. We report a survived case of B. cereus meningitis/brain abscess in severe neutropenia, presenting as immune reconstitution syndrome. CASE PRESENTATION: A 54-year-old Japanese female with acute myelogenous leukemia developed B. cereus bacteremia and meningitis during consolidation chemotherapy. At the onset, she presented with mild meningism. She had marked leukocytopenia (WBC <100/µL, neutrophils 0/µL) and lumbar puncture yielded only mild pleocytosis. She was transferred to intensive care unit, and meropenem, linezolid and vancomycin was started. With intensive therapy, she recovered and once became afebrile. On day 19, however, her fever, meningism and consciousness level dramatically worsened despite recovery of bone marrow function. The antimicrobial chemotherapy was continued and finally she was cured with no complications. CONCLUSIONS: With early diagnosis and prompt initiation and of antibiotics, the case was successfully treated without any sequelae. It is important to remember that, even under optimal antimicrobial therapy, bone marrow recovery can cause transient reaggravation of the disease. In such cases, timely and appropriate evaluation should be done to make the clinical decision to change, continue, or intensify treatment.

[Immunohistochemical evaluation of BCL-2 expression in acute myeloid leukemia, myeloid sarcoma, and blastic plasmacytoid dendritic cell neoplasm].

Venetoclax, a selective BCL-2 inhibitor, is prescribed clinically for acute myeloid leukemia (AML) treatment. However, it is unclear if known chromosomal or genetic abnormalities associated with AML also influence BCL-2 expression. Few studies have examined BCL-2 expression in AML-related precursor neoplasms such as primary myeloid sarcoma (MS) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In this study, we examined BCL-2 expression using immunohistochemistry in 7 patients with AML, who also carried genetic and chromosomal abnormalities typical to AML including t (8;21), t (15;17), FLT3-ITD mutation, and complex karyotype, along with 1 patient with primary MS and 3 patients with BPDCN. As a result, expression of BCL-2 was observed in all patients with AML and 1 patient with primary MS. In the patients with BPDCN, BCL-2 was highly expressed in all regions with evidence of tumor cell infiltration, such as skin, bone marrow, and lymph node. These results could be used as evidence in the support of administering venetoclax to adverse-risk patients with AML, MS, or BPDCN.

Granisetron plus aprepitant versus granisetron in preventing nausea and vomiting during CHOP or R-CHOP regimen in malignant lymphoma: a retrospective study.

BACKGROUND: Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen includes a high dose of prednisolone (100 mg/body), which exhibits an anticancer and antiemetic effect. However, its optimal use for antiemetic therapy has not been established yet. We assessed the efficacy of granisetron plus aprepitant versus granisetron for CHOP or rituximab-CHOP (R-CHOP) regimen-induced nausea and vomiting in malignant lymphoma. METHODS: This retrospective and observational clinical study included patients who received CHOP or R-CHOP regimen as initiating chemotherapy between July 2010 and March 2016 (N = 39). Patients were assigned to an aprepitant [aprepitant (125 mg on day 1, 80 mg on days 2-3) plus granisetron (3 mg); n = 15] or control regimen group [granisetron (3 mg); n = 24]. Complete response (CR), defined as no vomiting and no use of rescue therapy during overall phase (0-120 h), was the primary endpoint. Secondary endpoints included the time to first vomiting and using rescue medication and complete protection (CP) defined as no vomiting and no retching and/or no nausea and no rescue therapy. The patient records were investigated, and data were retrospectively analyzed. RESULTS: CR rate CP rates did not significantly differ between the groups during the observation period (80.0% versus 83.3%, p = 1.000; and 80.0% versus 79.2%, p = 1.000, respectively). Additionally, the time to first vomiting and using rescue medication in did not significantly differ between the groups (p = 0.909). CONCLUSIONS: This study suggests that granisetron alone could be one treatment option in the management of CINV in patients with non-Hodgkin lymphoma receiving CHOP or R-CHOP regimen.

Indolent primary effusion lymphoma-like lymphoma in the pericardium: A case report and review of the literature.

We report a rare case of a 75-year-old man with a history of mild-to-moderate pericardial effusion that was detected on echocardiography performed in October 2011 when the patient was 69 years old. Follow-up echocardiography was performed every 6 months thereafter, showing that the pericardial effusion gradually subsided. However, in April 2017 he started experiencing several episodes of dyspnea, which prompted him to visit our hospital's outpatient department on June 22, 2017. Echocardiography revealed a large amount of pericardial effusion; thus, he was immediately hospitalized. After undergoing pericardiocentesis and drainage, 1740-ml of bloody pericardial fluid was collected. Serum antibody tests for human immunodeficiency virus, hepatitis C virus, and human herpes virus 8 were negative, whereas that for Epstein-Barr virus (EBV) was positive, indicating a prior infection. Cytopathological examination, immunocytochemical staining, lymphocyte surface marker analysis, and cytogenetic assessment were performed. EBV-encoded small ribonucleic acid in situ hybridization was negative. He was diagnosed with primary effusion lymphoma (PEL)-like lymphoma (LL) and was treated with 8 doses of rituximab 375 mg/m2 over a 2-month period. He has remained in complete response for the past 12 months. Our case shows the possibility of long-term existence of indolent PEL-LL in patients with mild-to-moderate pericardial effusion. .

A prospective multicenter observational study evaluating the risk of periendoscopic events in patients using anticoagulants: the Osaka GIANT Study.

Background and study aims An increasing number of patients have been using anticoagulants including anti-vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs); however, in patients using anticoagulants, limited data are available with regard to the risks of gastrointestinal bleeding and thromboembolic events during the peri-endoscopic period. We aimed to evaluate the peri-endoscopic bleeding and thrombotic risks in patients administered VKAs or DOACs. Patients and methods Consecutive patients using anticoagulants who underwent endoscopic biopsy, mucosal resection, or submucosal dissection were prospectively enrolled across 11 hospitals. The primary outcome assessed was difference in incidence of post-procedural gastrointestinal bleeding in patients using VKAs and DOACs. Duration of hospitalization and peri-procedural thromboembolic events were also compared. Results We enrolled 174 patients using VKAs and 37 using DOACs. In total, 16 patients using VKA were excluded from the analysis because of cancellation of endoscopic procedures and contraindications to the use of DOACs; 128 (81 %) patients using VKAs and 17 (46 %) using DOACs received heparin-bridging therapy (HB). The rate of post-procedural gastrointestinal bleeding in DOAC users was similar to that in VKA users (16.2 % vs. 16.4 %, P  = 1.000). Duration of hospitalization was significantly longer in patients using VKAs than in those using DOACs (median 15 vs. 7 days, P  < 0.0001). Myocardial infarction occurred during pre-endoscopic HB in one patient using VKAs. Conclusion DOAC administration showed similar post-procedural gastrointestinal bleeding risk to VKA administration in patients undergoing endoscopic procedures, but it shortened the hospital stay.

Chylous ascites, anti-interferon-gamma autoantibody, and angioimmunoblastic T-cell lymphoma: a rare but intriguing connection over Mycobacterium avium.

We report a case of non-AIDS (acquired immunodeficiency syndrome), non-CAPD (Continuous Ambulatory Peritoneal Dialysis), non-cirrhotic, Mycobacterium avium peritonitis, which is a rare form of mycobacterial infection. A 66-year-old Japanese man who had been treated previously for angioimmunoblastic T-cell lymphoma (AITL), had developed disseminated M. avium infection. Antimycobacterial regimen improved his symptoms; however, following an interruption in treatment, he developed chylous ascites. The patient died of uncontrolled peritonitis despite intensive treatment. Anti-interferon-γ autoantibody was positive, and AITL was presumed to be involved in autoantibody production. A rare coexistence of chylous ascites, autoantibody, and AITL taught us an intriguing lesson on the pathogenesis of M. avium infection. Particularly, we conclude that treatment strategies for M. avium infection should aim to restore immunity.

A novel mutation causing type 1 Gaucher disease found in a Japanese patient with gastric cancer: A case report.

RATIONALE: Gaucher disease (GD) is an autosomal recessive disorder that leads to multiorgan complications caused by ß-glucocerebrosidase deficiency due to mutations in the ß-glucocerebrosidase-encoding gene (GBA). GD morbidity in Japan is quite rare and clinical phenotype and gene mutation patterns of patients with GD in Japan and Western countries differ considerably. Of Japanese patients with GD, 57% develop types 2 or 3 GD with neurologic manifestations and younger onset, whereas only 6% of patients with GD develop those manifestations in Western countries. Thus, it is relatively difficult to find and diagnose GD in Japan. PATIENT CONCERNS: A 69-year-old Japanese female with mild anemia and thrombocytopenia but without neurologic symptoms was initially referred for gastric cancer. Preoperative F-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed accumulation in the bone marrow and paraabdominal lymph nodes. Following bone marrow aspiration found, abnormal foamy macrophages in the bone marrow and electron microscopy revealed that the macrophages were filled with tubular-form structures. Adding to these signs suggestive of a lysosomal disease, serum ß-glucocerebrosidase activity test found decreased. Sequencing of the patient's GBA gene revealed a RecNciI recombinant mutation and the novel mutation K157R (c.587A>G). DIAGNOSES: On the basis of these findings and clinical manifestations, the final diagnosis of type 1 GD was made. INTERVENTIONS: Enzyme replacement therapy (ERT) with velaglucerase α was started after the diagnosis of type 1 GD. OUTCOMES: The patient's ß-glucocerebrosidase activity as well as hemoglobin and platelet levels were restored by ERT without any side effects. Bone marrow aspirations 10 months after the start of the treatment with velaglucerase α showed reduction of Gaucher cells in bone marrow to 2% from 4% of total cellularity. LESSONS: This is the first report of F-FDG PET/CT application providing a clue for GD diagnosis. A novel mutation in GBA is described, which implies a potential pool of patients with GD with this mutation in Japan.

Infectious complications in adults undergoing intensive chemotherapy for acute myeloid leukemia in 2001-2005 using the Japan Adult Leukemia Study Group AML201 protocols.

PURPOSE: The Japan Adult Leukemia Study Group (JALSG) AML201 protocols are regimens for remission induction and consolidation chemotherapy of acute myeloid leukemia (AML) and have been widely accepted in Japan since 2001. Management of infectious complications during chemotherapy has a key role in the supportive care of AML patients. METHODS: By using case report forms collected in December 2001 and December 2005, we retrospectively analyzed the infectious complications in adult patients treated by using the JALSG AML201 protocols against AML (excluding promyelocytic leukemia). RESULTS: Of 980 patients, 80.2% experienced febrile neutropenia (FN), 8.3% bacteremia/fungemia, and 10.3% pulmonary infection at least once during remission-induction chemotherapy. Gram-positive bacteremia accounted for 65.1% of bacteremia/fungemia in 2001-2005, compared with 38.2% in 1987-1991 and 45.9% in 1992-1995. Of 750 patients, 81.9% experienced FN, 21.9% bacteremia/fungemia, and 9.1% pulmonary infection at least once during consolidation chemotherapy. During consolidation chemotherapy, bacteremia/fungemia and pulmonary infection were significantly more frequent in the high-dose cytarabine (HDAC) arm than in the conventional multiagent arm (25.9 vs. 17.9% and 12.7 vs. 7.7%, respectively). Invasive pulmonary aspergillosis accounted for 15.8% of pulmonary infections during remission induction and 19.7% during consolidation chemotherapy. CONCLUSIONS: Our data suggest that patterns of infectious complications have changed between 1987 and 2005, possibly because of chemoprophylaxis with oral fluoroquinolones and improved diagnosis of invasive pulmonary aspergillosis by serum antigen analysis.

Dual Threat of Epstein-Barr Virus: an Autopsy Case Report of HIV-Positive Plasmablastic Lymphoma Complicating EBV-Associated Hemophagocytic Lymphohistiocytosis.

Epstein-Barr virus (EBV) reactivation causes serious diseases in immunocompromised hosts, such as acquired immunodeficiency syndrome (AIDS). We report on a case of plasmablastic lymphoma (PBL) with hemophagocytic lymphohistiocytosis (HLH).A-53-year-old Japanese man was diagnosed with PBL and AIDS. In addition to combined antiretroviral therapy, HyperCVAD (cyclophosphamide, doxorubicin, vincristine, prednisone)/high-dose methotrexate + cytarabine was initiated immediately. Partial remission was attained with chemotherapy. However, the patient developed HLH and died despite intensive therapy. Autopsy findings suggested that PBL was controlled, and immunosuppression appeared to cause fatal infection. The patient showed high titers of EBV viral-capsid antigen (VCA)-IgG (1:2560) on PBL diagnosis and high EBV-DNA levels throughout the clinical course. Moreover, EBV-DNA was detected in the fraction of CD8-positive cells, which strongly supports the pathogenesis of EBV-associated HLH.Our report highlights the importance of EBV control in patients with EBV-positive AIDS lymphoma. EBV not only behaves as the etiologic pathogen of PBL but also can be a trigger of HLH, the fatal complication. Careful follow-up of the EBV status should be performed, and if needed, preemptive anti-EBV therapy should also be considered to prevent EBV-associated complications such as HLH.

[Significance of monitoring cerebrospinal fluid leukocyte counts in managing central nervous system disease of acute myeloid leukemia in patients presenting with intracerebral hemorrhage upon initial examination].

A 17-year-old woman was urgently transported to our hospital due to consciousness disturbance. A blood examination revealed intracerebral hemorrhage, WBC 233,800/l, blasts 93%, and disseminated intravascular coagulation. The results of bone-marrow aspiration indicated acute myeloid leukemia (M2 in FAB classification) with t (7;11) (p15;p15) and the resulting chimeric gene NUP98-HOXA9 and with FLT3-ITD. Following hematoma evacuation, induction therapy was initiated and the leukocytes in the cerebrospinal fluid observed in the spinal drainage were monitored. Because they increased on days 5 and 9 after the completion of induction therapy, intrathecal chemotherapy (IT) was performed; this finally contributed to controlling AML in the central nervous system (CNS), together with the restoration of normal hematopoiesis. Subsequently, after complete molecular remission with consolidation therapies containing high-dose cytarabine, a bone-marrow transplantation with a myeloablative regimen was conducted from a 1-allele mismatched sibling donor. Finally, the patient was discharged without major sequela on day 228 after the first visit. The management of CNS disease in AML with intracerebral hemorrhage remains unclear. Our case suggests that IT at the appropriate time based on the monitored number of cerebrospinal fluid leukocytes could be useful in controlling AML in the CNS after intracerebral hemorrhage.

Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group.

PURPOSE: We performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan. METHODS: We e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor. The results were compared to those of previous surveys conducted in 2001 and 2007, and also to the recommendations described in the guidelines. RESULTS: Usable responses were received from 141 out of 222 (63.5%) institutions. Chemotherapy for acute myeloid leukemia was performed in protective environment in 90% of the institutions, which increased compared to previous survey (76%). Fluoroquinolones and fluconazole were the most commonly used antimicrobial agents for antibacterial and antifungal prophylaxis, followed by sulfamethoxazole-trimethoprim and itraconazole, respectively. In empirical therapy for febrile neutropenia, monotherapy with ß-lactum antibiotics was the first-line therapy in most of the institutions. While empirical antifungal therapy was adopted for persistent fever in more than half of the institutions, preemptive/presumptive therapy was also used in approximately 40% of the institutions. Most of the clinicians were reluctant to use granulocyte-colony stimulating factor routinely in chemotherapy for acute myeloid leukemia. CONCLUSIONS: This study clarified the current clinical practices of infectious complications during chemotherapy for acute leukemia and would provide important information for the development of a suitable guideline in Japan.

Central nervous system involvement of acute promyelocytic leukemia, three case reports.

Central nervous system (CNS) involvement of acute promyelocytic leukemia (APL) causes poor prognosis. Our three cases show that CNS can be involved at the first hematological recurrence, but predicting this is difficult. Triple intrathecal treatment and craniospinal irradiation were effective, while arsenic oxide failed to prevent and improve CNS involvement.

Plasma presepsin level is an early diagnostic marker of severe febrile neutropenia in hematologic malignancy patients.

BACKGROUND: Febrile neutropenia (FN) is a common infectious complication in chemotherapy. The mortality of FN is higher in hematologic malignancy patients, and early diagnostic marker is needed. Presepsin is a prompt and specific marker for bacterial sepsis, but its efficacy in severe febrile neutropenia (FN) is not well confirmed. We tried to clarify whether it is a useful maker for early diagnosis of FN in patients during massive chemotherapy. METHODS: We measured plasma presepsin levels every 2-3 day in FN cases and evaluated its change during the course of massive chemotherapy. The patients had hematologic malignancy or bone marrow failure, and in all cases, neutropenia was severe during the episode. The baseline levels, onset levels, increase rate at FN onset, and onset / baseline ratio were evaluated for their efficacy of early FN diagnosis. RESULTS: Eleven episodes of bacteremia (six gram negatives and five gram positives) in severe neutropenia were analyzed in detail. While plasma presepsin level was strongly associated to the CRP level (r = 0.61, p < 0.01), it was not associated with the absolute WBC count (r = -0.19, p = 0.19), absolute neutrophil count (r = -0.11, p = 0.41) or absolute monocyte count (r = -0.12, p = 0.40). The average of onset presepsin level was 638 ± 437 pg/mL and the cutoff value (314 pg/mL) has detected FN onset in 9 of 11 cases. The two cases undetected by presepsin were both Bacillus species bacteremia. CONCLUSIONS: Plasma presepsin level is a reliable marker of FN even in massive chemotherapy with very low white blood cell counts. Closer monitoring of this molecule could be a help for early diagnosis in FN. But bacteremia caused by Bacillus species was an exception in our study.

Mycobacterium shigaense Causes Lymph Node and Cutaneous Lesions as Immune Reconstitution Syndrome in an AIDS Patient: The Third Case Report of a Novel Strain Non-tuberculous Mycobacterium.

A 40-year-old man complaining of progressive body weight loss was diagnosed to have acquired immunodeficiency syndrome. Within 2 weeks after the initiation of combination antiretroviral therapy, he developed fever, massive cervical lymphadenopathy and a protruding subcutaneous abscess. A lymph node biopsy and abscess drainage revealed non-caseous granuloma and mycobacterium. The mycobacterium belonged to Runyon II group, but it showed no matches to any previously reported species. According to sequence analyses, the strain was identified as Mycobacterium shigaense. After six months of antimycobacterial treatment, the lesions were all successfully cured. This is the third case report of the novel mycobacterium, M. shigaense, presenting in associatioin with immune reconstitution syndrome.