Hematology

Familial case of hereditary Pelger-Huët anomaly

Detection of Jordans’ anomaly using compact-type automated hematology analyzer

Macrophage elimination in bone marrow by dexamethasone palmitate is associated with successful engraftment in patients with hemophagocytic syndrome

Epigenetic abnormalities and therapies for hematological malignancies

The current state of human immunodeficiency virus-associated lymphoma in Japan: a nationwide retrospective study of the Japanese Society of Hematology Blood Disease Registry Abstract This retrospective nationwide study sought to clarify the current status of human immunodeficiency virus (HIV)-associated lymphoma in Japan, where the number of new HIV infections remains high. We extracted data of patients with HIV-associated lymphoma who were registered in the database of the Japanese Society of Hematology Blood Disease Registry from January 2012 to December 2015, and analyzed patient characteristics, pathological diagnosis, and outcomes. The study cohort included 79 patients, including 75 male patients, with a median age of 52.5 (25–88) years. Among the lymphoma subtypes reported, the most common was diffuse large B cell lymphoma (DLBCL), followed by Burkitt lymphoma and primary central nervous system lymphoma. Estimated 3-year overall survival (OS) of all types of HIV-associated lymphoma was 68.8% [95% CI 68.2–69.4%]. However, the rate of extranodal involvement at the time of diagnosis was 49.2% and half of DLBCL was international prognostic index high or high-intermediate, with poor prognosis. Patients with primary effusion lymphoma died within 6 months. Even in an era of combination antiretroviral therapy, HIV-associated lymphoma remains an important problem. Clinical manifestations identified in this study were aggressive, and outcomes remained poor, warranting continuous surveillance of HIV-associated lymphoma.

Hereditary spherocytosis caused by copy number variation in SPTB gene identified through targeted next-generation sequencing Abstract Hereditary spherocytosis (HS) is a heterogeneous genetic disorder characterized by spherocytosis on peripheral blood smear with hemolytic anemia, accompanied by signs of hemolysis. Herein, we report a 5-month-old Korean girl with HS resulting from a de novo 271 Kb microdeletion of 14q23.3. She presented with hemolytic anemia and mild splenomegaly. Spherocytosis was seen on examination of peripheral blood. Eosin-5′-maleimide (EMA) test and flow cytometric osmotic fragility test were positive. She had no relevant family history of spherocytosis. No pathogenic single nucleotide variants or small insertions/deletions were detected in HS-associated genes. Array comparative genomic hybridization analysis revealed a 271 Kb deletion at chromosome 14q23.3, encompassing the SPTB, CHURC1, GPX2, RAB15, FNTB, and MAX genes. We found a deletion affecting 5′ UTR, exon 1, and part of intron 1 of the SPTB gene using targeted next-generation sequencing (NGS) analysis, suggesting that NGS may be able to identify disease-causing copy number variations (CNVs), as well as small point mutations in HS patients. In addition, chromosomal microarray may be useful in defining combined deleted genes. Additional evaluations should thus be considered in the diagnosis of HS, especially when CNV is revealed as disease-causing abnormality.

Clinical update on hypomethylating agents Abstract Hypomethylating agents (HMAs), azacitidine and decitabine, are standards of care in higher-risk myelodysplastic syndromes and in acute myeloid leukemia patients ineligible for intensive therapy. Over the last 10 years, research efforts have sought to better understand their mechanism of action, both at the molecular and cellular level. These efforts have yet to robustly identify biomarkers for these agents. The clinical activity of HMAs in myeloid neoplasms has been firmly established now but still remains of limited magnitude. Besides optimized use at different stages of the disease, most of the expected clinical progress with HMAs will come from the development of second-generation compounds orally available and/or with improved pharmacokinetics, and from the search, so far mostly empirical, of HMA-based synergistic drug combinations.

New insights into the biology of acute myeloid leukemia with mutated NPM1 Abstract Acute myeloid leukemia (AML), the most common acute leukemia in adults, increases exponentially with age. While a number of recent advances have improved treatment, high cure rates have not yet been achieved. Nucleophosmin (NPM1) is found mutated in nearly one-third of newly diagnosed cases and leads to NPM1 protein that is mislocalized to the cytoplasm instead of the nucleolus. If the mechanistic basis through which this mislocalization leads to malignancy could be revealed, this AML subtype may be targetable with new drugs. Here, we review the structure and functions of the normal and mutant forms of nucleophosmin. We discuss several recent studies that have shed light on the pathophysiology of NPM1 mutations. We discuss the importance of HOX gene misregulation in NPM1-mutated leukemias, as well as evidence for the reliance of mutated NPM1 on its continued nuclear export. Together, these aspects, as well as new tools to manipulate and study NPM1, open the door to new therapeutic strategies that may ultimately improve treatment of this common subtype of AML.

Expression of mitochondrial genes predicts survival in pediatric acute myeloid leukemia Abstract Deregulated mitochondrial metabolism and biogenesis have been studied in acute myeloid leukemia (AML); yet, the relevance of mitochondrial-encoded gene expression on AML outcomes is unknown. This study was conducted to assess clinical significance of expression of mitochondrial-encoded genes, namely ND3, SDHB, Cytochrome b, Cytochrome C, and ATP6, in pediatric AML. Pediatric AML patients from July 2013 to June 2016 were enrolled in this prospective study. Relative genes expression was determined using real-time PCR, and expressed as fold change. 123 AML patients were enrolled, median age 10 (range 0.7–18 years). ND3 gene expression was significantly increased in poor-risk cytogenetics (P = 0.03). In univariate analysis, high ND3 and ATP6 gene expression was significantly associated with inferior EFS (P = 0.01 and P = 0.04, respectively) and OS (P = 0.02 and P = 0.01, respectively), whereas, in multivariate analysis, ND3 gene expression emerged as the only independent prognostic factor for EFS and OS (P = 0.04 and P = 0.03). ND3 gene expression is a significant predictor of EFS and OS in pediatric AML, and should be evaluated as a potential biomarker.

Characteristics of palliative home care for patients with hematological tumors compared to those of patients with solid tumors Abstract Home care medicine is a platform for providing supportive care for end-stage cancers. However, for undefined reasons, patients with hematological tumors (HTs) often fail to receive opportunities for home care. We, therefore, sought to delineate the clinical differences between solid tumors (STs) and HTs and to determine whether home care is effective for patients with HTs, as well as those with STs. We retrospectively analyzed the treatments, prognosis, and places of death of patients with STs (n = 99) and HTs (n = 20) who received palliative home care in our clinic and subsequently died between May 2016 and May 2018. Patients with HTs commonly required intravenous antibiotics, platelet transfusion, and red blood cell transfusion, while patients with STs tended to more frequently require the use of opioids. Importantly, there were no significant differences between the cohorts with respect to survival time and frequency of emergent visits to patients after their referral to us. Furthermore, most patients in both groups died at home. More than 50% of patients were not admitted to hospitals during our follow-up. Collectively, while therapeutic approaches sometimes differ, this study provides clinical evidence that palliative home care can be feasible even for patients with HTs.