Retrospective Analysis of Clinical Factors Relating to the Outcome of Gemtuzumab Ozogamicin Therapy

It is difficult to predict the clinical outcome of gemtuzumab ozogamicin (GO) therapy based solely on the previously identified predictive factors. We retrospectively analyzed the relationship between clinical factors and outcomes in 12 patients with relapsed or refractory acute leukemia who received GO monotherapy. The median patient age at initial GO infusion was 56 years, and the average initial dosage was 8.1 mg/m2. Four patients (33%) achieved an overall remission (OR). The time from diagnosis to GO infusion was significantly longer in patients with OR than in patients with no remission (NR)(1747 vs. 501 days, respectively; P < 0.01). The number of karyotype abnormalities before GO infusion was significantly greater in NR patients (9.5) than in OR patients (0.5; P = 0.03). Monocyte counts in the bone marrow before GO therapy were significantly lower in OR than in NR patients (100/μL vs. 1080/μL, respectively; P = 0.048). In a multivariate analysis, monocyte count was significantly associated with overall survival (P = 0.005). CD14 expression in OR patients was lower than in NR patients, with the exception of 4 patients whose French-American-British subtypes were M4 or M5 (OR, 0.3%; NR, 2.5%; P = 0.04). NR was noted in all 6 patients who underwent allogeneic stem cell transplantation before and/or after GO infusion. Patients showing good sensitivity to conventional chemotherapy with good survival after diagnosis tend to be sensitive to GO as well. A low monocyte count in the bone marrow at infusion of GO might indicate improved efficacy of GO therapy. Further investigation is warranted for establishing appropriate patient selection and for clarifying efficient conditions for GO therapy

Predicting the course of hematopoietic neoplasm through oral bacterial examination

Many medical institutions have recently conducted studies on the relationship between patients with hematopoietic neoplasms and oral cavity. Statistical analysis of the bacterial populations was performed in this study to identify how oral microflora and health conditions （e.g., dental caries and periodontal diseases） affect the prognosis of patients with hematopoietic neoplasms. Patients undergoing inpatient treatment from January to December 2020 at the Department of Hematology at Showa University, Japan, who required perioperative oral management were included in the study. The oral health of the patients was examined at the initial dental visit, and oral bacterial samples were collected from the tongue, buccal mucosa, and palate of 47 patients who consented to participate after receiving an explanation about the study. Statistical analyses performed after dividing the subjects into two groups following the treatment course showed that Stenotrophomonas maltophilia and Gemella sanguinis were significantly more common in the poor-course group. However, no significant difference in bacterial examination results was noted among the four groups （myeloid neoplasm chemotherapy, myeloid neoplasm hematopoietic stem cell transplantation （HSCT）, lymphoid neoplasm chemotherapy, and lymphoid neoplasm HSCT groups） classified based on disease and treatment method. The detection rate of bacteria potentially causing infectious diseases at the initial dental examination tended to be higher in this study in the poor-course group. The findings of the current study suggest that early detection of pathogenic bacteria after commencing hematology treatment could predict the poor-course that may lead to mortality or severe infections

Antarctic Study on Tropospheric Aerosol and Snow Chemistry (ASTASC) in JARE Phase X

The Tenth Symposium on Polar Science/Special session: [S] Future plan of Antarctic research: Towards phase X of the Japanese Antarctic Research Project (2022-2028) and beyond, Tue. 3 Dec. / Entrance Hall (1st floor) at National Institute of Polar Research (NIPR

Analysis of the MYD88 L265P mutation in IgM monoclonal gammopathy by semi-nested polymerase chain reaction-based restriction fragment length polymorphism method

MYD88 L265P mutation causes constitutive activation of NF-κB and possible driver mutation in B-cell lymphoid malignancies. It is frequently detected in Waldenstrom’s macroglobulinemia （WM） （50％-100％）, and its detection is important in diagnostic and therapeutic targets of this syndrome. Standard detection method of MYD88 L265P mutation in clinical practice has yet to be established. We developed semi-nested PCR-based restriction fragment length polymorphism （snPCR-RFLP） to detect the mutation. The snPCR-RFLP method is a modification of the PCR-RFLP method, which uses the restriction enzyme BsiEI that recognizes CGACT/CG, intending to increase detection sensitivity by amplification of mutated allele in the DNA sample using semi-nested PCR before enzyme digestion. The detection sensitivity of snPCR-RFLP was estimated as 0.1％, by detecting mutated allele in wild-type allele in the cloned plasmid DNA, which is comparable with allele-specific （AS） PCR method widely used as sensitive detection method. By analyzing 40 cases with IgM monoclonal gammopathy, snPCR-RFLP detected 29/40 （70％） of all cases, 22/31 （70.9％） of WM, and 6/9 （66.6%） of IgM-type monoclonal gammopathy with undetermined significance （IgMMGUS）, including five cases （three cases of WM and two cases of IgMMGUS） in which the mutation was detected only by snPCR-RFLP but not by Sanger sequencing method. Regarding DNA sample status, particularly five cases, a case was extracted from formalin-fixed paraffin-embedded tissue and four cases were extracted from cells by Ficoll-Hypaque density gradient. In correlation with clinical features, the MYD88 mutation detected by snPCR-RFLP method was associated with the adverse prognostic index （WMIPSS） of WM using patient age, hemoglobin （Hb） level, platelet count, β2MG level, and serum IgM level （p＝0.055）. The snPCR-RFLP method is a clinically useful MYD88 mutation detection method that can be performed in general laboratories

Mast Cell Infiltration is Associated with Myelofibrosis and Angiogenesis in Myelodysplastic Syndromes

Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by persistent peripheral cytopenia with morphological and functional abnormalities of hematopoietic cells. Mast cells infiltrate into or around tumor tissues and play a role in remodeling of the stromal microenvironment, contributing to tumor progression. Increased mast cell numbers are associated with fibrosis, angiogenesis and a poor prognosis in human carcinomas. The aim of this study was to determine whether mast cell infiltration contributes to myelofibrosis or angiogenesis in myelodysplastic syndromes. We evaluated the correlation between mast cell density and the extent of myelofibrosis and angiogenesis in myelodysplastic syndromes. Fifty bone marrow biopsies taken from patients with a diagnosis of myelodysplastic syndromes were examined. Grading of myelofibrosis was evaluated by silver impregnation staining. Mast cell density and microvessel density were evaluated by immunohistochemistry. Human mast cells have been divided into two phenotypes. We designated a tryptase-positive mast cell as MCT and a chymase-positive mast cell as MCTC. Microvessels were identified by CD34-positive endothelial cells. Microvessel density and the extent of myelofibrosis were significantly greater in patients with high MCT and MCTC density compared to those with low MC density. Based on this, we suggest that the presence of high mast cell numbers is associated with myelofibrosis and angiogenesis in myelodysplastic syndromes

A Cluster of Respiratory Syncytial Virus Infections in a Hospital Ward for Adult Immunocompromised Patients

Four male patients admitted to the same ward in the first half of September 201Y were identified to have respiratory syncytial virus（RSV）infection. Their ages ranged from 49 to 85 years（median 72.5）. One patient was infected with human immunodeficiency virus and three patients had hematological malignancies. Following immuno-chromatological testing with a nasal cavity swab, RSV infection was diagnosed. Although blood and sputum cultures were performed in three patients, no significant bacteria were detected. Two cases responded to supportive therapy. However, one patient died secondary to multiple myeloma, and another patient developed pneumonia and died with an exacerbation of leukemia. RSV infections in immunocompromised hosts are associated with a poor prognosis. Early diagnosis will facilitate isolation of infected individuals to prevent hospital outbreaks

Natural Killer Immunotherapy for Minimal Residual Disease Eradication Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia

The most common cause of death in patients with acute myeloid leukemia (AML) who receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) is AML relapse. Therefore, additive therapies post allo-HSCT have significant potential to prevent relapse. Natural killer (NK)-cell-based immunotherapies can be incorporated into the therapeutic armamentarium for the eradication of AML cells post allo-HSCT. In recent studies, NK cell-based immunotherapies, the use of adoptive NK cells, NK cells in combination with cytokines, immune checkpoint inhibitors, bispecific and trispecific killer cell engagers, and chimeric antigen receptor-engineered NK cells have all shown antitumor activity in AML patients. In this review, we will discuss the current strategies with these NK cell-based immunotherapies as possible therapies to cure AML patients post allo-HSCT. Additionally, we will discuss various means of immune escape in order to further understand the mechanism of NK cell-based immunotherapies against AML