Although the outcome of patients with ALL has dramatically improved, we still need novel therapy to treat refractory cases and reduced toxicities of conventional therapy in ALL patients. Imatinib-combined with chemotherapy resulted in a good outcome and some patients with Ph-positive ALL may not need HSCT. Tyrosine kinase inhibitors could also be used for those with Ph-like ALL having ABL and PDGFRB translocations. Immunotherapy such as blinatumomab bispecific antibody and CAR-T cell treatment have been developed and are recently covered by health insurance in Japan. NUDT15 polymorphism is appreciated as a major role player in 6-mercaptopirine metabolism and genetic polymorphism examination is recently covered by health insurance in Japan. The prevalence of cancer predisposition genes has recently been extensively studied and some genes such as TP53 is also involved in ALL leukemogenesis and therapy-related cancer may be another important issue in leukemia treatment. Thus, the development of genomic medicine will not only expand our knowledge but also contribute to personalized medicine in the context of leukemogenesis, sensitivity to drugs, toxicity, and subsequent occurrence of secondary cancer.
Philadelphia chromosome-like (also known as BCR-ABL1-like) acute lymphoblastic leukemia (Ph-like ALL) is a new high-risk subtype of B-cell ALL (B-ALL) that exhibits a mRNA expression profile similar to that of Ph positive ALL. Ph-like ALL patients harbor a variety of gene alterations that activate kinase and cytokine receptor signaling pathways. Ph-like ALL are subcategorized into the following three groups based on gene alterations: 1) JAK/STAT type; 2) ABL-class type and 3) others. Preclinical studies and case reports in human show efficacy of kinase inhibitors targeting activated signaling pathways, such as JAK inhibitor and tyrosine kinase inhibitor. Several clinical trials to assess the efficacy of Ruxolitinib and Dasatinib are in progress for JAK/STAT- and ABL-class- type Ph-like ALL patients, respectively; however, their diagnostic methods and therapeutic strategies are not fully generalized. Development of new diagnostic and therapeutic strategies are in need to improve their clinical outcomes.
Chronic active EB virus infection is an intractable disease. EBV latently infects T cells or NK cells, proliferates in a clonal manner, infiltrates organs, and triggers various symptoms. The prognosis is generally poor; in the absence of treatment, organ complications and a blast crisis often cause death. Recently, we performed a large-scale, comprehensive genetic analysis of patients with chronic active EB virus infection, and found: 1) it is unlikely that any primary immunodeficiency is in play (because mutations in germ cell sequences were rarely observed); 2) EBV-infected cells contained mutations in driver genes such as DDX3X and KMT2D and, in cases that could be observed over time, clonal evolution of EBV-infected cells was evident; and, 3) defective EBV was frequently observed and may be involved in disease onset. This review outlines the pathology of chronic active EB virus infection revealed by our genetic analyses, and the latest views on optimal diagnosis and treatment.
The role of low-dose valacyclovir (VCV) in preventing the occurrence of herpes zoster in children after transplantation was evaluated. Low-dose VCV was administered for 17 transplants in 16 patients who underwent transplantation in and after July 2015, and the results compared to that of 24 transplants in 22 patients without herpes zoster prophylaxis in and prior to June 2015. The dose of oral VCV was approximately 10 mg/kg/day once daily, and therapy was continued until the completion of immunosuppressive treatment (administration period: 11.4±9.9 months). In the non-VCV group, herpes zoster developed in approximately half of the patients with a history of varicella. In the VCV group, herpes zoster did not develop during the treatment with VCV, whereas three patients (17.6%) developed herpes zoster after the completion of VCV therapy. Patients with a history of varicella before transplantation and those not receiving prophylaxis with VCV are considered at risk for post-transplant herpes zoster. Long-term low-dose VCV administration is safe and effective as prophylaxis for herpes zoster, and in patients with a history of varicella, at a minimum, it is desirable to continue prophylactic administration until immunocompetence is restored to some extent.
We report a summary of 105 decision-making information sessions (DISs) for unrelated donor consent in the Japan Marrow Donor Program (JMDP) between 2004 and 2019. We retrospectively compared data from our cases with those of cases of JMDP during the same period. The median age of our patients during the 15-year period was 37 years, and the male-to-female ratio was 1.8 to 1. During that period, 18,515 people participated in the JMDP; their median age was 37 years, and the male-to-female ratio was 2.0 to 1. The coordination period included confirmatory typing (CT), DISs, and hematopoietic cell transplantation (HCT). We found a significant difference (P=0.004) in the period from CT to DISs between our cases (38.7 days) and the JMDP cases (45.3 days) but no difference in the period from DISs to HCT between the two groups. With regard to the day of the week for the DISs, 36.2% of our cases were conducted on Saturdays and Sundays, in comparison with 6.4% of the JMDP cases. We believe that selecting Saturdays and Sundays as possible dates for the DISs may have led to a shorter coordination period.
Purpose: In this study, we investigated diurnal variations in suspended particulate matter (PM) that resulted from human transit within a bio-clean room (BCR) used for hematopoietic stem cell transplantation. Methods: From April 2017 to March 2020, we measured airborne PM in BCR over time; we analyzed the fluctuating patterns of PM associated with daily human transit within BCR using a commercially available particle counter. Results: Daily fluctuations in PM revealed average peak times at 07 : 40, 10 : 00, and 16 : 15; these daytime fluctuations returned to a steady level during the overnight hours. Increases in airborne PM correlated with human activity in BCR, including visits required for patient care and vital sign assessments. The half-time of PM decay was 17.2-23.8 min and 12.6-23.4 min when measured before and after restricting access to BCR, respectively. The average concentration of PM detected during the daytime hours, especially in afternoon, decreased significantly once BCR restrictions were in place. Conclusion: PM detected in BCR fluctuated in dynamic manner based on the extent of human transit within the facility. These characteristics should be monitored to prevent unnecessary particle diffusion.
There is an increased risk of late complications such as chronic graft-versus-host disease and secondary malignancies among patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT), which could lead to deterioration in the quality of life and late mortality. Recently, the long-term follow-up (LTFU) clinics have been recognized as an important intervention to patients who underwent allo-HCT. In 2017, an LTFU clinic was established at the Wakayama Medical University. However, visitation to the LTFU clinic was difficult, especially for patients from remote areas. Thus, using internet telemedicine and medical information cooperation system called Seishu LINK, we set up a remote LFTU clinic in the Kinan Hospital, in which five patients were already catered. Despite a few flickering screen issues and acoustic noises in the system, medical interviews and patient guidance were successful. Furthermore, developing a remote LTFU clinic system for allo-HCT survivors in Wakayama, Japan, is our next step.
Chronic graft-versus-host disease (GVHD) is more common in the elderly after hematopoietic stem cell transplantation (HCT) and reduces their quality of life (QOL). At this institution, long-term follow-up (LTFU) outpatients are taught self-care referring to the mental component summary (MCS), physical component summary (PCS), and role-social component summary (RCS), which are summary scores of the MOS 36-item Short Form Health Survey (SF-36). We report two patients in their 70s whose QOL criteria differed during the course of chronic GVHD and the status of meeting self-care requisites affected the RCS. The QOL is associated not only with physical function, but also with social background and ability to play a role. The QOL of elderly patients after HCT was suggested to depend on the ability of self-care to maintain important and unique lifestyles for the elderly.