International Journal of Hematology最新文献

We investigated the cost-effectiveness of treating iron deficiency anemia (IDA) with ferric citrate hydrate (FC) in Japan. We employed four treatment strategies: switching from sodium ferrous citrate (SF) to FC at (1) 500 mg (approximately 120 mg of iron) per day or (2) 1000 mg (approximately 240 mg of iron) per day in patients with SF-induced nausea/vomiting, or starting treatment with FC at (3) 500 mg/day or (4) 1000 mg/day. We evaluated the cost-effectiveness of these strategies compared with SF 100 mg (100 mg of iron) per day. Incremental effects over 26 weeks relative to SF 100 mg were 0.0052 quality-adjusted life years (QALYs) for (1) and (2), and 0.0044 QALYs for (3) and (4). From the payer's perspective, incremental cost-effectiveness ratios (ICERs: JPY/QALY) against SF 100 mg were: (1) 1,107,780, (2) 2,257,477, (3) 5,588,430, and (4) 11,544,816. All four FC strategies were dominant (less costly and more effective) from a limited societal perspective. Treatment with FC for IDA was cost-effective (ICER ≤ JPY 5,000,000/QALY) when switching strategies from the payer perspective, and cost-saving (all FC strategies) from limited societal perspectives. Individual patients' characteristics and cost-effectiveness should be considered in treatment selection.

Here, we report a rare case of relapsed adult T-cell leukemia-lymphoma (ATL) with evidence of clonal relapse 26 years after initial diagnosis. The patient had been diagnosed with an aggressive form of lymphoma-type ATL 26 years prior and did not receive further ATL treatment for approximately 26 years after achieving complete remission. We used nested PCR to identify the amplification of ATL clone-specific accumulation sites in DNA from hematoxylin and eosin-stained specimens from the patient. Furthermore, the sequence of amplicons obtained from peripheral blood mononuclear cells and lymphoma cells from the previously diagnosed ATL were identical, indicating that a human T-cell leukemia virus-type 1 (HTLV-1)-infected clone identical to the one that recently caused ATL was present in the original lymphoma tissue. Although we were unable to identify this clone as the cause of the previous ATL, the peripheral leukemia cells revealed an ATL clone that was present in the tumor cells of a lymph node diagnosed 26 years earlier. To our knowledge, this is the first report demonstrating survival of HTLV-1-infected clones for a quarter of a century in a patient with recurrent ATL.

Objective: Chimerism analysis is an important post-transplant assessment for allogeneic hematopoietic stem cell transplant (HCT) recipients. Although various chimerism analysis techniques are already established, they are limited in terms of sensitivity, versatility, and turnaround time. Our objective was to develop a digital droplet polymerase chain reaction (ddPCR) assay for chimerism analysis using ABO gene polymorphisms as markers.

Methods: Our new chimerism analysis method utilizes ddPCR to assess the ABO gene polymorphisms that encode the ABO blood genotype. ABO genotypes were determined in blood samples from 15 HCT recipients using the O panel (rs8176719) and B panel (rs8176746 and rs8176747).

Results: The two panels distinguished six ABO genotypes (AA, AO, BB, BO, AB, and OO). The results of chimerism analysis using ABO genotypes with ddPCR were compatible with those of established methods, such as SRY gene analysis and the use of short tandem repeat markers via standard PCR. Our method could distinguish chimerism in 77% of donor and recipient combinations in the Japanese population.

Conclusions: We developed a sensitive and rapid chimerism analysis method for HCT using ABO gene polymorphisms in ddPCR.

The Japanese Society on Thrombosis and Hemostasis (JSTH) published the first-ever disseminated intravascular coagulation (DIC) guidelines in 2009. Fifteen years later, the JSTH developed new guidelines covering DIC associated with various underlying conditions. These guidelines were developed in accordance with the GRADE system to determine the strength of the recommendations and certainty of the evidence. This article was drafted as Part 1 of an overall DIC guideline covering various underlying conditions, with sepsis as the subject. In this section, seven key clinical issues (questions) are set. Question 1, regarding DIC diagnosis, introduces several diagnostic criteria, such as the JAAM-2, ISTH overt, SIC, and JSTH DIC criteria and recommends choosing the appropriate diagnostic criteria for DIC based on an understanding of their diagnostic properties. For pharmacotherapy in DIC patients with sepsis, we recommend the administration of antithrombin (Question 2) and recombinant thrombomodulin (Question 3) (both GRADE 1B). However, we do not make a clear recommendation regarding the administration of heparin (Question 6) and serine protease inhibitors (Question 7) because of the lack of evidence. Combination therapy, order of administration, and other administration methods for antithrombin and recombinant thrombomodulin are proposed as important future research questions (Questions 4 and 5).

HM-SCREEN-Japan is a multicenter collaborative project in Japan to evaluate the clinical utility of a cancer genome panel in the treatment of acute myeloid leukemia (AML). The HM-SCREEN-JAPAN02 study used the Amoy Myeloid Panel^® with the HANDLE system, which enables efficient and rapid sequencing, as the genomic testing kit. The Amoy Myeloid Panel^® targets 53 genes with established clinical significance or high prevalence. The study analyzed bone marrow fluid or peripheral blood. Multiple time points for submission were allowed to evaluate clonal changes over time. A total of 179 tests/145 patients with one or more pathogenic mutations (23 patients submitted specimens at multiple time points) were included in the analysis. A variety of patterns were detected, including acquisition of new resistance-associated genetic mutations and pathogenic mutations remaining after clinical remission. The median time required for sequencing and annotation was 8 days. TP53 and NRAS mutations were associated with increased risk of death (hazard ratio = 3.98 and 5.50, respectively). In a survey of physicians at the participating centers, 63% reported that the genomic panel was clinically useful, particularly for assessing clinical risk and evaluating indications for hematopoietic stem cell transplantation.

Disseminated intravascular coagulation (DIC) associated with hematologic malignancies, particularly acute promyelocytic leukemia (APL), is characterized by marked fibrinolytic activation, which leads to severe bleeding complications. Therefore, appropriate diagnosis and management of DIC are crucial for preventing bleeding-related mortality. However, to date, no clinical guidelines have specifically addressed hematologic malignancy-associated DIC. Therefore, we developed diagnostic and management algorithms for DIC based on a systematic literature review. Notably, these guidelines recommend using the JSTH DIC diagnostic criteria (2017 version) or the former Ministry of Health and Welfare DIC diagnostic criteria (1983 version) to diagnose DIC. Furthermore, in the management of DIC, it is essential to treat the underlying disease through transfusion of platelet concentrates and fresh frozen plasma, if necessary. A systematic review of antifibrinolytic and anticoagulant therapies concluded that tranexamic acid therapy is not strongly recommended for patients with APL undergoing treatment with all-trans retinoic acid (Grade 1C). The use of recombinant thrombomodulin is weakly recommended (Grade 2B), whereas the use of other anticoagulants, including heparin and serine protease inhibitors, is weakly not recommended (Grade 2C). Therefore, we hope that these guidelines will help physicians find the best possible solutions in clinical practice.

Recent trends in the treatment of primary immune thrombocytopenia (ITP) were investigated using a claims database that included data from 16,161 Japanese patients with ITP collected from April 2014 to August 2022. Of the 4144 adult patients analyzed, 1276 received corticosteroids. The mean and median durations of corticosteroid use were 115.31 and 41 days, respectively. The time to withdrawal of corticosteroids was significantly shorter in 2020 to 2021 than in 2015 to 2019. Additionally, the number of prescriptions for thrombopoietin receptor agonists increased from 2015 to 2021 and exceeded that of corticosteroids in 2021. While these results suggest a trend towards reduction in corticosteroid use in real-world settings in Japan, 12.00% of patients received a corticosteroid dose of ≥ 10 mg/day at Week 12. Furthermore, 23.05% of patients continued to receive corticosteroids at Week 24, indicating that some patients were still receiving long-term corticosteroid treatment. The risk of adverse outcomes was significantly associated with corticosteroid use. In conclusion, new treatment options may lead to more sophisticated ITP management with less corticosteroid use, although further research and reconsideration of clinical practice guidelines is needed.

Background: In Italy, the demand for allogeneic transplantation exceeds the number of compatible donors in the Italian Bone Marrow Donor Registry (IBMDR). This study aimed to explore the knowledge, beliefs, opinions, values, and feelings of the Italian population regarding stem cell donation.

Methods: An online survey was shared via social media. Respondents were retrospectively identified as registered on the IBMDR (donor group) or never registered (non-donor group). Statistical analyses confirmed the relationship between knowledge level and willingness to donate. Six machine learning classifiers were trained using questionnaire responses to predict the probability of IBMDR registration.

Results: A total of 1518 respondents participated. Characteristics identified in the non-donor group were a lower level of knowledge regarding donation needs (51.7% vs 24.4%, p < 0.001) and negative feelings such as fear (Z = - 2.2642, p = 0.02), confusion (Z = 4.4821, p < 0.001), and uncertainty (Z = 3.3425, p < 0.001). Higher knowledge predicted a greater likelihood of IBMDR enrollment. Machine learning analysis showed an AUC ranging from 0.65 to 0.81, depending on the classifier.

Conclusions: The results underscore the need to improve strategies to raise awareness and knowledge of stem cell donation among the Italian population.

The GVH3001 study assessed the efficacy and safety of ibrutinib in Japanese patients with steroid-dependent or -refractory chronic graft-versus-host disease (cGVHD). However, the effects of ibrutinib on lung function and reduction in corticosteroid dose, which is a measurable factor associated with improved quality of life, could not be adequately assessed in patients who initially presented with lung involvement. This post hoc analysis aimed to evaluate temporal changes in daily corticosteroid dose, as well as effectiveness outcomes based on lung function and symptom burden (percent predicted forced expiratory volume in 1 s [%FEV₁] and Lee cGVHD Symptom Scale lung subscale score, respectively) in the subgroup of patients with cGVHD who had lung involvement at baseline. Seven of the 19 patients in the GVH3001 study had lung involvement at baseline. The daily corticosteroid dose for cGVHD decreased in five of these patients, and %FEV₁ remained relatively stable in two patients but increased to > 80% in one patient. Lee cGVHD Symptom Scale scores were relatively stable throughout the study in patients with lung involvement. Ibrutinib may allow corticosteroid dose reduction without worsening lung function or increasing symptom burden in previously treated patients with cGVHD and associated lung involvement.

T cell-replete haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) is a potentially curative therapy for pediatric intractable hematological malignancies due to its graft-versus-leukemia efficacy. This single-center cohort study examined the effects of graft composition (T cell type and dose) on pediatric TCR-haplo-HSCT outcomes in 32 children with relapsed/intractable hematological malignancies. Graft T cell composition was classified using flow cytometry. High graft CD8⁺ T cell doses reduced disease relapse and improved overall survival and event-free survival, but did not increase transplant-related mortality and the incidence of grade III/IV acute graft-versus-host disease. Doses of grafted CD3⁺, CD4⁺, and CD34⁺ T cells did not affect patient outcomes. Children with differing event-free survival times were divided by a graft CD8⁺ T cell dose cut-off of 2.03 × 10⁸ kg^-1. These findings revealed that grafted CD8⁺ T cells improved the graft-versus-leukemia effect of pediatric TCR-haplo-HSCT without increasing the risk of transplant-related mortality.