International Journal of Hematology最新文献

Cytomegalovirus (CMV) reactivation remains a major complication after hematopoietic cell transplantation (HCT), particularly in high-risk settings. Although the antigenemia (AG) assay has long been the standard CMV monitoring tool in Japan, quantitative PCR (qPCR) offers improved sensitivity and is now widely adopted. We analyzed a total of 1878 samples from 231 HCT recipients who underwent CMV monitoring at multiple centers. We evaluated the correlation between AG and qPCR results, determined qPCR thresholds equivalent to AG positivity, and compared actual AG-guided therapy durations with simulated qPCR-guided therapy. Among 1878 sample sets, AG and qPCR showed strong correlation (r = 0.65) and high concordance (87.6%). Median qPCR values increased with AG positivity level. ROC analysis identified qPCR cut-offs corresponding to 2 and 10 AG-positive cells as 99.5 and 815 IU/mL, respectively. Of 57 qPCR-only episodes, 32 resolved without AG conversion; higher qPCR levels were associated with treatment need. Simulated qPCR-guided therapy durations closely matched AG-guided therapy (median 4 weeks), but some cases required longer treatment. qPCR-based CMV monitoring is concordant with AG and feasible for preemptive therapy. Careful interpretation of low-level viremia is warranted to avoid overtreatment. Further data are needed to refine qPCR thresholds in transplant settings.

Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed/refractory B-cell malignancies, as supported by real-world evidence (RWE). However, limited RWE exists on the management of adverse events during the perioperative period following CAR-T infusion. This study was conducted to obtain RWE on perioperative management using the Japanese Diagnosis Procedure Combination database, a comprehensive repository of Japanese health and medical service data. Between November 2019 and March 2022, 388 patients received CAR-T therapy. Of these, 312 had large B-cell lymphoma (LBCL) and 76 had B-cell acute lymphoblastic leukemia (B-ALL). The number of CAR-T infusions increased every 6-month interval, correlating with the rise in LBCL cases. Tocilizumab was administered for cytokine release syndrome in 56.1% of LBCL and 42.1% of B-ALL patients. Steroids were used for 22.9% and 81.3%, respectively. Prophylaxis for fungal infections was administered during CAR-T infusion in most LBCL and B-ALL patients. Treatment intensity was escalated in 2.8% of LBCL and 7.0% of B-ALL patients, and treatment for cytomegalovirus infection was initiated in approximately 7% of patients. This analysis elucidated perioperative management strategies based on patients' medication histories.

Langerhans cell histiocytosis (LCH) is a rare type of histiocytosis with various clinical manifestations. The differential diagnosis for an infiltrative process in the mesentery includes histiocytosis, such as Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD), but mesenteric involvement has never been reported. Here we present the first documented case of LCH. A 24-year-old man presented with diabetes insipidus and was diagnosed with LCH via mesenteric biopsy, which demonstrated mesenteric involvement and the BRAF^N486_P490del mutation. He was treated with trametinib 2 mg once daily, and FDG-PET/CT at 6 months after treatment initiation showed complete remission. Our report suggests that trametinib is a promising treatment option for non-BRAF^V600E mutant LCH with mesenteric involvement.

Idiopathic portal hypertension-related refractory ascites (IRA) is a rare but potentially life-threatening complication following allogeneic hematopoietic cell transplantation (allo-HCT). Its pathogenesis remains unclear, and optimal diagnostic and therapeutic strategies have yet to be established. Here, we report a case of a 58-year-old man who developed progressive ascites after allo-HCT. Although the clinical findings met diagnostic criteria for hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), liver histology revealed no hallmark features of VOD/SOS, such as sinusoidal dilatation or central venous fibrosis. Instead, portal venopathy with lymphocytic infiltration and fibrosis suggested a subclinical chronic graft-versus-host disease (GVHD)-like pathology, supporting a diagnosis of IRA by exclusion. Treatment with belumosudil, one of the available treatment options for chronic GVHD, was ineffective. Subsequent treatment with ibrutinib, a Bruton's tyrosine kinase inhibitor, led to resolution of ascites within three days. This is the second reported case of successful treatment of IRA with ibrutinib, and highlights the importance of considering ibrutinib-responsive immune-mediated mechanisms in the differential diagnosis of post-transplant ascites. Given the fundamental differences in treatment strategies between IRA and VOD/SOS, our findings underscore the need for accurate diagnosis, including histopathological evaluation, to guide effective therapy and improve patient outcomes in this challenging clinical scenario.

Immunity acquired before hematopoietic stem cell transplantation (HSCT) may decrease or disappear following HSCT, and it is unclear whether the first vaccination after HSCT in patients with an antigen exposure history before HSCT elicits a primary or secondary immune response. The Quantification of Antigen-Specific Antibody Sequence (QASAS) method enables real-time assessment of responses to SARS-CoV-2 antigen exposure through B-cell receptor (BCR) repertoire analysis. Using this method, we evaluated the disappearance of immunological memory after HSCT. First, in individuals without hematologic disorders, primary SARS-CoV-2 antigen exposure elicited no immune response at 7 days post-exposure but demonstrated activation between 14 to 21 days. In contrast, repeated exposure elicited early responses (secondary immune responses) at 7 days post-exposure. We then enrolled HSCT patients with pre-HSCT SARS-CoV-2 antigen exposure history and collected samples before and after vaccination. Despite prior exposure history, patients receiving their first vaccination after HSCT showed no response around 7 days post-exposure but responded at 14 days. In conclusion, even with pre-HSCT antigen exposure, the first vaccination after HSCT induced a primary immune response. This demonstrates that first vaccination after HSCT should be considered to induce a primary immune response, regardless of previous infection or vaccination history.

Background: Iron deficiency anemia (IDA) is the leading cause of nutritional anemia. In some cases, oral iron therapy (OIT) fails to achieve an optimal therapeutic response. Oral doses of iron acutely increase serum hepcidin, resulting in decreased iron absorption and poor response treatment.

Objective: The primary objective was to assess the efficacy of alternate-day versus twice-daily OIT in children with IDA. The secondary objective was to study the effects of alternate versus twice-daily OIT on serum hepcidin levels and to compare gastrointestinal side effects between groups.

Methods: This was an RCT of 40 IDA patients, aged 6 months 10 years. The first group received twice-daily OIT, and the second group received alternate-day OIT. Serum hepcidin levels were measured at baseline and 48 h after starting OIT. Changes in hemoglobin level were noted after 30 days.

Results: Patients who received alternate-day OIT had increase hemoglobin (P = 0.002) and decrease serum hepcidin (P = 0.01). Four of twenty in the alternate-day group (20%) had gastrointestinal side effects (P = 0.01).

Conclusion: Children who received alternate-day OIT had lower serum hepcidin levels, which resulted in better iron absorption and compliance, significant improvement in hemoglobin levels, and fewer gastrointestinal side effects.

Chimeric antigen receptor (CAR) T cell therapy has significantly improved outcomes for patients with refractory B cell lymphoma. However, rare cases of secondary T cell lymphomas have raised safety concerns. Here, we present a case of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) that developed eight months following CD19-directed CAR T cell therapy (lisocabtagene maraleucel) in a 66-year-old male patient with recurrent diffuse large B cell lymphoma. The patient initially achieved complete remission but later developed a subcutaneous mass and systemic lymphadenopathy. Histopathology and flow cytometry confirmed a diagnosis of PTCL-NOS with a CD3 + , CD8 + , and CD30 + phenotype, as well as clonal T cell receptor gene rearrangements. No immunoglobulin rearrangements were detected, ruling out a lineage switch. Furthermore, the CAR transgene was undetectable by RNA-in situ hybridization, and flow cytometry showed no CAR protein expression, suggesting that the lymphoma was not caused by CAR gene integration. This case highlights the importance of re-biopsy in cases of suspected relapse following CAR T cell therapy, and emphasizes the need for long-term monitoring. While a direct causal link remains unclear, industry-academia collaboration is crucial for investigating the mechanisms underlying secondary T cell malignancies and improving the safety of CAR T cell therapy.

Introduction: Graft-versus-host disease (GVHD) is a serious immune reaction that usually occurs after allogenic stem cell transplants and can affect organs, such as skin, gastrointestinal (GI) system, and liver. The development of GVHD after autologous stem cell transplantation (auto-SCT) is rarely observed and only a few cases have been reported in the literature.

Case presentation: A 21-year-old patient who underwent auto-SCT for neurofibromatosis type 1 developed severe GI-GVHD confirmed by histopathology. She responded inadequately to systemic corticosteroids, indicating steroid-refractory disease. Subsequent addition of the JAK1/2 inhibitor ruxolitinib resulted in rapid clinical improvement.

Conclusion: This clinical case scenario suggests that ruxolitinib could be a treatment option in rare cases of GVHD following auto-SCT.

A Japanese woman presented with a history of neonatal jaundice and recurrent episodes of severe fatigue and jaundice during viral infections in her late teens. Her mother, aunt, and grandmother had similar clinical histories. During an admission for fever and fatigue, blood tests revealed acute hemolysis and an abnormal hemoglobin band on high-performance liquid chromatography. β-globin gene sequencing identified a codon 34 substitution from GTC (Val) to GAC (Asp), confirming the presence of the unstable hemoglobin variant Hb Santander. This very rare hemoglobinopathy was previously reported only in a single sporadic case involving a Spanish man; this is the first documented case in a Japanese family. Our observation of four affected individuals across three generations provided insight into the progression of Hb Santander from birth to old age. Unstable hemoglobin variants can lead to recurrent, severe episodes of acute hemolytic crisis. Chronic hemolysis in the steady state was compensated without anemia or polycythemia but was associated with an increased risk of gallstone formation. Hb Santander does not appear to be a life-shortening hemoglobinopathy; however, clinical vigilance is necessary for acute hemolysis triggered by drugs or infections and for gallstones at a younger age, particularly in patients with Gilbert syndrome.