International Journal of Hematology最新文献

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.

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.

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.

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.

Pericardial effusion (PCE) is a serious complication after allogeneic hematopoietic cell transplantation, but its etiology is not fully understood, particularly the role of viral reactivation. We investigated the presence of DNA viruses in pericardial fluid from nine umbilical cord blood transplant recipients who underwent pericardiocentesis. Multiplex PCR detected DNA viruses in seven patients (78%), with Epstein-Barr virus being most common. The clinical context of viral detection appeared to differ by onset timing. In early-onset PCE (< 100 days), viral presence was often systemic and likely secondary to severe inflammation. In contrast, late-onset cases frequently occurred with chronic graft-versus-host disease and showed localized viral reactivation within the pericardium. These findings suggest DNA viruses are potential contributors to post-transplant PCE. Viral evaluation of pericardial fluid should be considered in these patients as it may influence therapeutic strategies.

Functional hyposplenism, defined as impaired splenic function in the absence of splenectomy, increases susceptibility to life-threatening infections. Although Howell-Jolly bodies (HJBs) are well-established markers for this condition, the predictive value of spleen volume for infection risk remains unclear. We retrospectively analyzed 95 non-splenectomized patients with HJBs from 2014 to 2024. We measured spleen volume by computed tomography and compared results with ideal values. We evaluated the associations between splenic volume and infections using univariate and multivariate logistic regression analyses. The median patient age was 66 years (range, 16-95); 72% were male. The median spleen volume was 34 mL, lower than the ideal median of 210 mL. Forty-eight percent of patients experienced at least one infection. Univariate analysis identified age ≥ 65 years and spleen volume < 34 mL as significantly associated with sepsis. Both factors remained independent predictors in multivariate analysis (age ≥ 65: odds ratio [OR], p = 0.039; spleen volume < 34 mL: OR 3.0, p = 0.047). Age ≥ 65 also predicted any infection (OR 3.1, p = 0.013), while low spleen volume demonstrated a trend toward significance (OR 2.2, p = 0.064). In non-splenectomized patients with HJBs, reduced spleen volume and older age independently increase susceptibility to sepsis. Computed tomography-based measurements may help identify functional hyposplenism and guide targeted prophylactic measures.

Chronic myeloid leukemia (CML) and BCR::ABL1-negative MPN were thought to be mutually exclusive, but synchronous and sequential cases have been reported. We screened 35,001 patients for BCR::ABL1 fusion or JAK2, CALR, or MPL mutations to investigate the sequential development of CML and BCR::ABL1 negative-MPNs. We discovered that 5.6% had primary CML followed by BCR::ABL1-negative MPN, and 5.8% had the reverse sequence. Notably, we identified higher JAK2 variant allele frequencies (VAFs) in patients developing secondary CML. Previous MPN did not compromise the effectiveness of tyrosine kinase inhibitors (TKI) in treating secondary CML. The emergence of secondary MPN appeared to be unrelated to JAK2 VAF progression or BCR::ABL1 transcript levels. Our research indicates that newly detected leukocytosis or thrombocytosis should prompt consideration of secondary MPN. It also showed that secondary CML had no negative impact on response to therapy when patients were treated according to CML guidelines.

CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. The safety of CPX-351 in Japanese patients was verified by comparing safety data from the Japanese phase 1/2 study and the global phase 3 study. This analysis included 47 patients in the safety analysis set of the Japanese study and 153 patients who received CPX-351 and were included in the intention-to-treat analysis for the global study. In both the Japanese and global studies, the most frequent adverse events were febrile neutropenia (FN) (Japanese: 85.1%, global: 70.0%) and pneumonia (25.5% and 24.2%). Median time to occurrence was 8 and 11 days for FN, and 17 and 23 days for pneumonia. Median time to hematologic recovery was 36 and 41 days for neutrophils (> 1000/μL), and 36 and 44 days for platelets (> 100,000/μL). In the global study, univariate analysis was performed after one cycle of induction therapy to investigate factors that delay neutrophil and platelet recovery, but no specific factors were identified. In these analyses, the pattern and frequency of adverse events were similar in Japanese and non-Japanese patients, with no need for race- or region-specific management.

Systemic chronic active Epstein-Barr virus disease (sCAEBV) is an intractable disorder characterized by clonal proliferation of EBV-infected T- and NK-cells, leading to persistent systemic inflammation and progression to hemophagocytic lymphohistiocytosis (HLH). The EBV genome encodes 40 mature microRNAs known as miR-BARTs. The expression of miR-BARTs has been reported in other EBV-positive diseases and is associated with tumorigenesis. In this study, we investigated the expression of miR-BARTs in sCAEBV. Expression of miR-BARTs was highly abundant in 4 sCAEBV-derived EBV-positive T- or NK-cell lines and in EBV-infected T- or NK-cells from 23 sCAEBV patients. The highest expression levels were observed for miR-BART7-3p. Sequence analysis revealed no deletions in the EBV genome encoding miR-BARTs. Inhibition of miR-BART7-3p altered the expression of immune-related genes in sCAEBV-derived cell lines. Abundant miR-BART expression was also observed in patients' plasma, with miR-BART7-3p showing the highest levels. Notably, miR-BART7-3p expression was detected in macrophages within the spleen of an sCAEBV patient with HLH. These findings suggest that miR-BARTs are highly expressed and secreted by EBV-infected cells in sCAEBV. We hypothesize that secreted miR-BARTs may be taken up by monocytes, potentially regulating their functions and contributing to inflammation in sCAEBV. Further studies are needed to elucidate these mechanisms.