Turkish Journal of Hematology最新文献

Objective: Immune-related pancytopenia (IRP) is characterized by autoantibody-mediated destruction or suppression of bone marrow cells, leading to pancytopenia. This study aimed to explore the role of TRAPPC4 (trafficking protein particle complex subunit 4) as a key autoantigen in IRP, including epitope identification and immune activation mechanisms.

Methods: A total of 90 participants were included in the study, divided into four groups: 30 newly diagnosed IRP patients, 25 IRP remission patients, 20 patients with control hematologic conditions (severe aplastic anemia [SAA] and myelodysplastic syndrome [MDS]), and 15 healthy controls. TRAPPC4 was identified using affinity screening with a phage random peptide library and confirmed with ELISPOT and epitope prediction software. TRAPPC4 expression in bone marrow cells and serum antibody titers was assessed via flow cytometry, ELISA, and real-time PCR. Immune cell profiling of peripheral blood mononuclear cells (PBMNCs) was conducted using flow cytometry.

Results: TRAPPC4 was overexpressed on CD34+ bone marrow hematopoietic progenitor cells in newly diagnosed IRP patients compared to remission patients, disease controls (SAA and MDS), and healthy controls, with no significant differences observed in CD15+ granulocytes or CD235a+ nucleated red blood cells. The epitope peptide YTADGKEVLEYLG activated Th2 cells, as confirmed by ELISPOT. Newly diagnosed IRP patients exhibited elevated TRAPPC4 mRNA and protein levels in bone marrow mononuclear cells and higher serum antibody titers compared with controls. Immune profiling revealed increased CD19+ and CD5+CD19+ B lymphocytes in IRP patients.

Conclusion: TRAPPC4 was found as a key autoantigen in IRP, along with CD34+ cells as primary targets of autoantibody attacks. The identification of TRAPPC4 and its epitope provided insights into IRP pathogenesis and suggested potential diagnostic and therapeutic strategies.

Objective: This study aims to determine the genotypic characteristics of Hereditary Spherocytosis (HS) patients in Turkiye and to examine the correlation between genotype and phenotype.

Materials and methods: Herein we had 18 patients who were admitted to pediatric hematology outpatient clinic with hemolytic anemia, jaundice, cholelithiasis, and splenomegaly. According to the Eber's classification, the patients' clinical presentations were categorized as mild, moderate, and severe. The next-generation sequencing method was used to analyze single nucleotide and copy number variations in all genes associated with HS via clinical exome sequencing (CES). The relationship between the genes with detected variants and the clinical presentation in the patients was investigated.

Results: In total, 21 variants were detected in five HS-related genes. Twelve of them were previously reported variants, and nine of them were novel variants. Seven of them were pathogenic and two of them were classified as Variant of Uncertain Significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG). Herein we have discussed the phenotypic effects of novel pathogenic variants in SPTA1, SPTB, ANK1, SLC4A1, and EPB42 genes. Patients with EPB42 and SLC4A1 gene pathogenic variants had less severe clinical findings compared to other gene variants according to Eber's classification. On the other hand, patients carrying pathogenic variants of SPTA1 and SPTB genes had more severe clinical presentation.

Conclusion: Molecular diagnosis of HS is important for treatment, prediction of the clinical outcome, and appropriate genetic counseling. As a result, our study contributes to the genotype-phenotype distribution of HS by introducing novel variants to the literature.

Objective: In this study, we aimed to obtain real-life data on the use of antimyeloma agents, which significantly increase overall survival (OS) in multiple myeloma (MM) patients, in primary plasma cell leukemia (pPCL) patients with poor prognosis.

Materials and methods: Data from 53 patients who were diagnosed with pPCL between 2011 and 2020 and who used at least one proteasome inhibitor (PI) and/or immunomodulatory (IMID) agent were analyzed retrospectively. Depending on the year of the pPCL diagnosis, 20% leukocytes or ≥2x10⁹/L plasma cells in the peripheral blood was used as a diagnostic criterion.

Results: The median age of the patients was 58 years and 23 (43.4%) patients were over 65 years of age. For first-line treatment, PI or IMID alone was used by 31 (58.5%) patients, and PI and IMID were used simultaneously by 15 (28.3%) patients. Additionally, 21 (39.6%) patients received transplantation and 13 (24.5%) patients received maintenance treatment. The median progression-free survival was 4 (range: 1-42) months. When patients whose primary disease was refractory to first-line therapy were excluded, the duration of treatment was 6.5 months. The median OS was 15 months with a median follow-up duration of 15 months. Only 7 (13.2%) of the patients were alive at the last follow-up visit. Those with higher β2-microglobulin levels and International Staging System stage 3 and non-transplant patients receiving first-line treatment had shorter OS (p=0.005, p=0.02, and p=0.008, respectively). The concomitant use of PIs and IMIDs, the addition of chemotherapy to induction therapy, and the response to induction therapy or maintenance therapy did not affect OS.

Conclusion: In this study, as in previous similar studies, we could not see an increased survival trend in pPCL, which is observed in MM. New studies are needed for pPCL, which is likely to increase with new diagnostic criteria, based on current agents and information from MM.

Objective: Acquired hemophilia A (AHA) is a rare autoimmune disease characterized by the presence of autoantibodies against coagulation factor VIII, leading to spontaneous hemorrhage in patients without a prior family or personal history of bleeding. This study describes the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcomes of 41 AHA patients together with specific case reports.

Materials and methods: Diagnosis and treatment of these patients occurred between 2005 and 2023. The median age at diagnosis was 67.8 (range: 15-93) years. Among the 41 patients, 10 (24%) cases were idiopathic, 4 (10%) were postpartum, 18 (44%) involved autoimmune diseases, and 9 (22%) involved a diagnosis of cancer.

Results: The diagnostic delay exceeded 30 days in 15 of the 41 cases (36.5%). A total of 38 of the 41 (93%) patients presented with spontaneous bleeding, with mucocutaneous bleeding being the most common presentation (23/41, 56%). Four patients experienced postpartum bleeding. Clinical remission was achieved by 100% of patients and no patients died.

Conclusion: Hemostatic and immunosuppressive therapy is essential in AHA, and it should be started as soon as possible in patients with bleeding. However, a significant delay in diagnosis was observed in these cases. The absence of mortality is likely attributable to the management of the disease within a specialized hemostasis and thrombosis unit, which offers a clinical ward, a specialized laboratory, and a dedicated ambulatory service. The Italian Society for the Study of Haemostasis and Thrombosis is working to secure recognition of this essential role in every hospital.