Turkish Journal of Hematology最新文献

Objective: This study was planned to evaluate long-term post-transplant complications in patients who underwent transplantation with the diagnosis of Fanconi anemia (FA) in childhood in our bone marrow transplantation unit and who were still being followed. It was predicted that the results would show the critical importance of determining disease-specific post-transplant long-term follow-up plans and putting them into practice in terms of early detection of complications and improving the survival rates and quality of life of FA patients.

Materials and methods: In this single-center, cross-sectional study, according to current recommendations, we analyzed the long-term outcomes of 36 patients with FA with a median age of 18.1 years (range: 6.1-36 years, male/female ratio: 24/12) who underwent HSCT in the Pediatric Bone Marrow Transplantation Unit between 1995 and 2019 and survived at least 1 year following the transplantation.

Results: The median long-term follow-up time was 8 years (range: 1-25 years). Gonadal dysfunction was detected in approximately 35% of our patients; more specifically, 31% of the patients had hypergonadotropic hypogonadism and 4% had hypogonadotropic hypogonadism. When the patients were evaluated for growth impairment, 7 of 12 patients who had reached their final adult heights and 12 of 21 patients who had not yet completed their growth had height standard deviation (SD) scores below -2 SDs. Three patients (9%) developed subclinical hypothyroidism, 2 (6%) had overt hypothyroidism, and 1 (3%) had central hypothyroidism. Although none of our patients fully met the criteria for metabolic syndrome, 23% had insulin resistance and 39% had dyslipidemia. Evaluation of organ dysfunctions revealed that nearly 50% of the patients had obstructive and 21% had restrictive changes in their pulmonary function tests. Hepatosteatosis was detected in 15% of the patients and mild valve dysfunction was detected in 50% of evaluable patients. Three patients developed secondary malignancies. Squamous cell cancer developed in 2 patients and basal cell cancer in 1 patient.

Conclusion: A risk-defined multidisciplinary approach for the long-term follow-up of children with FA undergoing HSCT is essential for early detection and management of late effects.

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 trafficking protein particle complex subunit 4 (TRAPPC4) as a key autoantigen in IRP, including epitope identification and immune activation mechanisms.

Materials and methods: A total of 90 participants were included in the study, divided into four groups: 30 newly diagnosed IRP patients, 25 patients with IRP in remission, 20 patients with other hematological conditions (severe aplastic anemia [SAA] and myelodysplastic syndrome [MDS]) as a patient control group, and 15 healthy individuals as a healthy control group. TRAPPC4 was identified using affinity screening with a phage-display 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 assay, and real-time polymerase chain reaction. Immune cell profiling of peripheral blood mononuclear cells was conducted using flow cytometry.

Results: TRAPPC4 was overexpressed in the CD34+ bone marrow hematopoietic progenitor cells of newly diagnosed IRP patients compared to patients in remission, the patient control group (SAA and MDS), and the healthy control group, with no significant differences observed for 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 to controls. Immune profiling revealed increased CD19+ and CD5+CD19+ B lymphocytes in IRP patients.

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

Objective: Classical Hodgkin lymphoma (CHL) is a common lymphoid neoplasm with a wide range of differential diagnoses. Although it has a specific immunophenotype, aberrant expression of antigens can cause problems at its diagnosis. In this study we evaluated the usefulness of GATA3 in the differential diagnosis of CHL.

Materials and methods: One hundred cases of CHL and a control group of 106 lymphoma cases, which included anaplastic large-cell lymphoma both positive and negative for anaplastic lymphoma kinase (ALK), Epstein-Barr virus (EBV)-positive large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, primary mediastinal large B-cell lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma, and mediastinal gray-zone lymphoma, were included in the study. GATA3 immunohistochemistry was applied to all cases and nuclear expression was accepted as positive. Expression status of GATA3 was compared between the CHL group and the control group, as well as among each lymphoma subtype. In addition, whether the biopsy type affected diagnostic performance was assessed. For CHL, the relationship with EBV status and GATA3 expression was evaluated.

Results: GATA3 expression was significantly higher in CHL cases compared to the control group (p<0.001). When compared among individual subgroups, GATA3 was found to be useful in the differential diagnosis of all except for ALK-negative anaplastic large-cell lymphoma (p=0.678) and mediastinal gray-zone lymphoma (p=0.327). GATA3 expression was significantly higher in EBV-negative CHL (p=0.02). In core-needle biopsies, the diagnostic performance was limited (p=0.178).

Conclusion: GATA3 is a useful marker for differentiating CHL from B-cell non-Hodgkin lymphomas but its efficiency is limited in ALK-negative anaplastic large-cell lymphoma and mediastinal gray-zone lymphoma. Due to heterogeneous reactions, its diagnostic value is limited in core-needle biopsies.

Objective: Preimplantation genetic diagnosis (PGD) with human leukocyte antigen (HLA) typing represents a significant advancement in treating inherited hematological disorders, particularly thalassemia major. This technology enables the birth of healthy children who can serve as compatible stem cell donors for their affected siblings. Türkiye is a world leader in both PGD+HLA typing technology and hematopoietic stem cell transplantation (HSCT) from savior siblings born through PGD+HLA typing. This study investigated the experiences of Turkish parents who underwent successful savior sibling procedures using PGD+HLA typing and then successful HSCT from the savior sibling for the treatment of the child with thalassemia major. We aimed to understand the medical, psychological, and sociocultural dimensions of this complex process within the Turkish healthcare context.

Materials and methods: A qualitative study was undertaken using a descriptive phenomenological approach. In-depth interviews were conducted with parents from 16 families who had successfully completed PGD+HLA matching and subsequent stem cell transplantation processes from the savior sibling to the child with thalassemia. Data were analyzed using Colaizzi’s seven-step method and MAXQDA 20.0 software.

Results: The analysis revealed six main themes: disease stage, treatment, recovery process, social/family, support systems, and recommendations. Parents reported significant emotional challenges but demonstrated unexpected resilience. Religious and cultural factors played nuanced roles, with most parents viewing the process as compatible with their beliefs. Economic burdens, prolonged hospitalizations, and geographical access to treatment centers emerged as key challenges. Extended family support and professional healthcare guidance were identified as crucial support mechanisms.

Conclusion: This study highlights the complex interplay between advanced medical technologies and traditional values in Turkish society. The findings emphasize the need for comprehensive and culturally sensitive support systems and long-term follow-up for families. The results suggest the value of implementing multidisciplinary care teams and developing specialized support programs for families undergoing savior sibling procedures.

Objective: This study aimed to determine the genotypic characteristics of patients with hereditary spherocytosis (HS) in Türkiye and to examine the correlation between genotype and phenotype.

Materials and methods: We analyzed the cases of 18 patients admitted to the pediatric hematology outpatient clinic with hemolytic anemia, jaundice, cholelithiasis, and splenomegaly. According to the Eber classification, the patients’ clinical presentations were categorized as mild, moderate, or severe. Next-generation sequencing was used to analyze single-nucleotide and copy-number variations in all genes associated with HS via clinical exome sequencing. Relationships between the genes with detected variants and the clinical presentations of the patients were investigated.

Results: In total, 21 variants were detected in 5 HS-related genes. Twelve of them were previously reported variants and 9 were novel variants. Seven of them were pathogenic and two were classified as variants of uncertain significance according to the American College of Medical Genetics and Genomics. We discuss the phenotypic effects of novel pathogenic variants in the SPTA1, SPTB, ANK1, SLC4A1, and EPB42 genes. Patients with pathogenic EPB42 and SLC4A1 variants had less severe clinical findings compared to other gene variants according to the Eber classification. On the other hand, patients with pathogenic variants of SPTA1 and SPTB had more severe clinical presentation.

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

Objective: TAFRO syndrome, entailing thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly, was previously considered a subtype of idiopathic multicentric Castleman disease (iMCD-TAFRO), with the diagnosis requiring pathology supporting Castleman disease. However, lymph node biopsies may be difficult for TAFRO patients (TAFRO without pathological evidence: TAFRO-w/op-iMCD), and sometimes these biopsies do not confirm iMCD (TAFRO-w/o-iMCD). We aimed to compare the clinical features and prognosis of TAFRO subgroups.

Materials and methods: We retrospectively analyzed the cases of 50 iMCD-TAFRO and 11 TAFRO-w/o-iMCD patients treated from May 2015 to April 2024.

Results: The groups showed no significant differences in clinical presentation or laboratory data. Both groups of patients were treated with iMCD-targeted strategies addressing cytokine storms. With a median follow-up of 21.4 (range: 0.5-107.0) months, there were no significant differences between iMCD-TAFRO and TAFRO-w/o-iMCD patients in 3-month response rate (72.1% vs. 88.9%, p=0.525), 6-month response rate (70.0% vs. 83.3%, p=0.849), or best overall response rate (77.6% vs. 90.0%, p=0.645). The estimated 3-year progression-free survival rate (65.8% vs. 90.0%, log-rank p=0.163) and the estimated 3-year overall survival rate (77.0% vs. 100%, log-rank p=0.145) were also not significantly different. Cox univariate analysis showed that decreased estimated glomerular filtration rate (<60 mL/min/1.73 m²) was associated with an increased risk of disease progression (hazard ratio: 4.133, 95% confidence interval: 1.561-10.940, p=0.004).

Conclusion: iMCD-TAFRO and TAFRO-w/o-iMCD could be considered overlapping entities and these patients should be treated promptly, targeting cytokine storms with similar strategies for each group of patients.