ダイアモンド・ブラックファン貧血

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome (CBMFS) primarily managed with corticosteroids and blood transfusions; however, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the sole curative option when these therapies fail or relapse occurs. We report the case of a 21-year-old woman diagnosed with DBA caused by an RPS19 mutation shortly after birth. Although she responded well to corticosteroid therapy until 18 years of age, discontinuation led to relapse and subsequent transfusion dependence, necessitating allogeneic transplantation. In the absence of a human leukocyte antigen (HLA)-matched donor, she underwent post-transplantation cyclophosphamide (PT-Cy)-based haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) at 21 years of age, utilizing her father as the donor. Myeloablative conditioning was performed using fludarabine, melphalan, and busulfan. For acute graft-versus-host disease (GVHD) prophylaxis, PT-Cy (50 mg/kg on days 3 and 4), tacrolimus, and mycophenolate mofetil were administered, resulting in successful neutrophil engraftment on day 16 post-transplantation. Although the patient developed acute GVHD (grade II), it resolved with corticosteroid therapy. Post-discharge, she was readmitted due to acute gastrointestinal GVHD (grade II), which improved after methylprednisolone administration. She was discharged on day 92 and achieved complete transfusion independence for the past 5 years, making this the first reported case of long-term survival following PT-Cy-based haplo-PBSCT for this condition. Including our patient, there are only four reported cases of allo-HSCT using PT-Cy for adult patients with DBA; notably, all patients survived without developing severe GVHD or infectious complications. Generally, transplant outcomes for DBA worsen with increasing age due to severe GVHD and organ damage secondary to long-term iron overload. Given that DBA is a non-malignant disease, meticulous attention must be paid to prevent unnecessary GVHD and graft failure. In adult patients with DBA, PT-Cy yielded successful engraftment and safety, with no incidence of severe GVHD, leading to long-term survival and minimal complications. These findings suggest that allo-HSCT utilizing PT-Cy remarkably expands donor options for congenital bone marrow failure syndromes. Consequently, this approach is expected to become a promising therapeutic strategy not only for hematologic malignancies but also for non-malignant disorders.

We assessed the effect of iron overload (IO) on mortality and complications following hematopoietic stem cell transplantation (HSCT) in patients with Diamond-Blackfan anemia syndrome (DBAS) in a systematic review of individual participant data and cohort data from observational studies. PubMed and EMBASE were searched up to 24 November 2025. Eligible studies included English or Dutch observational studies of pediatric or adult patients with confirmed DBAS undergoing HSCT, with documented transfusion history and sufficient follow-up. Abstract-only and congress publications were excluded. The search identified 993 records, of which 42 studies comprising 443 patients were included. Mortality related to IO was inconsistently reported. When reported, infections (31 cases) and graft-versus-host disease (18 cases) were the most frequent causes of death. IO assessment varied substantially, with heterogeneous diagnostic criteria and measurement methods. Although it has been demonstrated that IO affects patient outcomes in DBAS, the available evidence is currently insufficient to determine its direct association with mortality after HSCT specifically. Risk of bias assessment using ROBINS-E indicated high risk of bias, mainly due to exposure measurement and missing data, resulting in very low certainty of evidence. The effect of IO on HSCT outcomes in DBAS cannot be determined due to heterogeneous exposure definitions and methodological limitations. Importantly, the absence of a demonstrable association should not be interpreted as evidence that IO is safe in the transplant setting. Pretransplant IO should therefore be considered a clinically relevant potential risk factor for posttransplant morbidity and mortality, although current DBAS-specific evidence is insufficient to quantify its independent effect on HSCT outcomes. Future studies should incorporate standardized biochemical and imaging-based assessment of iron burden and systematically report iron chelation strategies to improve understanding of its impact on transplant outcomes, particularly in older patients.

UNLABELLED: Pure red cell aplasia (PRCA) is a rare hematological disorder with diverse etiologies and variable regional prevalence. Data from tropical, resource-limited settings are sparse. This study presents the largest single-center PRCA cohort from South Asia, aiming to delineate the etiological spectrum, clinical features, and diagnostic challenges in this unique population. A retrospective analysis was conducted on 116 PRCA patients diagnosed between March 2017 and March 2025 at a tertiary care center in South Asia. Etiological classification was based on clinical, laboratory, and bone marrow findings, with supplementary molecular and serological testing where available. Demographic, clinical, and laboratory data were analyzed to identify correlations with PRCA subtypes. Secondary PRCA accounted for 74% of cases, with parvovirus B19 infection being the most common etiology (31% isolated, 14% overlap syndromes). Idiopathic/autoimmune PRCA constituted 19%, while drug-induced cases accounted for 6.9% and malignancy-associated PRCA 8.6%. Thymoma-associated PRCA was rare (1.7%). Pediatric cases (28.5%) exhibited higher rates of parvovirus and idiopathic PRCA. One case of congenital PRCA, diagnostic of Diamond-Blackfan anemia, was reported.The etiological profile of PRCA in tropical South Asia is distinct, dominated by infectious and idiopathic causes. A tiered, resource-sensitive diagnostic approach is essential. Bone marrow morphology, especially identification of giant pronormoblasts, contributed significantly for the diagnosis in resource-constrained settings. Our findings emphasize the need for regionally tailored diagnostic and management strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12288-025-02271-w.

Inherited bone marrow failure syndromes (IBMFS) represent a genetically heterogeneous group of. disorders often overlapping with acquired aplastic anemia and myelodysplastic neoplasms. Accurate genetic diagnosis is essential for guiding management, stem cell transplantation, and cancer surveillance. Data on IBMFS genetics from India remain limited. This study aimed to characterize the genetic variant profile in a North Indian cohort of patients presenting with bone marrow failure (BMF). We retrospectively analyzed 167 patients with clinical suspicion of BMF evaluated at a single tertiary center over four years. Clinical features, somatic abnormalities, hematological parameters, and bone marrow findings were systematically documented. Chromosomal breakage studies and PNH flow cytometry were performed where indicated. Genetic testing included targeted NGS panels (98 cases) and whole exome sequencing (69 cases), with variants interpreted using ACMG guidelines. The median patient age was 10 years (range 1 month-44 years), with a male-to-female ratio of 2.4:1. Physical anomalies were present in 29.3% of patients. Pancytopenia was the most frequent hematological finding (69%). NGS identified 113 distinct variants in 94/167 patients (56.3%) Pathogenic or likely pathogenic variants were found in 28.7% of cases. FANCA was the most frequently mutated gene, followed by RPS19, SBDS, TERT, and ADA2. Variants associated with Fanconi anemia were predominant (22 cases), followed by dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Emerging syndromes involving DNAJC21, ERCC6L2, and MYSM1 were also identified. Genetic testing revealed diverse IBMFS-associated variants, with FANCA mutations being most common. Incorporating comprehensive NGS into diagnostic workflows is critical for differentiating IBMFS from acquired BMF, guiding therapy, donor selection, and long-term surveillance.

OBJECTIVE: To summarize the early recognition clues, genetic characteristics, and short-term outcomes of children with Diamond-Blackfan anemia (DBA) in order to provide a reference for the differential diagnosis of severe anemia in early infancy. METHODS: A retrospective analysis was conducted on 11 children clinically diagnosed with DBA at the Department of Pediatric Hematology of the Third Affiliated Hospital of Zhengzhou University between May 2020 and December 2024. Their general condition, initial presentation, associated phenotypes, lab and bone marrow examination results, genetic testing results, treatment methods, and follow-up outcomes were collected and analyzed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2026-056). RESULTS: A total of 11 clinically diagnosed children were included, 6 of whom had onset in the neonatal period and 5 in infancy. Severe anemia in early infancy was a common feature, with hemoglobin levels ranging from 16 to 71 g/L (median value = 42 g/L), and mean corpuscular volume (MCV) being mostly normal or elevated. All 11 bone marrow examinations showed reduced erythroid lineage. Seven cases had confirmed structural malformations, and five cases had developmental delays. In terms of genetics, five DBA-related genes were involved, with RPS19 being the most common. Ten cases had pathogenic/likely pathogenic or DBA-related supportive variants detected, and one case had an RPS29 variant of uncertain significance related to the phenotype. All children had a history of blood transfusions. Among the 10 cases that could be followed up, glucocorticoid treatment was temporarily effective in six cases, three developed iron overload, two relapsed, and one underwent hematopoietic stem cell transplantation and survived. CONCLUSION: Early identification of DBA should focus on the core combination of severe anemia in early infancy, normal or increased MCV, reduced reticulocytes, and suppressed erythroid lineage in the bone marrow, while also considering the presence of congenital anomalies. Genetic testing has facilitated to clarify the molecular typing and explain the phenotypes. The absence of typical malformations does not rule out DBA, and infants with early severe anemia should undergo bone marrow and genetic evaluation as soon as possible.