Background: Hereditary hemolytic anemia (HHA) refers to a heterogeneous group of genetic disorders that share one common feature: destruction of circulating red blood cells (RBCs). The destruction of RBCs may be due to membranopathies, enzymopathies, or hemoglobinopathies. Because these are genetic disorders, incorporation of next-generation sequencing (NGS) has facilitated the diagnostic process of HHA. Method: Genetic data from 29 patients with suspected hereditary anemia in a tertiary hospital were retrospectively reviewed to evaluate the efficacy of NGS on hereditary anemia diagnosis. Targeted NGS was performed with custom probes for 497 genes associated with hematologic disorders. After genomic DNA was extracted from peripheral blood, prepared libraries were hybridized with capture probes and sequenced using NextSeq 550Dx (Illumina, San Diego, CA, USA). Result: Among the 29 patients, ANK1 variants were detected in five, four of which were pathogenic or likely pathogenic variants. SPTB variants were detected in six patients, five of which were classified as pathogenic or likely pathogenic variants. We detected g6pd pathogenic and spta1 likely pathogenic variants in two patients and one patient, respectively. Whole-gene deletions in both HBA1 and HBA2 were detected in two patients, while only HBA2 deletion was detected in one patient. One likely pathogenic variant in PLKR was detected in one patient, and one likely pathogenic variant in ALAS2 was detected in another. Conclusion: Here, NGS played a critical role in definitive diagnosis in 18 out of 29 patients (62.07%) with suspected HHA. Thus, its incorporation into the diagnostic workflow is crucial.

The Korean Society of Pediatric Neuro-Oncology (KSPNO) conducted treatment strategies for children with medulloblastoma (MB) by using alkylating agents for maintenance chemotherapy or tandem high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) according to the risk stratification. The purpose of the study was to assess treatment outcomes and complications based on risk-adapted treatment and HDC. Fifty-nine patients diagnosed with MB were enrolled in this study. Patients in the standard-risk (SR) group received radiotherapy (RT) after surgery and chemotherapy using the KSPNO M051 regimen. Patients in the high-risk (HR) group received two and four chemotherapy cycles according to the KSPNO S081 protocol before and after reduced RT for age following surgery and two cycles of tandem HDC with ASCR consolidation treatment. In the SR group, 24 patients showed 5-year event-free survival (EFS) and overall survival (OS) estimates of 86.7% (95% confidence interval [CI], 73.6-100%) and 95.8% (95%CI, 88.2-100%), respectively. In the HR group, more infectious complications and mortality occurred during the second HDC than during the first. In the HR group, the 5-year EFS and OS estimates were 65.5% (95%CI, 51.4-83.4) and 72.3% (95%CI, 58.4-89.6), respectively. High intensity of alkylating agents for SR resulted in similar outcomes but with a high incidence of hematologic toxicity. Tandem HDC with ASCR for HR induced favorable EFS and OS estimates compared to those reported previously. However, infectious complications and treatment-related mortalities suggest that a reduced chemotherapy dose is necessary, especially for the second HDC.

Peripheral blood stem cell transplantation (PBSCT) is an important therapeutic measure for both hematologic and non-hematologic diseases. For PBSCT to be successful, sufficient CD34⁺ cells need to be mobilized and harvested. Although risk factors associated with poor mobilization in patients with hematologic diseases have been reported, studies of patients with non-hematologic diseases and those receiving plerixafor are rare. To identify factors associated with poor mobilization, data from autologous PBSC harvest (PBSCH) in 491 patients were retrospectively collected and analyzed. A multivariate analysis revealed that in patients with a hematologic disease, an age older than 60 years (odds ratio [OR] 1.655, 95% confidence interval [CI] 1.049–2.611, p = 0.008), the use of myelotoxic agents (OR 4.384, 95% CI 2.681–7.168, p < 0.001), and a low platelet count (OR 2.106, 95% CI 1.205–3.682, p = 0.009) were associated with poor mobilization. In patients with non-hematologic diseases, a history of radiation on the pelvis/spine was the sole associated factor (OR 12.200, 95% CI 1.934–76.956, p = 0.008). Among the group of patients who received plerixafor, poor mobilization was observed in 19 patients (19/134, 14.2%) and a difference in the mobilization regimen was noted among the good mobilization group. These results show that the risk factors for poor mobilization in patients with non-hematologic diseases and those receiving plerixafor differ from those in patients with hematologic diseases; as such, non-hematologic patients require special consideration to enable successful PBSCH.

Seoyoung Lim, B.S., Yu Jeong Choi, M.D., Eunju Yeom, B.S., Won Kee Ahn, M.D., Seung-Tae Lee, M.D., Jong Rak Choi, M.D., Seungmin Hahn, M.D., and Saeam Shin, M.D.. Ann Lab Med 2025;45:339-42. https://doi.org/10.3343/alm.2024.0622