Background: We compared the immunoglobulin (IG) heavy chain (IGH) leader and FR1 primer sets to measure clone sizes and detect immunoglobulin heavy chain variable (IGHV) region somatic hypermutations (SHMs) in Korean patients with chronic lymphocytic leukemia (CLL). We also analyzed IGH and immunoglobulin kappa (IGK) to identify Korean-specific IGs in CLL. Methods: Next-generation sequencing (NGS)–based gene rearrangements and IGHV SHMs were assessed in 40 patients using IGH leader, IGH FR1, and IGK primers. Flow cytometry, karyotyping, interphase FISH, and NGS-based variant analyses were performed for 165 genes. Results: Clonal IGH and IGK rearrangements were detected in 100.0% and 97.5% of patients, respectively. Clonal size was generally smaller per NGS than per flow cytometry, particularly when using the IGH leader (median: 52.5%) versus the IGH FR1 primer set (73.2%). IGHV SHMs occurred in approximately 70% of patients; 10% showed primer set discrepancies. The incidence of IGHV SHMs was low in patients at high risk (i.e., with TP53 abnormalities; complex karyotypes; and ATM, NOTCH1, SF3B1, or BIRC3 variants). IGHV3 was the most common IGHV (58.3%), and IGHV4-34 was most frequently identified (14.6%). IGHV1 and IGHV1-69 usage differed significantly between Koreans and westerners. IGHJ4 was the most common IGHJ (56.3%). A single IGKV–IGKJ gene rearrangement was most frequently observed (18.9%), whereas intron-KDE was the most common rearrangement (30.6%). Conclusions NGS may underestimate CLL clonal size, particularly when using the IGH leader primer set. IGHV SHMs were inversely associated with negative prognostic factors.Our data suggest ethnic differences in CLL pathogenesis.

Background: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

Purpose: Minimal residual disease (MRD)-guided therapy is the global standard treatment for pediatric acute lymphoblastic leukemia (ALL). We assessed the impact of MRD-driven intensification along with protocol-defined risk groups in pediatric ALL treatment. Methods: This retrospective analysis included 209 patients with ALL (treated between January 2013 to June 2023).MRD was assessed using six- to eight-color flow cytometry at the end of each phase before the maintenance phase.Post-induction treatment was determined based on early response, National Cancer Institute risk, and cytogenet‑ ics. High-risk (HR) patients followed the Korean HR or CCG-1882 protocols and standard-risk (SR) patients followed the modified COG-AALL0331 protocol. Treatment was intensified if flow-MRD ≥ 0.1% was identified. Results: Overall, 103 and 106 patients were classified as having SR and HR, respectively. The 5-year overall survival (OS) and event-free survival (EFS) were 92.5% and 84.3%, respectively. Thirty SR and 18 HR patients received intensi‑ fied chemotherapy. Treatment intensification significantly improved EFS in patients with high MRD (94.2% vs. 75.5%, p = 0.04), particularly in post-induction patients with high MRD (90.0% vs. 19.0%, p = 0.035). The difference in survival between rapid early responder (RER) and slow early responder (SER) groups was eliminated after MRD-based intensifi‑ cation. The implementation rates of treatment intensification varied over time (9.1% before 2015, 28.6% during 2016– 2019, and 13.9% during 2020–2023), reflecting improved risk stratification and therapy selection. Conclusion MRD-guided therapy intensification markedly improved survival outcomes in patients with pediatric ALL when combined with risk-based protocols, highlighting the importance of MRD monitoring for optimizing riskadapted treatment strategies.

Objective: We aimed to investigate the incidence of delayed-onset neurological deficits (DONDs), DOND-related reoperation rates following adult spinal deformity (ASD) surgery, and efficacy of transverse process hooks (TPHs) at the uppermost instrumented vertebra (UIV) compared to pedicle screws (PSs). Methods: We included 90 consecutive patients who underwent instrumented fusion from the sacrum to the distal thoracic spine for ASD, with a minimum follow-up of 24 months. Clinical and radiological outcomes were compared between 33 patients in the TPH group and 57 patients in the PS group, using the Scoliosis Research Society-22 Outcomes questionnaire (SRS-22), Medical Outcomes Study Questionnaire Short-Form 36 (SF-36), and various spinal sagittal parameters. Results: While absent in the TPH group, myelopathy occurred in 15.8% of the PS group, wherein 15 patients underwent reoperation. The change in the proximal junctional angle, from the pre- to postoperative assessment, was lower in the TPH group than in the PS group (0.2 vs. 6.6, p=0.002). Postoperative facet degeneration in the PS group progressed more significantly than in the TPH group (0.5 vs. 0.1, p=0.002). Surgical outcomes were comparable for both groups, except for the back visual analogue scale (3.5 vs. 4.1, p=0.010) and SRS-22 domains, including pain and satisfaction (3.3 vs. 2.9, p=0.033; 3.7 vs. 3.3, p=0.041). No intergroup difference was observed in SF-36. Conclusion Using TPHs at the UIV level can prevent DOND, and thereby prevent postoperative myelopathy that necessitates reoperation; thus, TPHs is preferable over PSs in ASD surgery.

Objective: Chordoma, a rare malignant tumor originating from embryonal notochord remnants, exhibits high resistance to conventional treatments, making surgical resection imperative. However, the factors influencing prognosis specifically for cervical spine chordoma have not been clearly identified. We investigate the prognosis of cervical spine chordoma with factors influential in a nationwide multicenter retrospective study. Methods: This study included all patients diagnosed with cervical spine chordoma at 7 tertiary referral centers from January 1998 to March 2023, excluding those with clivus and thoracic spine chordomas extending into the cervical spine. Local recurrence (LR) was identified through follow-up magnetic resonance imaging, either as reappearance in completely resected tumors or regrowth in residual tumors. The study assessed LR and overall survival, analyzing factors influencing LR and death. Results: Forty-five patients with cervical spine chordoma had a mean age of 46.4 years. Over a median follow-up of 52 months, LR and distant metastasis were observed in 21 (46.7%) and 4 patients (8.9%), respectively, and 16 patients (36%) were confirmed dead. The 5-year and 10-year cumulative LR rates were 51.3% and 60%, respectively, while the 5-year and 10-year survival rates were 82% and 53%. Age was the only significant factor affecting mortality (hazard ratio, 1.04; 95% confidence interval, 1.04–1.07; p=0.015). Notably, the degree of resection and adjuvant therapy did not statistically significantly impact local tumor control and mortality. Conclusion This study, the largest multicenter retrospective analysis of cervical spine chordoma in Korea, identified age as the only factor significantly affecting patient survival.

Objective: We aimed to investigate the incidence of delayed-onset neurological deficits (DONDs), DOND-related reoperation rates following adult spinal deformity (ASD) surgery, and efficacy of transverse process hooks (TPHs) at the uppermost instrumented vertebra (UIV) compared to pedicle screws (PSs). Methods: We included 90 consecutive patients who underwent instrumented fusion from the sacrum to the distal thoracic spine for ASD, with a minimum follow-up of 24 months. Clinical and radiological outcomes were compared between 33 patients in the TPH group and 57 patients in the PS group, using the Scoliosis Research Society-22 Outcomes questionnaire (SRS-22), Medical Outcomes Study Questionnaire Short-Form 36 (SF-36), and various spinal sagittal parameters. Results: While absent in the TPH group, myelopathy occurred in 15.8% of the PS group, wherein 15 patients underwent reoperation. The change in the proximal junctional angle, from the pre- to postoperative assessment, was lower in the TPH group than in the PS group (0.2 vs. 6.6, p=0.002). Postoperative facet degeneration in the PS group progressed more significantly than in the TPH group (0.5 vs. 0.1, p=0.002). Surgical outcomes were comparable for both groups, except for the back visual analogue scale (3.5 vs. 4.1, p=0.010) and SRS-22 domains, including pain and satisfaction (3.3 vs. 2.9, p=0.033; 3.7 vs. 3.3, p=0.041). No intergroup difference was observed in SF-36. Conclusion Using TPHs at the UIV level can prevent DOND, and thereby prevent postoperative myelopathy that necessitates reoperation; thus, TPHs is preferable over PSs in ASD surgery.