Purpose: 46,XX disorders of sex development (DSD) involve atypical genitalia accompanied by a normal female karyotype. This study was performed to investigate the clinical characteristics and long-term outcomes of patients with 46,XX DSD. Methods: The study included 34 patients with 46,XX DSD who presented with ambiguous genitalia or delayed puberty. Patients with congenital adrenal hyperplasia were excluded. Clinical phenotypes and overall outcomes were analyzed retrospectively. Results: Age at presentation ranged from birth to 40 years (median, 0.6 years), and the follow-up period ranged from 0.3 to 29.7 years (median, 8.8 years). Twenty patients were assigned female (58.8%). Etiologies included disorders of gonadal development (n=22), exogenous androgen exposure during pregnancy (n=5), association with syndromic disorders or genital anomalies (n=2), and unclassified causes (n=5). Ovotestis was the most frequent gonadal pathology (41.7%). Müllerian duct remnants were usually underdeveloped (52.9%) or absent (23.5%). Spontaneous puberty occurred in 17 of the 21 patients of pubertal age, while 9 patients required sex hormone replacement therapy. Gonadal complications were observed in 4 patients (gonadal tumors [n=3], and spontaneous gonadal rupture [n=1]), and gender dysphoria occurred in 1 patient who was assigned male. Conclusion This study described the wide phenotypic spectrum and pubertal outcome of patients with 46,XX DSD. Long-term multidisciplinary monitoring for pubertal development, fertility, gender identity, and gonadal complications is recommended.

Purpose: Pancreatic cancer has a poor prognosis; however, the implementation of neoadjuvant treatment enables borderline resectable cases to undergo curative resection and improves the overall survival rate. Attempts have been made to expand the eligibility criteria for neoadjuvant treatment, even in resectable cases. Some studies have suggested a correlation between vein abutment and poor prognosis or that the abutment angle may affect prognosis. This study investigated the anatomical factors affecting the vessel abutment angle and its prognostic value in pancreatic cancer. Methods: Patients with pancreatic ductal adenocarcinoma who underwent surgery between 2012 and 2017 were included in this study. Patients who underwent neoadjuvant treatment were excluded. Data from only the intent-to-treat pancreaticoduodenectomy group were included in the analysis. Clinicopathological characteristics; preoperative factors such as CA 19-9, preoperative biliary drainage, American Society of Anesthesiologists physical status classification, portal vein/superior mesenteric vein contact angle measured via CT scan; and intraoperative factors were collected for analysis. Results: A total of 365 patients were included in this study, and the abutment group included 92 patients (25.2%). The abutment and no-contact groups did not show any significant differences in terms of the overall survival or diseasefree survival rate. Among the abutment groups, patients with less than 90° and 90°–180° did not show any significant differences. In the multivariate analysis, the only preoperative factor that had a prognostic effect was CA 19-9, a biological factor. Conclusion When there is no vessel invasion in the abutment group, upfront surgery should be considered because the angle does not affect the overall prognosis.

Purpose: This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies. Methods: Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed. Results: The median follow-up durations in the HRD and UCB groups were 7.0 and 10.9 years, respectively. The cumu‑ lative incidence of acute graft-versus-host disease (GVHD) grades II–IV and moderate-to-severe chronic GVHD did not differ significantly between the groups. However, the HRD group demonstrated significantly lower rates of acute GVHD grades III–IV (4.9% vs. 29.2%, p = 0.009) and non-relapse mortality (2.6% vs. 34.2%, p < 0.001) but a higher relapse incidence (32.1% vs. 8.8%, p = 0.004) than the UCB group. The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, respectively. Multivariate analysis identified disease status as a significant risk factor for overall survival (hazard ratio, 3.24; p = 0.016). Additionally, UCB HSCT exhibited a trend toward worse event-free survival compared to HRD HSCT (hazard ratio, 2.63; p = 0.05). Conclusions These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients, with a trend toward improved survival over a long-term follow-up period exceeding a median of 7 years. Thus, HRD HSCT may be a valuable option for pediatric patients with‑ out human leukocyte antigen-matched donors.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma.Radiation therapy (RT) has served as the primary treatment option for PMBCL; however, its role has been questioned with the advent of intensified immunochemotherapy. This study aimed to investigate the role of consolidative RT in the primary treatment of PMBCL. Methods: This single-center retrospective study analyzed the survival outcomes of 65 patients newly diagnosed with PMBCL. The patients were divided into three treatment groups: (1) EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), (2) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and (3) R-CHOP with consolidative RT. Results: The objective response and complete remission rates were 86.2% and 63.1%, respectively, with 3-year pro‑ gression-free survival (PFS) and overall survival (OS) rates of 72% and 81%, respectively. All patients in the R-CHOP + RT group achieved an objective response with better PFS) than those who did not receive consolidative RT (p = 0.028), although there was no significant difference in OS (p = 0.102). Consolidative RT benefited patients with an initially bulky disease or insufficient end-of-treatment response. The predictive value of  18 F-fluorodeoxyglucose positronemission tomography-computed tomography (PET-CT) in assessing the treatment response in PMBCL was revali‑ dated, showing that patients who achieved negative end-of-treatment PET-CT had significantly better survival outcomes than others. Conclusions R-CHOP is a useful alternative regimen when intensified chemotherapy is not feasible. Consolidative RT should be considered in cases with an initially bulky disease and insufficient end-of-treatment response.

Purpose: Given that 40%-50% of primary central nervous system lymphoma (PCNSL) tissues exhibit aberrancy on 9p24.1, immune checkpoint inhibitors (ICI) may work for the disease. Materials and Methods: To define the role of ICIs in PCNSL, we carried out a nationwide retrospect analysis for 22 patients who had been treated with nivolumab monotherapy for relapsed or refractory PCNSL. Results: The median age at diagnosis was 66, and male: female ratio was 1:1. Patients received nivolumab after a median of 3 lines (range, 2 to 6) of therapy and at the median age of 67 years (range, 37 to 82 years). Eleven patients (50%) were refractory to the last treatment prior to nivolumab. With a median follow-up duration of 22.3 months (95% confidence interval [CI], 13.1 to 31.5), nine patients (41%) had an objective response (6 complete responses, 3 partial responses), and the median duration of response was 20.9 months (95% CI, 1.7 to 40.0). The median progression-free survival and overall survival were 2.1 months (95% CI, 0.2 to 4.0) and 18.9 months (95% CI, 5.0 to 32.8), respectively. Nivolumab was generally well-tolerated as no patients required dose reduction and only two patients required delay of treatment. Conclusion Our study suggests that nivolumab can be a reasonable option with the durable response for RR PCNSL.

Purpose: Extranodal natural killer/T-cell lymphoma (ENKTL) predominantly manifests in East Asia and Latin America. Despite shared intrinsic factors, such as ethnic and genetic backgrounds, the progression of ENKTL can be influenced by extrinsic factors related to changing lifestyle patterns. Materials and Methods: This study collected stool samples from newly diagnosed (ND)–ENKTL patients (n=40) and conducted whole genome shotgun sequencing. Results: ND-ENKTL revealed reduced alpha diversity in ND-ENKTL compared to healthy controls (HCs) (p=0.008), with Enterobacteriaceae abundance significantly contributing to the beta diversity difference between ENKTL and HCs (p < 0.001). Functional analysis indicated upregulated aerobic metabolism and degradation of aromatic compounds in ND-ENKTL. Enterobacteriaceae were associated not only with clinical data explaining disease status (serum C-reactive protein, stage, prognosis index of natural killer cell lymphoma [PINK], and PINK-E) but also with clinical outcomes (early relapse and short progression-free survival). The relative abundance of Enterobacteriaceae at the family level was similar between ENKTL and diffuse large B-cell lymphoma (DLBCL) (p=0.140). However, the ENKTL exhibited a higher abundance of Escherichia, in contrast to the prevalence of Enterobacter and Citrobacter in DLBCL. Linear regression analysis demonstrated a significant association between Escherichia abundance and programmed cell death-ligand-1 (PD-L1) levels in tissue samples (p=0.025), whereas no correlation with PD-L1 was observed for Enterobacteriaceae at the family level (p=0.571). Conclusion ND-ENKTL exhibited an abundance of Enterobacteriaceae and a dominant presence of Escherichia. These microbial characteristics correlated with disease status, treatment outcomes, and PD-L1 expression, suggesting the potential of the ENKTL microbiome as a biomarker and cause of lymphomagenesis, which warrants further exploration.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Purpose: In Korea, the Act on Hospice and Palliative Care and Decisions on Life-Sustaining Treatment (LST) was implemented on February 4, 2018. We aimed to investigate relevant factors and clinical changes associated with LST decisions after law enforcement. Materials and Methods: This single-center retrospective study included patients who completed LST documents using legal forms at Asan Medical Center from February 5, 2018, to June 30, 2020. Results: 5,896 patients completed LST documents, of which 2,704 (45.8%) signed the documents in person, while family members of 3,192 (54%) wrote the documents on behalf of the patients. Comparing first year and following year of implementation of the act, the self-documentation rate increased (43.9% to 47.2%, p=0.014). Moreover, the number of LST decisions made during or after intensive care unit admission decreased (37.8% vs. 35.2%, p=0.045), and the completion rate of LST documents during chemotherapy increased (6.6% vs. 8.9%, p=0.001). In multivariate analysis, age < 65 (odds ratio [OR], 1.724; 95% confidence interval [CI], 1.538 to 1.933; p < 0.001), unmarried status (OR, 1.309; 95% CI, 1.097 to 1.561; p=0.003), palliative care consultation (OR, 1.538; 95% CI, 1.340 to 1.765; p < 0.001), malignancy (OR, 1.864; 95% CI, 1.628 to 2.133; p < 0.001), and changes in timing on the first year versus following year (OR, 1.124; 95% CI, 1.003 to 1.260; p=0.045) were related to a higher self-documentation rate. Conclusion Age < 65 years, unmarried status, malignancy, and referral to a palliative care team were associated with patients making LST decisions themselves. Furthermore, the subject and timing of LST decisions have changed with the LST act.