Long-Term Efficacy and Safety of Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria and High Disease Burden: Real-World Data From Korea

Background@#Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. @*Methods@#This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. @*Results@#At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. @*Conclusion@#These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) as Conditioning Therapy for Autologous Stem Cell Transplantation in Patients with Relapsed or High-Risk Non-Hodgkin’s Lymphoma: A Multicenter Randomized Phase II Study bythe Consortium for Improving Survival of Lymphoma (CISL) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL. @*Materials and Methods@#Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS). @*Results@#Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation. @*Conclusion@#There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia

Background/Aims@#Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database. @*Methods@#This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]). @*Results@#The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS. @*Conclusions@#Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.

Multicenter retrospective analysis of patients with chronic lymphocytic leukemia in Korea

Background@#Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. @*Methods@#The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). @*Results@#The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P ＜0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively. @*Conclusion@#This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.

Characteristics and survival of patients with atypical chronic myeloid leukemia

No abstract available.

Post-transplant Lymphoproliferative Disorder in Transplanted Kidney Causing Urinary Tract Obstruction / 대한이식학회지

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication resulting in mortality and renal graft failure. PTLD is a heterogeneous disorder, which causes different clinical forms of disease from non-specific viral syndrome to malignant lymphoma and has various etiologies, clinical features, and treatment strategies. Here, we report on a patient who had a PTLD in the hilum of a transplanted kidney at 5 months after renal transplantation. The PTLD resulted in hydronephrosis of the transplanted kidney and graft dysfunction by local urinary tract obstruction. Despite treatment including immunosuppression reduction and rituximab administration, we removed the transplanted kidney from the recipient because the PTLD did not respond to the therapy.

Extranodal natural killer/T-cell lymphoma of the tenosynovium of the hand

No abstract available.

Utilization of Post-centrifugal Plasma Filtration for Treatment of Hyperviscosity Syndrome due to Waldenstrom's Macroglobulinemia: A Case Report / 대한수혈학회지

Waldenstrom's macroglobulinemia is characterized by overproduction of immunoglobulin M (IgM), which can lead to development of a hyperviscosity syndrome. Plasmapheresis has been used to reduce plasma viscosity and IgM levels. However, plasmapheresis not only removes pathogenic substances but also the normal components in plasma. Post-centrifugal plasma filtration (PCPF) using a filter with an appropriate pore size has been shown to be effective for selective removal of macromolecules in plasma without requiring a replacement fluid. Here, we report on a patient with hyperviscosity syndrome due to Waldenstrom's macroglobulinemia, which was ameliorated by a single treatment of PCPF using an Evaflux 5A filter. After centrifugation, the separated plasma of the patient was subjected to membrane filtration for removal of IgM in the plasma. After PCPF, a 56.5% reduction in the IgM level (from 9,370 mg/dL to 4,080 mg/dL) was achieved, whereas the level of albumin showed a slight decrease, from 2.7 g/dL to 2.4 g/dL (11.1% reduction). The patient's symptoms were relieved and she was discharged on the seventh hospital day.

Artifactual Hyperbilirubinemia due to Paraprotein Interference in a Case of Multiple Myeloma / 임상검사와정도관리

When analyzing samples containing paraproteins, various interference effects are encountered in the clinical laboratory. Precipitation of paraproteins mostly interferes with the assays that use photometric detection. Herein, we present a case of a patient with multiple myeloma who had paraproteins and spuriously elevated total bilirubin levels (31.1 mg/dL), which were measured by using Roche total bilirubin assay on the Modular DPE (Roche Diagnostics, Switzerland) chemical analyzer. The total bilirubin concentration reduced from 31.1 mg/dL to 1.5 mg/dL, when tested after three fold dilution of the sample on Modular DPE chemical analyzer.

A patient with acquired hemophilia A induced by clopidogrel

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Treatment with clopidogrel is a cause of AHA, but its clinical course is unknown. Recently, we treated a 65-year-old man who was hospitalized for cerebellar infarction and had a prolonged activated partial thromboplastin time (aPTT) with soft tissue oozing after 3 weeks of clopidogrel use. We terminated clopidogrel administration and transfused the patient with fresh frozen plasma. However, the aPTT increased up to 98.8 seconds, and the FVIII and FVIII inhibitor levels were <1% and 5.4 Bethesda units/mL, respectively. Clopidogrel-associated AHA was considered, and we began steroid treatment. Two months later, FVIII, FVIII inhibitor, and aPTT values were normalized. No further bleeding or aPTT prolongation has been reported during the 2-year follow-up period. AHA should be considered in patients taking clopidogrel and experiencing bleeding, unless the platelet count and coagulation screen are normal.

Rapid Isolation of Adipose Tissue-Derived Stem Cells by the Storage of Lipoaspirates

PURPOSE: This study examined a rapid isolation method decreasing the time and cost of the clinical application of adipose tissue-derived stem cells (ASCs). MATERIALS AND METHODS: Aliquots (10 g) of the lipoaspirates were stored at 4degrees C without supplying oxygen or nutrients. At the indicated time points, the yield of mononuclear cells was evaluated and the stem cell population was counted by colony forming unit-fibroblast assays. Cell surface markers, stem cell-related transcription factors, and differentiation potentials of ASCs were analyzed. RESULTS: When the lipoaspirates were stored at 4degrees C, the total yield of mononuclear cells decreased, but the stem cell population was enriched. These ASCs expressed CD44, CD73, CD90, CD105, and HLA-ABC but not CD14, CD31, CD34, CD45, CD117, CD133, and HLA-DR. The number of ASCs increased 1x1014 fold for 120 days. ASCs differentiated into osteoblasts, adipocytes, muscle cells, or neuronal cells. CONCLUSION: ASCs isolated from lipoaspirates and stored for 24 hours at 4degrees C have similar properties to ASCs isolated from fresh lipoaspirates. Our results suggest that ASCs can be isolated with high frequency by optimal storage at 4degrees C for 24 hours, and those ASCs are highly proliferative and multipotent, similar to ASCs isolated from fresh lipoaspirates. These ASCs can be useful for clinical application because they are time- and cost-efficient, and these cells maintain their stemness for a long time, like ASCs isolated from fresh lipoaspirates.

Predictive Value of the ERCC1 Expression for Treatment Response and Survival in Advanced Gastric Cancer Patients Receiving Cisplatin-based First-line Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to determine whether the ERCC1 expression is effective to predict the clinical outcomes of patients with advanced gastric cancer (AGC) and who were treated with cisplatin-based first-line chemotherapy. MATERIALS AND METHODS: A total of 89 measurable AGC patients received cisplatin and capecitabine, with or without epirubicin, as a part of a randomized phase II study. Patients were included for the current molecular analysis if they had received two or more cycles of chemotherapy, their objective tumor responses were measured and if their paraffin-embedded tumor samples were available. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and the patients were divided into two groups (positive or negative) according to the presence of IHC staining of the tumor cell nuclei. RESULTS: Of the 32 eligible patients, 21 patients (66%) had tumor with a positive expression of ERCC1 and the remaining 11 patients had tumor with a negative ERCC1-expression. The ERCC1-negative patients achieved a higher response rate than that of the ERCC1-positive patients (44% vs. 28%, respectively), although the difference was not statistically significant (p=0.42). The median survival time for the all patients was 14.6 months (95% CI: 13.6 to 15.6 months). The one-year survival rate was similar for the ERCC1-negative patients (61%) and the ERCC1-positive patients (70%). CONCLUSION: In the current study, the tumor ERCC1 expression by IHC staining could not predict the clinical response or survival of AGC patients who were treated with cisplatin-based first-line chemotherapy. The ERCC1 protein expression does not appear to be a useful tool for the selection of tailored chemotherapy for these patients.

Reversible Pituitary Dysfunction in a Patient with Cushing's Syndrome due to Adrenal Adenoma / 대한내분비학회지

A 45-year-old woman who complained of weight gain and irregular menstruation was diagnosed as having Cushing's syndrome due to a 3 cm sized left adrenal adenoma. She underwent left adrenalectomy, and she also underwent combined anterior pituitary tests before and 9 months after the surgery. The growth hormone and adrenocorticotropic hormone levels failed to respond to hypoglycemia before the surgery, but their responses recovered after the surgery. Cortisol and thyroid stimulating hormone failed to respond to hypoglycemia and thyrotropin releasing hormone (TRH) before the surgery, respectively, but these were improved after the surgery. Luteinizing hormone, follicle stimulating hormone, and prolactin adequately responded to gonadotropin-releasing hormone and TRH, respectively, before and after the surgery. However, the basal levels of these hormones were higher after adrenalectomy, suggesting that hypercortisolemia had a significant influence on all the pituitary hormones.

A Case of Acromegaly Caused by Double Pituitary Adenomas / 대한내분비학회지

Acromegaly is a clinical syndrome, which is caused by an excess of growth hormone (GH), most commonly secreted from a pituitary solitary adenoma. However, our patient had bilateral GH-secreting pituitary tumors, the incidence of which has been reported in only 1.3 to 1.69% of all acromegalic patients. A 59-year-old female, with no family history of pituitary adenomas, demonstrated an increased level of serum insulin-like growth factor-1 (IGF-1), and GH not suppressed after 75 g oral glucose loading. On a preoperative MRI, only one pituitary tumor, measuring 1.1 x 0.7 cm, could be observed using sellar MRI. After surgical resection of the tumor, her headache and myalgia were sustained, and the IGF-1 level was still in a high titer. Therefore, a follow-up sellar MRI was taken, and a 0.6 x 0.7 cm sized newly growing pituitary tumor was found on the other side. With a retrospective review of radiological examinations, the patient was found to have bilateral tumors. The 0.3 cm sized tumor on the left was too small to be detected on the preoperative MRI. As the patient preferred medical treatment after surgery, she was treated with sandostatin analogues. Acromegaly with bilateral GH-secreting pituitary tumors, is a very rare disease, with no previous case having been reported in Korea. Herein, we report the case with a review of the literature.

A Case of Multiple Endocrine Neoplasia Type 1 with Papillary Thyroid Carcinoma / 대한내분비학회지

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN 1). It is an hereditary syndrome characterized by neoplastic disorders such as pituitary adenoma, parathyroid adenoma or hyperplasia and pancreatic neuroendocrine tumor, such as gastrinoma just like in our case. But sometimes pheochromocytoma, mucosal ganglioneuromas, lipoma, forgut carcinoid and thyroid disease could be accompany the disease, but coincidental papillary thyroid carcinoma was never reported before in Korea. Herein we represent a 39-year-old woman who manifested typical features of MEN 1 with coincidental papillary thyroid carcinoma. Despite with definite family history of MEN 1, her genetic analysis of DNA had not found any germline mutation in MEN 1 gene. Unidentified culprit gene unable further genetic study of finding LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN 1. As we have experienced a case of MEN 1 combined with papillary thyroid carcinoma, we report it with the review of literature.

A Case of Acromegaly with Gall Bladder Cancer / 대한내분비학회지

Acromegaly is a systemic endocrine disorder due to an excessive release of growth hormone, which increases the serum levels of insulin-like growth factor-1(IGF-1). Elevated levels of these hormones are assumed to increase the incidence of malignant tumors in patients with acromegaly, due to by stimulating the growth and maturation of cells. In particular, IGF-1 is considered to be closely related with the development of colon polyps and colon cancers. Studies suggest that various malignant tumors, including thyroid cancer, brain tumor and renal cell carcinomas, are also more common in patients with acromegaly. Here, a case of gall bladder cancer in a patient with acromegaly, and the possible relationships between these two disorders, is reported.

Effects of Psychiatric Rehabilitation on the Number of Relapse, Number of Admission, Days of Hospitalization, and Direct Treatment Costs of Schizophrenic Patients: Two-Year Follow-up Study / 신경정신의학

OBJECTIVE: We evaluated the clinical efficacy of a comprehensive psychiatric rebabiliation of schizophrenia, including family psychoeducation,patient education,socail skills tranining,group psychotherapy,art therapy,and ocupational therapy. METHOD: From September 1993 to february 1995,173 chronic schizophrenics who met DSM-lV criteria and were discharged from a locked ward were assigned into the psychiatric rehabilitation service group(psychiatric rehabilitation group,n=46) or the customary out patient service group(out-patient group,n=127)prospectively,but not randomly. Assignment was based on preferences of patients and their relatives. Each subject included in the psychiatric rehabilitation group received twice weekly patient education,social skills training, family psychoeducation, group psychotherapy, art therapy, occupational therapy and maintenance chemotherapy during a 6-month period. Those in the out-patient group received individual supportive psychotherapy and maintenance chemotherapy according to their clinical needs for 10-20 minutes once per week. After entry into the study,all subjects were assessed for the number of readmission,days of hospitalization,and the direct treatment costs through the first and second year of follow-ups. These outcome variables were also compared pre-and post-2 years at the time point of entry into the study. Aftercare chemotherapy on a weekly to monthly basis continued for the remailder of the two year follow-up period. RESULTS: With regard to the mean number of hospital admissions per vear,the mean days of hospitalization per year, and the direct treatment costs per year, psychiatric rehabilitation broup had significantly decreased all clinical outcomes 2 years after compared with before receiving psychiatric rehabilitation. But there were no significant differences in the all clinical outcomes between between before and after study intake in the out-patient group. For the number of relapse regardless of drug compliance, 4 patients(9%) during first year and 14 patients(30%) during second year were relapsed in the 46 subjects of the psychiatric rehabiliation group. In contrast, 75 patients(59%) during first year and 90 patients(71%) during second year relapsed in the out-patient group. When considering the effect of drug noncompliance to relapse,4(9%) and 14 patients(30%) were relapsed while on medication respectively during the first and second year in the 46 of the psychiatric rehabilitation group, vs. 27(34%) of 79 patients on medication during the first year and 31(46%) of 68 patients on medication during the second year were relapsed in the out-patient group. CONCLUSIONS: These results indicate that the comprehensive psychiatric rehabiliation can be useful therapeutic intervention both to improve the clinical outcomes of schizophrenic patients and to reduce the economical burden of their relatives.