Advances in genomics and molecular biology over the past 20 years have resulted in numerous approved molecular targeted cancer therapies. The two main approaches for targeted cancer therapy are monoclonal antibodies and small molecules. Targeted therapy is expected to exert few side effects, but a new class of toxicities has been reported. Thus, the classical chemotherapy-induced toxicities of alopecia, myelosuppression, mucositis, nausea, and vomiting have been replaced in patients receiving targeted therapies by dermatologic, cardiovascular, gastrointestinal, endocrine, ocular, and pulmonary toxicities, and infusion reactions.Current Concepts: Targeted therapy toxicities vary, but common side effects include skin rash, diarrhea, and stomatitis. Most of these side effects are mild and can be prevented and treated. Rare and dangerous side effects, including pneumonitis, cardiotoxicities, and infusion reactions, can also be induced by targeted therapies. In most cases, toxicities are low grade (grade ≤2) and can be treated effectively, but in some cases, they can be fatal without appropriate intervention. Symptoms can be nonspecific, rendering identification of early symptoms challenging. Physicians should thus be aware of these side effects and manage toxicities appropriately.Discussion and Conclusion: The side effects of targeted therapy exert a critical impact on survival and quality of life. Most patients receiving targeted therapy need help to prevent and relieve toxicities. Management of the toxicities of targeted therapy involves patient monitoring, adjusting therapeutic dose or frequency, and providing supportive care. Serious side effects require early detection and prompt intervention, including discontinuation of targeted therapy and the use of corticosteroids.

Recent advances in molecular biology and genomics have revolutionized the understanding of the intricate molecular underpinnings of cancer. Next-generation sequencing analysis now allows identification of specific actionable genetic alterations. This breakthrough has paved the way for precision medicine in oncology, redefining the conventional clinical trial landscape and enabling personalized approaches to cancer treatment.Current Concepts: The shift toward precision medicine involves a fundamental departure from the traditional Phases 1–4 clinical trial protocols. Instead of using uniform treatment pathways, personalized therapies are designed based on the genetic profiles of individual patients. Tumor-agnostic clinical trials are becoming as a prominent concept, encompassing innovative adaptive designs that adapt treatments to specific genetic variations. Master protocols such as umbrella studies, basket trials, platform studies, and master observational trials exemplify this transformation.Discussion and Conclusion: International precision medicine research is characterized by exemplar studies such as the NCI-MATCH study in the United States, the Drug Rediscovery Protocol study in the Netherlands, and the Targeted Agent and Profiling Utilization Registry study in the United States. Korean oncology research also contributed to the international effort in precision medicine through initiatives like K-MASTER and the Korean Precision Medicine Networking Group, which is making commendable contributions to the global precision medicine movements.

No abstract available.
Plasmacytoma

In allogeneic transplantation, including the B6 anti-BALB.B settings, H60 and H4 are two representative dominant minor histocompatibility antigens that induce strong CD8 T-cell responses. With different distribution patterns, H60 expression is restricted to hematopoietic cells, whereas H4 is ubiquitously expressed. H60-specific CD8 T-cell response has been known to be dominant in most cases of B6 anti-BALB.B allo-responses, except in the case of skin transplantation. To understand the mechanism underlying the subdominance of H60 during allogeneic skin transplantation, we investigated the dynamics of the H60-specific CD8 T cells in B6 mice transplanted with allogeneic BALB.B tail skin. Unexpectedly, longitudinal bioluminescence imaging and flow cytometric analyses revealed that H60-specific CD8 T cells were not always subdominant to H4-specific cells but instead showed a brief dominance before the H4 response became predominant. H60-specific CD8 T cells could expand in the draining lymph node and migrate to the BALB.B allografts, indicating their active participation in the anti-BALB.B allo-response. Enhancing the frequencies of H60-reactive CD8 T cells prior to skin transplantation reversed the immune hierarchy between H60 and H4. Additionally, H60 became predominant when antigen presentation was limited to the direct pathway. However, when antigen presentation was restricted to the indirect pathway, the expansion of H60-specific CD8 T cells was limited, whereas H4-specific CD8 T cells expanded significantly, suggesting that the temporary immunodominance and eventual subdominance of H60 could be due to their reliance on the direct antigen presentation pathway. These results enhance our understanding of the immunodominance phenomenon following allogeneic tissue transplantation.
Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology/metabolism ; CD8-Positive T-Lymphocytes/*immunology ; Epitopes, T-Lymphocyte/*immunology ; Female ; Graft Rejection/*immunology ; Interferon-gamma ; Lymphocyte Activation/immunology ; Lymphocyte Count ; Mice ; Minor Histocompatibility Antigens/*immunology/metabolism ; *Skin Transplantation ; Transplantation, Homologous

PURPOSE: With the implementation of the Act on Life Sustaining Treatment, hospice-palliative care will be extended to non-cancer diseases including the acquired immunodeficiency syndrome (AIDS). However, there are concerns about negative perceptions and prejudice toward AIDS patients. The purpose of this study was to investigate factors related with willingness to volunteer (WV) for patients with end-stage AIDS among hospice volunteers. METHODS: Participants were 326 hospice volunteers from 19 institutions. A self-administered questionnaire was employed to investigate the participants' WV for end-stage AIDS patients, and the questions were answered using an 11-point rating scale. Demographics, volunteer activity, satisfaction with hospice volunteering, knowledge of AIDS, and attitudes towards AIDS patients (i.e., fear AIDS patients, negative attitude towards AIDS patients, personal stigmatization and stigmatizing attitude) were also investigated. A multiple regression analysis was performed to examine factors associated with WV for patients with end-stage AIDS. RESULTS: WV for patients with end-stage AIDS was 2.82 points lower than that for cancer patients (P < 0.001). The multiple regression analysis showed that the higher the level of satisfaction with hospice volunteering (P=0.002) and the lower the level of “personal stigmatization” (P < 0.001), participants showed greater WV for end-stage AIDS patients. CONCLUSION: The level of satisfaction with hospice volunteering and “personal stigmatization” were factors associated with participants' WV for patients with end-stage AIDS.
Acquired Immunodeficiency Syndrome ; Delivery of Health Care ; Demography ; Hospices* ; Humans ; Prejudice ; Stereotyping ; Volunteers*

We report a 62-year-old woman with multiple myeloma associated with cryoglobulinemia accompanied by gangrene of the digits. She presented with generalized purplish net-like discoloration (livedo reticularis), which was more prominent in the lower extremities. Multiple small shallow ulcers with crusts were found in places. In addition, gangrene was observed in both ear helices, both index fingers, and several toes. The patient had monoclonal gammopathy consisting of IgG and kappa (3.95 g/dL), cryoglobulinemia, and bone marrow plasmacytosis (42%). A biopsy of a discolored skin patch on the lower leg revealed leukocytoclastic vasculitis. She was diagnosed with multiple myeloma associated with cryoglobulinemia. Immediate plasmapheresis halted the progression of the skin lesions and digital gangrene. Two cycles of thalidomide plus dexamethasone therapy led to a partial response. This case highlights the need to search for cryoglobulinemia and multiple myeloma when we see livedo reticularis or multiple skin ulcers with obscure causes.
Biopsy ; Bone Marrow ; Cryoglobulinemia ; Dexamethasone ; Ear ; Female ; Fingers ; Gangrene ; Humans ; Immunoglobulin G ; Leg ; Livedo Reticularis ; Lower Extremity ; Middle Aged ; Multiple Myeloma* ; Paraproteinemias ; Plasmapheresis ; Skin ; Skin Ulcer ; Thalidomide ; Toes ; Ulcer ; Vasculitis*

We report two cases of hemolytic uremic syndrome (HUS) associated with Escherichia coli O114. Two cases were similar and showed the same clinical courses. After prodrome of diarrhea and vomiting lasting 1-2 days, azotemia persisted for about 10 days, and during that period, the patients were on peritoneal dialysis. They recovered without any sequelae after about 15 days. Direct multiplex PCR of stool culture revealed eae and stx2 gene and the result of ELISA done on the colony positive of eae gene confirmed Escherichia coli O114. This is the first report of HUS associated with Escherichia coli O114. We recommend, Shiga toxin producing bacterial infection must be considered and efforts should be made to scrutinize the organism in all diarrhea-prodrome HUS patients.
Azotemia ; Bacterial Infections ; Diarrhea ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli* ; Escherichia* ; Hemolytic-Uremic Syndrome* ; Humans ; Multiplex Polymerase Chain Reaction ; Peritoneal Dialysis ; Shiga Toxin ; Vomiting

Background/Aims: Recent changes in the diagnostic criteria for myeloproliferative neoplasms (MPNs) and increasing patient numbers necessitate updating of the data on vascular events in patients with such disorders. Methods: In this single-center study, thrombotic and hemorrhagic events were retrospectively analyzed in patients diagnosed with essential thrombocythemia (ET), polycythemia vera (PV) prefibrotic/early primary myelofibrosis (pre-PMF), or PMF, based on the 2016 World Health Organization diagnostic criteria. Results: Of a total of 335 consecutive patients (139 ET, 42 pre-PMF, 124 PV, and 30 PMF patients; 192 males and 143 females) of median age 64 years (range, 15 to 91), 112 (33.4%) experienced a total of 126 thrombotic events before diagnosis, at the time of diagnosis, or during follow-up over a median of 4.6 years (range, 0.1 to 26.5). Cerebrovascular thrombosis (18.8%) was the most common initial event, followed by coronary heart disease (10.1%) and splanchnic (1.5%) and peripheral thrombosis (1.5%). Arterial thrombosis was more common than venous thrombosis (31.3% vs. 2.1%, respectively; p = 0.001). Thrombosis was most frequent in PV patients (39.5%), followed by patients with pre-PMF (38.1%), ET (30.9%), and PMF (13.3%). Of the 112 patients who experienced thromboses, 53 (47%) and 39 (33.9%) had thrombotic events before and at the time of MPN diagnosis, respectively. Twenty-seven patients (8.1%) experienced 29 hemorrhagic events, of which gastrointestinal bleeding (n = 20) was the most common. Conclusions Most thrombotic events occurred before or at the time of diagnosis, and the prevalence of arterial thrombosis was markedly higher than that of venous thrombosis in patients with MPN.

BACKGROUND/AIMS: Renal complications related to BCR-ABL1-negative myeloproliferative neoplasms (MPNs) have not been examined fully in Asian populations. METHODS: We analyzed estimated glomerular filtration rate (eGFR) and its changes with time retrospectively in patients with BCR-ABL1-negative MPN from 2005 to 2015. RESULTS: The prevalence of chronic kidney disease (CKD) was 11% (6.6% having stage 3 and 4.4% having stage 4). In a linear regression analysis of eGFR versus time (years), overall, patients showed increased eGFR (mL/min/1.73 m2) by 0.51 (95% confidence interval [CI], –0.30 to 1.33; p = 0.22). Patients with polycythemia vera (PV), and those treated with hydroxyurea, showed statistically significant increases in eGFR (1.59; 95% CI, 0.28 to 2.90; p = 0.22 in PV; and 1.55; 95% CI, 0.56 to 2.54; p = 0.22 in treatment with hydroxyurea). In total, 17 patients (20.5%) showed rapid loss of eGFR (<–3 mL/min/1.73 m2per year). This rapid loss in eGFR was associated with a higher incidence of kidney disease (23.5% vs. 6.1%, p= 0.05) and a higher percentage of patients with high neutrophil (>7.0 × 109 /L) and high monocyte (> 0.7 × 109 /L) counts (76.5% vs. 50%, p=0.05; 52.9% vs. 28.8%, p= 0.06, respectively). More patients had high serum lactate dehydrogenase (> 500 U/L) levels (52.9% vs. 25.8%, p = 0.03) at diagnosis. CONCLUSIONS: CKD is prevalent in patients with BCR-ABL1-negative MPN. Active cytoreductive therapy has the potential to improve kidney function in BCR-ABL1-negative MPN.
Asian Continental Ancestry Group ; Diagnosis ; Glomerular Filtration Rate ; Humans ; Hydroxyurea ; Incidence ; Kidney ; Kidney Diseases ; L-Lactate Dehydrogenase ; Linear Models ; Monocytes ; Neutrophils ; Polycythemia Vera ; Prevalence ; Renal Insufficiency, Chronic* ; Retrospective Studies*

Purpose: Six forms relating to decisions on life-sustaining treatment (LST) for patients at the end-of-life (EOL) in hospital are required by the “Act on Decision of LST for Patients at the EOL.” We investigated the preparation and creation status of these documents from the database of the National Agency for Management of LST. Materials and Methods: We analyzed the contents and details of each document necessary for decisions on LST, and the creation status of forms. We defined patients completing form 1 as “self-determined” of LST, and those whose family members had completed form 11/12 as “family decision” of LST. According to the determination subject, we compared the four items of LST on form 13 (the paper of implementation of LST) and the documentation time interval between forms. Results: The six forms require information about the patient, doctor, specialized doctor, family members, institution, decision for LST, and intention to use hospice services. Of 44,381 who had completed at least one document, 36,693 patients had form 13. Among them, 11,531, 10,976, and 12,551 people completed forms 1, 11, and 12, respectively. The documentation time interval from forms 1, 11, or 12 to form 13 was 8.6±13.6 days, 1.0±9.5 days, and 1.5±9.7 days, respectively. Conclusion The self-determination rate of LST was 31% and the mean time interval from self-determination to implementation of LST was 8.6 days. The creation of these forms still takes place when the patients are close to death.