Treatment pattern of chronic lymphocytic leukemia/small lymphocytic lymphoma in Korea: a multicenter retrospective study (KCSG LY20-06)

Background/Aims@#Little attention is paid to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Korea due to the rarity of the disease. With its rising incidence, we aimed to evaluate recent changes in treatment patterns and survival outcomes of patients with CLL/SLL. @*Methods@#A total of 141 patients diagnosed with CLL/SLL between January 2010 and March 2020 who received systemic therapy were analyzed in this multicenter retrospective study. @*Results@#The median patient age was 66 years at diagnosis, and 68.1% were male. The median interval from diagnosis to initial treatment was 0.9 months (range: 0–77.6 months), and the most common treatment indication was progressive marrow failure (50.4%). Regarding first-line therapy, 46.8% received fludarabine, cyclophosphamide, plus rituximab (FCR), followed by chlorambucil (19.9%), and obinutuzumab plus chlorambucil (GC) (12.1%). The median progression-free survival (PFS) was 49.3 months (95% confidence interval [CI], 32.7–61.4), and median overall survival was not reached (95% CI, 98.4 mo– not reached). Multivariable analysis revealed younger age (≤ 65 yr) (hazard ratio [HR], 0.46; p < 0.001) and first-line therapy with FCR (HR, 0.64; p = 0.019) were independently associated with improved PFS. TP53 aberrations were observed in 7.0% (4/57) of evaluable patients. Following reimbursement, GC became the most common therapy among patients over 65 years and second in the overall population after 2017. @*Conclusions@#Age and reimbursement mainly influenced treatment strategies. Greater effort to apply risk stratifications into practice and clinical trials for novel agents could help improve treatment outcomes in Korean patients.

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea

Background@#Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. @*Methods@#An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. @*Results@#During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). @*Conclusion@#This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data. MATERIALS AND METHODS: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016. RESULTS: A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patients was 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment. CONCLUSION: Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.

A Paradigm Shift: Perioperative Iron and Erythropoietin Therapy for Patient Blood Management / 한양의대학술지

Allogeneic blood transfusion is often restricted due to its adverse effects, a lack of blood supply, and religious or cultural constraints. As a result, patient blood management (PBM) has been gaining attention. PBM is an evidence-based, patient-centered bundle of technologies that manages perioperative anemia and reduces bleeding during surgery. PBM improves the postoperative prognoses. Perioperative anemia is the main concern in PBM; therefore, to diagnose and treat it is important. This review focuses on the perioperative use of oral or intravenous iron and erythropoietin (EPO), in relevant fields such as cardiac surgery, orthopedics, and neurosurgery. IV administration of iron has been controversial due to safety concerns, such as increased risk of infection. However, using IV iron appropriately is beneficial in most surgical settings. Although recombinant human EPO may increase thromboembolic risks, this can be mitigated through various methods including limiting the target Hb level, using it in combination with IV iron, or prophylaxis for deep venous thrombosis. EPO is recommended in patients undergoing cardiac or orthopedic surgery. As PBM becomes globally implemented, the blood management methods, including tranexamic acid, hemostatic agents, and cell salvage have become more variable as well. Among them, administration of iron and EPO would be the most common pharmacologic choices based on current practice. However, controversy still exists. Therefore, further studies on iron and EPO are needed to ensure better and safer patient care.

Successful Treatment of Relapsed Acquired Amegakaryocytic Thrombocytopenia with Repeat Cyclosporine / 대한내과학회지

Acquired amegakaryocytic thrombocytopenia (AAMT) is an unusual disease characterized by severe thrombocytopenia resulting from a marked decrease in bone marrow megakaryocytes. Various pathogenic mechanisms have been suggested, and several treatments have been tried, with varying outcomes. In some case reports, cyclosporine and anti-thymocyte globulin have had good clinical results in the treat of AAMT. There are few reports on the treatment of relapsed AAMT with cyclosporine. We report a patient with relapsed AAMT who was treated successfully with an additional course of cyclosporine. The initial remission was achieved with cyclosporine 4 years earlier and a second remission was induced by cyclosporine. Cyclosporine may be effective for relapsed AAMT that previously responded to cyclosporine.

Isolated Myeloid Sarcoma Presenting as Cord Compression by Paraspinal Mass / 이화의대지

Myeloid sarcoma is a rare tumor mass consisting of immature granulocytic cells occurring in an extramedullary site or in a bone. It has often been observed during the course of an acute leukemia, myelodysplastic syndrome or myeloproliferative neoplasms, and it can involve any site of the body. However, it rarely present in the absence of bone marrow infiltration, especially for the isolated spinal myeloid sarcoma. In this report, we describe a case of isolated myeloid sarcoma that showed spinal compression. A 66-year-old male, with no underlying disease or medication history, presented with a progressive back pain and numbness in bilateral lower extremities that had begun two weeks before. He was diagnosed with myeloid sarcoma with no evidence of bone marrow involvement. Tumor cells were positive for CD34, c-KIT, and Bcl-2 on the immunohistochemical stain. He was treated with systemic chemotherapy with daunorubicin plus cytosine arabinoside and achieved a partial response.

Progression of Extramedullary Plasmacytoma in a Multiple Myeloma Patient with No Increment in Serum M Protein Level / 대한내과학회지

A 76 year-old female who was diagnosed with multiple myeloma (IgG, lambda) had received bortezomib, melphalan and prednisolone as first-line treatment. After completing six cycles of chemotherapy, her serum monoclonal protein level decreased from 7.28 g/dL to 0.65 g/dL, indicating a partial response. However, at the next scheduled visit she complained of slowly progressing dyspnea. On chest X-ray, newly developed pleural effusion was found, and rapidly progressing extramedullary plasmacytoma was detected in the anterior mediastinum on chest computerized tomography. However, there was no change in her serum monoclonal protein level. In Korea, extramedullary involvement is encountered in 5% of patients with multiple myeloma. However, evaluation of treatment response using solely the serum monoclonal protein level may not accurately reflect disease status in these patients.

Two Cases of Treatment with Intrathecal Rituximab for Primary Central Nervous System Lymphoma / 대한내과학회지

Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin's lymphoma (NHL), usually composed of diffuse large B-cells. Although rituximab is known for its curative effect on B-cell NHL, data on the use of intrathecal rituximab for PCNSL are limited. In this report, we present two patients showing relapsed PCNSL with lymphomatous meningitis. Both patients were refractory to conventional methotrexate-based intrathecal chemotherapy. However, after intrathecal rituximab with or without conventional intrathecal chemotherapy, both patients showed stable disease on magnetic resonance brain imaging and cerebrospinal fluid analysis. There were no serious adverse events during each of 3 and 6 cycles with intrathecal rituximab immunotherapy.

A Case of Invasive Thymoma with Endotracheal Polypoid Growth / 결핵및호흡기질환

Thymomas are one of the most common neoplasms of the mediastinum derived from thymic epithelium. It is common that invasive thymoma invades the lung, pericardium, and great vessels. Airway compression by mass effect also occurs, but direct polypoid tumor growth into the airway is extremely rare. Only 20 cases of invasive thymoma with endobronchial polypoid growth have previously been reported globally. However, there is no case report of invasive thymoma with endotracheal growth. Herein, we report a rare case of invasive thymoma with endotracheal polypoid growth in a 28-year-old woman.

A Case of Intracardiac Thymic Carcinoma Presenting as Congestive Hepatopathy / 대한내과학회지

Thymic carcinoma is a rare but aggressive epithelial neoplasm with a strong propensity for early local invasion and widespread metastasis. It is common for thymic carcinomas to invade the lungs, pericardium, and great vessels. However, invasion of thymic carcinoma into the right atrium, right ventricle, mediastinum, and superior vena cava is very rare. There have been sporadic reports on intracardiac thymic carcinomas globally and only one case report in South Korea to date. We herein report a case of intracardiac thymic carcinoma presenting as right-sided heart failure with congestive hepatopathy.

Imatinib-Mesylate Induced Interstitial Pneumonitis in Two CML Patients / 결핵및호흡기질환

Imatinib mesylate, a selective inhibitor of BCR-ABL kinase activity, has demonstrated significant clinical efficacy in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). It has become the standard of treatment for these diseases. Although the toxicity profile of imatinib is superior to that of interferon or other cytotoxic agents, some adverse events including edema, gastrointestinal toxicities and hematologic toxicities are commonly observed in the patients treated by imatinib. We present two cases of imatinib induced interstitial pneumonitis during the treatment of a chronic phase of CML.

Primary Cardiac Lymphoma Presenting With Atrioventricular Block

Primary cardiac lymphomas (PCL) are extremely rare. Clinical manifestations may be variable and are attributed to location. Here, we report on a case of PCL presenting with atrioventricular (AV) block. A 55 year-old male had experienced chest discomfort with unexplained dyspnea and night sweating. His initial electrocardiogram (ECG) revealed a first degree AV block. Along with worsening chest discomfort and dyspnea, his ECG changed to show second degree AV block (Mobitz type I). Computed tomography (CT) scan showed a cardiac mass (about 7 cm) and biopsy was performed. Pathologic finding confirmed diffuse large B-cell lymphoma. The patient was treated with multi-drug combination chemotherapy (R-CHOP: Rituximab, cyclophoshamide, anthracycline, vincristine, and prednisone). After treatment, ECG changed to show normal sinus rhythm with complete remission on follow-up CT scan.

Korean Patients with Superwarfarin Intoxication and Their Outcome

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.

A Case of Hantavirus Pulmonary Syndrome Mimicking Apalastic Anemia with Invasive Aspergillosis

Hantavirus is known to a causative agent of hemorrhagic fever with renal syndrome and it can cause hantavirus pulmonary syndrome, a rare disease in Korea. Hantavirus pulmonary syndrome is usually associated with pulmonary hemorrhage and fever. The common hematologic features of this syndrome are elevated hematocrit level, leukocytosis and thrombocytopenia. We report a case of hantavirus pulmonary syndrome with pancytopenia. This patient with severe neutropenia with pulmonary infiltration mimicked aplastic anemia with invasive aspergillosis.

Gemcitabine and Carboplatin Combination Chemotherapy for Elderly Patients with Advanced Non-small Cell Lung Cancer: A Feasibility Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although platinum based chemotherapy is known to improve the survival duration for the patients with non-small cell lung cancer, the role of platinum for elderly patient is not yet clear. We administered gemcitabine and carboplatin combination therapy to elderly patients with NSCLC. The aim of this study was to evaluate the efficacy and toxicities of this regimen for elderly patients. MATERIALS AND METHODS: The eligibility criteria were as follows: pathologically confirmed NSCLC, an age > or = 65 years, advanced disease with stage IIIB or IV and the patients were chemotherapy-naive. The treatment regimen was as follows; gemcitabine 1,000 mg/m2 was administered on days 1 and 8 and carboplatin AUC=5 was administered on day 1. This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of the response rate, the time to progression and the overall survival duration. RESULTS: From Dec 2001 to Feb 2005, a total of 20 pa-tients were entered into this study. The median patient age was 68 years (range: 65~75). 19 patients were evaluable for their treatment response. A partial response was obtained in 8 patients (response rate: 42.1%, 95% CI: 19.4~64.8%). The median time to progression and the survival duration were 136 days and 453 days, respectively. Among a total of 65 cycles of treatment, grade 3 or 4 leukopenia and thrombocytopenia were observed in 7.7% and 13.9% of the cycles, respectively. Grade 3 or 4 vomiting was observed in 7.7% of the cycles. Grade 3 skin rash developed in 1.5% of the cycles. 1 patient died of septic shock after chemotherapy. CONCLUSIONS: Gemcitabine and carboplatin combination chemotherapy was relatively safe and effective for treating elderly patients with NSCLC.

A Phase II Trial of Paclitaxel, 5-fluorouracil (5-FU) and Cisplatin in Patients with Metastatic or Recurrent Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We wanted to assess the effectiveness and safety of combination chemotherapy with paclitaxel, 5-fluorouracil (5-FU) and cisplatin for treating advanced gastric cancer. MATERIALS AND METHODS: Patients with metastatic or recurrent gastric cancer were entered into this study. Paclitaxel at a dose of 135 mg/m2 on day 1, 5-FU 1 g/m2/ day in a 24 hour continuous infusion from day 1 to day 4 and cisplatin 60 mg/m2 on day 1 were administered. This regimen was repeated every 3 weeks. RESULTS: A total of 34 patients were enrolled in this study. Among them, 33 patients were finally evaluable for their response. 17 (51.5%) patients had a partial response (95% CI: 26.0~77.0%). The median duration of overall survival was 13.2 months. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15.2% and 1.1% of all the cycles, respectively. Grade 3 stomatitis and neurotoxicity were observed in 20.6% and 1.1% of all patients, respectively. Grade 4 non-hematologic toxicity was not observed. CONCLUSIONS: The regimen of paclitaxel, 5-FU and cisplatin demonstrated activity and accepatable toxicity for treating metastatic gastric cancer.

Combination chemotherapy with topotecan and vincristine for patients with refractory or recurrent small cell lung cancer / 대한내과학회지

BACKGROUDN: Small cell lung cancer (SCLC) is a chemotherapy-sensitive tumor. However, the duration of response is usually short and most patients experience relapses. Topotecan is commonly used for treatment of these patients. Nevertheless, the response rate of topotecan as a single regimen is only about 20% and the resulting severe myelosuppression is troublesome. Vincristine is also an active agent, and it does not compromise the marrow function. In this background, we evaluated the efficacy and toxicities of topotecan and vincristine combination chemotherapy. METHODS: Patients with pathologically confirmed SCLC refractory to or recurrent after platinum-based chemotherapy were eligible for this study. The treatment regimen was as follows; topotecan 1.5 mg/m2/day IV bolus on day 1, 2 and 3 and vincristine 1.5 mg/m2 (maximum 2 mg on day 1 (on every cycle)) and day 2 (on odd cycles only). This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of response rate, time to progression and overall survival duration. The toxicities were assessed according to NCI-CTC version 3.0. RESULTS: A total of 19 patients were entered into this study. The median age was 63 years (range 43-85 years). Partial response was obtained for 3 patients (response rate 15.8%, 95% CI: 0-32.5%). The median time to progression and survival duration was 51 days and 199 days, respectively. For a total of 52 cycles of treatment, grade 3 or 4 neutropenia and thrombocytopenia were observed in 25.0% and 11.5% of the patients, respectively. Grade 2 neurotoxicities were observed in 15.4% of the patients. There was no treatment-related mortality. CONCLUSIONS: The topotecan and vincritine combination is active and safe for patients with recurrence or refractory SCLC. However, the benefit of adding vincristine to topotecan needs to be confirmed in further studies.

The Clinical Efficacy of Helicobacter pylori Eradication in Patients with Helicobacter pylori-positive Chronic Thrombocytopenic Purpura

BACKGROUND: Helicobacter pylori (H. pylori) have been implicated in the pathogenesis of some autoimmune diseases including idiopathic thrombocytopenic purpura (ITP). Several studies have recently shown a high prevalence of H. pylori infection in patients with ITP, and reported platelet recovery after bacterial eradication therapy. The prevalence of H. pylori infection, and the effect of its eradication, in Korean patients with chronic ITP were investigated. METHODS: The study included 35 patients, from 8 hospitals, with chronic ITP. The H. pylori infection was assessed by the urea breath test, rapid urease test or microbial culture. H. pylori eradication was performed with the amoxicillin, clarithromycin and omeprazole regimen for 7 days, or the bismuth, metronidazole and tetracycline regimen for 10 days. Eradication was assessed by urea breath test 4 weeks after treatment. Platelet counts were monitored serially after the end of treatment. RESULTS: Thirty five patients with chronic ITP were evaluated, including 12 males and 23 females, with a median age of 57 years (range 30~79). The median platelet count before eradication was 23,000/microliter (range 4,000~66,000/microliter). Sixteen patients had previously undergone a splenectomy. The H. pylori infection was found in 23 (65%) of the 35 patients. Eradication, was performed in 21 patients, and 6 (28.5%) had a significant increase in their platelet counts after both 2 weeks and 2 months. The median response duration was 7.6 months, ranging from 1~27 months. CONCLUSION: This study confirmed the efficacy of H. pylori eradication in increasing the platelet count in adult chronic ITP patients. The investigation and eradication of H. pylori infection in ITP patients must be considered a simple and inexpensive tool in management of this chronic disease.

A Case of Extramedullary Progression Despite of Serologic Improvement in a Patient Treated with Thalidomide for Multiple Myeloma

Thalidomide is an anti-angiogenic agent widely used in patients with multiple myeloma. The response to therapy is commonly monitored using serum and/or urine M protein, as these are known to reflect the tumor burden. Although extramedullary plasmacytomas are tissues with high neovascularization, it has been suggested in some reports that the response to thalidomide in these patients may be inferior, despite changes in the serum M protein level. Herein, we report the case of a patient who newly developed hepatosplenic extramedullary plasmacytoma, despite reduction in the serum M protein level following thalidomide treatment.

A Phase II Study of Combination Chemotherapy with Gemcitabine, 5-fluorouracil, and Cisplatin for Advanced Pancreatic Cancer / 대한소화기학회지

BACKGROUND/AIMS: Gemcitabine has been the standard regimen for advanced pancreatic cancer, but the effect on the response rate and survival is still disappointing, leading to many trials of combination chemotherapy. 5-FU and cisplatin were combined with gemcitabine in this trial, as they are synergistic with gemcitabine and each other as well. This study was aimed to assess the effectiveness and safety of combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer. METHODS: Patients with advanced pancreatic cancer were entered into this study. Gemcitabine at a dose of 800 mg/m2 on day 1 and 8, 5-FU 1,000 mg/m2/day from day 1 to 3 for 72 hours, and cisplatin 60 mg/m2 on day 2, 24 hours after the start of gemcitabine were administered every 3 weeks. RESULTS: From December 2001 to January 2004, twenty patients were enrolled in this study. Among 17 of these patients assessable, 3 patients had a partial remission with the response rate of 17.7% (95% confidence interval, 6.2-41.0%). The median time to disease progression was 230 days and median duration of survival was 322 days. Among total of 91 cycles, leukopenia, neutropenia, and thrombocytopenia of grade 3 or 4 occurred in 12 cycles (13.2%), 12 cycles (13.2%), and 23 cycles (24.4%), respectively. Grade 3 or 4 mucositis developed at 2 cycles (2.2%), and nausea and vomiting were encountered in 3 cycles (3.3%). CONCLUSIONS: Combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer is active and well-tolerated, warranting a phase III study.