Cyclophosphamide, Bortezomib, and Dexamethasone Consolidation in Patients with Multiple Myeloma after Stem Cell Transplantation: The KMM130 Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#A three-drug combination of cyclophosphamide, bortezomib, and dexamethasone (CVD) shows significant efficacy and manageable toxicity as induction therapy in patients with multiple myeloma. @*Materials and Methods@#In this phase II study, we enrolled 45 patients who achieved a very good partial response (VGPR) or partial response (PR) after autologous stem cell transplantation (ASCT) and evaluated the efficacy and toxicity of CVD consolidation. CVD consolidation comprised three cycles of cyclophosphamide 300 mg/m2 orally on days 1, 8, and 15, and bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, and 22, along with dexamethasone 20 mg orally or intravenously on days 1 and 2, 8 and 9, 15 and 16, and 22 and 23. @*Results@#At enrollment, 39 patients (86.7%) showed VGPR, and nine (13.3%) presented with PR. Nineteen patients (45.2%) achieved a complete response or better as their best response after the end of consolidation. Overall, 22 of 42 patients (52.4%) experienced an improved response status with CVD consolidation. Three-year overall survival and progression-free survival rates were 89.0% and 42.7%, respectively. The most common non-hematologic toxicities were peripheral neuropathy and infection (20.5%), with no grade ≥ 3 neuropathy observed. @*Conclusion@#These results showed that CVD consolidation therapy improved the response with reasonable toxicity in patients with residual disease after ASCT. This trial was registered with the Clinical Research Information Service, Republic of Korea (KCT0001327).

Real-World Treatment Patterns and Clinical Outcomes in Korean Patients With AML Ineligible for First-Line Intensive Chemotherapy: A Subanalysis of the CURRENT Study, a Non-Interventional, Retrospective Chart Review

Background@#Although most elderly patients with acute myeloid leukemia (AML) are ineligible for intensive chemotherapy (ICT), treatment options remain limited. CURRENT (UMIN000037786), a real-world, non-interventional, retrospective chart review, evaluated clinical outcomes, clinicopathologic characteristics, and treatment patterns in these patients.We present results from a subanalysis of Korean patients in this study. @*Methods@#Patients were aged ≥ 18 years with primary or secondary AML ineligible for ICT who initiated first-line systemic therapy or best supportive care (BSC) between 2015 and 2018 across four centers in Korea. Primary endpoint was overall survival (OS) from diagnosis.Secondary endpoints included progression-free survival (PFS), time to treatment failure, and response rates. Data analyses were primarily descriptive, with time-to-event outcomes estimated using the Kaplan-Meier method, and Cox regression used to determine prognostic factors for survival. @*Results@#Among 194 patients enrolled, 84.0% received systemic therapy and 16.0% received BSC. Median age at diagnosis was 74 and 78 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 was reported in 73.0% and 48.4% of patients, respectively;poor cytogenetic risk was reported in 30.1% and 16.1% of patients. Median OS was 7.83 vs.4.50 months, and median PFS was 6.73 vs. 4.50 months in the systemic therapy vs. BSC groups. Prognostic factors affecting OS included secondary AML (hazard ratio, 1.67 [95% confidence interval, 1.13–2.45]), ECOG performance status ≥ 2 (2.41 [1.51–3.83]), poor cytogenetic risk (2.10 [1.36–3.24]), and Charlson comorbidity index ≥ 1 (2.26 [1.43–3.58]). @*Conclusion@#Clinical outcomes are poor in Korean patients with AML ineligible for ICT who are prescribed current systemic therapies or BSC. There is a substantial unmet need for novel agents (monotherapy or in combination) to improve clinical outcomes in this patient population.

Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia

Background/Aims@#We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). @*Methods@#We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. @*Results@#The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. @*Conclusions@#Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

How myeloproliferative neoplasms patients’ experience and expectations differ from physicians’: the international MPN Landmark survey

Background/Aims@#Recent advances in the understanding of the pathophysiology of myeloproliferative neoplasms (MPN) were not paralleled with advances in treatment options; thus many questions regarding optimal MPN management remain unanswered. Here, we report the results of descriptive survey study of Korean MPN patients and their attending physicians. @*Methods@#A total of 105 Korean patients (myelofibrosis [MF], 39; polycythemia vera [PV], 25; essential thrombocythemia [ET], 41) and 30 physicians completed the Landmark Health Survey, then data from the survey were analyzed. @*Results@#Among the MPN-Symptom Assessment Form symptoms, the most severe symptom reported was ‘fatigue or tiredness’ in MF and ET patients and ‘itching’ in PV patients. The majority of the patients agreed that MPN reduced their quality of life (QoL). Interestingly, physicians gave higher scores regarding the impact of MPN on patient’s daily and social life compared to patients themselves. For patients, the most important treatment goal was symptom improvement regardless of MPN subtype, while for physicians the highest priority for treatment was better QoL regardless of MPN subtype. Generally, both patients and physicians were satisfied with the overall treatment/management of MPN and communications. However, many patients felt there was not enough time during the appointment for discussion, while many physicians felt they lacked effective drugs to offer to their patients. @*Conclusions@#Our study suggests there are room for better-standardized monitoring of symptoms and treatment options and those continuous efforts to bridge the gap between patients and physicians are necessary for better care of MPN patients.

Incidence of Venous Thromboembolism: The 3 rd Korean Nationwide Study

Background@#The incidence of venous thromboembolism (VTE) has gradually increased in the Korean population. This study aimed to evaluate the annual age- and sex-adjusted incidence rates (ASR) of VTE and anticoagulation trends between 2014 and 2018. @*Methods@#Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified VTE patients between 2014 and 2018 using both diagnostic and medication anticoagulant codes assigned within 6 months of the initial index event. Anticoagulant patterns were classified as follows: direct oral anticoagulants (DOAC), panticoagulants, warfarin, and mixed anticoagulation regimens. @*Results@#We identified 95,205 patients with VTE (female, 56.8%). The ASR for VTE per 100,000 person-years increased from 32.8 in 2014 to 53.7 cases in 2018 (relative risk of 1.63; 95% confidence interval, 1.6–1.67). The VTE incidence rates were 25 times higher in the ≥ 80 group than in the 30s group. VTE occurred 1.29 times more often in women than in men. The proportion of DOAC prescriptions increased from 40.5% to 72.8%, whereas warfarin prescriptions decreased from 27% to 5.6% in 2014 and 2018. @*Conclusion@#In Korea, the ASRs of VTE continued to increase since 2014, but the rate of increase slowed in 2018. The VTE occurred more often in the elderly and in women. Five years after the introduction of DOACs in 2013, they accounted for 73% of all anticoagulants used to treat VTE.

Recent advances in the management of immune-mediated thrombotic thrombocytopenic purpura

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially life-threatening thrombotic microangiopathy caused by autoantibody-mediated severe ADAMTS13 deficiency. TTP should be suspected in patients with microangiopathic hemolytic anemia and thrombocytopenia without a definite cause. Early detection of iTTP and prompt treatment with plasma exchange and corticosteroids are essential. Rituximab administration should be considered for refractory or relapsed iTTP, and can be used as a first-line adjuvant or preemptive therapy. Treatment with caplacizumab, a novel anti-von Willebrand factor nanobody, resulted in a faster time to platelet count response, significant reduction in iTTP-related deaths, and reduced incidence of refractory iTTP. TTP survivors showed a higher rate of chronic morbidities, including cardiovascular disease and neurocognitive impairment, which can lead to a poor quality of life and higher mortality rate. Meticulous long-term follow-up of TTP survivors is crucial.

R-MPV followed by high-dose chemotherapy with thiotepa-based and autologous stem cell transplantation for newly diagnosed primary central nervous system lymphoma: a single-center experience

Background@#High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as a consolidation treatment is a promising approach for eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL). @*Methods@#In this retrospective analysis, 22 patients with newly diagnosed PCNSL received chemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Those who showed complete or partial response subsequently received consolidation HDC-ASCT with a thiotepa-based conditioning regimen but did not undergo radiotherapy. @*Results@#The PCNSL patients had a median age of 57 years (range, 49‒67 yr); of the total patients, 9.1% had a performance status of 2 or higher, and 72.1% had multiple lesions.Approximately 82% of patients received six cycles of induction chemotherapy, which was well tolerated with excellent disease control. The rate of confirmed or unconfirmed complete response increased from 45.5% at the period of interim analysis to 81.8% prior to the initiation of HDC-ASCT. With a median follow-up of 19.6 months (range, 7.5‒56.5 mo), the 2-year progression-free survival and overall survival estimates were 84% and 88%, respectively. No treatment-related deaths occurred. Grade 3 toxicity was recorded in 90.9% of the patients after undergoing the HDC-ASCT, and the most common grade 3 adverse event was febrile neutropenia without sepsis. @*Conclusion@#The discussed treatment approach is feasible in patients with newly diagnosed PCNSL, yielding encouraging results.

Guidelines for Safe Drug Use / 대한내과학회지

Background/Aims@#In Korea, medications are available by prescription from a physician, or can be purchased over-the-counter (OTC) without a prescription. Education regarding both prescribed and OTC drugs is important to minimize side effects and avoid drug abuse. The risk of side effects due to polypharmacy is increasing due to the growing number of elderly patients with comorbidities. @*Methods@#There are various clinical guidelines for physicians, but it is difficult for patients and their caregivers to find published guidelines regarding drug use. In this regard, experts from nine subspecialties of internal medicine, geriatric medicine, and guideline development methodology formed a working group to develop guidelines for safe drug use under the Clinical Practice Guidelines Committee of the Korean Association of Internal Medicine. @*Results@#The main contents of this guideline are 1) safe and effective drug administration, 2) the proper use of analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs), 3) the proper use of tranquilizers and sleeping pills to prevent drug abuse, 4) points to be aware of when taking multiple medications. @*Conclusions@#The guidelines were developed for patients and their caregivers to understand the general principles and precautions for drug use, including commonly used painkillers, mood stabilizers, sleeping pills, and polypharmacy. These guidelines could also be used as educational materials for physicians, nurses, and healthcare workers to educate patients and their caregivers.

Guidelines for Safe Drug Use / 대한내과학회지

Background/Aims@#In Korea, medications are available by prescription from a physician, or can be purchased over-the-counter (OTC) without a prescription. Education regarding both prescribed and OTC drugs is important to minimize side effects and avoid drug abuse. The risk of side effects due to polypharmacy is increasing due to the growing number of elderly patients with comorbidities. @*Methods@#There are various clinical guidelines for physicians, but it is difficult for patients and their caregivers to find published guidelines regarding drug use. In this regard, experts from nine subspecialties of internal medicine, geriatric medicine, and guideline development methodology formed a working group to develop guidelines for safe drug use under the Clinical Practice Guidelines Committee of the Korean Association of Internal Medicine. @*Results@#The main contents of this guideline are 1) safe and effective drug administration, 2) the proper use of analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs), 3) the proper use of tranquilizers and sleeping pills to prevent drug abuse, 4) points to be aware of when taking multiple medications. @*Conclusions@#The guidelines were developed for patients and their caregivers to understand the general principles and precautions for drug use, including commonly used painkillers, mood stabilizers, sleeping pills, and polypharmacy. These guidelines could also be used as educational materials for physicians, nurses, and healthcare workers to educate patients and their caregivers.

The 2020 revision of the guidelines for the management of myeloproliferative neoplasms

In 2016, the World Health Organization revised the diagnostic criteria for myeloproliferative neoplasms (MPNs) based on the discovery of disease-driving genetic aberrations and extensive analysis of the clinical characteristics of patients with MPNs. Recent studies have suggested that additional somatic mutations have a clinical impact on the prognosis of patients harboring these genetic abnormalities. Treatment strategies have also advanced with the introduction of JAK inhibitors, one of which has been approved for the treatment of patients with myelofibrosis and those with hydroxyurea-resistant or intolerant polycythemia vera. Recently developed drugs aim to elicit hematologic responses, as well as symptomatic and molecular responses, and the response criteria were refined accordingly. Based on these changes, we have revised the guidelines and present the diagnosis, treatment, and risk stratification of MPNs encountered in Korea.

Updated recommendations for the treatment of venous thromboembolism

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants.The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

Prominent seasonal variation in pulmonary embolism than deep vein thrombosis incidence: a Korean venous thrombosis epidemiology study

Background/Aims@#Seasonal variation is an environmental factor proposed to affect the incidence of venous thromboembolism (VTE). However, VTE seasonal variation is not well studied in Asian populations, which have different genetic determinants of VTE compared to Westerners. The present study aimed at investigating seasonal variation of VTE occurrence and the effect of various demographic factors (i.e., age, sex, and co-morbidities) on variation. @*Methods@#VTE seasonal variation was evaluated in 59,626 index cases (from January 2009 to December 2013) in the Korean Health Insurance Review and Assessment Service database. We quantified and compared VTE occurrence across four seasons, and additionally assessed monthly through a chronobiological analysis. @*Results@#VTE incidence varied both seasonally and monthly, with new cases peaking in the winter (January and February) and the lowest incidence in the summer (August and September). After adjusting for sex, age, type of VTE, and combined cancer diagnosis, winter remained a significant independent factor driving VTE incidence. Additionally, seasonal variation was prominent in patients aged 60 years or older and in patients with pulmonary embolism, but not so prominent in patients of aged less than 60 years and patients with deep vein thrombosis. @*Conclusions@#Seasonal variation was a weak but independent contributor to VTE incidence in a Korean population diagnosed from 2009 to 2013, especially in those individuals with old age or suffering from a pulmonary embolism.

Drug use evaluation of opioid analgesics in pain management among patients with hematopoietic stem cell transplantation

Background@#Hematopoietic stem cell transplantation (HSCT) patients usually experience mucositis, musculoskeletal pain associated with high-dose chemotherapy, radiation, post-HSCT infection, or graft-versus-host disease. Pain management is important for the patients’ quality of life. We evaluated appropriate opioid analgesic use in HSCT patients to propose effective pain management strategies. @*Methods@#A retrospective analysis was conducted using electronic medical records of adult patients with HSCT treated with opioids for moderate to severe pain at Seoul National University Bundang Hospital. The numeric rating scale (NRS) was used in pain management. NRS scores of 4‒10 correspond to moderate to severe pain. Appropriate opioid analgesic use was evaluated following published cancer pain management guidelines. @*Results@#In total, 119 cases were evaluated, including 369 episodes of moderate to severe pain.Mucositis-related, musculoskeletal, and headache pain occurred in 62.6%, 25.8%, and 6.0% of episodes, respectively. Frequently used opioids were intravenous tramadol (84.9%), fentanyl patch (73.9%), and intravenous morphine sulfate (68.9%). Intravenous and topical administrations were used for mucosal pain. In total, 95.0% of patients received appropriate short-acting opioids for initial pain management, 80.5% received appropriate doses of short-acting opioids, appropriate opioids dose adjustment was done after first assessment in 95.5% of patients, and 85.6% were converted to appropriate long-acting opioids. @*Conclusion@#Short-acting opioid analgesic use for initial pain management and dose adjustment after assessment were appropriate. However, initial and conversion dosages recommended by guidelines may be difficult to implement considering the severity of HSCT patients.Pain management guidelines specific for HSCT patients should be developed in the future.

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome

BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, “41%, and 36%” for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Efficacy of parenteral glutamine supplementation in adult hematopoietic stem cell transplantation patients

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) patients need parenteral nutrition because of nausea, vomiting, and mucositis caused by conditioning regimens. The demand for glutamine increases during the HSCT period. We evaluated the effects of glutamine-containing parenteral nutrition on the clinical outcomes of HSCT patients. METHODS: In this retrospective analysis, we reviewed HSCT patients from Seoul National University from August 2013 to July 2017. Depending on their glutamine supplementation status, 91 patients were divided into 2 groups: glutamine group (N=44) and non-glutamine group (N=47). We analyzed the rate of weight change, infection (clinically/microbiologically documented), complications (duration of mucositis and neutropenia, acute graft versus host disease), and 100-days mortality in each group. RESULTS: Regarding the clinical characteristics of the patients, there were no significant differences between the 2 groups except that there was a larger proportion of myeloablative conditioning regimen in the glutamine group (P=0.005). In the glutamine group, the average number of days of glutamine use, parenteral nutrition, and mucositis was 7.6±1.4, 14.6±9.9, and 13.3±9.5, respectively. Furthermore, multivariate analysis revealed odds ratios of 0.37 (95% CI, 0.14–0.96; P=0.042) and 0.08 (95% CI, 0.01–0.98; P=0.048) for clinically documented infection and 100-days mortality, respectively, in the glutamine group. CONCLUSION: Results showed that the glutamine group had less clinically documented infection and 100-days mortality than the non-glutamine group, but the other outcomes did not show significant differences. The extended duration of glutamine supplementation according to the period of total parenteral nutrition and mucositis should be considered.

Differential impact of anti-thymocyte globulin dosing by disease risk index in alternative donor peripheral blood stem cell transplantation in patients with acute leukemia or myelodysplastic syndrome after reduced intensity conditioning

No abstract available.

Current Management of Cancer-associated Venous Thromboembolism: Focus on Direct Oral Anticoagulants

Cancer-associated venous thromboembolism (CAT) is a common complication associated with high morbidity and mortality. In accordance with major clinical trials comparing low-molecular-weight heparin (LMWH) with a vitamin K antagonist (VKA), LMWH is currently the standard treatment for CAT, owing to its efficacy for thrombosis recurrence and improved safety profile compared to VKA. Over the past few years, direct oral anticoagulants (DOACs) have emerged as potential alternative therapies to LMWH due to their convenient route of administration and predictable pharmacokinetics, but evidence for their use in CAT is inconclusive, as only a small fraction of the study populations in these trials had CAT. Recently, two large head-to-head trials comparing DOACs to LMWH in CAT patients reported comparable efficacies of DOACs with increased bleeding risk. Occasionally, CAT treatment can be challenging due to the heterogeneity of underlying malignancies and comorbidities. Renal insufficiency and gastrointestinal defects are the main obstacles in anticoagulant selection. Careful choice of treatment candidates and proper anticoagulant strategies are critical for the treatment of CAT; hence, more studies are required to address these challenges.

Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. MATERIALS AND METHODS: We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. RESULTS: The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. CONCLUSION: Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

Long-term rivaroxaban for the treatment of acute venous thromboembolism in patients with active cancer in a prospective multicenter trial

BACKGROUND/AIMS@#Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients.@*METHODS@#In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication.@*RESULTS@#Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died.@*CONCLUSIONS@#Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

Evaluation of Antiemetic Therapy for Breakthrough Nausea and Vomiting in Patients with Hematopoietic Stem Cell Transplantation

BACKGROUND: The patients receiving hematopoietic stem cell transplantation (HSCT) are known to have a high incidence of breakthrough nausea and vomiting due to the conditioning regimen. The purpose of this study was to evaluate the adequacy of antiemetic therapy for breakthrough nausea and vomiting in patients receiving HSCT and to propose an effective treatment regimen. METHODS: We retrospectively reviewed the electronic medical records of 109 adult patients. The collected data were used to identify (1) antiemetic and dosing regimens prescribed for controlling breakthrough nausea and vomiting, (2) the rate of patients who developed breakthrough nausea and vomiting, and (3) the percent of antiemetics prescribed on the day of symptom onset. Based on the National Comprehensive Cancer Network guideline, we assessed the suitability of antiemetics for breakthrough nausea and vomiting, and prescription timing. RESULTS: All patients were prescribed pro re nata antiemetics. About 40.0%, 41.4%, and 18.6% of patients were using one, two, and three or more additional drugs for breakthrough nausea and vomiting, respectively. The most frequently administered drugs were intravenous metoclopramide (43.8%) and granisetron patch (36.2%). Breakthrough nausea and vomiting occurred in 87 patients (79.1%) and they developed symptoms 320 cases. About 220 cases (68.8%) were treated with additional antiemetics on the day of symptom onset and the rate of symptom resolution was only 10.3% (9 patients). CONCLUSION: The breakthrough nausea and vomiting in patients receiving HSCT occurred very frequently and was hard to control, thus requiring more rapid and aggressive treatments.