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2.
Sci Rep ; 10(1): 1801, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019993

RESUMO

Non-vitamin K antagonist anticoagulants (NOACs) have been used to prevent thromboembolism in patients with atrial fibrillation (AF) and shown favorable clinical outcomes compared with warfarin. However, off-label use of NOACs is frequent in practice, and its clinical results are inconsistent. Furthermore, the quality of anticoagulation available with warfarin is often suboptimal and even inaccurate in real-world data. We have therefore compared the effectiveness and safety of off-label use of NOACs with those of warfarin whose anticoagulant intensity was accurately estimated. We retrospectively analyzed data from 2,659 and 3,733 AF patients at a tertiary referral center who were prescribed warfarin and NOACs, respectively, between 2013 and 2018. NOACs were used at off-label doses in 27% of the NOAC patients. After adjusting for significant covariates, underdosed NOAC (off-label use of the reduced dose) was associated with a 2.5-times increased risk of thromboembolism compared with warfarin, and overdosed NOAC (off-label use of the standard dose) showed no significant difference in either thromboembolism or major bleeding compared with warfarin. Well-controlled warfarin (TTR ≥ 60%) reduced both thromboembolism and bleeding events. In conclusion, the effectiveness of NOACs was decreased by off-label use of the reduced dose.

3.
Am J Hematol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919872

RESUMO

Patients with transplant-ineligible relapsed and refractory multiple myeloma (RRMM) have a short life expectancy, especially when they have failed both the proteasome inhibitor and immunomodulator therapies. This study aimed to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCd) in elderly patients with RRMM. This phase 2 clinical trial recruited 55 elderly patients with RRMM. The patients underwent a 28-day treatment cycle: pomalidomide (4 mg/day on days 1-21, administered orally) and cyclophosphamide (400 mg/day on days 1, 8, and 15; administered orally) plus dexamethasone. The median (range) age of the patients was 73.3 (64-86) years, and 8 (14.5%) patients who were ≥ 80 years old. Eight (14.5%) and 31 (56.4%) patients exhibited stage III (revised international staging system) and frail status (simplified frailty scale), respectively. The overall response rate (ORR) and clinical benefit rate (CBR) of PCd therapy were 58.2% and 72.7%, respectively. The median PFS and median overall survival (OS) were 6.90 months (95% CI, 4.7-9.0) and 18.48 months (95% CI, 9.4-27.6), respectively. The incidence rate of grade ≥ 3 non-hematological toxicities was 70.8%. In particular, the incidence rate of primary infection was 45.4%, including 21.8% for pneumonia, 9.0% for sepsis, and 14.6% for febrile neutropenia. In conclusion, PCd is an effective regimen for elderly patients with RRMM who had failed both bortezomib and lenalidomide treatments, but in whom the treatment-associated infection is the main cause of morbidity and mortality.

4.
Ann Hematol ; 99(2): 255-264, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897676

RESUMO

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Proteínas de Neoplasias/sangue , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína C-Reativa/metabolismo , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Recidiva , Taxa de Sobrevida , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
5.
Arch Pharm Res ; 43(1): 100-109, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31989478

RESUMO

Insufficient efficacy of current single drug therapy of cancers have led to the advancement of combination drug-loaded formulations. Specifically, polymeric micelles have been focused on as efficient injectable vehicles for the delivery of several anticancer drugs simultaneously to cancer cells. These nano delivery systems have evolved with advancements in the area of nanotechnology. The current review presents a summary of the past events that have led to the procession of nanomicelles and novel nanotechnologies for combinatorial drug delivery. It also focuses on the advantages, disadvantages, and considerations for the design of nanotechnologies for combinatorial drug delivery systems. The opportunities and challenges of nanotechnologies in drug delivery to overcome current disadvantages are also discussed. Furthermore, we have added findings regarding the trends and perspectives regarding nanotechnologies for combinatorial anticancer drug delivery.

6.
Clin Cancer Res ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941832

RESUMO

PURPOSE: Immune-checkpoint inhibitors have shown therapeutic efficacy in various malignant diseases. However, anti-programmed death (PD)-1 therapy has not shown clinical efficacy in multiple myeloma. EXPERIMENTAL DESIGN: Bone marrow (BM) mononuclear cells were obtained from 77 newly diagnosed multiple myeloma patients. We examined the expression of immune-checkpoint receptors in BM CD8+ T cells and their functional restoration by ex vivo treatment with anti-PD-1 and TGFß inhibitors. RESULTS: We confirmed the upregulation of PD-1 and PD-L1 expression in CD8+ T cells and myeloma cells, respectively, from the BM of multiple myeloma patients. PD-1-expressing CD8+ T cells from the BM of multiple myeloma patients coexpressed other checkpoint inhibitory receptors and exhibited a terminally differentiated phenotype. These results were also observed in BM CD8+ T cells specific to myeloma antigens NY-ESO-1 and HM1.24. BM CD8+ T cells from multiple myeloma patients exhibited reduced proliferation and cytokine production upon T-cell receptor stimulation. However, anti-PD-1 did not increase the proliferation of BM CD8+ T cells from multiple myeloma patients, indicating that T-cell exhaustion in multiple myeloma is hardly reversed by PD-1 blockade alone. Intriguingly, anti-PD-1 significantly increased the proliferation of BM CD8+ T cells from multiple myeloma patients in the presence of inhibitors of TGFß, which was overexpressed by myeloma cells. CONCLUSIONS: Our findings indicate that combined blockade of PD-1 and TGFß may be useful for the treatment of multiple myeloma.

7.
Blood ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31978221

RESUMO

Complement C5 inhibition is the standard of care (SoC) for patients with paroxysmal nocturnal hemoglobinuria (PNH) with significant clinical symptoms. Constant and complete suppression of the terminal complement pathway and the high serum concentration of C5 pose challenges to drug development that result in intravenous (IV) only treatment options. Crovalimab, a Sequential Monoclonal Antibody Recycling Technology (SMART) antibody was engineered for extended self-administered subcutaneous dosing of small volumes in diseases amenable for C5 inhibition. A three-part open label adaptive Phase I/II trial was conducted to assess safety, pharmacokinetics, pharmacodynamics and exploratory efficacy in healthy volunteers (Part 1), complement blockade naive (Part 2) and C5-inhibitor treated PNH patients (Part 3). 29 patients were included in Part 2 (n=10) and Part 3 (n=19). Crovalimab concentrations exceeded the pre-specified 100µg/mL level and resulted in complete and sustained terminal complement pathway inhibition in both PNH treatment naive and C5-inhibitor pretreated patients. Hemolytic activity and free C5 levels were suppressed below clinically relevant thresholds (liposome assay: <10U/mL; fC5 <50ng/mL). Safety was consistent with the known profile of C5 inhibition. As expected, formation of drug-target-drug complexes (DTDC) was observed in all 19 patients switching to crovalimab, manifesting in transient mild or moderate vasculitic skin reactions in 2/19 participants. Both events resolved under continued treatment with crovalimab. Subcutaneous 680mg (4mL) crovalimab administered once every 4 weeks provides complete and sustained terminal complement pathway inhibition in patients with PNH warranting further clinical development. (ClinicalTrials.gov identifier, NCT03157635.).

8.
Korean J Intern Med ; 35(1): 25-40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31935318

RESUMO

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.

9.
Clin Cardiol ; 43(1): 78-85, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729782

RESUMO

BACKGROUND: Age is a well-established risk factor for thromboembolic events in patients with atrial fibrillation (AF). However, the mechanism underlying the association between age and thromboembolic events in AF remains unknown. METHODS: The prognostic value of age as a risk factor for thromboembolic events was analyzed using data from the Korean National Health Insurance Service (NHIS). In a large-scale single-center registry, cardiac hemodynamic parameters were examined to elucidate the cause of increased risk of thromboembolic events in older patients. RESULTS: NHIS sample cohort data including 5896 patients with AF revealed that the risk of thromboembolic complication differed significantly according to age despite equal CHA2 DS2 -VASc score. In the registry of 2801 patients, age showed significant correlations with left atrium (LA) diameter, LA volume, E/e', pulmonary artery pressure, and LA appendage flow velocity. Older patients had a significantly higher prevalence of spontaneous echocontrast (odds ratio [OR] = 1.030; P < .001). Age (OR = 1.031; P < .001), E/e' (OR = 1.065; P = .004), and LA appendage flow velocity (OR = .988; P = .009) were significant predictors for thromboembolic events in multivariate analyses. In data from the NHIS, CHA2 DS2 -VASc score did not outperform age to predict thromboembolic events. CONCLUSIONS: Age is a significant risk factor for thromboembolic events in patients with AF, and old age is associated with adverse cardiac hemodynamics. This study suggests that older patients with AF are at high risk of thromboembolic events regardless of CHA2 DS2 -VASc score.

10.
Korean J Intern Med ; 35(1): 231-239, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30685961

RESUMO

BACKGROUND/AIMS: The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. METHODS: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. RESULTS: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was -19.0 in the bDMARD group and -12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. CONCLUSION: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

11.
Ann Hematol ; 99(2): 309-319, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872360

RESUMO

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva , República da Coreia/epidemiologia , Taxa de Sobrevida
12.
Ann Hematol ; 99(1): 213, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31844930

RESUMO

An additional affiliation for the first author was not indicated. Hyewon Lee is also affiliated with: Department of Internal Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31831372

RESUMO

BACKGROUND: For patients with multiple myeloma (MM) that relapsed after treatment with bortezomib- and lenalidomide-based regimens, there were no other treatment options in Korea until 2016. We aimed to determine the efficacy of thalidomide plus dexamethasone-based regimens in patients with relapsed/refractory MM (RRMM). PATIENTS AND METHODS: We conducted a multicenter retrospective analysis in Korea for patients with RRMM treated with thalidomide-based regimens who previously received bortezomib and immunomodulatory agents (IMiDs), including thalidomide and lenalidomide. RESULTS: In 47 patients with RRMM, the median age was 64 years and the median number of previous treatment lines, including bortezomib and IMiDs, was 3. Primary resistance to bortezomib and lenalidomide was observed in 12 (26%) and 8 (17%) patients, respectively. The most common regimen was a combination of thalidomide, cyclophosphamide, and dexamethasone. The overall response rate was 38%; 2 patients (4%) experienced a complete response, and 2 patients (4%) experienced a very good partial response. The overall response rate of patients previously exposed to thalidomide was 53%. The median progression-free survival was 5.9 months, and overall survival was 9.2 months. Patients with disease that responded to the thalidomide-based regimen had better progression-free survival compared to those who did not (median, 8.8 vs. 2.5 months; P = .008). The most common adverse events were anemia (51%) for hematologic toxicities and peripheral neuropathy (30%) for nonhematologic toxicities. CONCLUSION: Thalidomide-based regimens are potential salvage treatment options for patients with RRMM, even those with disease with prior resistance to IMiDs.

14.
Acute Crit Care ; 34(4): 263-268, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31795624

RESUMO

BACKGROUND: Left ventricular (LV) distension is a recognizable problem accompanied by subsequent complications during venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, no gold standard for LV decompression has been established, and no minimal flow requirement has been designated. Thus, we evaluated the efficacy of the 8-Fr Mullins sheath for left heart decompression during VA-ECMO in adult patients. METHODS: Left heart decompression was performed when severe pulmonary edema was detected on chest radiography or when no generation of pulse pressure followed severe LV dysfunction in patients receiving VA-ECMO. We punctured the interatrial septum and inserted an 8-Fr Mullins sheath into the left atrium via the femoral vein. The sheath was connected to the venous catheter used for ECMO. The catheter was maintained during VA-ECMO. RESULTS: The left heart decompression procedure was performed in seven of 35 patients who received VA-ECMO between February 2017 and June 2018. Three patients had acute myocardial infarction; three, fulminant myocarditis; and one, dilated cardiomyopathy. Four patients showed noticeable improvement of pulmonary edema within 3 days, and three patients with a pulse pressure of <10 mm Hg showed an increase in pulse pressure of >20 mm Hg within 24 hours from the left heart decompression procedure. All seven patients were successfully weaned from VA-ECMO. No complications related to the left heart decompression procedure occurred. CONCLUSIONS: An 8-Fr sheath may be a possible option for left heart decompression in adult patients with LV distension under VA-ECMO who are expecting recovery of LV function.

15.
Hypertens Res ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811243

RESUMO

The central hemodynamic characteristics of young adults with isolated systolic hypertension (ISH) remain controversial, particularly regarding the extent of pulse pressure amplification (PPamp) compared with that of normotensives (NTs). Given the lack of ambulatory blood pressure monitoring (ABPM)-based data, this study evaluated 509 untreated young adults (18-35 years) who had undergone ABPM during the last decade, 109 who had undergone both ABPM and SphygmoCor analysis, and 26 newly recruited NTs. The agreement rate between office BP- and ABPM-based subtype classification was alarmingly low (50.7%). ISH was distinguishable from systolic-diastolic hypertension, the predominant subtype characterized by increased central BPs and stiffened arteries. The central hemodynamic parameters were all similar between patients with ISH and white-coat hypertension (WC). ISH patients had central BPs that were, albeit higher than those of NTs, at an upper-normal level that was comparable to those of WC patients. ISH patients had similar cfPWV but significantly higher PPamp than NTs (p = 0.032). The central hemodynamic parameters of the participants were further analyzed according to central pressure waveform types (A vs. B vs. C). Type C waves were associated with the highest PPamp and lowest cfPWV, whereas type A waves were associated with the lowest PPamp and highest cfPWV. Subjects with type B waves, an intermediate form, also had considerably high PPamps. Waveform composition differed significantly across hypertension subtypes (p < 0.001). ISH patients mostly had type B or C waves (96.7%), with only 3.3% having type A waves. This study based on a refined diagnosis showed that the ambulatory ISH of young adults arises from highly elastic arteries and related robustness of PPamp and shares similar central hemodynamic characteristics with WC patients.

16.
J Clin Med ; 8(12)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766393

RESUMO

The Cockcroft-Gault (CG) formula is recommended to guide clinicians in the choice of the appropriate dosage for direct oral anticoagulants (DOACs). However, the performance of the CG formula varies depending on the patient's age, weight, and degree of renal function. We aimed to compare the validity of the CG formula with that of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) formulae for dosing DOACs. A total of 6268 consecutive patients on anticoagulants for atrial fibrillation (AF) were retrospectively investigated. Among underweight and elderly patients, the CG formula underestimated renal function compared with the non-CG formulae. However, the concordant rate of drug indications between the CG and the non-CG formulae was approximately 94%. On-label uses under the three formulae were associated with a lower risk of major bleeding (but not thromboembolism) compared to warfarin. Although we found differences in estimating renal function and the proportions of drug indications between the CG and non-CG formulae, the risks of thromboembolism and major bleeding were similar to those with warfarin regardless of which formula was used.

17.
J Am Heart Assoc ; 8(21): e012697, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31668140

RESUMO

Background Stroke and thromboembolic events may still occur in "clinically low-risk" atrial fibrillation (AF) patients as categorized by CHA2DS2-VASc score. Our aim was to assess the proportion of "clinically low-risk" patients using a nongender CHA2DS2-VASc (ie, CHA2DS2-VA) score of 0 to 1 among patients who experienced AF-associated stroke and to identify markers associated with stroke in "clinically low-risk" patients. Methods and Results We retrospectively recruited nonvalvular AF patients who experienced embolic stroke between 2013 and 2016 from 9 institutes in Korea. AF patients with CHA2DS2-VA score of 0 to 1 at the time of stroke were analyzed and compared with "clinically low-risk" AF patients without stroke. A total of 3033 subjects with AF-associated stroke were recruited. Of these, 583 patients (19.2%) had CHA2DS2-VA score of 0 to 1. On multivariate analysis, age (≥60 years), N-terminal pro B-type natriuretic peptide (≥300 pg/mL), creatinine clearance (<50 mL/min), and left atrial dimension (≥45 mm) were independently associated with stroke. With the combined application of these 4 factors (collectively, ABCD score) to the "clinically low-risk" patients, the c-index was 0.858 (95% CI 0.838-0.877; P<0.001). Conclusions The present study suggests a new insight into how additional use of markers can further refine stroke risk differentiation among AF patients initially classified as "clinically low-risk." Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03147911.

18.
Blood Cancer J ; 9(10): 83, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594919

RESUMO

Pomalidomide is a third generation immunomodulatory drug which in combination with dexamethasone, has been shown to be active in relapsed/refractory multiple myeloma. However, the data in Asian patients remain limited. We conducted a prospective phase two clinical trial in major cancer centers in Singapore, South Korea, Taiwan, Japan and Hong Kong to assess the efficacy and safety of pomalidomide and dexamethasone combination (PomDex) +/- cyclophosphamide in Asian patients with relapsed/refractory multiple myeloma who failed lenalidomide and bortezomib. Patients were treated with pomalidomide (4 mg daily for 21 days every 4 weeks) and dexamethasone (40 mg weekly). If there is less than a minimal response after three cycles of PomDex, cyclophosphamide 300 mg/m2 can be added (PomCyDex). A total of 136 patients were enrolled. The median PFS was 9 and 10.8 months for the PomDex and PomCyDex group, respectively. The median OS was 16.3 months. This regimen appears to be active across age groups and prior lines of treatment. This combination was overall well tolerated with grade 3 and 4 adverse events of mainly cytopenias. PomDex is highly active and well-tolerated in Asian patients. The addition of cyclophosphamide can improve the response and outcomes further in patients with suboptimal response to PomDex.

19.
J Korean Med Sci ; 34(39): e258, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31602828

RESUMO

Para-Bombay phenotypes are rare blood groups that have inherent defects in producing H antigens associated with FUT1 and/or FUT2. We report the first case of para-Bombay blood type in a Southeast Asian patient admitted at a tertiary hospital in Korea. A 23-year-old Indonesian man presented to the hospital with fever and was diagnosed with a disseminated nontuberculous mycobacterium infection and anemia. During blood group typing for blood transfusion, cell typing showed no agglutination with both anti-A and anti-B reagents. Serum typing showed strong reactivity against B cells and trace agglutination pattern with A1 cells. His red blood cells failed to react with anti-H reagents. Direct sequencing of FUT1 and FUT2 revealed a missense variation, c.328G>A (p.Ala110Thr, rs56342683, FUT1*01W.02), and a synonymous variant, c.390C>T (p.Asn130=, rs281377, Se357), respectively. This highlights the need for both forward and reverse grouping.

20.
Cancer Commun (Lond) ; 39(1): 58, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619290

RESUMO

BACKGROUND: The response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III-IV CD20-positive MZL who had responded to first-line R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R-CVP warrants further investigation. METHODS: Prior to rituximab-maintenance therapy, patients received 6-8 cycles of first-line R-CVP therapy for stage III-IV MZL. Rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and vincristine (1.4 mg/m2; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1-5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R-CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m2 every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. RESULTS: 47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R-CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R-CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). CONCLUSION: Rituximab-maintenance therapy following first-line R-CVP demonstrated good PFS in patients with stage III-IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov: NCT01213095.

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