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BACKGROUND/AIM: In diffuse large B-cell lymphoma (DLBCL), sarcopenia is associated with increased side-effects of chemotherapy and poor survival, especially in elderly patients. Anemia, a complex condition resulting from cancer itself and inflammation, might have a correlation with loss of muscle mass and might also indicate a worse outcome. In this study, we aimed to investigate the association of the skeletal muscle index (SMI) at the third lumbar vertebra (L3) with hemoglobin (Hb) levels and its predictive value for the outcome of DLBCL. PATIENTS AND METHODS: The study included patients, aged 70 or older, newly diagnosed with DLBCL who received immunochemotherapy. Sex-specific L3-SMI was measured by computed tomography, and Hb levels before treatment were recorded. The Kaplan-Meier method and Cox regression model were used to analyze survival and prognostic factors. RESULTS: Anemia was correlated with a low SMI. The presence of either low L3-SMI or anemia (Hb <10.5 g/l) indicated a poor prognosis for both progression-free and overall survival. A novel score combining L3-SMI, and Hb and lactate dehydrogenase levels as independent predictive factors was proposed for treatment response, progression-free and overall survival after adjusting for International Prognostic Index. CONCLUSION: This study highlights the importance of sarcopenia and anemia in patients with DLBCL, particularly in the elderly population. The proposed novel score combining L3-SMI, Hb, and lactate dehydrogenase may provide additional prognostic information for patients with DLBCL, aiding in treatment decisions and management.
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Anémie , Lymphome B diffus à grandes cellules , Sarcopénie , Mâle , Femelle , Humains , Sujet âgé , Sarcopénie/complications , Sarcopénie/diagnostic , Muscles squelettiques/anatomopathologie , Pronostic , Lymphome B diffus à grandes cellules/complications , Lymphome B diffus à grandes cellules/traitement médicamenteux , Anémie/complications , Lactate dehydrogenases , Études rétrospectivesRÉSUMÉ
BACKGROUND: Persistent false lumen (FL) perfusion with aneurysmal formation is common after thoracic endovascular aortic repair (TEVAR) for typical extended aortic dissection and is associated with poor outcomes. Endovascular FL embolization (FLE) has recently been tried for treatment of postdissection aortic aneurysm (PDAA). However, most reports address thoracic rather than abdominal FLE. In this study, we present the results of abdominal FLE in patients with residual patent abdominal FL following stent-graft repair for aortic dissection. METHODS: Between 2015 and 2019, 24 patients (mean age: 56.7 ± 11.8 years, range: 40-84 years, 18 male) received endovascular abdominal FLE using vascular plugs, coils, or candy plugs as the main surgery (5 patients) or auxiliary procedure (19 patients) after earlier stent-graft repair for aortic dissection (Type A: 9, Type B: 15). The medical records were reviewed and aortic remodeling was examined comparing the preembolization computed tomography (CT) and the most recent CT before reintervention. RESULTS: Technical success was achieved without any intraoperative complications, early morbidity, or mortality. Median follow-up was 34.4 months (range: 12-71). Regarding thoracic FL, 15 patients exhibited complete thrombosis before the procedure and did not change status thereafter except for 1 patient with distal stent-graft-induced new entry. In the other 9 patients, 6 exhibited increased thrombosis. With regard to the abdominal aorta, increased FL thrombosis only occurred in 8 patients with 3 (12.5%) achieving complete thrombosis. The maximal thoracic aortic diameter did not change (1.4 ± 5.6 mm) statistically, but the abdominal diameter increased significantly (4.3 ± 3.7 mm, p < 0.005). CONCLUSION: From our results, abdominal FLE is a safe procedure. However, covering all the re-entry tears is complex and the possibility of complete FL thrombosis is low. The abdominal aortic diameter appears to become enlarged in these patients. Continuous follow-up is necessary after FLE.
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Anévrysme de l'aorte thoracique , , Implantation de prothèses vasculaires , Procédures endovasculaires , Thrombose , Humains , Mâle , Adulte , Adulte d'âge moyen , Sujet âgé , Anévrysme de l'aorte thoracique/chirurgie , Résultat thérapeutique , /chirurgie , Endoprothèses , Thrombose/chirurgie , Études rétrospectivesRÉSUMÉ
BACKGROUND: Pump exchange surgery of left ventricular assist device (LVAD) has been demonstrated in several studies; however, information for Asian patients was limited. CASE PRESENTATION: A 63-year-old man underwent a pump upgrade from HeartMate II to HeartMate 3 for driveline damage through limited left anterior thoracotomy and lower partial sternotomy. He did not experience any hemodynamic adverse events or device malfunction during postoperative follow-ups of 12 months. We also reviewed all published cases with HeartMate II exchange to HeartMate 3. CONCLUSIONS: The case demonstrated that it was safe and feasible to perform HMII LVAD exchange to HM3 through a limited approach for Asian patients.
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Dispositifs d'assistance circulatoire , Mâle , Humains , Adulte d'âge moyen , Dispositifs d'assistance circulatoire/effets indésirables , Période postopératoire , SternotomieRÉSUMÉ
Background: A combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard treatment for diffuse large B-cell lymphoma (DLBCL). However, no standard treatment has been established for older patients (age ≥ 75 years). This study retrospectively analyzed different treatment strategies in older patients with DLBCL with different chemotherapy regimens and compared the survival rate of patients using oral or intravenous form cyclophosphamide and etoposide in a single center. Methods: We reviewed the records of older patients with DLBCL, aged ≥ 75 years, from January 2010 to August 2019. The different treatment combinations, clinical characteristics, response rates, and toxicity profiles were analyzed. The median overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier (KM) method. Cox regression model was used to identify the risk factors. Results: Eighty-four patients were included. One-quarter of the patients received cytoreduction treatment because of their poor medical condition at the time of diagnosis. Twenty-six percent of the patients were aged ≥ 85 at the time of diagnosis and 46.7% completed the treatment course. Patients receiving non-anthracycline-containing (non-ACR) treatment had worse Charlson comorbidity index, worse PFS, lower body mass index, or were older. The mean anthracycline accumulative dose in the anthracycline-containing (ACR) group was 134 mg/m2. The median OS was 17.2 months and median PFS was 7.7 months. The PFS of R-CHOP is better than R-mini-CHOP and R-CVOP without statistical significance, but OS of R-CHOP is not better than the other regimens. Conclusion: The toxicity, efficacy, and KM curve for OS and PFS in the non-ACR group were lower compared to ACR group, without statistical significance. R-CVOP had similar OS with R-mini-CHOP in our study. The result does not mean etoposide could totally substitute for anthracycline, but etoposide did have lower early progression rate (12.5%), and it may be an option for frail patients with comorbidity. Oral form cyclophosphamide and etoposide could be considered as a substitute for intravenous administration because of the similar effect and toxic profile.
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Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.
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Antinéoplasiques , Leucémie myéloïde chronique BCR-ABL positive , Leucopénie , Thrombopénie , Antinéoplasiques/effets indésirables , Humains , Leucémie myéloïde chronique BCR-ABL positive/diagnostic , Leucémie myéloïde chronique BCR-ABL positive/traitement médicamenteux , Leucopénie/induit chimiquement , Chromosome Philadelphie , Inhibiteurs de protéines kinases/usage thérapeutique , Pyrimidines , Taïwan/épidémiologie , Thrombopénie/induit chimiquement , Résultat thérapeutiqueRÉSUMÉ
Complete disease journey and risk factors for poor outcomes are needed to facilitate effectiveness evaluations of new therapies and clinical decision-making in B-cell Non-Hodgkin lymphoma (B-NHL), particularly in Asia where such data are lacking. This retrospective cohort study used electronic medical records from a regional medical centre in southern Taiwan to follow-up 441 patients newly diagnosed with common B-NHL subtypes: Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone Lymphoma (MZL), Mantle Cell Lymphoma (MCL), and Waldenström macroglobulinemia (WM), between 01-Jan-2008 and 31-Dec-2013, until 31-Dec-2017. Treatment pathways were modelled using a Markov approach. Stage III/IV disease at diagnosis was frequent for patients with DLBCL, FL, MCL and WM. Hepatitis B surface antigen/hepatitis C virus seropositivity was 18.6%/12.3%. Clinical responses to 1st-line treatment were observed in 76.0% (DLBCL), 87.3% (FL), 86.0% (MZL), 60.0% (MCL), and 42.9% (WM) of patients. For DLBCL, disease control was achieved by ~ 50% after 1st-line, ~ 24% after 2nd-line, ~ 17% after 3rd-line. Patients with Stage III/IV DLBCL or age > 65 years at diagnosis had lower rates of active treatment, poorer disease control and higher mortality than patients with early stage disease or age ≤ 65 years. Disease flare < 6 months after 1st-line treatment was significantly associated with mortality. Despite good clinical response rates for some sub-types, survival remains poor. New treatments are needed to improve the outcome of B-NHL.
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Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Leucémie chronique lymphocytaire à cellules B/anatomopathologie , Lymphome B de la zone marginale/anatomopathologie , Lymphome folliculaire/anatomopathologie , Lymphome B diffus à grandes cellules/anatomopathologie , Lymphome à cellules du manteau/anatomopathologie , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Études de suivi , Humains , Leucémie chronique lymphocytaire à cellules B/traitement médicamenteux , Leucémie chronique lymphocytaire à cellules B/épidémiologie , Lymphome B de la zone marginale/traitement médicamenteux , Lymphome B de la zone marginale/épidémiologie , Lymphome folliculaire/traitement médicamenteux , Lymphome folliculaire/épidémiologie , Lymphome B diffus à grandes cellules/traitement médicamenteux , Lymphome B diffus à grandes cellules/épidémiologie , Lymphome à cellules du manteau/traitement médicamenteux , Lymphome à cellules du manteau/épidémiologie , Mâle , Adulte d'âge moyen , Pronostic , Études rétrospectives , Taux de survie , Taïwan/épidémiologie , Jeune adulteRÉSUMÉ
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Western countries but very rare in Asia. Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 194 patients with CLL were analysed to determine the ethnic difference in genetic abnormalities. Mutated IGHV was detected in 71·2% of Taiwanese CLL and IGHV3-23 was the most frequently used gene. Stereotyped BCR was present in 18·3% with subset 8 being the most frequent. All cases with subset 8 belonged to IGHV 4-39 and were exclusively associated with un-mutated IGHV and poor outcome. Mutation frequencies of SF3B1 (9·7%), NOTCH1 (8·6%), BIRC3 (1·1%), ATM (16·9%) or TP53 (8·1%), and frequencies of cytogenetic abnormalities including trisomy 12 (18·6%), del(17p) (10·4%), del(13q) (43·7%) and IGH translocation (10·1%) were comparable to those reported from Western countries, except del(11q) (6·9%) which was lower in our patients. Patients with un-mutated IGHV, subset 8, disrupted TP53, trisomy 12, and SF3B1 mutations had a worse outcome compared to patients without these mutations. In conclusion, IGHV3-23 usage, stereotyped subset 8 and lower frequency of del(11q) show an ethnicity-dependent association in Taiwanese CLL patients.
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Gènes de chaine lourde d'immunoglobuline/génétique , Région variable d'immunoglobuline/génétique , Leucémie chronique lymphocytaire à cellules B/génétique , Mutation , Asiatiques/génétique , Aberrations des chromosomes , Analyse de mutations d'ADN/méthodes , Humains , Chaines lourdes des immunoglobulines/génétique , Estimation de Kaplan-Meier , Pronostic , Protéines proto-oncogènes c-bcr/génétique , Facteurs de risque , TaïwanRÉSUMÉ
Bortezomib is a proteasome inhibitor, approved for treating newly diagnosed and relapsed multiple myeloma (MM). This realworld, multicenter, observational, non-interventional study of bortezomib was designed to collect and analyze prospective data in Taiwanese patients with relapsed or refractory MM. The primary endpoints included clinical effectiveness outcomes (disease response, disease progression [PD], time-to-response, time-toprogression, response duration, and overall survival [OS]). Secondary endpoints were safety and healthcare resource utilization. Total 100 patients (median [range] age 64.9 [37.0-85.5] years) were enrolled; 47 patients completed the study. Of the withdrawn patients (n=53), there were 48 deaths (PD-related death: n=35, adverse events [AEs]-related: n=12, other reason: n=1), and 5 due to loss to follow-up. Four patients in Cycle 1, 6 patients each in Cycle 2 and 5, 7 in Cycle 3, 10 patients in Cycle 4, 5 patients in Cycle 6, and 3 patients each in Cycle 7 and 8 achieved overall response during the study. Time-to-response was 4.68 months (95%CI: 3.2, NE) and response duration was 10.08 months (95%CI: 2.3, 28.6). Median OS was 9.8 months (95%CI: 3.8, 13.7), and median time-to-progression was 11.3 months (95%CI: 6.2, 20.2). Most common non-hematological AEs were diarrhea (n=32) and hypoesthesia (n=25); most common hematological AE was thrombocytopenia (n=18). Efficacy and safety profile of bortezomib in Taiwanese patients with MM was similar to global and other Asian population. Study provides a critical insight on use of bortezomib in realworld clinical practice, which can be helpful for Taiwanese healthcare providers' decision-making processes.
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BACKGROUND: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), is approved for the treatment of patients with chronic myeloid leukemia (CML) in many countries, including Taiwan. Though a number of controlled clinical trials have demonstrated the safety and efficacy of nilotinib, studies assessing the safety and efficacy of nilotinib in routine clinical practice are limited. METHODS: The current study was an open-label, single-arm study conducted across 12 centers in Taiwan in adult patients with CML in chronic or accelerated phase with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to one or more previous TKIs. The primary objective was to collect the long-term safety data in patients treated with nilotinib 400 mg, twice daily for up to 2 years. RESULTS: The study enrolled 85 patients with CML, including 76 in the chronic phase (CML-CP) and 9 in the accelerated phase (CML-AP). Overall, 1166 adverse events (AEs) were reported in 80 patients (94.1%), of which 70 AEs (6%) in 28 patients (32.9%) were serious and 336 AEs (28.8%) reported in 60 patients (70.6%) were drug-related. Common drug-related AEs were thrombocytopenia (21.2%), increased alanine aminotransferase (21.2%) and pruritus (17.7%). Of the 85 patients, 19 switched from imatinib due to intolerance - AEs were resolved in 16 of these 19 patients (84.2%). By 24 months, the cumulative rates of complete cytogenetic response (CCyR), major molecular response (MMR), MR4.0 (BCR-ABL1IS ⩽0.01%) and MR4.5 (BCR-ABL1IS ⩽0.0032%) were 75.3, 56.8, 16.2 and 7.4%, respectively. Patients with CML-CP at baseline had higher overall survival (OS) and progression-free survival (PFS) than those with CML-AP. CONCLUSION: This is the first study that demonstrated that nilotinib is effective and well-tolerated in patients resistant or intolerant to imatinib in the real-world setting in Taiwan, reflecting effective management of CML by physicians under routine clinical practice in Taiwan.
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Exogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term = ADI-PEG20&rank = 12 ). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to ≤10 µM. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.
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Antinéoplasiques/usage thérapeutique , Hydrolases/usage thérapeutique , Leucémie aigüe myéloïde/traitement médicamenteux , Polyéthylène glycols/usage thérapeutique , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Moelle osseuse/anatomopathologie , Femelle , Analyse de profil d'expression de gènes , Humains , Leucémie aigüe myéloïde/anatomopathologie , Mâle , Adulte d'âge moyen , Études prospectives , Résultat thérapeutique , Jeune adulteRÉSUMÉ
Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare acquired disorder. The aim of this study was to investigate the demographics, clinical manifestations, and outcomes of PNH patients in southern Taiwan. Data on PNH patients diagnosed over a 30-year period (1985-2015) were retrospectively collected from four tertiary medical centers in southern Taiwan. Blood samples were collected for hematologic panel testing and flow cytometry detection of PNH clones. Radiologic studies were performed to assess the frequency of complications. Twenty-four patients were enrolled in this study. The median duration of disease in the study participants was 10.8 years. The median granulocyte PNH clone size was 92.5% (range, 1.3%-99.8%), and the median lactate dehydrogenase (LDH) level was 2920.2 ± 1462.0 IU/L. The incidence of thromboembolism and impaired renal function was 16.7% and 29.2%, respectively. The primary treatment strategies included steroids (79.2%), androgens (42.0%), eculizumab (33.3%), immunosuppressants (16.7%), and anticoagulants (4.2%). In eight patients treated with eculizumab, there was a marked reduction in the LDH levels of 14.89-fold-1.63-fold that of the upper limit of normal; seven patients exhibited decreased transfusion requirements. Twenty-one patients were alive with regular follow-up at the time of publication. Our study demonstrates that PNH patients in southern Taiwan may exhibit different clinical characteristics and outcomes relative to patients in other countries. There was a trend toward a greater PNH granulocyte clone size, which may lead to more hemolysis. In our study, the percentage of patients with impaired renal function, but not the percentage of patients with thrombotic events, was higher than values reported worldwide and in the observational cross-sectional International PNH Registry. More large-scale studies with comprehensive data on the clinical response to different treatments are needed.
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Transplantation de cellules souches hématopoïétiques , Hémoglobinurie paroxystique/diagnostic , Enregistrements , Insuffisance rénale chronique/diagnostic , Thromboembolie/diagnostic , Adolescent , Adulte , Sujet âgé , Androgènes/usage thérapeutique , Anticorps monoclonaux humanisés/usage thérapeutique , Anticoagulants/usage thérapeutique , Enfant , Femelle , Granulocytes/métabolisme , Granulocytes/anatomopathologie , Hémoglobinurie paroxystique/complications , Hémoglobinurie paroxystique/métabolisme , Hémoglobinurie paroxystique/thérapie , Humains , Immunosuppresseurs/usage thérapeutique , L-Lactate dehydrogenase/sang , Mâle , Adulte d'âge moyen , Insuffisance rénale chronique/complications , Insuffisance rénale chronique/métabolisme , Insuffisance rénale chronique/thérapie , Études rétrospectives , Stéroïdes/usage thérapeutique , Taïwan , Centres de soins tertiaires , Thromboembolie/complications , Thromboembolie/métabolisme , Thromboembolie/thérapieRÉSUMÉ
Prior studies found bendamustine is efficacious in patients with indolent B-cell non-Hodgkin lymphoma (NHL). To date, no studies have reported the efficacy of bendamustine in a Chinese population. This multicentre phase II trial evaluated the pharmacokinetics (PK), safety and efficacy of bendamustine monotherapy in Chinese patients in Taiwan with pretreated indolent B-cell NHL or mantle cell lymphoma (MCL). For PK assessments, patients were randomized (n = 16; 11 with indolent B-cell NHL and five with MCL) to 90 or 120 mg/m(2) of bendamustine for the first cycle. Plasma levels of bendamustine and its two metabolites were analyzed. For efficacy and safety evaluations, bendamustine 120 mg/m(2) was given to all patients every 3 weeks starting at cycle 2 for a minimum of a total of six cycles. The median age of patients was 61.7 years, and the majority were men (75%). The median number of prior treatments was 4 (range, 1-9 regimens), and all patients were previously treated with rituximab. Bendamustine plasma concentration peaked near the end of infusion and was rapidly eliminated with a mean elimination half-life (t(1/2)) of 0.67-0.8 h. Of the evaluable patients (n = 14), the overall response rate was 78.6%, including 7.2% of patients having a complete response. Mean progression-free survival was 27.5 weeks. The most common grade 3-4 adverse events were leucopenia (56.3%), neutropenia (56.3%) and thrombocytopenia (25%). In conclusion, bendamustine was efficacious and well tolerated in Taiwanese patients with indolent NHL and MCL with a similar PK profile to that of other populations.
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Chlorhydrate de bendamustine/usage thérapeutique , Lymphome B/traitement médicamenteux , Lymphome malin non hodgkinien/traitement médicamenteux , Sujet âgé , Sujet âgé de 80 ans ou plus , Chlorhydrate de bendamustine/administration et posologie , Chlorhydrate de bendamustine/pharmacocinétique , Femelle , Humains , Lymphome B/anatomopathologie , Lymphome à cellules du manteau/anatomopathologie , Lymphome malin non hodgkinien/anatomopathologie , Mâle , Adulte d'âge moyen , Pronostic , TaïwanRÉSUMÉ
BACKGROUND: Genome-wide-association studies have identified the TMPRSS6 polymorphism rs855791 has the strongest association with red blood cell indices or iron parameters in general population. Whether this genetic variant influences the susceptibility of iron deficiency anemia (IDA) in women with menstruation has not been well studied. METHODS: In this case-control study, we enrolled 67 women with IDA and 107 healthy volunteers, and analyzed their complete blood counts, rs855791 genotypes, and menstrual amounts. Menstrual blood loss was evaluated with a pictorial blood-loss assessment chart. RESULTS: There were significantly fewer rs855791 C homozygotes in the IDA group than in the healthy group (11.9% vs. 25.2%, p = 0.03). The odds ratio (OR) of C homozygotes having IDA versus non-CC subjects having IDA was 0.4 (95% CI, 0.17 - 0.95, p = 0.04). When the analysis was confined to study subjects with menorrhagia, this difference became more prominent (9.6% vs. 28.6%, p = 0.01; OR, 0.27, 95% CI, 0.09 - 0.77, p = 0.01). For women with non-CC genotypes, there was an inverse correlation between hemoglobin levels and menstrual loss (p < 0.001); however, this association was not found for those with genotypes CC (p = 0.15). CONCLUSIONS: Our study suggests homozygosity for TMPRSS6 rs855791 C genotype has a protective role against IDA in women at reproductive age, especially in those with menorrhagia.
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Anémie par carence en fer/génétique , Études d'associations génétiques , Protéines membranaires/génétique , Serine endopeptidases/génétique , Adulte , Anémie par carence en fer/sang , Anémie par carence en fer/complications , Anémie par carence en fer/anatomopathologie , Études cas-témoins , Femelle , Prédisposition génétique à une maladie , Génotype , Humains , Ménorragie/sang , Ménorragie/complications , Ménorragie/génétique , Ménorragie/anatomopathologie , Menstruation/sang , Menstruation/génétique , Adulte d'âge moyen , Facteurs de risqueRÉSUMÉ
Some chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitor (TKI) do not respond or relapse. BCR-ABL1 mutations are the principal cause of TKI resistance, but the kinetics of emerging mutations in CML patients treated with imatinib remain to be determined. To investigate the emergence dynamics of mutations and their effects on outcomes, we conducted a systematically longitudinal study of BCR-ABL1 mutation dynamics during TKI therapy. Seminested polymerase chain reaction followed by denaturing high-performance liquid chromatography with sequence confirmation were used to detect BCR-ABL1 mutations in 202 CML patients with imatinib resistance at different CML phases. We detected 68 mutations in 58 imatinib-failure patients. Mutations were present in 27.6% of patients who failed front-line imatinib therapy and in 68.1% with advanced disease. Mutations were not detected in patients before commencing imatinib treatment. Pyrosequencing was then used to quantitatively monitor the mutant levels sequentially and also traced back for their earlier appearance. The mutants differed in rapidity of emergence which appeared to arise in different time frame as well as in speed of rising mutant levels. In the 78 front-line imatinib-failure patients, mutation positive patients had significantly higher risk of disease progression or relapse and inferior progression-free survival compared to those without mutations (p=0.006). Our study demonstrates kinetics of different BCR-ABL1 mutant emergence and an association between BCR-ABL1 mutations and disease progression.
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Antinéoplasiques/usage thérapeutique , Protéines de fusion bcr-abl/génétique , Leucémie myéloïde chronique BCR-ABL positive/traitement médicamenteux , Leucémie myéloïde chronique BCR-ABL positive/génétique , Mutation , Pipérazines/usage thérapeutique , Inhibiteurs de protéines kinases/usage thérapeutique , Protein-tyrosine kinases/antagonistes et inhibiteurs , Pyrimidines/usage thérapeutique , Benzamides , Femelle , Humains , Mésilate d'imatinib , Adulte d'âge moyen , Échec thérapeutiqueRÉSUMÉ
PURPOSE: This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics. PATIENTS AND METHODS: Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m(2) per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m(2) per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded. RESULTS: The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%). CONCLUSION: In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis.
Sujet(s)
Antimétabolites antinéoplasiques/usage thérapeutique , Azacitidine/analogues et dérivés , Comportement de choix , Cytarabine/usage thérapeutique , Leucémie aigüe myéloïde/thérapie , Soins palliatifs , Participation des patients , Sujet âgé , Sujet âgé de 80 ans ou plus , Antimétabolites antinéoplasiques/administration et posologie , Antimétabolites antinéoplasiques/effets indésirables , Azacitidine/administration et posologie , Azacitidine/effets indésirables , Azacitidine/usage thérapeutique , Cytarabine/administration et posologie , Cytarabine/effets indésirables , Prise de décision , Décitabine , Calendrier d'administration des médicaments , Femelle , Humains , Estimation de Kaplan-Meier , Leucémie aigüe myéloïde/traitement médicamenteux , Mâle , Neutropénie/induit chimiquement , Soins palliatifs/méthodes , Induction de rémission , Appréciation des risques , Facteurs de risque , Thrombopénie/induit chimiquement , Résultat thérapeutiqueRÉSUMÉ
Hepatitis B virus (HBV) reactivation is a well-known complication after rituximab therapy in patients with B cell lymphoma. Traditionally, hepatitis B surface antibody (anti-HBs) is a protective antibody, but the effect of rituximab on these antibodies has not been well studied. In 29 B cell lymphoma patients who were positive for anti-HBs before rituximab therapy, anti-HBs serologies before and after rituximab therapy were compared. Anti-HBs titers after rituximab treatment were significantly lower (P < 0.001) than those before treatment. None of the ten cases with pre-treatment anti-HBs titers above 100 mIU/mL became negative for anti-HBs after rituximab therapy. In contrast, 8 of the 19 patients with pre-treatment anti-HBs titers below 100 mIU/mL lost their anti-HBs (P = 0.027). Of these, one patient developed HBsAg seroreversion and HBV reactivation after rituximab therapy. Regarding patients with loss of anti-HBs or not, there was no significant difference in pre- and post-treatment immunoglobulin G levels between both groups. The rate of anti-HBs loss increased with advanced lymphoma stage and international prognostic index (P = 0.002 and <0.001, respectively). Multiple logistic regression analysis showed that pre-treatment anti-HBs titer is the only independent factor influencing the loss of anti-HBs (per one log mIU/mL, odds ratio, 0.003; 95% confidence interval, 0.000-0.302; P = 0.014). In conclusion, we found that anti-HBs titers decreased significantly (P < 0.001) after rituximab treatment. B cell lymphoma patients with low pre-treatment anti-HBs titers (<100 mIU/mL) were more likely to lose anti-HBs antibodies and were at risk of HBV reactivation after rituximab immunochemotherapy.
Sujet(s)
Anticorps monoclonaux d'origine murine/effets indésirables , Anticorps monoclonaux d'origine murine/usage thérapeutique , Anticorps de l'hépatite B/analyse , Antigènes de surface du virus de l'hépatite B/immunologie , Lymphome B/traitement médicamenteux , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Anticorps monoclonaux d'origine murine/administration et posologie , Antinéoplasiques/administration et posologie , Antinéoplasiques/effets indésirables , Antinéoplasiques/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Cyclophosphamide/administration et posologie , Cyclophosphamide/effets indésirables , Doxorubicine/administration et posologie , Doxorubicine/effets indésirables , Femelle , Anticorps de l'hépatite B/sang , Humains , Lymphome B/sang , Lymphome B/immunologie , Lymphome B/virologie , Mâle , Adulte d'âge moyen , Prednisone/administration et posologie , Prednisone/effets indésirables , Études rétrospectives , Rituximab , Tests sérologiques , Titrimétrie/méthodes , Vidarabine/administration et posologie , Vidarabine/effets indésirables , Vidarabine/analogues et dérivés , Vincristine/administration et posologie , Vincristine/effets indésirables , Activation virale/effets des médicaments et des substances chimiquesRÉSUMÉ
BACKGROUND: Brown adipose tissue (BAT) has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[(18)F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in people living in the tropics, where the influence of outdoor temperature was low. METHODS: (18)F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA) of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and (18)F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature. RESULTS: Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (p = 0.043) and a higher TMA (p = 0.028) than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (p = 0.016). CONCLUSIONS: Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.
Sujet(s)
Tissu adipeux brun/métabolisme , Fluorodésoxyglucose F18 , Tumeurs/imagerie diagnostique , Climat tropical , Adolescent , Adulte , Sujet âgé , Répartition du tissu adipeux , Enfant , Femelle , Humains , Mâle , Adulte d'âge moyen , Imagerie multimodale , Analyse multifactorielle , Tumeurs/métabolisme , Tomographie par émission de positons , Études rétrospectives , Taïwan , Tomodensitométrie , Jeune adulteRÉSUMÉ
Hepatitis B virus (HBV) reactivation is a well-known complication of lymphoma treatment in the pre-rituximab era. This complication has not been as well studied, however, since monoclonal anti-CD20 antibody became the standard regimen for B cell lymphoma. In this retrospective study, 115 B cell lymphoma patients who received rituximab-containing therapy were analyzed. Of 15 hepatitis B surface antigen (HBsAg)-positive patients, five received lamivudine prophylaxis and did not develop HBV-related hepatitis during lymphoma treatment. Eight of ten HBV carriers without lamivudine prophylaxis experienced HBV-related hepatitis, including one fatal hepatic failure. Four (4.2%) of 95 HBsAg-negative patients developed de novo HBV-related hepatitis and two died of fulminant hepatitis. In conclusion, rituximab-based therapy may cause serious HBV-related complications and even death in both HBsAg-positive and HBsAg-negative patients.
Sujet(s)
Anticorps monoclonaux/effets indésirables , Virus de l'hépatite B/effets des médicaments et des substances chimiques , Lymphome B/complications , Activation virale/effets des médicaments et des substances chimiques , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Anticorps monoclonaux d'origine murine , Femelle , Hépatite B/étiologie , Hépatite B/prévention et contrôle , Antigènes de surface du virus de l'hépatite B/sang , Virus de l'hépatite B/physiologie , Humains , Incidence , Lamivudine/usage thérapeutique , Lymphome B/traitement médicamenteux , Mâle , Adulte d'âge moyen , Prémédication , Études rétrospectives , RituximabRÉSUMÉ
Pleural effusions and mediastinal masses are associated with certain types of hematologic malignancies. We report a 20-year-old man with a pleural effusion, a mediastinal mass, and a normal hemogram. The cytology of the pleural effusion initially suggested a lymphoma. However, an immunophenotypic study of the effusion revealed the following: TdT+, CD34+, CD19+, CD7(-), CD33(-), CD10(-), sIgM(-), and positive cytoplasmic mu heavy-chain immunoglobulins. After a bone marrow examination, we diagnosed the patient with pre-B acute lymphoblastic leukemia (ALL). This is the first reported case of a malignant pleural effusion and a mediastinal mass that preceded pre-B ALL. After standard therapy for ALL, the patient has been disease-free for 7 years.
Sujet(s)
Tumeurs du médiastin/diagnostic , Épanchement pleural malin/diagnostic , Leucémie-lymphome lymphoblastique à précurseurs B/diagnostic , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Myélogramme , Survie sans rechute , Humains , Immunophénotypage , Mâle , Leucémie-lymphome lymphoblastique à précurseurs B/thérapie , Jeune adulteRÉSUMÉ
BACKGROUND: Hepatosplenic fungal infection is an important infectious complication in adult patients with acute leukemia. METHODS: From 2001 to 2004, 163 adult patients were diagnosed with acute leukemia at our center: 41 patients had acute lymphoblastic leukemia (ALL) and 122 patients had acute myeloid leukemia (AML). Their charts were retrospectively reviewed. RESULTS: Of these 163 patients, 16 patients (9.8%) developed hepatosplenic fungal infection: three were ALL patients and 13 were AML patients. All of these patients suffered from febrile neutropenia after chemotherapy. Duration of agranulocytosis (absolute neutrophil count < 500/dl) was 10 to 36 days, with a median of 20 days. Clinical presentations in these patients were fever (94%), diarrhea (50%), abdominal pain (44%), oral mucositis (44%), papular skin lesions (31%) and lower back pain (7%). Fourteen patients (88%) had elevated alkaline phosphatase levels between 197 U/l to 1172 U/l (normal range: 28-94 U/l). The most common infection sites found by computed tomography were the spleen (94%) and the liver (88%). All patients were treated with antifungal agents. No patient died as a result of the fungal infection episode. Nine patients (56%) died due to uncontrolled underlying hematological malignancies. The median duration of follow-up was 15.2 months (range: 2.3-47.4 months). CONCLUSION: Alkaline phosphatase level and computed tomography are useful tools for the diagnosis of hepatosplenic fungal infection. Infection-related mortality is very low with effective treatment. Treatment for underlying diseases should proceed as soon as possible if the infection has been controlled.