A Meta-Analysis of CAG (cytarabine, aclarubicin, G-CSF) Regimen for the Treatment of 1045 Patients with Leukemia in China and Japan,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3638-3638
Author(s):  
Guoqing Wei ◽  
Wanmao Ni ◽  
Dicky Chiao ◽  
He Huang ◽  
Zhen Cai ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Fixed Effects ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Early Death ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
China And Japan ◽  
Better Than

Abstract Abstract 3638 Background: CAG regimen (cytarabine, aclarubicin, G-CSF) has been commonly used in China and Japan for the treatment of AML and MDS. This study is to summarize the data and to analyze the efficacy as well as the toxic effects of CAG regimen in acute leukemia (AL) and MDS pts. Methods: The databases of PubMed, Wanfang Data, as well as American Society of Hematology (ASH) annual meeting abstracts were searched for articles published in English, Chinese and Japanese languages between January 1995 and December 2010. Eligible studies were relevant clinical trials on AL and MDS pts treated with CAG regimen. Complete remission (CR) rates and odds ratio (OR) were compared through a meta-analysis using a random-effects or fixed-effects model. Results: 37 trials with a total of 1045 AL and MDS pts were included for analysis. Among the 1045 pts treated with CAG, 819 pts were AML, 215 pts were de novo MDS or transformed AML (MDS/tAML), 6 pts were ALL, and 5 pts were biphenotypic acute leukemia (BAL). The AML CR rate of CAG from 29 studies was 58.0% (95% CI, 53.1%-62.7%). The MDS/t-AML CR rate from 12 studies was 45.7% (95% CI, 39.0%-52.4%). The AML CR rate was significantly better than that of MDS /tAML (Q=8.072, p<0.01). Among 819 AML pts, 327 pts were newly diagnosed, 370 pts were relapsed/refractory (R/R) AML. The AML status was not specified in the rest 122 pts. Interestingly, no significant difference in CR rates was noted between the newly diagnosed (57.0%, 95% CI 51.5%-62.3%) and R/R AML pts (60.1%, 95% CI 50.5%-68.9%) (Q=0.312, p>0.05). The CR rate for the 367 elderly AML pts was 52% (95% CI 51.5%-62.3%). The CR rate was also significantly higher in pts with favorable (64.5%, 95% CI 38.8%-83.9%) and intermediate (69.6%, 95% CI 60.4%-77.5%) cytogenetics than those with unfavorable one (29.5%, 95% CI 19.7%-41.8%) (p<0.05). There were 7 trials that compared the CR rates of CAG regimen with those of other induction regimens in AML pts. Surprisingly, the CR rate of CAG was significantly higher than those of other induction regimens (OR 2.425, 95% CI, 1.515–3.880). CAG regimens were well tolerated with cardiotoxicity in 0.42% cases (4/954) and early death occurred in 4.40% cases (44/1000). Conclusions: CAG regimen induced significantly higher CR rates in AML than in MDS pts. The CR rates of CAG regimen was significantly better than those of other induction regimens in AML pts. This regimen was well tolerated with low cardiotoxicity and early death rate. Disclosures: No relevant conflicts of interest to declare.

CAG (cytarabine, aclarubicin, G-CSF) Regimen Is Effective and Well Tolerated in 367 Elderly Patients with AML in China and Japan: A Meta-Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4290-4290
Author(s):  
Guoqing Wei ◽  
Delong Liu
Keyword(s):  
Elderly Patients ◽  
Fixed Effects ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Current Therapy ◽  
Newly Diagnosed ◽  
Fixed Effects Model ◽  
Elderly Aml ◽  
Significant Difference ◽  
China And Japan

Abstract Abstract 4290 Background: Current therapy is still unsatisfactory in elderly patients (pts) with acute myeloid leukemia (AML). CAG regimen (cytarabine, aclarubicin, G-CSF) has been commonly used in China and Japan for the treatment of elderly AML pts. The aim of this study is to summarize the data and to analyze the efficacy as well as the toxic effects of CAG regimen in elderly AML pts. Methods: The databases of PubMed, Wanfang Data, as well as American Society of Hematology (ASH) annual meeting abstracts were searched for articles published in English, Chinese and Japanese languages from January 1995 to December 2010. Eligible studies were relevant clinical trials of elderly AML pts treated with CAG regimen. Complete remission (CR) rate, odds ratio (OR) and 95% confidence intervals (CIs) of chemotherapy were compared through a meta-analysis using a random-effects or fixed-effects model. Results: 19 trials with a total of 367 elderly AML pts were identified and included for analysis. Among the 367 AML pts treated with CAG, 266 pts were newly diagnosed AML, 54 pts were relapsed/refractory (R/R) AML. The AML status was not specified in the rest 47 pts. The CR rate for the 367 elderly AML pts was 52.0% (95% CI 46.8%-57.2%). Interestingly, no significant difference in CR rates was noted between the newly diagnosed (54.7%, 95% CI 48.6%-60.7%) and R/R AML pts (45.7%, 95% CI 32.4%-59.6%) (Q=1.332, p=0.248). Three studies compared the CR rates of elderly AML pts according to the karyotype. The CR rate was significantly higher in pts with intermediate (72.4%, 95% CI 58.0%-83.3%) cytogenetics than those with unfavorable one (35.7%, 95% CI 18.7%-57.2%) (Q=7.803, p=0.005). These elderly AML pts tolerated CAG well with low cardiotoxicity (0.73%, 2/273) and ED (8.48%, 29/342). Conclusions: CAG regimen induced high CR rates in elderly pts with new and relapsed/ refractory AML. This regimen was well tolerated with low cardiotoxicity and early death rate. Disclosures: No relevant conflicts of interest to declare.

Meta-Analysis of CAG (cytarabine, aclarubicin, G-CSF) Regimen for the Treatment of 580 Patients with Acute Leukemia In China and Japan.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1064-1064
Author(s):  
Guoqing Wei ◽  
Delong Liu
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Randomized Study ◽  
Toxic Effects ◽  
Current Therapy ◽  
Newly Diagnosed ◽  
Elderly Aml ◽  
China And Japan

Abstract Abstract 1064 Background: Current therapy is still unsatisfactory in patients with high-risk AML (elderly, relapsed, refractory, and secondary). A CAG regimen has been commonly used in China and Japan for the treatment of this type of patients (pts). The CAG regimen consists of low-dose cytarabine 10 mg/m2 q12 SQ on d1–14, aclarubicin 7 mg/m2, QD on d1–8, or 14 mg/m2, QD on d1–4, and G-CSF 200 μg/m2, QD on d1–14. The aim of this study is to summarize the data and to analyze the efficacy as well as the toxic effects of CAG regimen in acute leukemia (AL) patients. Methods: A meta-analysis of 15 trials with a total of 580 AL pts was performed to summarize and analyze the efficacy of CAG regimen as well as the toxic effects. The literature search was conducted in PubMed, Google Scholar, and Medline, as well as ASH and ASCO meeting abstracts. Results: Among the 580 pts treated with CAG, 456 pts were AML, 100 pts were MDS/tAML,19 pts were ALL, 5 pts were BAL. 163 pts were newly diagnosed AML, 141/75 pts were relapsed/refractory (R/R). The CR rates of CAG in newly-diagnosed, relapsed, refractory, elderly AML patients were 63.9% (49%-67.6%), 83% (40%-86%), 30.4 (12.5%-48.4%), and 53.5% (31.5%-67%), respectively. The median OS in new, relapsed, elderly AML patients were 14.5m (9m-17m), 16m (15m-17m), and 8m (7m-9m), respectively. Data available from 4 trials which studied the efficacy of CAG in MDS/tAML patients showed that CR rate was 40.5% (38.5%-46.4%). There were only two small studies of CAG in ALL and in BAL that showed ORR of 100%. The toxicity of CAG in all reports were mild and the CAG regimen were well tolerated. Conclusion: This low-intensity CAG regimen appears to be very well tolerated with clear activity in high-risk AL pts. Randomized study may be warranted. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Safety of 5-Azacytidine Based Regimens in Old AML patients: a Retrospective Study of 29 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4148-4148
Author(s):  
France Roszkiewicz ◽  
Berengere Gruson ◽  
Ioana Vaida ◽  
Gandhi Damaj ◽  
Bruno Royer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Overall Response ◽  
Co Morbidity ◽  
Significant Difference ◽  
Wbc Count

Abstract Abstract 4148 Background 5-azacytidine (AZA) is an hypomethylating drug. The international multicenter AZA-001 trial established that AZA significantly improves overall survival (OS) in patients with high risk myelodysplastic syndromes (MDS) compared with conventional care regimens (Fenaux, Lancet Oncol 2009). Some recent reports have raised the question of a possible efficacy of AZA in selected patients with acute myeloid leukaemia (AML). In this study we retrospectively analysed the safety and efficacy of a 7 days-schedule of AZA alone or in combination with an HDAC inhibitor, Valproic acid (VA) and with All-trans retinoic acid (ATRA) in patients with newly-diagnosed and refractory/relapsed AML not eligible for intensive chemotherapy. Patients and Methods A monocentric retrospective study from October, 2006 until March, 2009 analysed 29 patients with AML. Among these patients. There were 11 males and 18 females, median age 70,8 years (range 51,2-84,1), AML de novo in 15 patients (3 relapse) and secondary in 14 patients (2 post MPD and 12 post MDS). Median WBC count was 2,5 (range 0,7-140).109/L, 4 patients had WBC more than 10.109/L. The median rate of bone marrow blasts is 30%. 12/27 (44%) patients and 15/26 (56%) have respectively an intermediate and poor risk caryotype. Fifteen (54%) were newly-diagnosed patients, 14 (46%) were refractory/relapsed patients. Median co morbidity index (Sorror, J Clin Oncol 2007) of patients is 2 (0-7). Patients received daily AZA 75mg/m2 J1-J7, ± VA 35 to 50 mg/kg J1-J7 and ATRA 45mg/m2 J8-J28 every 4 weeks. Results 5 azacytidine was used alone for 6/29 (21%) patients and in combination with VA and ATRA for 23/29 (79%) patients. Compliance to the planned therapy was good. Average number of AZA administration was 6 days. To date a total 150 treatment-cycles with a median of 5 cycles/patient were applied (1-14). Treatment was well tolerated. Neutropenia grade3III and thrombopenia grade3III occurred respectively in 26/150 cycles (17%) and in 31/150 (20%). Infections grade3III were observed in 14/150 cycles (9,3 %). Overall response was 62% (17/29): 9 complete response (CR=31%), 3 partial response (PR=10%), 5 haematological improvement (HI=21%), There were 2 stable diseases (SD=7%). 28% of responses were obtained after 1 cycle, 56% after 3 and 89% after 4. Median overall survival (OS) was 13,2 months (0.3-26). We did not observe any significant difference on OS regarding: age, cytogenetics, de novo vs secondary AML, newly diagnosed vs refractory/relapsed patients. OS for patients with SD was similar to patients with CR, PR or HI. WBC >10.109/L before treatment was not correlated with a shorter survival (7.73 months vs 13.2 months p=0,6). Correlation was found between OS and clearance of the creatinine (p=0.005). In conclusion, AZA based regimens seems well tolerated and an effective treatment in AML, with an overall response of 62% and an OS of 13,2 months. A minimum of 4 cycles of treatment is necessary to evaluate the efficacy. OS of patients achieving CR, PR or HI is not significantly different of those with SD. Treatment should be continued until progression of the disease. Disclosures: No relevant conflicts of interest to declare.

Complex Karyotype Predicts Outcome Better Than Monosomal Karyotype In Patients with MDS/Secondary Acute Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): a Retrospective Survey on Behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 578-578 ◽  
Author(s):  
Angelique .M. Brands-Nijenhuis ◽  
Michel van Gelder ◽  
Theo M. de Witte ◽  
Johannes Schetelig ◽  
Anja van Biezen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Leukemia ◽  
Conflicts Of Interest ◽  
Chromosome 7 ◽  
Complex Karyotype ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Significant Difference ◽  
Monosomal Karyotype ◽  
Better Than

Abstract Abstract 578 Introduction Monosomal Karyotype (MK) has been shown to be associated with a very poor prognosis in AML patients. Last year at ASH, we presented data from the EBMT on patients diagnosed with MDS and chromosome 7 abnormalities, showing that MK predicts better than complex karyotype (CK) for a dismal outcome after allogeneic HSCT (abstract #293). We now performed a retrospective analysis on data from the registry in the complete cohort of patients with MDS and secondary AL (sAL) to determine the effect of MK on outcome after allogeneic HSCT. Methods A total of 1689 patients from 172 centres in 23 countries with diagnosis MDS or secondary acute leukemia (sAL) with known cytogenetic abnormalities (karyotype only) at diagnosis or later in the disease course were assessed. 1437 were included in the analysis; 226 were excluded because of insufficient data. Kaplan-Meier survival curves were used and log rank test to determine statistical significance. Results 1041 patients were diagnosed with MDS and 396 with sAL. Median follow up for sAL patients was 7.5 months (range 0–253) and MDS 8.0 months (range 0–276). 201 patients fulfilled criteria for MK and 279 patients for complex karyotype (CK). MK outcome was worse than no MK: overall survival 32 months versus 97 months (p=0.002). CK outcome was worse than no CK: overall survival 26 months versus 100 months (p&lt;0.0001). No difference in outcome between MK and CK existed: overall survival of 32 months and 26 months respectively (p= 0.274). There was considerable overlap between MK and CK (i.e. patients fulfilling criteria both for MK and CK). To see how we could further differentiate, we analyzed three subgroups: MK but not CK (43 patients; MK+CK−), no MK but CK (98 patients; MK−CK+) and MK and CK (150 patients; MK+CK+). The survival of patients in each of these groups was compared with the group having no MK and no CK (n=1050). Overall survival was not different for patients with MK+CK− (median 13 vs 19 months, p=0.983), but for patients with MK-CK+ or MK+CK+ a significant difference in survival was observed with a median of 8 months (p=0.008) and 7 months (p&lt; 0.0001) respectively. MK−CK+ and MK+CK+ did not differ statistically (p=0.42) from each other. See figure. These results differ from the results presented at ASH last year. Since this cohort consists of patients with and without chromosome 7 abnormalities, we suspect that presence of this specific chromosomal aberration is the main reason for the observed difference. Multivariate analysis will be performed the coming months. Conclusion These results indicate that CK is a better predictor for poor outcome than MK after allogeneic HSCT in this cohort of MDS and sAL patients with and without chromosome 7 abnormalities. Disclosures: No relevant conflicts of interest to declare.

Early Deaths (ED) in Acute Promyelocytic Leukemia (APL) in France: A Retrospective Multicenter Study in 355 Patients (pts)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 890-890
Author(s):  
Rami Rahmé ◽  
Xavier Thomas ◽  
Christian Recher ◽  
Norbert Vey ◽  
Jacques Delaunay ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hospital Admission ◽  
Blood Count ◽  
Conflicts Of Interest ◽  
Early Death ◽  
Older Age ◽  
Similar Proportion ◽  
Newly Diagnosed ◽  
University Hospitals ◽  
Significant Difference

Abstract Abstract 890 Background: While, with the combination of ATRA and anthracycline-based chemotherapy, 90–95% of APL pts included in APL clinical trials achieve complete remission (CR), it has been suggested that the actual early death (ED) rate may be as high as 15–17%, many pts being unable to enter clinical trials (Park JH, Blood 2011, Lehmann S, Leukemia. 2011 ). In some cases, an important delay in starting ATRA was also incriminated in ED (Altman, Blood 2011). We assessed the early outcome of newly diagnosed APL pts diagnosed in 16 large French centers during a period of 5 years, included or not in a clinical trial. Methods: 16 French University hospitals retrospectively provided data on all their APL pts diagnosed between Dec 2006 and Dec 2011, included or not in APL 2006 trial, the only active French APL trial during that period, which randomly assessed the role of ATO and ATRA during consolidation treatment, after ATRA – anthracycline based chemotherapy induction, and which had no upper age limit for inclusions. Every effort was made to collect all cases, by checking all APL diagnoses made in the lab and including pts admitted directly to ICU or to departments other than that of hematology, to avoid any bias. Intervals between first blood count, hospital admission and ATRA onset were particularly analyzed. ED was defined as death within 30 days of admission, irrespective of its cause. Results: 355 cases of newly diagnosed APL were seen during that period: 52% men, median age 52 years (range 16 –87). 26% of the pts had WBC >10 G/L. 65.6% pts were included in APL 2006 trial and 34.4% not included. Reasons for non-inclusion in APL 2006 trial were: 32 patients refusing or unable to give consent (9%), 20 initial admissions in ICU (5.6%), 20 older age and/or comorbidities (5.6%), 8 previous cancer (2.3%), 11 contraindications to anthracyclines (3.1%), 5 other exclusion criteria (pregnancy, HIV, poor socioeconomic conditions) (1.4%), 2 deaths before ATRA onset (0.6%), 2 CNS bleeding at admission (0.6%) and 22 unknown reasons (6.2%). Pts not included were characterized by older age (median 62 vs 48 y, p < 0.0001) but a similar proportion of pts with high WBC (31% vs 24%,p=0.16). 20/33 (61%) pts aged ≥ 75 and 19/26 (73%) pts initially admitted in ICU were not included in APL 2006 trial. Median interval from first abnormal blood count to hospitalization was < 1 day (1 d and > 1 d in 20% and 22% pts, respectively), from hospitalization to ATRA onset < 1 day (1 d and > 1 d in 24.5% and 25% pts respectively) and from bone marrow aspirate to ATRA onset < 1 day (<1 d, 1 d, and > 1d in 66%, 19%, 15% pts respectively), without significant difference between pts included and not included in APL 2006. 316 (89.8%) pts reached CR, 1 had resistant leukemia and 35 pts (9.9%) had ED. 8 of the 35 ED (2.2% of the whole population) occurred before ATRA onset. Causes of ED in pts who received ATRA were: differentiation syndrome (DS) (n=5), CNS bleeding (n=4), sepsis (n=7), myocardial infarction (n=2), multiple organ failure (n=4), uncertain (n=5). No significant differences in the incidence of ED were seen based on the various intervals analyzed (from first blood count to hospital admission, admission to ATRA onset, BM aspirate to ATRA onset). In particular, ATRA onset within <1, 1 and >1 day of hospitalization was associated with ED rates of 9.4%, 7% and 8%, respectively (p=0.961). ED was seen in 3% (7/233) of pts included in APL 2006 trial and 23% (28/122) of non protocol pts (p < 0.0001), and the CR rate was 97% and 77% in APL trial and non protocol pts (p < 0.0001). In particular, in pts aged ≥ 75, the ED rate was 0% and 30% in protocol and non protocol pts, respectively (p=0.06). Still, overall, 16/26 (61.5%) of the pts admitted directly in ICU, 27/33 (82%) of the pts aged ≥ 75, and 77/92 (83.7%) of the pts with WBC > 10G/L achieved CR. Conclusions: (1) A large majority of APL pts are rapidly admitted to hospital and rapidly treated with ATRA in France, with an overall CR rate of 89.8%. (2) One third of the pts are not included in clinical trials, especially due to their age or critical condition, and their outcome is less favorable than that of protocol patients (77% versus 97% CR). On the other hand, 61.5% of the pts directly admitted to ICU and 82% of those aged ≥ 75 y achieved CR. (3) Our overall early death rate (9.9%) appears inferior to those published in several recent studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Closure of Patent Foramen Ovale in Preventing Subsequent Neurological Events: A Bayesian Network Meta-Analysis to Identify the Best Device

2020 ◽  
Vol 49 (2) ◽  
pp. 124-134
Author(s):  
Leonardo Varotto ◽  
Gianni Bregolin ◽  
Mariemma Paccanaro ◽  
Antonella De Boni ◽  
Carlo Bonanno ◽  
...  
Keyword(s):  
Patent Foramen Ovale ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Stroke Recurrence ◽  
Foramen Ovale ◽  
Significant Difference ◽  
Pfo Closure ◽  
Better Than

Background: Randomized-controlled trials (RCTs) reported a finding on the safety and efficacy of percutaneous patent foramen ovale (PFO) closure to prevent stroke recurrence. It showed that the Amplatzer (AMP) device appears to be superior to medical therapy (MT) in preventing strokes and episodes of atrial fibrillation (AF), than other devices. We performed a network meta-analysis (NMA) to evaluate the closure of PFO in preventing subsequent neurological events while investigating the results obtained by specific devices. Methods: We searched 3 databases (MEDLINE, EMBASE, CENTRAL/CCTR) and identified 6 RCTs until March 2019. We performed an NMA and used pooled ORs. Analyses were done in NetMetaXL1.6-WinBUGS1.4. Results: Six RCTs with 3,560 patients (mean age 45.2–46.2 years) were included in the present NMA. Depending on the device, 4 groups of patients were compared with MT: 1,889 patients undergoing PFO closure were significantly less likely to experience a stroke than 1,671 patients treated with MT (ORs 0.41; 95% Cr.I. 0.27–0.60 with fixed-effects model and ORs 0.22; 95% Cr.I. 0.05–0.70 with random-effects model). The patients with AMP showed a similar risk than those treated with Helex/Cardioform (HLX/CF) or with a group of 11 multiple devices. This suggests the equality between the 2 most currently used devices. When assessing TIA and, for the safety analysis, major bleeding, both models confirm no significant difference between any devices and MT. PFO closure increased the risk of new-onset AF: MT induces AF significantly less than all the devices. In favor of the AMP, there is a reduced number of cases of AF versus MT; however, no device superiority has been established in comparing HLX/CF and other devices in a random effect model. Conclusions: Our NMA provides evidence in favor of PFO closure with all the devices currently in use. We can conclude that these devices are better than MT, but not that 1 device is better than the rest in reducing stroke recurrences and AF episodes in the follow-up.

Insulin Glargine and Risk of Cancer: A Meta-Analysis

2012 ◽  
Vol 27 (3) ◽  
pp. 241-246 ◽  
Author(s):  
Xinli Du ◽  
Rihua Zhang ◽  
Yi Xue ◽  
Dong Li ◽  
Jinmei Cai ◽  
...  
Keyword(s):  
Insulin Glargine ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Long Term Effects ◽  
Open Label ◽  
Cancer Occurrence ◽  
Pubmed Database ◽  
Significant Difference ◽  
The Us ◽  
Risk Of Cancer

Aims Recently, more and more attention has been drawn on the long-term effects of insulin glargine. Here we strived to estimate the association of cancer occurrence with the use of insulin glargine. Methods We searched all the publications regarding the association between cancer occurrence and the use of insulin glargine using the US National Library of Medicine's PubMed database. Data were independently extracted and analyzed using random or fixed effects meta-analysis depending upon the degree of heterogeneity. Results Seven cohort studies were included in the meta-analysis. Cancer occurrence had no significant difference in glargine-treated patients compared to patients treated with other insulins (RR=0.86, 95% CI=0.69–1.07, p=0.17, Pheterogeneity <0.00001). In our subgroup analysis, glargine, compared to other insulins, did not increase the risk of breast cancer (RR=1.14, 95% CI=0.65–2.02, p=0.65, Pheterogeneity=0.002), prostate cancer (RR=1.00, 95% CI=0.79–1.26, p=0.99, Pheterogeneity=0.78), pancreatic cancer (RR=0.57, 95% CI=0.14–2.35, p=0.44, Pheterogeneity=0.0002) and gastrointestinal cancer (RR=0.80, heterogeneity 95% CI=0.62–1.02, p=0.07, Pheterogeneity=0.86). Conclusions This meta-analysis of open-label studies does not support an increased cancer risk in patients treated with insulin glargine. The result provides confidence for the development of insulin glargine, but needs confirmation by further clinical studies.

scholarly journals Efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of pneumocystis pneumonia in human immunodeficiency virus-negative immunodeficient patients: A systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248524
Author(s):  
Rui Li ◽  
Zhiyong Tang ◽  
Fu Liu ◽  
Ming Yang
Keyword(s):  
Human Immunodeficiency Virus ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Pneumocystis Pneumonia ◽  
Control Group ◽  
Drug Discontinuation ◽  
Efficacy And Safety ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Hiv Negative

Background Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine. Methods A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported. Results Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03). Conclusions TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.

scholarly journals Astarabine, a Novel Leukemia-Targeted Cytarabine Composition Allows, for the First Time, the Delivery of High Cytarabine Doses for Older or Unfit Patients with Acute Leukemia. Results of an Ongoing Phase I/IIa Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1650-1650
Author(s):  
Tsila Zuckerman ◽  
Stela Gengrinovitch ◽  
Ruth Ben-Yakar ◽  
Ron Hoffman ◽  
Israel Henig ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
De Novo ◽  
Intensive Therapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Unfit Patients ◽  
Equity Ownership ◽  
High Doses

Abstract Introduction: Therapy of acute myeloid leukemia (AML) has not changed significantly during several decades. High-dose cytarabine, although used as the first-line treatment for AML since 1970s and as a second-line treatment for acute lymphoblastic leukemia (ALL), is associated with severe side effects, such as cerebellar toxicity and bone marrow suppression. Hence, while the incidence of AML increases with age, doses of cytarabine are significantly attenuated or the drug is entirely excluded from the regimen used in older adults due to its potential toxicities, particularly in individuals with hepatic or renal dysfunction. Astarabine is a new composition of cytarabine covalently bound to asparagine. It is designed to target cytarabine to leukemic blasts, thus avoiding extramedullary toxicity. Leukemic cells, which are dependent on an external source of amino acids in general and asparagine in particular, due to their high metabolic rate, have a relatively increased uptake of Astarabine. Inside the blasts, Astarabine is cleaved to cytarabine, enabling targeted killing and relative sparing of normal hematopoiesis. As such, Astarabine may serve as an ideal therapy for leukemia, particularly for delivering high doses of cytarabine to medically unfit or older adults who otherwise can be given supportive therapy only. The aim of this study was to evaluate the safety and optimal dose of Astarabine in refractory/relapsed or medically unfit patients with acute leukemia. Methods: This Phase I/IIa prospective open label study enrolled patients aged ≥18 years with relapsed/refractory or newly-diagnosed acute leukemia unfit for intensive therapy, as judged by the treating physician. The study was approved by the Rambam IRB (approval #0384-11). Patients were enrolled into 6 Astarabine escalating-dose cohorts, each composed of 3-6 patients. Treatment was administered as a 1-hour single daily infusion for 6 days. For cohorts 1-4, Astarabine doses for each infusion were 0.5g/m2, 1.5g/m2, 3g/m2 and 4.5g/m2. The doses were reduced by 50% for patients >50 years. Since dose limiting toxicity (DLT) was not reached in cohorts 1-4, the study was extended to include cohorts 5 and 6 with daily Astarabine doses of 4.5g/m2 and 6g/m2, respectively, with no dose reduction for patients >50 years old. Results: The outcome of 15 patients is reported herein. Six patients with a median age of 64 years (range 27-81) had refractory/relapsed AML, 9 patients with a median age of 80 years (range 70-90) were newly diagnosed (secondary AML - 6, de-novo AML - 2, de-novo ALL - 1) and unfit for intensive therapy. Astarabine treatment was well-tolerated. Two patients died (one from pneumonia and one from sudden death 2 weeks from end of treatment) before completing 30 days post-treatment and hence were excluded from the outcome analysis. Response to the treatment was observed in the bone marrow of 6 of the 7 newly-diagnosed patients for whom bone marrow analysis was available, 3 of whom had a continuous complete remission (CR) for 4 (ongoing), 8, and 10 months post-treatment, and 3 had a continuous partial remission (PR) for 3,7, and 7 (ongoing) months. The median overall survival (OS) of the patients with CR/PR is 7 months to date (table 1). No significant response was observed in the relapsed/refractory patients, with a median OS of 2.5 months. Twelve patients died from disease progression. Conclusions: Astarabine, a new composition of leukemia-targeted cytarabine, is safe and very well tolerated, even in patients over 80 years of age, resulting in response in 6 of 7 newly diagnosed patients with acute leukemia. To the best of our knowledge, this is the first report permitting high-dose of cytarabine, considered a cornerstone of leukemia therapy, to be given to a population of patients that heretofore did not have this option. Further dose escalation studies are currently ongoing at a cytarabine-equivalent dose of 4.5 and 6 g/m2/day. A phase II study is planned to confirm these encouraging results and define the use of Astarabine for patients otherwise unable to receive high doses of cytarabine. Disclosures Zuckerman: BioSight Ltd: Consultancy, Research Funding. Gengrinovitch:BioSight Ltd: Employment, Equity Ownership, Patents & Royalties: Inventor all of the patents. Ben-Yakar:BioSight Ltd: Consultancy, Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Inventor of all patents.

Effectiveness and Safety Studies of Omalizumab in Children and Adolescents With Moderate-To-Severe Asthma

2021 ◽  
pp. 089719002110382
Author(s):  
Lu Cheng ◽  
Tianrui Yang ◽  
Xiang Ma ◽  
Yuling Han ◽  
Yongtai Wang
Keyword(s):  
Children And Adolescents ◽  
Allergic Asthma ◽  
Severe Asthma ◽  
Fixed Effects ◽  
Vital Capacity ◽  
Immunoglobulin E ◽  
Meta Analysis ◽  
Fixed Effects Model ◽  
Significant Difference ◽  
Severe Allergic Asthma

Background Omalizumab is currently approved for the treatment of moderate-to-severe allergic asthma in patients 6 years and older. Objective To assess the effectiveness and safety of subcutaneous omalizumab as an add-on therapy option for moderate–severe allergic asthma in patients aged 6—20 years old. Methods The studies published from July, 1970 to May, 2021 were searched from the electronic databases which followed keywords: (“anti-IgE” OR “anti-immunoglobulin E” OR “anti-IgE antibody” OR “omalizumab” OR “rhuMAb-E25” OR “Xolair”) AND “asthma” AND (“child” OR “children” OR “adolescents” OR “youth” OR “teenager” OR “kids” OR “pediatric”). Thirteen studies were pooled to determine the effectiveness and safety of omalizumab. Efficacy endpoints were evaluated using a fixed-effects model or a random-effects model depending on heterogeneity. Safety endpoints were evaluated by odds ratio. Results Thirteen studies were included. In this meta-analysis, our results showed that fractional exhaled nitric oxide and asthma control test scores were significantly improved with omalizumab treatment. Serum immunoglobulin E was also decreased in children with moderate-to-severe asthma after treatment with omalizumab. The analysis found that there was no significant difference between pre-and post-treatment in forced expiratory volume in one second/ forced vital capacity ratio, forced expiratory flow between 25 and 75% of vital capacity, or FEV1. Overall, more adverse events occurred with omalizumab compared to placebo. However, the degree was mild to moderate. Conclusion This meta-analysis indicates that omalizumab is safe and effective to treat children and adolescents with moderate-to-severe asthma.

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