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Expert Review of Clinical Pharmacology Mar 2019Induction chemotherapy based on anthracyclines and cytarabine (Ara-C) combination remains the standard of care for acute myeloid leukemia (AML) patients who are...
Induction chemotherapy based on anthracyclines and cytarabine (Ara-C) combination remains the standard of care for acute myeloid leukemia (AML) patients who are considered candidate for intensive and curative approaches. However, the toxicity of this regimen is high, with disappointing clinical outcomes among the so-called poor-prognosis AML subsets, which generally refer to patients with adverse cytogenetic risk, secondary AML including therapy-related AML, poor-prognosis mutations, especially FLT3-ITD, and relapse/refractory AML. Areas covered: To the best of our knowledge, the role and efficacy of 7 + 3 schedules containing daunorubicin (DNR) and Ara-C for certain types of poor-prognosis AML has not been systematically assessed. A critical approach to the role of DNR and Ara-C induction could be relevant to establish which patients should be enrolled in clinical trials using novel therapies. Expert commentary: In this regard, a recent randomized clinical trial (RCT) showed improved results in older patients with sAML or high-risk cytogenetics who received CPX-351 compared with standard 7 + 3 combination. We perform a systematic literature review to analyze the clinical outcomes reported with DNR plus Ara-C regimens in adult patients with poor-prognosis AML, the use of liposomal formulations of DNR and Ara-C and the RCTs which compared standard 7 + 3 with the addition of a third drug.
Topics: Adult; Animals; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Cytogenetic Analysis; Daunorubicin; Drug Administration Schedule; Humans; Leukemia, Myeloid, Acute; Mutation; Prognosis; Randomized Controlled Trials as Topic
PubMed: 30672340
DOI: 10.1080/17512433.2019.1573668 -
Asia-Pacific Journal of Clinical... Feb 2023Because of the high interindividual pharmacokinetic variability, several population pharmacokinetic (PopPK) models of doxorubicin (DOX) were developed to characterize... (Review)
Review
Because of the high interindividual pharmacokinetic variability, several population pharmacokinetic (PopPK) models of doxorubicin (DOX) were developed to characterize factors influencing such variability. However, significant predictors for DOX pharmacokinetics identified using PopPK models varied across studies. Thus, this review aims to summarize PopPK models of DOX and its metabolites (if any) as well as significant covariates influencing DOX (and its metabolites) pharmacokinetic variability. A systematic search from PubMed, CINAHL Complete, Science Direct, and SCOPUS databases identified 503 studies. Of these, 16 studies met the inclusion criteria and were included in this review. DOX pharmacokinetics was described with two- or three-compartment models. Most studies found a significant increase in DOX clearance with an increase in body surface area from the median value of 1.8 m . Moreover, this review identified that while a 10-year increase in patient age resulted in a decrease in DOX clearance in adults and the elderly, younger children had lower DOX clearance compared to older children. Further, low DOX exposure was observed in pregnant women, and thus dosage adjustment is required. Concerning model applicability, predictive performance assessment of these published models should be performed before implementing such models in clinical practice.
Topics: Pregnancy; Adult; Child; Humans; Female; Adolescent; Aged; Models, Biological; Doxorubicin; Databases, Factual
PubMed: 35415961
DOI: 10.1111/ajco.13776 -
Leukemia Research Oct 2023Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a...
Safety and efficacy of FLAG-Ida-based therapy combined with venetoclax for the treatment for newly diagnosed and relapsed/refractory patients with AML - A systematic review.
Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a systematic review to assess the safety and efficacy outcomes of FLAG-IDA in combination with VEN. The primary safety outcome was infection rate; the primary efficacy outcome was response to treatment (composite complete remission (CRc) and overall response rate (ORR). Risk of bias was assessed according to the ROBINS-I tool. Six studies including 221 patients with newly-diagnosed (ND AML (n = 120)) and R/R AML (n = 101) disease, were included in this systematic review. Pooling of results was not conducted due to major differences between studies. The reported rates of neutropenic fever, bacteremia, pneumonia and invasive fungal infections were at 44-55 %, 24-48 %, 12-30 % and 11-36 % of assessed patients, respectively. Time to ANC and platelet recovery ranged between 23 and 29 and 23-31 days, respectively. Early death rate was 8.7 % (14/160) patients: four patients at 30 days, additional ten in 60 days. CRc rates ranged between 53 % and 78 % for R/R AML. CRc for ND was reported by one study only (89 %). ORR were reported in 60-78 % of patients with R/R AML. Only one study reported an ORR for ND patients of 98 %. In our systematic review, FLAG-Ida plus VEN proved to be a potentially tolerable and effective regimen in ND and R/R AML patients. We suggest further evaluation and confirmation for the safety and efficacy of this new protocol in future RCTs.
Topics: Humans; Idarubicin; Leukemia, Myeloid, Acute; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 37598660
DOI: 10.1016/j.leukres.2023.107368 -
Health Technology Assessment... Mar 2006To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH)... (Review)
Review
Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.
OBJECTIVES
To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH) monotherapy and paclitaxel used alone or in combination with a platinum-based compound for the second-line or subsequent treatment of advanced ovarian cancer.
DATA SOURCES
Electronic databases covering publication years 2000-4. Company submissions.
REVIEW METHODS
Seventeen databases were searched for randomised controlled trials (RCTs) and systematic reviews for the clinical effectiveness of PLDH, topotecan and paclitaxel and economic evaluations of the cost-effectiveness of PLDH, topotecan and paclitaxel. Selected studies were quality assessed and data extracted, as were the three company submissions. A new model was developed to assess the costs of the alternative treatments, the differential mean survival duration and the impact of health-related quality of life. Monte-Carlo simulation was used to reflect uncertainty in the cost-effectiveness results.
RESULTS
Nine RCTs were identified. In five of these trials, both the comparators were used within their licensed indications. Of these five, three included participants with both platinum-resistant and platinum-sensitive advanced ovarian cancer, and a further two only included participants with platinum-sensitive disease. The comparators that were assessed in the three trials that included both subtypes of participants were PLDH versus topotecan, topotecan versus paclitaxel and PLDH versus paclitaxel. In the further two trials that included participants with the subtype of platinum-sensitive disease, the comparators that were assessed were single-agent paclitaxel versus a combination of cyclophosphamide, doxorubicin and cisplatin (CAP) and paclitaxel plus platinum-based chemotherapy versus conventional platinum-based therapy alone. A further four trials were identified and included in the review in which one of the comparators in the trial was used outside its licensed indication. The comparators assessed in these trials were oxaliplatin versus paclitaxel, paclitaxel given weekly versus every 3 weeks, paclitaxel at two different dose levels and oral versus intravenous topotecan. Four studies met the inclusion criteria for the cost-effectiveness review. The review of the economic evidence from the literature and industry submissions identified a number of significant limitations in existing studies assessing the cost-effectiveness of PLDH, topotecan and paclitaxel. Analysis 1 assessed the cost-effectiveness of PLDH, topotecan and paclitaxel administered as monotherapies. Sensitivity analysis was undertaken to explore the impact of patient heterogeneity (e.g. platinum-sensitive and platinum-resistant/refractory patients), the inclusion of additional trial data and alternative assumptions regarding treatment and monitoring costs. In the base-case results for Analysis 1, paclitaxel monotherapy emerged as the cheapest treatment. When the incremental cost-effectiveness ratios (ICERs) were estimated, topotecan was dominated by PLDH. Hence the options considered in the estimation of the ICERs were paclitaxel and PLDH. The ICER for PLDH compared with paclitaxel was pound 7033 per quality-adjusted life-year (QALY) in the overall patient population (comprising platinum-sensitive, -refractory and -resistant patients). The ICER was more favourable in the platinum-sensitive group ( pound 5777 per QALY) and less favourable in the platinum-refractory/resistant group ( pound 9555 per QALY). The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of the additional trial data resulted in less favourable estimates for the ICER for PLDH versus paclitaxel compared with the base-case results. The ICER of PLDH compared with paclitaxel was pound 20,620 per QALY in the overall patient population, pound 16,183 per QALY in the platinum-sensitive population and pound 26,867 per QALY in the platinum-resistant and -refractory population. The results from Analysis 2 explored the cost-effectiveness of the full range of treatment comparators for platinum-sensitive patients. The treatment options considered in this model comprised PLDH, topotecan, paclitaxel-monotherapy, CAP, paclitaxel/platinum combination therapy and platinum monotherapy. Owing to the less robust approaches that were employed to synthesise the available evidence and the heterogeneity between the different trials, the reliability of these results should be interpreted with some caution. Topotecan, paclitaxel monotherapy and PLDH were all dominated by platinum monotherapy (i.e. higher costs and lower QALYs). After excluding these alternatives, the treatments that remained under consideration were platinum monotherapy, CAP and paclitaxel-platinum combination therapy. Of these three alternatives, platinum monotherapy was the least costly and least effective. The ICER for CAP compared with platinum monotherapy was pound 16,421 per QALY. The ICER for paclitaxel-platinum combination therapy compared with CAP was pound 20,950 per QALY.
CONCLUSIONS
For participants with platinum-resistant disease there was a low probability of response to treatment with PLDH, topotecan or paclitaxel. Furthermore, there was little difference between the three comparators in relation to overall survival. The comparators did, however, differ considerably in their toxicity profiles. Given the low survival times and response rates, it appears that the maintenance of quality of life and the control of symptoms and toxicity are paramount in this patient group. As the three comparators differed significantly in terms of their toxicity profiles, patient and physician choice is also an important element that should be addressed when decisions are made regarding second-line therapy. It can also be suggested that this group of patients may benefit from being included in further clinical trials of new drugs. For participants with platinum-sensitive disease there was a considerable range of median survival times observed across the trials. The most favourable survival times and response rates were observed for paclitaxel and platinum combination therapy. This suggests that treatment with combination therapy may be more beneficial than treatment with a single-agent chemotherapeutic regimen. In terms of single-agent compounds, the evidence suggests that PLDH is more effective than topotecan. Evidence from a further trial that compared PLDH and paclitaxel suggests that there is no significant difference between these two comparators in this trial. The three comparators did, however, differ significantly in terms of their toxicity profiles across the trials. Although treatment with PLDH may therefore be more beneficial than that with topotecan, patient and physician choice as to the potential toxicities associated with each of the comparators and the patient's ability and willingness to tolerate these are of importance. Assuming the NHS is willing to pay up to pound 20,000-40,000 per additional QALY, PLDH appears to be cost-effective compared with topotecan and paclitaxel monotherapy, in terms of the overall patient population and the main subgroups considered. The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of additional trial data gave less favourable estimates for the ICER for PLDH versus paclitaxel monotherapy, compared with the base-case results. Although the ICER of PLDH compared with paclitaxel monotherapy was less favourable, PLDH was still cost-effective compared with topotecan and paclitaxel monotherapy. For platinum-sensitive patients, the combination of paclitaxel and platinum appears to be cost-effective. On the strength of the evidence reviewed here, it can be suggested that participants with platinum-resistant disease may benefit from being included in further clinical trials of new drugs. To assess the effectiveness of combination therapy against a single-agent non-platinum-based compound, it can be suggested that a trial that compared paclitaxel in combination with a platinum-based therapy versus single-agent PLDH would be a reasonable option.
Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Cost-Benefit Analysis; Doxorubicin; Female; Humans; Liposomes; Ovarian Neoplasms; Paclitaxel; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Survival Analysis; Topotecan
PubMed: 16545208
DOI: 10.3310/hta10090 -
Clinical Oral Investigations Jan 2023To investigate the association between asthma and oral conditions in children and adolescents. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the association between asthma and oral conditions in children and adolescents.
MATERIAL AND METHODS
Observational studies that evaluated the association between asthma and oral conditions in children and/or adolescents were retrieved from five databases, grey literature and reference lists up to April 7, 2022. Meta-analyses were performed, and I statistics were calculated. The mean difference was used as a measure of effect for continuous variables. Event frequencies were evaluated to determine odds ratios for dichotomous variables. Publication bias was investigated using Egger's test. The methodological quality (JBI) and certainty of the evidence (GRADE) were assessed.
RESULTS
Forty-two studies were eligible, and sixteen were included in the meta-analysis. Mean dmft (MD: 1.11, 95%CI: 0.48-1.73), DMFT (MD: 1.01, 95% CI: 0.45-1.56), dmfs (MD: 3.62, 95%CI: 2.60-4.63) and DMFS (MD: 4.47, 95%CI: 0.98-7.96) indices were significantly higher in asthmatic children and adolescents compared to those without asthma. In the analysis of biofilm, asthmatic children and adolescents had a higher Plaque Index compared to those without asthma (MD: 0.18, 95%CI: 0.03-0.33).
CONCLUSION
Asthmatic children and adolescents may be more likely to develop tooth decay and build up biofilm compared to those without asthma. It is suggested that there are no differences between asthmatic and non-asthmatic children and adolescents regarding gingivitis, developmental defects of enamel or erosive tooth wear. The certainty of the evidence was classified as 'very low'.
CLINICAL RELEVANCE
Knowledge of the risks that asthma and asthma medications for oral health can assist in counselling families of children and adolescents with this condition in terms of control and prevention measures for oral problems.
Topics: Adolescent; Child; Humans; Dental Caries; Doxorubicin; Fluorouracil; Gingivitis; Oral Health; Asthma
PubMed: 36459238
DOI: 10.1007/s00784-022-04803-4 -
Cancer Nursing 2014The central nervous system is a unique sanctuary site for malignant disease. To ensure optimal disease control, intrathecal (IT) chemotherapy is commonly given in... (Review)
Review
BACKGROUND
The central nervous system is a unique sanctuary site for malignant disease. To ensure optimal disease control, intrathecal (IT) chemotherapy is commonly given in conjunction with standard chemotherapy protocols, thus providing the opportunity for medication errors.
OBJECTIVE
A systematic review of the current literature on medication errors associated with the administration of IT chemotherapy was conducted.
METHODS
English-language literature published from January 1960 through June 2013 was accessed. Case reports, clinical studies, and review articles pertaining to IT medication errors were included in the review. References of all relevant articles were searched for additional citations.
RESULTS
Twenty-two cases of accidental IT overdoses have been reported with methotrexate and 1 with cytarabine. There have been numerous cases of antineoplastic agents intended for administration by the parenteral route being inadvertently given intrathecally. Vincristine has been implicated 31 times (25 deaths), as well as vindesine, asparaginase, bortezomib, daunorubicin, and dactinomycin. This has led to profound toxicity and, commonly, death. Unfortunately, many cases go unrecognized or unreported.
CONCLUSIONS
The best method for eliminating the risk of IT medication errors is to develop effective methods of prevention and incorporate them into oncology and hematology practice internationally. Strategies include abolishing the syringe as a method of vinca alkaloid administration and substituting small-volume intravenous bags, and developing novel methods for intraspinal drug administration.
IMPLICATIONS FOR PRACTICE
The nursing profession is in a unique position to influence change and lead the way in establishing preventative strategies into current practice.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cytarabine; Evidence-Based Medicine; Humans; Injections, Spinal; Medication Errors; Methotrexate; Vincristine
PubMed: 24201315
DOI: 10.1097/NCC.0000000000000108 -
European Journal of Drug Metabolism and... Jul 2022Almost 15 years after the introduction of transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) therapy, the mean... (Meta-Analysis)
Meta-Analysis
Systematic Review and Pharmacokinetic Meta-analysis of Doxorubicin Exposure in Transcatheter Arterial Chemoembolization and Doxorubicin-Eluted Beads Chemoembolization for Treatment of Unresectable Hepatocellular Carcinoma.
BACKGROUND
Almost 15 years after the introduction of transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) therapy, the mean peak plasma concentration (C) and area under the concentration-time curve (AUC) for doxorubicin have still not been systematically reviewed or meta-analyzed.
OBJECTIVE
To conduct a systematic review and meta-analysis of available data and establish a reference range for C and AUC of doxorubicin DEB-TACE and TACE, as well as explore the potential influence of microspheres' size and type on these parameters.
METHODS
PubMed, EMBASE, and Web of Science were searched from August 1992 through December 2021. Studies measuring exposure parameters among HCC patients treated with doxorubicin DEB-TACE without restriction on language were included. Two independent reviewers extracted and unified data sets for pooled estimate analysis. The quality of the evidence was assessed via the Grading of Recommendations Assessment, Development and Evaluation framework. The ClinPK Statement checklist and Newcastle-Ottawa Scale (NOS) were used to determine the quality of studies.
RESULTS
Out of 666 studies, 246 full-text were reviewed, and 8 studies entered the meta-analysis (120 patients). C and AUC of doxorubicin were 7.52-fold (95% CI 7.65 to 7.42-fold; P < 0.0001) and 1.91-fold (95% CI 1.95 to 1.88-fold; P = 0.0001) lower with DEB-TACE compared to TACE. Significant reduction in pooled standardized mean difference (SMD) of C and AUC was observed with DEB-TACE versus TACE in direct comparison analysis (- 2.93; 95% CI - 3.60 to - 2.26, P < 0.00001, and - 1.73 95% CI - 2.55 to - 0.91, P < 0.0001, respectively). Moreover, in DEB-TACE stratification analysis, small microspheres revealed higher C, AUC and tumor response rate as well as lower complication rate.
LIMITATION
The heterogeneity could not be completely addressed through sensitivity and stratification analysis.
CONCLUSION
This meta-analysis provides exposure parameters of doxorubicin and justifies the advantage of DEB-TACE over TACE in terms of safety for patients with unresectable HCC. This study showed a marked association between the size of microsphere and exposure parameters of doxorubicin supporting the preference for small microspheres in DEB-TACE. The moderate and low quality of evidence is assigned to the C and AUC, respectively.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Humans; Liver Neoplasms; Microspheres
PubMed: 35543895
DOI: 10.1007/s13318-022-00762-z -
European Journal of Pharmacology Aug 2021The safe development of nanotechnology and usage of nanoparticles (NPs) require the cellular toxicity examination of these NPs. Systematic studies are necessary to...
The safe development of nanotechnology and usage of nanoparticles (NPs) require the cellular toxicity examination of these NPs. Systematic studies are necessary to collect related data and comparison of the physicochemical features of NPs and their effects on cellular viability on model systems. In the present study, we systematically reviewed original studies, which investigated the cytotoxic effects and apoptosis of free NPs (loaded with doxorubicin (Dox)/or methotrexate (MTX)) via in vitro models. Articles were systematically collected by screening the literature published online in the following databases; PUBMED and SCOPUS and Web of Science and EMBASE. 23 in vitro cytotoxicity studies with 8 apoptosis examinations were found on osteosarcoma (OS) cell lines (mostly on MG-63). 43.47% of the synthesized NPs (10 studies) showed no cytotoxicity to OS cells. 39.13% of the synthesized NPs (9 studies) showed time and/or concentration related-cytotoxicity. Potent cytotoxic synthesized NP did not state. Significance difference between the half-maximal inhibitory concentration (IC50) of drug and drug/NP reported in all studies. Involved NPs in this systematic review for delivery of Dox/or MTX to OS cells have higher safety index and biocompatibility, although small and positively charged NPs acted more toxic in comparison to larger and negative ones, apoptosis rate like cytotoxicity index was notable in drug/NP group, to apply them in clinical works. Future studies are required to address the mechanisms involved in cytotoxicity and apoptosis with a special focus on in vivo investigations.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Death; Doxorubicin; Drug Delivery Systems; Humans; Methotrexate; Nanoparticles; Osteosarcoma
PubMed: 33933464
DOI: 10.1016/j.ejphar.2021.174131 -
Urologic Oncology May 2022The purpose of this systematic literature review and meta-analysis was to compare the pathological response rate and prognosis of the dose dense Methotrexate,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this systematic literature review and meta-analysis was to compare the pathological response rate and prognosis of the dose dense Methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) regimen and gemcitabine and cisplatin (GC) regimen as neoadjuvant chemotherapy choices for bladder cancer.
METHODS
A literature review of articles published before February 28, 2021, was conducted using the PubMed, Web of Sciences and Embase databases. Data for comparison included pathological response rate and overall survival.
RESULTS
Five studies including 1,206 patients were identified and assessed for the meta-analysis. The pooled analysis yielded an odds ratio value of 1.29 (95% CI, 0.86-1.92) with a downstaging rate and an odds ratio value of 1.57 (95% CI, 1.10-2.25) with a complete response rate when comparing ddMVAC with the GC regimen. The pooled analysis yielded a hazard ratio of 0.47 (95% CI, 0.30-0.72) with regard to overall survival between the two regimens.
CONCLUSION
Compared with the GC regimen, ddMVAC has a better pathological response rate, especially the complete response rate, and provides longer overall survival as a neoadjuvant chemotherapy regimen for bladder cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Female; Humans; Male; Methotrexate; Neoadjuvant Therapy; Retrospective Studies; Urinary Bladder Neoplasms; Vinblastine
PubMed: 34949512
DOI: 10.1016/j.urolonc.2021.11.016 -
Clinical Lymphoma, Myeloma & Leukemia Dec 2018The 2 main formulations of anthracycline used for acute myeloid leukemia (AML) induction therapy are idarubicin (IDA) and daunorubicin. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The 2 main formulations of anthracycline used for acute myeloid leukemia (AML) induction therapy are idarubicin (IDA) and daunorubicin.
PATIENTS AND METHODS
The present systematic review and meta-analysis compared the efficacy and toxicity between IDA and high-dose daunorubicin (HDD) for induction therapy for adult AML. Relevant studies reported before June 2018 were searched from the Medline and Embase databases.
RESULTS
A total of 5 studies with 1809 participants (3 randomized controlled studies and 2 retrospective cohort studies) met the eligibility criteria and were included in the meta-analysis. The patients in the IDA arm for induction therapy had a significantly greater complete response rate after the first course of induction therapy compared with those in the HDD arm (66.7% vs. 61.1%, respectively; odds ratio, 1.23; P = .04; I = 0%). A significantly lower rate of refractory AML was also observed in the IDA group than in the HDD group (16.8% vs. 20.7%, respectively; odds ratio, 0.77; P = .04; I = 0%). However, no difference was found in the long-term overall survival between the 2 groups. Also, the induction mortality rate, febrile neutropenia rate, and cardiotoxicity rate were not significantly different between the 2 groups. The major limitation was the relatively small number of included studies, which could have limited the power of the meta-analysis to demonstrate significant long-term benefits.
CONCLUSION
The complete response rate after the first course of induction therapy was significantly greater among adult patients with AML who had received IDA as part of induction therapy compared with those who had received HDD.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Daunorubicin; Female; Humans; Idarubicin; Leukemia, Myeloid, Acute; Male; Middle Aged; Odds Ratio; Remission Induction; Treatment Outcome; Young Adult
PubMed: 30241991
DOI: 10.1016/j.clml.2018.08.008