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Cancer Jul 2010The optimal postremission therapy in adults with acute lymphoblastic leukemia (ALL) is still a matter of debate. The objective of this study was to compare the various... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal postremission therapy in adults with acute lymphoblastic leukemia (ALL) is still a matter of debate. The objective of this study was to compare the various potential therapeutic options for patients who achieved first complete remission.
METHODS
The authors conducted a systematic review and meta-analysis of randomized trials, including patients with standard-risk (SR) All and high-risk (HR) ALL who received first postremission therapy. Outcomes assessed were all-cause mortality (ACM), disease recurrence (relapse), and nonrelapse mortality (NRM). Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled.
RESULTS
Overall, there was a significant reduction in ACM in the allogenic stem cell transplantation (alloSCT) arm (RR, 0.88; 95% CI, 0.8-0.97) compared with autologous stem cell transplantation (ASCT) or chemotherapy. Subgroup analyses revealed a similar pattern among SR patients (RR, 0.8; 95% CI, 0.68-0.94) but a nonsignificant advantage for alloSCT among HR patients (RR, 0.88; 95% CI, 0.76-1.01). There was an increase in NRM (RR, 2.99; 95% CI, 1.37-6.53) and a decrease in the relapse rate in the alloSCT arm (RR, 0.52; 95% CI, 0.33-0.83). There was no difference in ACM or the relapse rate between the ASCT and chemotherapy arms.
CONCLUSIONS
Overall, alloSCT was superior to ASCT or chemotherapy for patients with ALL in first complete remission. The survival advantage was of greater statistical significance for patients with SR ALL than for patients with HR ALL.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Randomized Controlled Trials as Topic; Recurrence; Remission Induction
PubMed: 20564092
DOI: 10.1002/cncr.25136 -
BMC Cancer Nov 2023Children with acute lymphoblastic leukaemia (ALL) experience multiple symptoms that occur in complicated patterns and negatively affect patient outcomes. To date, no... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Children with acute lymphoblastic leukaemia (ALL) experience multiple symptoms that occur in complicated patterns and negatively affect patient outcomes. To date, no systematic review has been performed on the prevalence of symptoms in children with ALL.
OBJECTIVE
The study aimed to report and analyse the prevalence of symptoms in children with ALL during treatment.
METHODS
A systematic search was conducted in eight databases (PubMed, Ovid Embase, Web of Science, CINAHL, PsycINFO, China WanFang Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure) for studies published between January 1, 2000, and August 12, 2023. The methodological quality of the included studies was evaluated and a meta-analysis was performed to pool the prevalence of symptoms.
RESULTS
In total, 17 studies were included, from which 34 symptoms were identified. The symptom prevalence ranged between 1.5 and 91.0% and the most frequent symptoms observed were fatigue, lack of energy, dry mouth, lack of appetite, sweating, and feeling irritable, which occurred in at least 60% of the patients.
CONCLUSIONS
Symptoms remain highly prevalent in paediatric patients with ALL, which provides support for the need for symptom assessment in the clinical setting. Specific intervention is urgently needed to mitigate the symptoms in children with ALL and help them cope with the symptom burden.
Topics: Humans; Child; Prevalence; Emotions; China; Fatigue; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37968600
DOI: 10.1186/s12885-023-11581-z -
Technology in Cancer Research &... 2021Monoclonal antibodies targeting cluster of differentiation (CD) proteins have been incorporated into standard treatments for multiple types of hematologic malignancies,... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Monoclonal antibodies targeting cluster of differentiation (CD) proteins have been incorporated into standard treatments for multiple types of hematologic malignancies, including acute lymphoblastic leukemia (ALL). This systematic review and meta-analysis investigated the efficacy of using CD-targeted antibodies for ALL.
MATERIALS AND METHODS
The EMBASE and MEDLINE databases were searched for research papers using immunotherapy- and ALL-related terms from inception to July 2021. Eligible studies were randomized, controlled trials (RCTs) or cohort studies in which ALL patients received CD-targeted immunotherapy or conventional chemotherapy as the induction or salvage therapy. The reports had to report our primary outcomes of interest: overall survival (OS), relapse-free survival (RFS), or complete remission (CR), with the patient number for each outcome. The effect estimates with 95% confidence interval (CI) from each study were combined to calculate the pooled-effect estimate, using the Hantel-Maenszel method.
RESULTS
Five RCTs and 9 retrospective cohort studies were eligible for the meta-analysis. ALL patients given CD-targeted immunotherapy in the induction or salvage therapy had significantly higher OS and RFS rates than those administered conventional chemotherapy only, with pooled odds ratios (OR) of 2.11 (95% CI, 1.76-2.53; I, 0%) and 2.25 (95% CI, 1.62-3.14; I, 61%), respectively. The rates of achieving CR and minimal residual disease negativity were also higher for the immunotherapy group, with pooled ORs of 1.70 (95% CI, 1.07-2.69; I, 79%) and 2.98 (95% CI, 1.17-7.58; I, 90%), while developing less risk for febrile neutropenia (pooled OR, 0.22; 95% CI, 0.08-0.58; I, 84%). Subgroup analyses revealed that all antibody types yielded dramatically better OS rates than those for patients administered chemotherapy alone.
CONCLUSIONS
The ALL patients receiving CD-targeted immunotherapy as induction or salvage therapy had significantly higher response rates and survival outcomes, as well as lower odds of acquiring febrile neutropenia, than the patients given conventional chemotherapy.
Topics: Antibodies, Bispecific; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Febrile Neutropenia; Humans; Immunotherapy; Induction Chemotherapy; Inotuzumab Ozogamicin; Molecular Targeted Therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rituximab; Salvage Therapy; Survival Rate
PubMed: 34350787
DOI: 10.1177/15330338211037434 -
Pediatric Blood & Cancer Feb 2013Treatment of the central nervous system (CNS) is an essential therapy component for childhood acute lymphoblastic leukemia (ALL). Individual patient data from 47 trials... (Meta-Analysis)
Meta-Analysis Review
Treatment of the central nervous system (CNS) is an essential therapy component for childhood acute lymphoblastic leukemia (ALL). Individual patient data from 47 trials addressing 16 CNS treatment comparisons were analyzed. Event-free survival (EFS) was similar for radiotherapy versus intrathecal (IT), and radiotherapy plus IT versus IV methotrexate (IV MTX) plus IT. Triple intrathecal therapy (TIT) gave similar EFS but poorer survival than intrathecal methotrexate (IT MTX), but additional IV MTX improved both outcomes. One trial resulted in similar EFS and survival with IV MTX plus IT MTX versus TIT alone. Radiotherapy can generally be replaced by IT therapy. TIT should be used with effective systemic therapy such as IV MTX.
Topics: Antineoplastic Agents; Central Nervous System; Central Nervous System Neoplasms; Child; Humans; Injections, Spinal; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Randomized Controlled Trials as Topic
PubMed: 22693038
DOI: 10.1002/pbc.24228 -
PloS One 2021Hematopoietic stem cell transplantation (HSCT) is the current mainstay treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However,... (Meta-Analysis)
Meta-Analysis
Is stem cell transplantation still needed for adult Philadelphia chromosome-positive acute lymphoblastic leukemia receiving tyrosine kinase inhibitors therapy?: A systematic review and meta-analysis.
BACKGROUND
Hematopoietic stem cell transplantation (HSCT) is the current mainstay treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, tyrosine kinase inhibitors (TKI) also play a significant role in the treatment of these patients. We conducted this systematic review and meta-analysis to compare the efficacy of allogeneic (allo-) HSCT, autologous (auto-) HSCT, and chemotherapy (CMT) alone-all in combination with TKIs in adult Ph+ ALL patients.
MATERIALS AND METHODS
This systematic review identified studies from the EMBASE and MEDLINE databases from inception to April 2021 using search terms related to "ALL" and "HSCT." Eligible studies could be randomized controlled trials or cohort studies that included adult Ph+ ALL patients who received a TKI and either allo-HSCT, auto-HSCT, or CMT alone, and that reported the number of patients in each group for each of our primary outcomes of interest: overall survival (OS) or disease-free survival (DFS). Point estimates and associated 95% confidence intervals (CI) from each study were combined using the Hantel-Maenszel method.
RESULTS
After two rounds of review, 26 cohort studies were determined to be eligible for the meta-analysis. Adult Ph+ ALL patients who received HSCT had better survival outcomes than those who did not receive any HSCT (pooled odds ratio [OR] for OS of 1.61, 95%CI: 1.08-2.40; I2 = 59%, and for DFS of 3.23, 95%CI: 2.00-5.23; I2 = 62% for allo-HSCT; and, pooled OR for OS of 7.04, 95%CI: 1.97-25.15; I2 = 0%, and for DFS of 5.78, 95%CI: 1.04-32.19; I2 = 42% for auto-HSCT). Allo-HSCT recipients had comparable OS and DFS, but lower relapse rate compared to auto-HSCT recipients. Funnel plot generally demonstrated no presence of publication bias.
CONCLUSIONS
This systematic review and meta-analysis demonstrated superior results of HSCT in Ph+ ALL patients compared to CMT alone. Moreover, auto-HSCT could be implemented with comparable survival outcomes to allo-HSCT in patients with no available donor or when haploidentical HSCT is not feasible.
Topics: Allografts; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Molecular Targeted Therapy; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors
PubMed: 34181696
DOI: 10.1371/journal.pone.0253896 -
Environmental Health : a Global Access... Jun 2010A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).
METHODS
A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size).
RESULTS
In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant.
CONCLUSIONS
Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML.
Topics: Benzene; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Occupational Exposure; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors
PubMed: 20584305
DOI: 10.1186/1476-069X-9-31 -
Cancer Medicine Dec 2021This study seeks to clarify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) is necessary for adult patients with Philadelphia chromosome-positive... (Meta-Analysis)
Meta-Analysis
Comparison of allogeneic hematopoietic stem cell transplantation and TKI combined with chemotherapy for adult philadelphia chromosome positive acute lymphoblastic leukemia: a systematic review and meta-analysis.
OBJECTIVE
This study seeks to clarify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) is necessary for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in post-remission based on a comparison with tyrosine kinase inhibitor (TKI) combined with chemotherapy.
METHODS
We searched the Pubmed, Embase, and Web of Science databases and limited the date range for the studies from January 2010 to August 2020. A hazard ratio (HR) with a 95% confidence interval (CI) was employed to assess overall survival (OS) and relapse-free survival (RFS), and an odds ratio (OR) with a 95% CI was used to evaluate the ratio of non-relapsed mortality (NRM) and non-relapsed survival (NRS). All analyses were conducted with Stata software 16.0 and Revman 5.3.
RESULTS
Fifteen studies, totaling 959 patients, were included in our analysis. Among those patients, 473 underwent allo-HSCT, and 486 received TKI plus chemotherapy. The pooled results showed no difference in OS between outcomes for patients receiving TKI plus chemotherapy and those treated with allo-HSCT (HR = 0.76, 95% CI [0.51-1.12], p = 0.16). Patients undergoing allo-HSCT did better than those receiving TKI plus chemotherapy regarding RFS (HR = 0.48, 95% CI [0.37-0.63], p = 0.00), and NRS (OR = 2.64, 95% CI [1.25-5.57], p = 0.00). The NRM rate of the TKI plus chemotherapy group was significantly lower than the allo-HSCT group (OR = 2.33, 95% CI [1.51-3.59], p = 0.00).
CONCLUSION
TKI combined with chemotherapy can be considered a post-remission treatment option for adult Ph+ ALL patients who are ineligible for allo-HSCT. However, more prospective studies with large sample sizes should be carried out in the future.
Topics: Acute Disease; Adolescent; Adult; Aged; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors; Transplantation Conditioning; Transplantation, Homologous; Young Adult
PubMed: 34761879
DOI: 10.1002/cam4.4413 -
Transplantation and Cellular Therapy Jul 2021Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for patients with acute lymphoblastic leukemia (ALL). Both total body irradiation... (Meta-Analysis)
Meta-Analysis
Impact of Total Body Irradiation-Based Myeloablative Conditioning Regimens in Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: Systematic Review and Meta-Analysis.
Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for patients with acute lymphoblastic leukemia (ALL). Both total body irradiation (TBI)-based and chemotherapy only-based myeloablative transplantation conditioning regimens have been applied, but the optimal regimen remains unclear. We performed a systematic review to assess the efficacy of TBI-based versus chemotherapy only-based myeloablative conditioning regimens. We searched PubMed, Embase, and Cochrane databases and meeting abstracts for all studies comparing TBI-based and chemotherapy only-based conditioning regimens in patients who underwent allo-HCT for ALL. Two authors independently reviewed all studies for inclusion and extracted data related to overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), relapse, and acute and chronic graft-versus-host disease (GVHD). Eight studies were included in the final analysis. The overall methodological quality of the included studies was optimal. TBI-based regimens showed evidence of benefit compared with chemotherapy only-based conditioning regimens in terms of relapse (relative risk [RR], 0.82; 95% confidence interval [CI], 0.72 to 0.94; 6 studies, 5091 patients), OS (hazard ratio [HR], 0.76; 95% CI, 0.64 to 0.89; 7 studies, 4727 patients), and PFS (HR, 0.74; 95% CI, 0.63 to 0.85; 7 studies, 4727 patients). The TBI-based regimen did not increase the likelihood of grade II-IV acute GVHD (RR, 1.12; 95% CI, 0.92 to 1.36; 5 studies, 4996 patients) or chronic GVHD (RR, 1.10; 95% CI, 1.00 to 1.21; 5 studies, 4490 patients), or NRM (RR, 0.94; 95% CI, 0.69 to 1.28; 6 studies, 4522 patients). However, TBI-based regimens were associated with an increased risk of grade III-IV acute GVHD (RR, 1.29; 95% CI, 1.01 to 1.63; 3 studies, 3675 patients). A subgroup comparison of patients age ≥16 years showed similar results. This systematic review represents evidence supporting the use of TBI-based conditioning regimen in patients undergoing allo-HCT for ALL who are candidates for myeloablative conditioning, as it offers better OS, PFS, and less relapse with acceptable NRM.
Topics: Adolescent; Hematopoietic Stem Cell Transplantation; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transplantation Conditioning; Transplantation, Homologous; Whole-Body Irradiation
PubMed: 33798768
DOI: 10.1016/j.jtct.2021.03.026 -
American Journal of Hematology May 2012Survival of adults with acute lymphoblastic leukemia (ALL) is inferior to that of pediatric patients. Strategies to improve the outcome of adult population are... (Meta-Analysis)
Meta-Analysis Review
Survival of adults with acute lymphoblastic leukemia (ALL) is inferior to that of pediatric patients. Strategies to improve the outcome of adult population are warranted. This study aims to evaluate the efficacy and safety of pediatric-inspired regimens given to adolescents and young adults (AYA), usually defined as 16-39 years, with ALL. Systematic review and meta-analysis of comparative trials of AYA patients with ALL given induction chemotherapy with either pediatric-inspired regimens or conventional-adult chemotherapy was conducted. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Our search yielded 11 trials, including 2,489 patients. AYA patients given pediatric-inspired regimens had a statistically significant lower all cause mortality rate at 3 years (RR 0.58; 95% CI 0.51-0.67). Complete remission rate after induction chemotherapy and event free survival were superior in the pediatric-inspired regimens arm (RR 1.05; 95% CI 1.01-1.10 and RR 1.66; 95% CI 1.39-1.99, respectively). Relapse rate was also lower in patients given pediatric-inspired regimens (RR 0.51; 95% CI 0.39-0.66) with comparable nonrelapse mortality between the two groups (RR 0.53, 95% CI 0.19-1.48). Pediatric-inspired regimens are superior to conventional-adult chemotherapy in AYA ALL patients. Further randomized controlled studies to investigate this approach in adult ALL patients are warranted.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Disease-Free Survival; Female; Humans; Male; Multicenter Studies as Topic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Risk; Survival Analysis; Survival Rate; Treatment Outcome; Young Adult
PubMed: 22388572
DOI: 10.1002/ajh.23149 -
Frontiers in Oncology 2024Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side... (Review)
Review
Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.
PubMed: 38450195
DOI: 10.3389/fonc.2024.1324859