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Hematology. American Society of... Dec 2022The outcome for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved, mostly based on the use of pediatric-inspired intensive...
The outcome for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved, mostly based on the use of pediatric-inspired intensive protocols. Due to increasing disease resistance and treatment-related toxicity with age, further improvements are now expected from the expanding knowledge of ALL biology, more accurate risk stratification, and the early introduction of targeted small molecules and immunotherapy. In the last decade, the rate of AYA with B-cell precursor ALL with undetermined genetic drivers ("B-other") has shrunk from 40% to fewer than 10%. The high-risk subgroup of Philadelphia-like ALL is the most frequent entity diagnosed in this age range, offering a multitude of potentially actionable targets. The timely and accurate identification of these targets remains challenging, however. Early minimal residual disease (MRD) monitoring has become a standard of care for the risk stratification and identification of patients likely to benefit from an allogeneic hematopoietic stem cell transplantation. Recently approved immunotherapies are moving frontline to eradicate MRD, to improve the outcome of high-risk patients, and, eventually, to reduce treatment burden. Comprehensive care programs dedicated to AYA with cancer aim at improving inclusion in specific clinical trials and at giving access to appropriate psychosocial support, fertility preservation, and survivorship programs.
Topics: Young Adult; Adolescent; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematopoietic Stem Cell Transplantation; Neoplasm, Residual; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Immunotherapy
PubMed: 36485092
DOI: 10.1182/hematology.2022000336 -
Cancer Epidemiology Jun 2020The association of population mixing (PM) with childhood acute lymphocytic leukemia (ALL) has been reproduced in multiple studies. However, the mechanism underlying this...
BACKGROUND
The association of population mixing (PM) with childhood acute lymphocytic leukemia (ALL) has been reproduced in multiple studies. However, the mechanism underlying this association is unknown.
METHODS
Ecological study of incidence of pediatric ALL among 253 counties in the State of Texas (USA) using surrogates of genetic and environmental PM. ALL incidence data were obtained from Texas Cancer Registry and county population statistics from the US Census Bureau. Poisson regression was used to compare ALL incidence and PM.
RESULTS
There is substantial and variable genetic and environmental PM among counties in Texas. Indicators of genetic PM including proportion of multiracial households, ratio of Hispanics to non-Hispanics, and ratio of foreign to native-born residents were all significantly associated with a higher incidence of ALL (IRR 1.81 (95CI 1.05-3.13), 1.67 (95CI 1.16-2.37), and 1.59 (95CI 1.03-2.48), respectively). Surrogates of environmental PM namely population density and persons per household were not associated with incidence of ALL; IRRs 1.29 (95CI 0.4-4.15) and 1.47 (95CI 0.89-2.43).
CONCLUSIONS
These findings are consistent with prior patterns and magnitudes of PM association with ALL. Our findings suggest that the implicated mechanism of leukemogenesis in PM may be genetically transmitted rather than environmental.
Topics: Child; Female; Humans; Incidence; Infant; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult
PubMed: 32353774
DOI: 10.1016/j.canep.2020.101722 -
The Lancet. Haematology Feb 2023Previous studies have identified racial and ethnic disparities in childhood acute lymphocytic leukaemia survival. We aimed to establish whether disparities persist in...
BACKGROUND
Previous studies have identified racial and ethnic disparities in childhood acute lymphocytic leukaemia survival. We aimed to establish whether disparities persist in contemporaneous cohorts and, if present, are attributable to differences in leukaemia biology or insurance status.
METHODS
Patients with newly diagnosed acute lymphocytic leukaemia in inpatient and outpatient centres in the USA, Canada, Australia, and New Zealand, aged 0-30 years, who had race or ethnicity data available, enrolled on eight completed Children's Oncology Group trials (NCT00103285, NCT00075725, NCT00408005, NCT01190930, NCT02883049, NCT02112916, NCT02828358, and NCT00557193) were included in this secondary analysis. Race and ethnicity were categorised as non-Hispanic White, Hispanic, non-Hispanic Black, non-Hispanic Asian, and non-Hispanic other. Event-free survival and overall survival were compared across race and ethnicity groups. The relative contribution of clinical and biological disease prognosticators and insurance status was examined through multivariable regression models, both among the entire cohort and among those with B-cell lineage versus T-cell lineage disease.
FINDINGS
Between Jan 1, 2004, and Dec 31, 2019, 24 979 eligible children, adolescents, and young adults with acute lymphocytic leukaemia were enrolled, of which 21 152 had race or ethnicity data available. 11 849 (56·0%) were male and 9303 (44·0%) were female. Non-Hispanic White patients comprised the largest racial or ethnic group (13 872 [65·6%]), followed by Hispanic patients (4354 [20·6%]), non-Hispanic Black patients (1517 [7·2%]), non-Hispanic Asian (n=1071 [5·1%]), and non-Hispanic other (n=338 [1·6%]). 5-year event-free survival was 87·4% (95% CI 86·7-88·0%) among non-Hispanic White patients compared with 82·8% (81·4-84·1%; hazard ratio [HR] 1·37, 95% CI 1·26-1·49; p<0·0001) among Hispanic patients and 81·8% (79·3-84·0; HR 1·45, 1·28-1·65; p<0·0001) among non-Hispanic Black patients. Non-hispanic Asian patients had a 5-year event-free survival of 88·1% (95% CI 85·5-90·3%) and non-Hispanic other patients had a survival of 82·8% (76·4-87·6%). Inferior event-free survival among Hispanic patients was substantially attenuated by disease prognosticators and insurance status (HR decreased from 1·37 [1·26-1·49; p<0·0001] to 1·11 [1·00-1·22; p=0·045]). The increased risk among non-Hispanic Black patients was minimally attenuated (HR 1·45 [1·28-1·65; p<0·0001] to 1·32 [1·14-1·52; p<0·0001]). 5-year overall survival was 93·6% (91·5-95·1%) in non-Hispanic Asian patients, 93·3% (92·8-93·7%) in non-Hispanic White patients, 89·9% (88·7-90·9%) in Hispanic, 89·7% (87·6-91·4%) in non-Hispanic Black patients, 88·9% (83·2-92·7%) in non-Hispanic other patients. Disparities in overall survival were wider than event-free survival (eg, among non-Hispanic other patients, the HR for event-free survival was 1·43 [1·10-1·85] compared with 1·74 [1·27-2·40] for overall survival). Disparities were restricted to patients with B-cell acute lymphocytic leukaemia, no differences in event-free survival or overall survival were seen in the T-cell acute lymphocytic leukaemia group.
INTERPRETATION
Substantial disparities in outcome for B-cell acute lymphocytic leukaemia persist by race and ethnicity, but are not observed in T-cell acute lymphocytic leukaemia. Future studies of relapsed patients, access to and quality of care, and other potential aspects of structural racism are warranted to inform interventions aimed at dismantling racial and ethnic disparities.
FUNDING
National Cancer Institute and St Baldrick's Foundation.
Topics: Adolescent; Humans; Child; Male; Female; Young Adult; White People; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Black or African American; Ethnicity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell
PubMed: 36725118
DOI: 10.1016/S2352-3026(22)00371-4 -
Journal of Pediatric Hematology/oncology Jan 2022Many studies have shown that IKAROS family zinc finger 1 (IKZF1) rs4132601 polymorphism is strongly linked to acute lymphoblastic leukemia (ALL) in children, but their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many studies have shown that IKAROS family zinc finger 1 (IKZF1) rs4132601 polymorphism is strongly linked to acute lymphoblastic leukemia (ALL) in children, but their conclusions have been inconsistent.
OBJECTIVE
This meta-analysis is set out to investigate the association between IKZF1 rs4132601 polymorphism and its susceptibility to childhood ALL.
DATA AND METHODS
On the basis of inclusion criteria, PubMed, EMBASE, Web of Science, CNKI, China Wanfang, VIP, and other databases were searched from the time of the establishment of the library database to December 2019 for all case-control studies. Stata 15.0 was applied for meta-analysis to calculate the combined odds ratio (OR) value and 95% confidence interval (CI) of each genotype at IKZF1 rs4132601. Subgroup analysis done by ethnicity, sensitivity analysis, and publication bias assessment was further performed.
RESULTS
Nine pieces of literature was included in this meta-analysis, including 2281 children with ALL and 2923 controls. There were significant differences in the allelic model (T vs. G: combined OR=0.75, 95% CI: 0.68-0.82, P<0.05) in both Asian and Caucasian children. In addition to this, there were statistically significant differences in the dominant, homozygous and heterozygous genetic model in both Asian and Caucasian children. The difference was significant in the recessive genetic model (TT vs. TG+GG: combined OR=0.75, 95% CI: 0.67-0.84) in Caucasian children, but not in Asian children (combined OR=0.85, 95% CI: 0.70-1.04, P>0.05).
CONCLUSION
There is a strong correlation between IKZF1 rs4132601 polymorphism and ALL in children. Compared with the G allele, T alleles can lower the risk of childhood ALL, and TT, TT+TG and TG genotypes can also reduce the risk of ALL in children.
Topics: Asian People; Child; Genetic Predisposition to Disease; Humans; Ikaros Transcription Factor; Models, Genetic; Polymorphism, Genetic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; White People
PubMed: 33661176
DOI: 10.1097/MPH.0000000000002130 -
BMC Cancer Dec 2022To evaluate the prognostic factors and outcome for acute lymphoblastic leukemia (ALL) in children with MLL rearrangement (MLL-r).
PURPOSE
To evaluate the prognostic factors and outcome for acute lymphoblastic leukemia (ALL) in children with MLL rearrangement (MLL-r).
METHODS
A total of 124 pediatric patients who were diagnosed with ALL were classified into two groups based on the MLL-r status by using a retrospective case-control study method from June 2008 to June 2020.
RESULTS
The prevalence of MLL-r positive in the whole cohort was 4.9%. The complete remission (CR) rate on Day 33 in the MLL-r positive group was not statistically different from the negative group (96.8% vs 97.8%, P = 0.736). Multivariate analysis showed that T-cell, white blood cell counts (WBC) ≥ 50 × 10/L, MLL-AF4, and D15 minimal residual disease (MRD) positive were independent risk factors affecting the prognosis of MLL-r positive children. Stem cell transplantation (SCT) was a favorable independent prognostic factor affecting event-free survival (EFS) in MLL-r positive patients (P = 0.027), and there was a trend toward an independent prognostic effect on overall survival (OS) (P = 0.065). The 10-year predicted EFS for patients with MLL-AF4, MLL-PTD, MLL-ENL, other MLL partner genes, and MLL-r negative cases were 46.67 ± 28.61%, 85.71 ± 22.37%, 75 ± 32.41%, 75 ± 32.41%, and 77.33 ± 10.81%, respectively (P = 0.048). The 10-year predicted OS were 46.67 ± 28.61%, 85.71 ± 22.37%, 75 ± 32.41%, 75 ± 32.41%, and 85.2 ± 9.77%, respectively (P = 0.049). The 124 patients with ALL were followed up and eventually 5 (4%) cases relapsed, with a median relapse time of 3.9 years.
CONCLUSION
Patients with MLL-r positive ALL have moderate remission rates, but are prone to relapse with low overall survival. The outcome of MLL-r positive ALL was closely related to the partner genes, and clinical attention should be paid to screening for MLL partner genes and combining them with other prognostic factors for accurate risk stratification.
Topics: Humans; Child; Case-Control Studies; Prognosis; Retrospective Studies; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Chromosome Aberrations; Recurrence
PubMed: 36461002
DOI: 10.1186/s12885-022-10378-w -
Cancer Genetics Apr 2019An alarming increase in acute lymphoblastic leukemia among children and males has drawn attention of investigators to delve into the genetic causes of ALL and to... (Review)
Review
An alarming increase in acute lymphoblastic leukemia among children and males has drawn attention of investigators to delve into the genetic causes of ALL and to discover new therapeutic strategies with better prognosis. Although the survival rate in children is much higher than adults, but there's a need to find new potential molecular targets with better treatment outcome. Genomic profiling has made it possible to identify various genetic defects important for driving leukemogenesis. Study of the genetic lesions not only give a better understanding of genes function but also helps to target various signaling pathways involved in disease progression. The current review provides an overview of important genetic defects and dysregulation in their downstream signaling pathways in acute lymphoblastic leukemia.
Topics: Disease Progression; Humans; Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Signal Transduction
PubMed: 31109597
DOI: 10.1016/j.cancergen.2019.02.002 -
Nature Reviews. Disease Primers Jun 2024
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38871713
DOI: 10.1038/s41572-024-00531-z -
Clinical Advances in Hematology &... Apr 2017Acute lymphoblastic leukemia (ALL) is an uncommon disease with poor outcomes in older patients. Although intensive chemotherapy can induce complete responses in older... (Review)
Review
Acute lymphoblastic leukemia (ALL) is an uncommon disease with poor outcomes in older patients. Although intensive chemotherapy can induce complete responses in older patients, the mortality rate is unacceptably high. The 5-year survival rate for patients achieving a remission ranges from 17% to 23%. ALL is usually more aggressive in older patients, and these patients' reduced functional capacity renders them less able to tolerate treatment. The need for less-intensive, more-efficient treatment modalities in this population of frail and high-risk patients is evident. Clinicians should strongly consider treatment in clinical trials for their older patients. If such trials are not available on site, physicians should refer older patients to tertiary centers for possible enrollment in a study. Significant advances have been made in the past decade toward understanding the biology of ALL and in developing novel therapeutic agents. Blinatumomab, inotuzumab ozogamicin, and newer-generation tyrosine kinase inhibitors appear to be promising agents. Clinical studies show remarkable results with these agents, either alone or in combination with low-dose chemotherapy. Now that clinical trials are being designed with less-intensive treatment regimens and broad entry criteria, older age is less likely to be an exclusionary factor. However, clinical trials that enroll older patients with ALL should include detailed documentation of their underlying comorbidities, cognitive function, and performance status.
Topics: Age Factors; Aged; Aged, 80 and over; Combined Modality Therapy; Disease Management; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome
PubMed: 28591103
DOI: No ID Found -
Hematology. American Society of... Nov 2018Acute lymphoblastic leukemia (ALL) is characterized by genetic alterations that block differentiation, promote proliferation of lymphoid precursor cells, and are... (Review)
Review
Acute lymphoblastic leukemia (ALL) is characterized by genetic alterations that block differentiation, promote proliferation of lymphoid precursor cells, and are important for risk stratification. Although ALL is less common in adolescents and young adults (AYAs) and adults than children, survival rates are inferior, and long-term prognosis for adults is poor. Thus, ALL remains a challenging disease to treat in the AYA and adult populations. A major contributing factor that influences prognosis in this population is the reduced prevalence of genetic subtypes associated with favorable outcome and a concomitant increase in subtypes associated with poor outcome. Recent advances in genomic profiling across the age spectrum continue to enhance our knowledge of the differences in disease biology between children and adults and are providing important insights into novel therapeutic targets. Philadelphia chromosome-like (Ph-like) ALL is one such subtype characterized by alterations that deregulate cytokine receptor or tyrosine kinase signaling and are amenable to inhibition with approved tyrosine kinase inhibitors. One of the greatest challenges now remaining is determining how to implement this breadth of genomic information into rapid and accurate diagnostic testing to facilitate the development of novel clinical trials that improve the outcome of AYAs and adults with ALL.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis
PubMed: 30504302
DOI: 10.1182/asheducation-2018.1.137 -
Best Practice & Research. Clinical... Mar 2021Chimeric antigen receptor T cell therapy targeting CD19 (CART19) has shown remarkable results in patients with relapsed/refractory (r/r) B cell acute lymphoblastic... (Review)
Review
Chimeric antigen receptor T cell therapy targeting CD19 (CART19) has shown remarkable results in patients with relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (ALL). In patients 25 years of age or younger CART19 therapy is an accepted standard of care, while the treatment of older adults is less straight forward and possible only in the context of a clinical trial. Treatment of older patients with CAR T cells requires careful consideration of overall treatment goals, suitability of a consolidative hematopoietic stem cell transplant (HSCT), alternative treatment options, patient risk profile, and anticipated responses and toxicities of the specific CAR T cell products available. Here we use patient guided examples to inform approaches to care.
Topics: Aged; Antigens, CD19; Humans; Immunotherapy, Adoptive; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Chimeric Antigen
PubMed: 33762110
DOI: 10.1016/j.beha.2021.101256