New Approaches to Treating Challenging Subtypes of ALL in AYA Patients

Prescott, Kevin; Jacobs, Michael; Stock, Wendy; Wynne, Joseph

doi:10.1007/s11899-020-00597-y

Cited by 3 publications

(4 citation statements)

References 87 publications

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“…Widely considered a poor prognostic subgroup in the past, its management has greatly improved through the use of pediatric-inspired protocols in adults [12,13], including a refined risk stratification with measurable residual disease (MRD) monitoring. In several clinical trials, the overall survival was more than 80% in children and adolescents [14] and 70% in younger adults [15]. However, it is still less than 50% in older adults [13,16], and refractory/relapsed cases (R/R) do not benefit from available salvage treatments and fare very badly, either with chemotherapy regimens, such as FLAG-IDA, or with the most recently approved drug, nelarabine [17].…”

Section: Immature T-cell Acute Lymphoblastic Leukemia (T-all)mentioning

confidence: 99%

“…Ultimately, AYA (adolescent and young adult) patients deserve a separate paragraph, since this age category has been treated differently with pediatric or pediatric-inspired adult protocols with different intensification schedules and strategies. In the USA, a general approach for AYA patients with ETP-ALL is to pursue allo-SCT in CR1 if they are good candidates for transplantation and have slower clearance of MRD [15]. The European Society for Blood and Marrow Transplantation has no position regarding AYA patients but do not recommend allo-SCT for children with ETP-ALL [65,66].…”

Section: Cell-immunotherapy: Allo-sctmentioning

confidence: 99%

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Early T-Cell Precursor ALL and Beyond: Immature and Ambiguous Lineage T-ALL Subsets

Genescà

Starza

2022

Cancers

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A wide range of immature acute leukemias (AL), ranging from acute myeloid leukemias with minimal differentiation to acute leukemias with an ambiguous lineage, i.e., acute undifferentiated leukemias and mixed phenotype acute leukemia with T- or B-plus myeloid markers, cannot be definitely assigned to a single cell lineage. This somewhat “grey zone” of AL expresses partly overlapping features with the most immature forms of T-cell acute lymphoblastic leukemia (T-ALL), i.e., early T-cell precursor ALL (ETP-ALL), near-ETP-ALL, and pro-T ALL. These are troublesome cases in terms of precise diagnosis because of their similarities and overlapping phenotypic features. Moreover, it has become evident that they share several genomic alterations, raising the question of how their phenotypes reflect distinct AL entities. The aim of this review was to provide a systematic overview of the genetic events associated with immature T-ALL and outline their relationship with treatment choices and outcomes, especially looking at the most recent preclinical and clinical studies. We wish to offer a basis for using the genetic information for new diagnostic algorithms, in order to better stratify patients and improve their management with more efficient and personalized therapeutic options. Understanding the genetic profile of this high-risk T-ALL subset is a prerequisite for changing the current clinical scenario.

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Section: Immature T-cell Acute Lymphoblastic Leukemia (T-all)mentioning

confidence: 99%

Section: Cell-immunotherapy: Allo-sctmentioning

confidence: 99%

Early T-Cell Precursor ALL and Beyond: Immature and Ambiguous Lineage T-ALL Subsets

Genescà

Starza

2022

Cancers

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“…Unlike children, AYA patients have ALL with lower incidence of good prognostic cytogenetic and molecular markers (like t(12;21)/ETV6-RUNX1, as well as hyperdiploidy). On the other side, there is an increased prevalence of resistant ALL subtypes in AYA population, like Philadelphia chromosome positive ALL (Ph+ ALL), Philadelphia chromosome like ALL (Ph-like ALL), ALL with t(4;11) and others [3]. There is also a higher incidence of T-cell ALL among AYA patients in contrast to children, especially the high risk early T precursor (ETP) ALL.…”

Section: Contributing Factors For Different Outcome Between Children ...mentioning

confidence: 99%

“…In this subtype of ALL, many kinases (ABL, PDG-FRB, JAK2, JAK-STAT,…) can be activated, which further provide proliferative advantage to leukemic cells, but on the other side they also can be targets for specific treatment with TKIs or JAK2 inhibitors. There is no standard diagnostic and therapeutic approach to these patients, so it is recommended to enroll patients with Ph-like ALL in a clinical trial or to use innovative drug (blinatumomab) to eradicate MRD and proceed with an allogeneic transplant [3]. ETP ALL is relatively rare (around 15% of T ALL), with a characteristic immunophenotype: CD1a − , CD8 − , CD5 − (dim) and positivity for one or more stem cell or myeloid antigens and poor response to treatment.…”

Section: Current Treatment and Novel Approaches In The Treatment Of A...mentioning

confidence: 99%

The current approach and the treatment of adolescents and young adults with acute lymphoblastic leukemia

Sekulić

2022

Med pregl

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Introduction. The treatment outcome of adolescents and young adults with acute lymphoblastic leukemia is much poorer in contrast to pediatric patients. By changing the concept of the treatment for patients who are adolescents and young adults with acute lymphoblastic leukemia, especially with the use of pediatric regimens, significant improvement in survival has been made (current 5-year survival rate goes up to 70%). Contributing factors for different outcomes between children and adolescents and young adults with acute lymphoblastic leukemia. Beside the differences between pediatric and adult protocols, there are several factors which can explain the different outcomes between these groups of patients with acute lymphoblastic leukemia. One of the main factors is different biology of the leukemias and, on the other side, lower accrual rates in clinical trials in adolescents and young adults and their specific psychosocial factors, like poor compliance with the treatment and missed appointments. Current treatment and novel approaches in the treatment of adolescents and young adults with acute lymphoblastic leukemia. Current treatment approach to the adolescent and young adults with acute lymphoblastic leukemia is based on the pediatric protocols with the risk-adapted strategy, which depends primarily on the cytogenetics and postinduction minimal/measurable residual disease. The main goal of the novel treatment, especially with the use of targeted therapy and innovative immunotherapies incorporated in the pediatric protocols, is to achieve a deep and durable leukemia-free survival. To transplant or not to transplant adolescents and young adults with acute lymphoblastic leukemia is still a matter of debate, particularly in the era of pediatric regimens and the new sequence algorithm with the upfront use of novel drugs. Conclusion. Adolescent and young adult patients with acute lymphoblastic leukemia should be treated in specialized centers by an experienced multidisciplinary team with close attention to their particular needs.

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Long-Term Outcomes among Adolescent and Young Adult Survivors of Acute Leukemia: A Surveillance, Epidemiology, and End Results Analysis

Berkman

Andersen

Cuglievan

et al. 2022

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: There is a growing population of adolescent and young adult (AYA, age 15–39 years) acute leukemia survivors in whom long-term mortality outcomes are largely unknown. Methods: The current study utilized the Surveillance, Epidemiology, and End Results (SEER) registry to assess long-term outcomes of AYA acute leukemia 5-year survivors. The impact of diagnosis age, sex, race/ethnicity, socioeconomic status, and decade of diagnosis on long-term survival were assessed utilizing an accelerated failure time model. Results: A total of 1,938 AYA acute lymphoblastic leukemia (ALL) and 2,350 AYA acute myeloid leukemia (AML) survivors diagnosed between 1980 and 2009 were included with a median follow-up of 12.3 and 12.7 years, respectively. Ten-year survival for ALL and AML survivors was 87% and 89%, respectively, and 99% for the general population. Survival for AYA leukemia survivors remained below that of the age-adjusted general population at up to 30 years of follow-up. Primary cancer mortality was the most common cause of death in early survivorship with noncancer causes of death becoming more prevalent in later decades of follow-up. Male AML survivors had significantly worse survival than females (survival time ratio: 0.61, 95% confidence interval: 0.45–0.82). Conclusions: AYA leukemia survivors have higher mortality rates than the general population that persist for decades after diagnosis. Impact: While there have been improvements in late mortality, long-term survival for AYA leukemia survivors remains below that of the general population. Studies investigating risk factors for mortality and disparities in late effects among long-term AYA leukemia survivors are needed.

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New Approaches to Treating Challenging Subtypes of ALL in AYA Patients

Cited by 3 publications

References 87 publications

Early T-Cell Precursor ALL and Beyond: Immature and Ambiguous Lineage T-ALL Subsets

Early T-Cell Precursor ALL and Beyond: Immature and Ambiguous Lineage T-ALL Subsets

The current approach and the treatment of adolescents and young adults with acute lymphoblastic leukemia

Long-Term Outcomes among Adolescent and Young Adult Survivors of Acute Leukemia: A Surveillance, Epidemiology, and End Results Analysis

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