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  1. Article ; Online: Future of Treatment of Adolescents and Young Adults With ALL: A Vision for Collaboration and Equity.

    Newman, Haley / Hunger, Stephen P

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2023  Volume 42, Issue 6, Page(s) 665–674

    Abstract: Over the past several decades, survival of children with ALL has improved dramatically with treatment regimens refined through cooperative group trials. Despite aggressive treatment and iterative therapy changes for adolescents and young adults (AYAs), ... ...

    Abstract Over the past several decades, survival of children with ALL has improved dramatically with treatment regimens refined through cooperative group trials. Despite aggressive treatment and iterative therapy changes for adolescents and young adults (AYAs), improvement has not been as promising. Comparisons between pediatric and adult clinical trials have consistently demonstrated superior outcomes for AYAs treated on pediatric ALL protocols, leading to the implementation of pediatric-inspired ALL protocols by several groups worldwide and/or expansion of the age limit of pediatric trials to include the full spectrum of the AYA population. Despite these efforts, AYAs in both pediatric and adult settings continue to have inferior survival compared with younger children with ALL. Real-world data suggest that uptake of pediatric-style treatment is variable, and even with identical pediatric-style treatment, AYAs still fare worse than younger children. As we enter an era of immunotherapy and precision medicine for newly diagnosed ALL, now is an opportune time to consider how best to approach future therapy for AYA patients. Comparisons of pediatric and adult treatment approaches and subanalyses of AYA patients will help guide harmonization of treatment. The focus of the next stage of ALL therapy for AYA should not only involve novel treatment approaches but also standardization and optimization of supportive care measures, psychosocial support, adherence interventions, oncofertility treatment, and survivorship care. All these efforts should simultaneously work to address health disparities to ensure that a future of improved outcomes is experienced equitably for all AYA patients.
    MeSH term(s) Adolescent ; Humans ; Young Adult ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
    Language English
    Publishing date 2023-10-27
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.23.01351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: How I treat early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) in children.

    Summers, Ryan J / Teachey, David Trent / Hunger, Stephen P

    Blood

    2024  

    Abstract: Early T-precursor acute lymphoblastic leukemia (ETP-ALL) is a unique subtype of immature T-ALL that was initially associated with a dramatically inferior prognosis as compared to non-ETP T-ALL (Not-ETP) when it was first described in 2009. Analyses of ... ...

    Abstract Early T-precursor acute lymphoblastic leukemia (ETP-ALL) is a unique subtype of immature T-ALL that was initially associated with a dramatically inferior prognosis as compared to non-ETP T-ALL (Not-ETP) when it was first described in 2009. Analyses of larger patient cohorts treated with more contemporary regimens, however, have shown minimal survival differences between ETP and Not-ETP. In this manuscript we utilize representative cases to explore therapeutic advances and address common clinical questions regarding management of children, adolescents, and young adults with ETP-ALL. We describe our recommended treatment approach for a child or adolescent with newly diagnosed ETP-ALL, with an emphasis on the prognostic significance of induction failure and detectable minimal residual disease and the role for hematopoietic stem cell transplant in first remission. We discuss the interplay between the ETP immunophenotype and genomic markers of immaturity in T-ALL. Finally, we review novel therapeutic approaches that should be considered when managing relapsed or refractory ETP-ALL.
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023023155
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  3. Article ; Online: More Is Not Always Better: The Perils of Treatment Intensification in Pediatric Acute Lymphoblastic Leukemia.

    Hunger, Stephen P

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2019  Volume 37, Issue 19, Page(s) 1601–1603

    MeSH term(s) Asparaginase ; Child ; Humans ; Longitudinal Studies ; Polyethylene Glycols ; Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Chemical Substances Polyethylene Glycols (3WJQ0SDW1A) ; pegaspargase (7D96IR0PPM) ; Asparaginase (EC 3.5.1.1)
    Language English
    Publishing date 2019-05-14
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.19.00889
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  4. Article ; Online: Advancing Diagnostics and Therapy to Reach Universal Cure in Childhood ALL.

    Pieters, Rob / Mullighan, Charles G / Hunger, Stephen P

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2023  Volume 41, Issue 36, Page(s) 5579–5591

    Abstract: Systemic combination chemotherapy and intrathecal chemotherapy markedly increased the survival rate of children with ALL. In the past two decades, the use of minimal (measurable) residual disease (MRD) measurements early in therapy improved risk group ... ...

    Abstract Systemic combination chemotherapy and intrathecal chemotherapy markedly increased the survival rate of children with ALL. In the past two decades, the use of minimal (measurable) residual disease (MRD) measurements early in therapy improved risk group stratification with subsequent treatment intensifications for patients at high risk of relapse, and enabled a reduction of treatment for low-risk patients. The recent development of more sensitive MRD technologies may further affect risk stratification. Molecular genetic profiling has led to the discovery of many new subtypes and their driver genetic alterations. This increased our understanding of the biological basis of ALL, improved risk classification, and enabled implementation of precision medicine. In the past decade, immunotherapies, including bispecific antibodies, antibody-drug conjugates, and cellular therapies directed against surface proteins, led to more effective and less toxic therapies, replacing intensive chemotherapy courses and allogeneic stem-cell transplantation in patients with relapsed and refractory ALL, and are now being tested in newly diagnosed patients. It has taken 50-60 years to increase the cure rate in childhood ALL from 0% to 90% by stepwise improvements in chemotherapy. This review provides an overview of how the developments over the past 10-15 years mentioned above have significantly changed the diagnostic and treatment approach in ALL, and discusses how the integrated use of molecular and immunotherapeutic insights will very likely direct efforts to cure those children with ALL who are not cured today, and improve the quality of life for survivors who should have decades of life ahead. Future efforts must focus on making effective, yet very expensive, new technologies and therapies available to children with ALL worldwide.
    MeSH term(s) Child ; Humans ; Quality of Life ; Neoplasm Recurrence, Local/drug therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Neoplasm, Residual/drug therapy
    Language English
    Publishing date 2023-10-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.23.01286
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Anti-CD7 CAR T cells for T-ALL: impressive early-stage efficacy.

    Teachey, David T / Hunger, Stephen P

    Nature reviews. Clinical oncology

    2021  Volume 18, Issue 11, Page(s) 677–678

    MeSH term(s) Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocytes
    Language English
    Publishing date 2021-09-27
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2491410-1
    ISSN 1759-4782 ; 1759-4774
    ISSN (online) 1759-4782
    ISSN 1759-4774
    DOI 10.1038/s41571-021-00556-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Curing pediatric cancer: A global view. Examples from acute lymphoblastic leukemia.

    Duffy, Caitlyn / Hunger, Stephen P / Bhakta, Nickhill / Denburg, Avram E / Antillon, Federico / Barr, Ronald D

    Cancer

    2024  

    Language English
    Publishing date 2024-03-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.35290
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  7. Article ; Online: Integrated Risk Stratification Using Minimal Residual Disease and Sentinel Genetic Alterations in Pediatric Acute Lymphoblastic Leukemia.

    Hunger, Stephen P

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2017  Volume 36, Issue 1, Page(s) 4–6

    MeSH term(s) Child ; Genotype ; Humans ; Mutation ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Language English
    Publishing date 2017-11-13
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.2017.76.0504
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  8. Article ; Online: CML in blast crisis: more common than we think?

    Hunger, Stephen P

    Blood

    2017  Volume 129, Issue 20, Page(s) 2713–2714

    MeSH term(s) Blast Crisis ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Chemical Substances Imatinib Mesylate (8A1O1M485B)
    Language English
    Publishing date 2017-05-18
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2017-04-776369
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The genomic landscape of pediatric acute lymphoblastic leukemia and precision medicine opportunities.

    Tran, Thai Hoa / Hunger, Stephen P

    Seminars in cancer biology

    2020  Volume 84, Page(s) 144–152

    Abstract: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and constitutes approximately 25 % of cancer diagnoses among children under the age of 15 (Howlader et al., 2013) [1]. Overall, about half of ALL cases occur in children and ... ...

    Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and constitutes approximately 25 % of cancer diagnoses among children under the age of 15 (Howlader et al., 2013) [1]. Overall, about half of ALL cases occur in children and adolescents and it is the most common acute leukemia until the early 20s, after which acute myeloid leukemia predominates. ALL is the most successful treatment paradigm in pediatric cancer medicine as illustrated by the significant survival rate improvement from ∼10 % in the 1960s to >90 % today (Hunger et al., 2015) [2]. This remarkable success stems from the progressive improvement in the efficacy of risk-adapted multiagent chemotherapy regimens with effective central nervous system (CNS) prophylaxis via well-designed randomized clinical trials conducted by international collaborative consortia, enhanced supportive care measures to decrease treatment-related mortality, in-depth understanding of the genetic basis of ALL, and refinement in treatment response assessment through serial minimal residual disease (MRD) monitoring (Pui et al., 2015) [3]. These advances collectively contribute to a decline in mortality rate of 23.5% for children diagnosed with ALL in the US from 2000 to 2010 (Smith et al., 2014) [4]. Nevertheless, outcomes of older adolescents and young adults with ALL still lag behind those of their younger counterparts despite pediatric-inspired chemotherapy regimens (Stock et al., 2019) [5], relapsed/refractory childhood ALL is associated with poor outcomes (Rheingold et al., 2019) [6], and ALL still represents the leading causes of cancer-related deaths (Smith et al., 2010) [7]. The last two decades have witnessed important genomic discoveries in ALL, enabled by advances in next-generation sequencing (NGS) technologies to characterize the landscape of germline and somatic alterations in ALL, some of which have important diagnostic, prognostic and therapeutic implications. Comprehensive genomic analysis of large cohorts of children and adults with ALL has revised the taxonomy of ALL in the molecular era by identifying novel clonal, subtype-defined chromosomal alterations associated with distinct gene expression signatures, thus reducing the proportion of patients previously labelled as "Others" from 25 % to approximately 5 % (Mullighan et al., 2019) [8]. Insights into the genomics of ALL further provide compelling biologic rationale to expand the scope of precision medicine therapies for childhood ALL. Herein, we summarize a decade of genomic discoveries to highlight three different facets of precision medicine in pediatric ALL: 1) inherited predispositions of ALL; 2) relevant molecularly targeted therapies in genomically-defined ALL subtypes; and 3) treatment response monitoring via pharmacogenomics and novel MRD biomarkers.
    MeSH term(s) Adolescent ; Child ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Neoplasm, Residual/genetics ; Precision Medicine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
    Language English
    Publishing date 2020-11-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1033980-2
    ISSN 1096-3650 ; 1044-579X
    ISSN (online) 1096-3650
    ISSN 1044-579X
    DOI 10.1016/j.semcancer.2020.10.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: ABL-class fusion positive acute lymphoblastic leukemia: can targeting ABL cure ALL?

    Tran, Thai Hoa / Hunger, Stephen P

    Haematologica

    2020  Volume 105, Issue 7, Page(s) 1754–1757

    MeSH term(s) B-Lymphocytes ; Child ; Fusion Proteins, bcr-abl/genetics ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Prognosis ; Recurrence
    Chemical Substances Fusion Proteins, bcr-abl (EC 2.7.10.2)
    Language English
    Publishing date 2020-06-29
    Publishing country Italy
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2020.252916
    Database MEDical Literature Analysis and Retrieval System OnLINE

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