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Archives of Pathology & Laboratory... Feb 2020In the 2016 update of the World Health Organization (WHO) classification of hematopoietic neoplasms, -like B-acute lymphoblastic leukemia/lymphoma (B-ALL) is added as a... (Review)
Review
CONTEXT.—
In the 2016 update of the World Health Organization (WHO) classification of hematopoietic neoplasms, -like B-acute lymphoblastic leukemia/lymphoma (B-ALL) is added as a new provisional entity that lacks the translocation but shows a pattern of gene expression very similar to that seen in B-ALL with .
OBJECTIVE.—
To review the kinase-activating alterations and the diagnostic approach for -like B-ALL.
DATA SOURCES.—
We provide a comprehensive review of -like B-ALL based on recent literature and the 2016 update of the World Health Organization classification of hematopoietic neoplasms.
CONCLUSIONS.—
Several types of kinase-activating alterations (fusions or mutations) are identified in like B-ALL. The main categories are alterations in the ABL class family of genes, encompassing (rare), and colony-stimulating factor 1 receptor () fusions, or the JAK2 class family of genes, encompassing alterations in , and other genes in this pathway. These alterations determine the sensitivity to tyrosine kinase inhibitors. As a wide variety of genomic alterations are included in this category, the diagnosis of -like B-ALL is extremely complex. Stepwise algorithms and comprehensive unbiased testing are the 2 ways to approach the diagnosis of -like B-ALL.
Topics: Fusion Proteins, bcr-abl; Humans; Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 31644323
DOI: 10.5858/arpa.2019-0194-RA -
Blood Advances Jan 2020Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) accounts for 15% to 30% of B-cell acute lymphoblastic leukemia in older children,... (Review)
Review
Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) accounts for 15% to 30% of B-cell acute lymphoblastic leukemia in older children, adolescents, and adults and is associated with high rates of conventional treatment failure and relapse. Current clinical trials are assessing the efficacy of the addition of tyrosine kinase inhibitors (TKIs) to chemotherapy for children and adults with Ph-like ALL harboring ABL class translocations or CRLF2 rearrangements and other JAK pathway alterations. However, real-time diagnosis of patients can be quite challenging given the genetic heterogeneity of this disease and the often cytogenetically cryptic nature of Ph-like ALL-associated alterations. In this review, we discuss the complex biologic and clinical features of Ph-like ALL across the age spectrum, available diagnostic testing modalities, and current clinical treatment strategies for these high-risk patients. We further propose a practical and step-wise approach to Ph-like ALL genetic testing to facilitate the identification and allocation of patients to appropriate clinical trials of TKI-based therapies or commercially available drugs. Although the majority of patients with Ph-like ALL can be successfully identified via current clinical assays by the end of induction chemotherapy, increasing diagnostic efficiency and sensitivity and decreasing time to test resulting will facilitate earlier therapeutic intervention and may improve clinical outcomes for these high-risk patients.
Topics: Adolescent; Adult; Child; Humans; Induction Chemotherapy; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors
PubMed: 31935290
DOI: 10.1182/bloodadvances.2019000163 -
Expert Review of Hematology Jan 2020: Historically, the majority of childhood cancers, including acute lymphoblastic leukemia (ALL), were not thought to have a hereditary basis. However, recent germline... (Review)
Review
: Historically, the majority of childhood cancers, including acute lymphoblastic leukemia (ALL), were not thought to have a hereditary basis. However, recent germline genomic studies have revealed that at least 5 - 10% of children with cancer (and approximately 3 - 4% of children with ALL) develop the disease due to an underlying genetic predisposition.: This review discusses several recently identified ALL predisposing conditions and provides updates on other more well-established syndromes. It also covers topics related to the evaluation and management of children and family members at increased ALL risk.: Germline predisposition is gaining recognition as an important risk factor underlying the development of pediatric ALL. The challenge now lies in how best to capitalize on germline genetic information to improve ALL diagnosis, treatment, and perhaps even prevention.
Topics: Child; Genetic Predisposition to Disease; Genetic Testing; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors
PubMed: 31657974
DOI: 10.1080/17474086.2020.1685866 -
Best Practice & Research. Clinical... Mar 2023Lymphoblastic lymphoma (LBL) is the second most common type of non-Hodgkin Lymphoma (NHL) in children, adolescents, and young adults (CAYA), accounting for 25-35% of all... (Review)
Review
Lymphoblastic lymphoma (LBL) is the second most common type of non-Hodgkin Lymphoma (NHL) in children, adolescents, and young adults (CAYA), accounting for 25-35% of all cases. T-lymphoblastic lymphoma (T-LBL) comprises 70-80% of cases, while precursor B-lymphoblastic lymphoma (pB-LBL) makes up the remaining 20-25% of cases. Event-free and overall survival (EFS and OS) for paediatric LBL patients both exceed 80% with current therapies. Treatment regimens, especially in T-LBL with large mediastinal tumours, are complex with significant toxicity and long-term complications. Though prognosis overall is good for T-LBL and pB-LBL with upfront therapy, outcomes for patients with relapsed or refractory (r/r) disease remain dismal. Here, we review new understanding about the pathogenesis and biology of LBL, recent clinical results and future directions for therapy, and remaining obstacles to improve outcomes while reducing toxicity.
Topics: Young Adult; Humans; Child; Adolescent; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Prognosis; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, B-Cell
PubMed: 36907639
DOI: 10.1016/j.beha.2023.101449 -
International Journal of Molecular... Mar 2022Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies characterized by abnormal proliferation of immature lymphoid cells. It is the... (Review)
Review
Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies characterized by abnormal proliferation of immature lymphoid cells. It is the most commonly diagnosed childhood cancer with an almost 80% cure rate. Despite favorable survival rates in the pediatric population, a significant number of patients develop resistance to therapy, resulting in poor prognosis. ALL is a heterogeneous disease at the genetic level, but the intensive development of sequencing in the last decade has made it possible to broaden the study of genomic changes. New technologies allow us to detect molecular changes such as point mutations or to characterize epigenetic or proteomic profiles. This process made it possible to identify new subtypes of this disease characterized by constellations of genetic alterations, including chromosome changes, sequence mutations, and DNA copy number alterations. These genetic abnormalities are used as diagnostic, prognostic and predictive biomarkers that play an important role in earlier disease detection, more accurate risk stratification, and treatment. Identification of new ALL biomarkers, and thus a greater understanding of their molecular basis, will lead to better monitoring of the course of the disease. In this article, we provide an overview of the latest information on genomic alterations found in childhood ALL and discuss their impact on patients' clinical outcomes.
Topics: Burkitt Lymphoma; Child; DNA Copy Number Variations; Genetic Markers; Humans; Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proteomics
PubMed: 35269896
DOI: 10.3390/ijms23052755 -
Haematologica Dec 2022Measurable residual disease (MRD) is the most powerful independent predictor of risk of relapse and long-term survival in adults and children with acute lymphoblastic...
Measurable residual disease (MRD) is the most powerful independent predictor of risk of relapse and long-term survival in adults and children with acute lymphoblastic leukemia (ALL). For almost all patients with ALL there is a reliable method to evaluate MRD, which can be done using multi-color flow cytometry, quantitative polymerase chain reaction to detect specific fusion transcripts or immunoglobulin/T-cell receptor gene rearrangements, and high-throughput next-generation sequencing. While next-generation sequencing-based MRD detection has been increasingly utilized in clinical practice due to its high sensitivity, the clinical significance of very low MRD levels (<10-4) is not fully characterized. Several new immunotherapy approaches including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T-cell therapies have demonstrated efficacy in eradicating MRD in patients with B-ALL. However, new approaches to target MRD in patients with T-ALL remain an unmet need. As our MRD detection assays become more sensitive and expanding novel therapeutics enter clinical development, the future of ALL therapy will increasingly utilize MRD as a criterion to either intensify or modify therapy to prevent relapse or de-escalate therapy to reduce treatment-related morbidity and mortality.
Topics: Adult; Child; Humans; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Immunotherapy, Adoptive; Recurrence
PubMed: 36453516
DOI: 10.3324/haematol.2022.280638 -
Indian Journal of Pharmacology 2022During present decade, targeted drug therapy has been the epitome for treatment of cancer. Drugs like Imatinib, a tyrosine kinase receptor inhibitor and Trastuzumab, an... (Review)
Review
During present decade, targeted drug therapy has been the epitome for treatment of cancer. Drugs like Imatinib, a tyrosine kinase receptor inhibitor and Trastuzumab, an human epidermal growth factor receptor-2/neu inhibitor, has been developed and accepted widely for management of chronic myeloid leukaemia and breast cancer respectively. Recent development among the various immunotherapies is adoptive cell transfer (ACT). Research on development of various types of ACT immunotherapy is going on, but so far, Chimeric antigen receptors T cell therapy (CAR-T) has achieved the maximum advancement in terms of clinical development. CARs are the modified receptors that integrates specificity and responsiveness onto immune cells to enhance the recognition of cancer cells. For the CAR-T, the T cells are sequestered from a blood of a participant via apheresis. DNA of particular antigen is injected into harvested T cells to generate CARs on cell surface. Following surface manifestation of receptors, multiplication is carried out in enriched media followed by infusion into patient. After infusion, CAR-T cells targeted and exterminate the cancer cells. Initially, only two drugs targeting CD19 as genetically modified autologous immunotherapy has been approved in CAR-T therapy i.e., Tisagenlecleucel and Axicabtagene Ciloleucel, which are discussed in detail in current review. Recently two more drugs got approval i.e., brexucabtagene ciloleucel and lisocabtagene maraleucel, both are directed against CD19, similar to tisagenlecleucel. CAR-T cell therapy is approved for management of Acute Lymphoblastic Leukaemia, Chronic Lymphocytic Leukaemia and lymphoma. CAR-T cell persistence responsible for effectiveness and safety concerns are barriers for their wide application among patients. Growth factor receptors and cluster of differentiation are new drugs targets that are being explored as effective immunotherapy against cancers.
Topics: Antigens, CD19; Humans; Immunotherapy; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Chimeric Antigen; T-Lymphocytes
PubMed: 35848695
DOI: 10.4103/ijp.ijp_531_20 -
Blood Jan 2020Improved personalized adjustment of primary therapy to the perceived risk of relapse by using new prognostic markers for treatment stratification may be beneficial to... (Review)
Review
Improved personalized adjustment of primary therapy to the perceived risk of relapse by using new prognostic markers for treatment stratification may be beneficial to patients with acute lymphoblastic leukemia (ALL). Here, we review the advances that have shed light on the role of IKZF1 aberration as prognostic factor in pediatric ALL and summarize emerging concepts in this field. Continued research on the interplay of disease biology with exposure and response to treatment will be key to further improve treatment strategies.
Topics: Animals; Child; Drug Resistance, Neoplasm; Gene Deletion; Humans; Ikaros Transcription Factor; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis
PubMed: 31821407
DOI: 10.1182/blood.2019000813 -
Acta Biochimica Et Biophysica Sinica Jun 2023Leukaemia is the common name for a group of malignant diseases of the haematopoietic system with complex classifications and characteristics. Remarkable progress has... (Review)
Review
Leukaemia is the common name for a group of malignant diseases of the haematopoietic system with complex classifications and characteristics. Remarkable progress has been made in basic research and preclinical studies for acute leukaemia compared to that of the many other types/subtypes of leukaemia, especially the exploration of the biological basis and application of immunotherapy in acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). In this review, we summarize the basic approaches to immunotherapy for leukaemia and focus on the research progress made in immunotherapy development for AML and ALL. Importantly, despite the advances made to date, big challenges still exist in the effectiveness of leukaemia immunotherapy, especially in AML. Therefore, we use AML as an example and summarize the mechanisms of tumour cell immune evasion, describe recently reported data and known therapeutic targets, and discuss the obstacles in finding suitable treatment targets and the results obtained in recent clinical trials for several types of single and combination immunotherapies, such as bispecific antibodies, cell therapies (CAR-T-cell treatment), and checkpoint blockade. Finally, we summarize novel immunotherapy strategies for treating lymphocytic leukaemia and clinical trial results.
Topics: Immunotherapy; Humans; Bone Marrow Transplantation; Cancer Vaccines; Tumor Escape; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37272727
DOI: 10.3724/abbs.2023101 -
Biology of Blood and Marrow... Nov 2019The role of hematopoietic cell transplantation (HCT) in adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic... (Review)
Review
Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy.
The role of hematopoietic cell transplantation (HCT) in adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of ALL experts developed consensus on the treatment recommendations based on the evidence. Allogeneic HCT offers a survival benefit in selected patients with ALL, and this review summarizes the standard indications as well as the areas of controversy. There is now greater experience with pediatric-inspired chemotherapy regimens that has transformed upfront therapy for adult ALL, resulting in higher remission rates and overall survival. This in turn has increased the equipoise around decision making for ALL in first complete remission (CR1) when there is no measurable residual disease (MRD) at the end of induction and/or consolidation. Randomized studies are needed for adults with ALL to compare allogeneic HCT in CR1 with pediatric-inspired chemotherapy alone. Indications for transplantation in the evolving landscape of MRD assessments and novel targeted and immune therapeutics remain important areas of investigation.
Topics: Adult; Hematopoietic Stem Cell Transplantation; Humans; Practice Guidelines as Topic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Societies, Medical; Transplantation Conditioning; United States
PubMed: 31446198
DOI: 10.1016/j.bbmt.2019.08.014