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Current Hematologic Malignancy Reports Oct 2021Rare malignancies developing from lymphocyte precursor cells, lymphoblastic leukemia (LBL), and acute lymphoblastic lymphoma (ALL) have historically been viewed as... (Review)
Review
PURPOSE OF REVIEW
Rare malignancies developing from lymphocyte precursor cells, lymphoblastic leukemia (LBL), and acute lymphoblastic lymphoma (ALL) have historically been viewed as different manifestations of the same disease process. This review examines data on their epidemiology, genetics, clinical presentation, and response to treatment while highlighting areas of similarity and divergence between these two clinical entities.
RECENT FINDINGS
Pediatric-type ALL chemotherapy regimens, compared to both lymphoma-type chemotherapy and adult-type ALL regimens, have led to improved outcomes for children, adolescents, and young adults with ALL. BCR-ABL-targeting tyrosine kinase inhibitors (TKIs) have improved outcomes in Philadelphia chromosome-positive (Ph +) ALL and in rare cases of Ph + LBL. Newer therapies including blinatumomab, inotuzumab, CAR-T therapy, and nelarabine have improved outcomes in selected cases of ALL and have an emerging role in the management of LBL. Better understanding of ALL and LBL biology allows for the development of therapies that target immunophenotypic or genetic features found in subsets of both diseases. Novel therapies are leading to improved outcomes in Ph + and relapsed and refractory disease.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Disease Management; Fusion Proteins, bcr-abl; Humans; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors
PubMed: 34417955
DOI: 10.1007/s11899-021-00648-y -
Seminars in Diagnostic Pathology Nov 2023Lymphoblastic leukemia/lymphoma (ALL/LBL), especially certain subtypes, continues to confer morbidity and mortality despite significant therapeutic advances. The... (Review)
Review
Lymphoblastic leukemia/lymphoma (ALL/LBL), especially certain subtypes, continues to confer morbidity and mortality despite significant therapeutic advances. The pathologic classification of ALL/LBL, especially that of B-ALL, has recently substantially expanded with the identification of several distinct and prognostically important genetic drivers. These discoveries are reflected in both current classification systems, the World Health Organization (WHO) 5th edition and the new International Consensus Classification (ICC). In this article, novel subtypes of B-ALL are reviewed, including DUX4, MEF2D and ZNF384-rearranged B-ALL; the rare pediatric entity B-ALL with TLF3::HLF, now added to the classifications, is discussed; updates to the category of B-ALL with BCR::ABL1-like features (Ph-like B-ALL) are summarized; and emerging genetic subtypes of T-ALL are presented. The second half of the article details current approaches to minimal/measurable residual disease (MRD) detection in B-ALL and T-ALL and presents anticipated challenges to current approaches in the burgeoning era of antigen-directed immunotherapy.
Topics: Humans; Child; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma
PubMed: 37953192
DOI: 10.1053/j.semdp.2023.10.001 -
European Journal of Haematology Sep 2023Dysregulation of BCL-2 family members has been reported in acute lymphocytic leukemia (ALL), with various BH3-dependencies of the leukemic clone. We conducted a...
OBJECTIVES
Dysregulation of BCL-2 family members has been reported in acute lymphocytic leukemia (ALL), with various BH3-dependencies of the leukemic clone. We conducted a multicenter retrospective cohort of patients with relapsed/refractory B or T ALL, with ven-chemotherapy or ven-navitoclax combinations, to assess efficacy and safety.
METHODS
Seventeen patients were included in the analysis, median age was 32 years, with 6 B-ALL and 11 T-ALL patients. Nine patients received venetoclax combined with chemotherapy, and 13 patients received venetoclax in combination with navitoclax, vincristine and asparaginase, of which 5 were already exposed to venetoclax in previous lines.
RESULTS
ORR was 55% and 46% among the ven-chemotherapy and the ven-navitoclax-chemotherapy, respectively. Most of the responders proceeded to an allogenic bone marrow transplant in both cohorts. The most common adverse effects of the ven-navitoclax combination were infectious complications and hepatotoxicity.
CONCLUSIONS
Our data demonstrated the possible efficacy of ven-chemotherapy and ven-navitoclax in r/r ALL with moderate toxicity.
Topics: Humans; Adult; Retrospective Studies; Salvage Therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Combined Chemotherapy Protocols; Leukemia, Myeloid, Acute
PubMed: 37254665
DOI: 10.1111/ejh.14015 -
Current Treatment Options in Oncology Mar 2017Opinion statementOver the past 15 years, the landscape of Ph+ ALL has changed dramatically. No longer the most dreaded form of acute leukemia, the advent of tyrosine... (Review)
Review
Opinion statementOver the past 15 years, the landscape of Ph+ ALL has changed dramatically. No longer the most dreaded form of acute leukemia, the advent of tyrosine kinase inhibitors (TKIs) has ushered in a new era, as TKIs have become the backbone of any treatment regimen for Ph+ ALL. A greater number achieve a complete remission allowing for more patients to get the transplant, although probably less patients need a transplant. For the first time in decades, there is hope for older patients with Ph+ ALL. Defining residual disease at an increasingly lower level of disease burdens termed minimal residual disease (MRD) has allowed treatment algorithms to be designed based on deep molecular responses. The aggregate of recent data suggest that this is the most important endpoint to predict for long-term outcome and to decide on the optimal post-remission approach, including transplant. Novel agents, such as blinatumumab, are likely to be incorporated into therapy for relapse and as initial therapy in an attempt to increase the number of patients who may have deep molecular responses. Many more patients with Ph+ ALL are long-term survivors, and the future is looking brighter for this group of patients.
Topics: Age Factors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Discovery; Hematopoietic Stem Cell Transplantation; Humans; Neoplasm, Residual; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors; Treatment Outcome
PubMed: 28382538
DOI: 10.1007/s11864-017-0455-3 -
Journal of Cellular Biochemistry Aug 2016Optimal function of multiple intracellular signaling pathways is essential for normal regulation of cellular transcription, translation, growth, proliferation, and... (Review)
Review
Optimal function of multiple intracellular signaling pathways is essential for normal regulation of cellular transcription, translation, growth, proliferation, and survival. Dysregulation or aberrant activation of such cascades can lead to inappropriate cell survival and abnormal cell proliferation in leukemia. Successful treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors targeting the BCR-ABL fusion gene is a prime example of effectively inhibiting intracellular signaling cascades. However, even in these patients resistance can develop via emergence of mutations or feedback activation of other pathways that cause refractory disease. Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway has been observed in different types of leukemia, including CML, acute myeloid leukemia, and acute lymphoblastic leukemia. Abnormal mTOR activity may contribute to chemotherapy resistance, while it may also be effectively targeted via molecular means and/or development of specific pharmacological inhibitors. This review discusses the role of PI3K/Akt/mTOR dysre-gulation in leukemia and summarizes the emergence of preliminary data for the development of novel therapeutic approaches. J. Cell. Biochem. 117: 1745-1752, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Drug Resistance, Neoplasm; Humans; Phosphatidylinositol 3-Kinases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 27018341
DOI: 10.1002/jcb.25559 -
Neurosurgical Review Oct 2017We conducted a comprehensive review of the literature to characterize the etiology of secondary glioma following acute lymphocytic leukemia (ALL) patients. The analysis... (Review)
Review
We conducted a comprehensive review of the literature to characterize the etiology of secondary glioma following acute lymphocytic leukemia (ALL) patients. The analysis included 98 cases with an average age of onset of ALL of 5.9 years (range 1.5 to 26). The average latency period was 7.8 years until diagnosis of secondary glioma. Radiation therapy was administered in 92 cases for the primary malignancy at an average dose of 20.7 Gy. The median survival time of patients treated with multimodality treatment for secondary glioma was 23 months (95 % confidence interval 12-27 months), and multimodality therapy improved survival time significantly (p = 0.0029). The exact cause for the development of glioma following ALL is not clear. The risk of a secondary glioma in childhood cancer survivors may be influenced by genetic and other predisposing factors as well as by treatment type. In patients diagnosed with ALL, the risk of secondary glioma warrants a longer follow-up period that continues long after the risk of relapse of the primary malignancy has passed. Moreover, multimodality therapy should be considered in cases of secondary glioma following ALL.
Topics: Adolescent; Adult; Brain Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Female; Glioma; Humans; Infant; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult
PubMed: 27159974
DOI: 10.1007/s10143-016-0733-8 -
Cancer Apr 2023In the year 2021, there were three new Food and Drug Administration approvals for all leukemia types: asciminib (Scemblix) for chronic myeloid leukemia, brexucabtagene...
In the year 2021, there were three new Food and Drug Administration approvals for all leukemia types: asciminib (Scemblix) for chronic myeloid leukemia, brexucabtagene autoleucel (Tecartus) for relapsed/refractory B-cell acute lymphocytic leukemia, and asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) for acute lymphocytic leukemia. This is down from 2017-2018 when eight new therapies were approved for acute myeloid leukemia alone. However, this decrease from prior years does not imply that little progress was made in our understanding or treatment of leukemias in 2021. Asciminib and brexucabtagene autoleucel, in particular, are representative of major developing trends. Asciminib, a targeted therapy, is only one of many drugs in development that are products of a bedside-to-bench approach fueled by new sequencing and other genetic technologies that have greatly increased our understanding of the biology behind hematologic diseases. Brexucabtagene autoleucel, an adoptive cell therapy, is the newest of several similar treatments for B cell-associated neoplasms, and it is representative of a massive push to develop novel immunotherapies for a broad range of hematologic malignancies. This commentary reviews the development of asciminib and brexucabtagene autoleucel and describes other major advances in the associated fields of targeted therapy and immunotherapy for leukemias.
Topics: Humans; T-Lymphocytes; Hematologic Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Immunotherapy, Adoptive
PubMed: 36585394
DOI: 10.1002/cncr.34619 -
American Journal of Ophthalmology Dec 2021
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence
PubMed: 34509433
DOI: 10.1016/j.ajo.2021.08.020 -
Current Oncology Reports May 2017This study aims to provide an overview of the classification, incidence, genomic alterations, and clinical implications of Philadelphia-like Acute Lymphoblastic Leukemia... (Review)
Review
PURPOSE OF REVIEW
This study aims to provide an overview of the classification, incidence, genomic alterations, and clinical implications of Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) in adults.
RECENT FINDINGS
Ph-like ALL is a high-risk subtype of B cell precursor ALL with characteristic genomic alterations in children and adults. A standard approach for diagnosis is missing and currently mainly based on gene expression analysis. The incidence is age depended and highest in adolescents and younger adults (age 16-39) where 19-28% of patients belong to this subtype. Ph-like ALL is associated with persistence of minimal residual disease (MRD) and inferior prognosis. Some genomic alterations respond to specific treatment approaches and provide hope for tailored therapies. Ph-like ALL in adults is an aggressive and high-risk subtype of B cell precursor ALL. Without consensus definition, diagnosis is difficult and current publications highlight the importance of stringent MRD monitoring to guide risk-adapted treatment strategies.
Topics: Adolescent; Adult; Female; Humans; Male; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Risk Factors; Young Adult
PubMed: 28361222
DOI: 10.1007/s11912-017-0589-2 -
Expert Opinion on Pharmacotherapy Dec 2016Advances in acute lymphocytic leukemia (ALL) therapy has led to long-term survival rates in children. However, only 30%-40% of adults achieve long-term disease-free... (Review)
Review
Advances in acute lymphocytic leukemia (ALL) therapy has led to long-term survival rates in children. However, only 30%-40% of adults achieve long-term disease-free survival. After relapse, the outcome of salvage chemotherapy is very disappointing with less than 10% of long survival. Novel agents are therefore desperately required to improve response rates and survival, but also the quality of life of patients. Areas covered: The following review is a comprehensive summary of various novel options reported over the past few years in the therapeutic area of adult ALL. Expert opinion: Identifying key components involved in disease pathogenesis may lead to new approaches. In a near future, the incorporation of monoclonal antibodies and T-cell directed approaches including blinatumomab and chimeric antigen receptor T cells may increase the cure rates and may reduce the need for intensive therapy.
Topics: Adenine Nucleotides; Adult; Antibodies, Monoclonal; Antineoplastic Agents; Arabinonucleosides; Clofarabine; Disease-Free Survival; Drug Discovery; Humans; Molecular Targeted Therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purine Nucleosides; Pyrimidinones; Quality of Life; Recurrence; Salvage Therapy
PubMed: 27759440
DOI: 10.1080/14656566.2016.1250884