scholarly journals Acute lymphoblastic leukemia in older adults: curtain call for conventional chemotherapy?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 7-14
Author(s):  
Marlise R. Luskin
Keyword(s):  
Older Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Conventional Chemotherapy ◽  
Novel Therapeutics ◽  
Treatment Regimens ◽  
Early Results ◽  
Frontline Treatment

Abstract Unlike younger adults with acute lymphoblastic leukemia (ALL), older adults are rarely cured due to a combination of intrinsic disease resistance and treatment-related toxicities. Novel therapeutics such as inotuzumab ozogamicin, blinatumomab, venetoclax, and ABL kinase inhibitors have high activity in ALL and are well tolerated by older adults. Frontline treatment regimens for older adults using novel therapeutics with reduction or omission of conventional chemotherapy are being developed with early results demonstrating high remission rates and lower toxicity, but long-term efficacy and toxicity data are lacking. Collaboration between academic and pharmaceutical stakeholders is needed to develop clinical trials to define the optimal treatment regimens for older adults with ALL.

scholarly journals Incorporation of nonchemotherapeutic agents in pediatric acute lymphoblastic leukemia

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 259-264 ◽  
Author(s):  
Lewis B. Silverman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
High Risk Patient ◽  
Newly Diagnosed ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Novel Treatments ◽  
Relapsed Disease ◽  
Multiagent Chemotherapy

AbstractWith current available therapies, the prognosis for most children and adolescents with acute lymphoblastic leukemia (ALL) is favorable. However, the multiagent chemotherapy regimens used to treat newly diagnosed patients are associated with many acute and long-term complications, and therapy for relapsed disease is intensive and suboptimally effective. Over the last decade, several nonchemotherapeutic approaches have been evaluated, with the goal of identifying more effective, less toxic therapies that can be used in conjunction with, or even replace, current regimens. Novel nonchemotherapeutic therapies with activity in ALL include (1) tyrosine kinase inhibitors in high-risk patient subsets in whom potentially targetable alterations have been identified and (2) immunotherapeutic approaches, such as monoclonal antibodies, immunotoxins, bispecific T-cell–engaging antibodies, and chimeric antigen receptor T cells. This review summarizes promising results from recent clinical trials of these novel treatments.

Acute Lymphoblastic Leukemia: Older Patients and Newer Drugs

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 131-136 ◽  
Author(s):  
Richard A. Larson
Keyword(s):  
Clinical Trials ◽  
Acute Lymphoblastic Leukemia ◽  
Older Patients ◽  
Lymphoblastic Leukemia ◽  
Intensive Chemotherapy ◽  
Conventional Chemotherapy ◽  
Term Survival ◽  
New Agents ◽  
Medical Disorders

Abstract Although the median age for adults with acute lymphoblastic leukemia (ALL) is older than 60 years, relatively few of these patients have been enrolled on prospective clinical trials. The presence of coexisting medical disorders and unfavorable cytogenetic and biological characteristics within this population presents considerable challenges for successful treatment using conventional chemotherapy programs. Selected patients have achieved remission and long-term survival following intensive chemotherapy. Preliminary data using several new agents that have shown promise for patients with ALL are described.

scholarly journals Evaluation and management of measurable residual disease in acute lymphoblastic leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062072091002 ◽  
Author(s):  
Iman Abou Dalle ◽  
Elias Jabbour ◽  
Nicholas J. Short
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Frontline Treatment ◽  
Measurable Residual Disease

With standard chemotherapy regimens for adults with acute lymphoblastic leukemia, approximately 90% of patients achieve complete remission. However, up to half of patients have persistent minimal/measurable residual disease (MRD) not recognized by routine microscopy, which constitutes the leading determinant of relapse. Many studies in pediatric and adult populations have demonstrated that achievement of MRD negativity after induction chemotherapy or during consolidation is associated with significantly better long-term outcomes, and MRD status constitutes an independently prognostic marker, often superseding other conventional risk factors. Persistence of MRD after intensive chemotherapy is indicative of treatment refractoriness and warrants alternative therapeutic approaches including allogeneic stem cell transplantation, blinatumomab, or investigational therapies such as inotuzumab ozogamicin or chimeric antigen receptor T cells. Furthermore, the incorporation of novel monoclonal antibodies or potent BCR-ABL1 tyrosine kinase inhibitors, such as ponatinib into frontline treatment may have the advantage of achieving higher rates of MRD negativity while minimizing chemotherapy-related toxicities. Many studies are therefore ongoing to determine whether this strategy can improve cure rates without the need for allogeneic stem cell transplantation.

Treatment of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia in Adults: A Broader Range of Options, Improved Outcomes, and More Therapeutic Dilemmas

2015 ◽  
pp. e352-e359 ◽  
Author(s):  
Adele K. Fielding
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
Improved Outcomes ◽  
Therapeutic Choice ◽  
Major Progress ◽  
Philadelphia Chromosome Positive

The article addresses selected key areas of flux in the management of Philadelphia chromosome–positive acute lymphoblastic leukemia. There is no doubt that tyrosine kinase inhibitors (TKIs) have made a major contribution to higher rates of complete remission and that more patients are now surviving long term. Many patients tolerate TKIs well, and remission can be achieved with minimal toxicity. Because remissions can include a proportion of patients who become BCR-ABL1 transcript negative, the question of whether allogeneic hematopoietic stem cell transplantation can be avoided requires discussion. Despite the major progress that has been made and the relative profusion of therapeutic choice compared with 10 years ago, evidence is still lacking for many of the major possible interventions, and how to combine them is unclear. Because of the rarity of the condition and the enticing possibility of increasing traction to therapy, clinical trials and international cooperation remain paramount.

Characterization of acute lymphoblastic leukemia progenitor cells

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2919-2925 ◽  
Author(s):  
Charlotte V. Cox ◽  
Roger S. Evely ◽  
Anthony Oakhill ◽  
Derwood H. Pamphilon ◽  
Nicholas J. Goulden ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Lymphoid Cells ◽  
Treatment Regimens ◽  
Leukemic Clone ◽  
B Lymphoid ◽  
Proliferation In Vitro

Abstract Only some acute lymphoblastic leukemia (ALL) cells are thought to be capable of proliferating to maintain the leukemic clone, and these cells may be the most relevant to target with treatment regimens. We have developed a serum-free suspension culture (SC) system that supported growth of B-ALL cells from 33 patients for up to 6 weeks. ALL cells from 28 cases (85%) were expanded in this system, and growth was superior in SC than in long-term bone marrow culture. To characterize ALL progenitors, cells were sorted for expression of CD34 and CD10 or CD19 and the subfractions assayed in SC and in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Cells capable of long-term proliferation in vitro and NOD/SCID repopulation were derived only from the CD34+/CD10- and CD34+/CD19- subfractions, and these cells could engraft secondary recipients. The engrafted cells had the same immunophenotype and karyotype as was seen at diagnosis, suggesting they had differentiated in vivo. These results demonstrate that ALL cells capable of long-term proliferation in vitro and in vivo are CD34+/CD10-/CD19-. This suggests that cells with a more immature phenotype, rather than committed B-lymphoid cells, may be the targets for transformation in B-ALL.

scholarly journals Acute Lymphoblastic Leukemia in the Older Adult

2019 ◽  
Vol 15 (2) ◽  
pp. 67-75 ◽  
Author(s):  
Ibrahim Aldoss ◽  
Stephen J. Forman ◽  
Vinod Pullarkat
Keyword(s):  
Older Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Older Adult ◽  
Older Patients ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Philadelphia Chromosome Positive

Acute lymphoblastic leukemia (ALL) in older adults presents a real challenge as a result of adverse disease biology and comorbidities that preclude delivering curative regimens. Conventional chemotherapy approaches have generally yielded unsatisfactory results in older patients with ALL as a result of excessive induction mortality, chemotherapy resistance of the leukemia, and the need to omit or dose reduce key drugs during the course of therapy because of adverse effects. Philadelphia chromosome–positive ALL represents about a quarter of newly diagnosed older adults, and the striking single-agent activity and excellent safety profile of tyrosine kinase inhibitors has allowed incorporation of these agents into therapy, significantly improving the outcome of older adults with Philadelphia chromosome–positive ALL. Allogeneic hematopoietic cell transplantation using reduced-intensity conditioning is a potentially curative approach in the older adult with ALL, and ironically, it may be better tolerated than intensive combination chemotherapy in a subset of older patients with ALL. Immunotherapies such as chimeric antigen receptor–modified T-cells, the bispecific T-cell–engaging antibody targeting CD19 (blinatumomab), and the antibody-drug conjugate targeting CD22 (inotuzumab) have shown safety and exceptional activity even in advanced ALL, and the efficacy of these agents has been observed irrespective of patient age. Several promising studies tailored specifically toward older adults with ALL are ongoing, with the majority of them incorporating novel immunotherapies, targeted therapies, or third-generation tyrosine kinase inhibitors into the front-line treatment regimen.

Sign in / Sign up

Export Citation Format

Share Document