scholarly journals Novel monoclonal antibody-based treatment strategies in adults with acute lymphoblastic leukemia

2019 ◽  
Vol 10 ◽  
pp. 204062071984949 ◽  
Author(s):  
Veronica A. Guerra ◽  
Elias J. Jabbour ◽  
Farhad Ravandi ◽  
Hagop Kantarjian ◽  
Nicholas J. Short
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
Poor Overall Survival ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Treatment Regimens ◽  
Treatment Paradigm

Adult acute lymphoblastic leukemia (ALL) has a poor overall survival compared with pediatric ALL where cure rates are observed in more than 90% of patients. The recent development of novel monoclonal antibodies targeting CD20, CD19, and CD22 has changed the long-term outcome of this disease, both in the frontline setting (e.g. rituximab) and for patients with relapsed/refractory disease (e.g. inotuzumab ozogamicin and blinatumomab). The CD3-CD19 bispecific T-cell-engaging antibody blinatumomab is also the first drug approved in ALL for patients with persistent or recurrent measurable residual disease, providing a new treatment paradigm for these patients. Several new agents are also in development that use novel constructs or target alternative surface epitopes such as CD123, CD25, and CD38. Herein, we review the role of monoclonal antibodies in adult ALL and summarize the current and future approaches in ALL, including novel combination therapies and the possibility of early incorporation of these agents into treatment regimens.

Modern Therapy of Acute Lymphoblastic Leukemia

2011 ◽  
Vol 29 (5) ◽  
pp. 532-543 ◽  
Author(s):  
Renato Bassan ◽  
Dieter Hoelzer
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Individual Risk ◽  
High Dose ◽  
Term Outcome ◽  
Hematopoietic Stem ◽  
Genetic Characteristics ◽  
Long Term Outcome ◽  
Therapeutic Decisions

Although acute lymphoblastic leukemia is curable in one third of adult patients, results vary greatly on account of different clinical, immunologic, and cytogenetic/genetic characteristics. These data, along with the kinetics of response to early treatment, help establish the individual risk class with considerable accuracy, and support risk-specific treatments that should warrant optimal results with as little as possible nonrelapse mortality. Modern first-line therapy consists of standard- and high-dose chemotherapy (increasingly inspired to pediatric principles), hematopoietic stem-cell transplantation, and new targeted therapy, all integrated with the analysis of prognostic factors and the study of subclinical residual disease for key therapeutic decisions. These changes are improving long-term outcome, which in ongoing studies is expected close to 50% or greater.

scholarly journals Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Vol 10 (9) ◽  
pp. 1926
Author(s):  
Hiroto Inaba ◽  
Ching-Hon Pui
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Detailed Analysis ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Response To Treatment ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Therapeutic Implications

The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved remarkably during the last five decades. Such improvements were made possible by the incorporation of new diagnostic technologies, the effective administration of conventional chemotherapeutic agents, and the provision of better supportive care. With the 5-year survival rates now exceeding 90% in high-income countries, the goal for the next decade is to improve survival further toward 100% and to minimize treatment-related adverse effects. Based on genome-wide analyses, especially RNA-sequencing analyses, ALL can be classified into more than 20 B-lineage subtypes and more than 10 T-lineage subtypes with prognostic and therapeutic implications. Response to treatment is another critical prognostic factor, and detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells. Such detailed analysis can facilitate the rational use of molecular targeted therapy and immunotherapy, which have emerged as new treatment strategies that can replace or reduce the use of conventional chemotherapy.

scholarly journals Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

2021 ◽  
Vol 19 (9) ◽  
pp. 1079-1109
Author(s):  
Patrick A. Brown ◽  
Bijal Shah ◽  
Anjali Advani ◽  
Patricia Aoun ◽  
Michael W. Boyer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Supportive Care ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Treatment Strategies ◽  
Adolescent And Young Adult ◽  
Cancer Center ◽  
Nccn Guidelines ◽  
Treatment Regimens

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.

Chemotherapy-Phased Imatinib Pulses Improve Long-Term Outcome of Adult Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09/00

2010 ◽  
Vol 28 (22) ◽  
pp. 3644-3652 ◽  
Author(s):  
Renato Bassan ◽  
Giuseppe Rossi ◽  
Enrico M. Pogliani ◽  
Eros Di Bona ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Adult Patients ◽  
Negative Group ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Positive Group ◽  
Disease Free

Purpose Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) –positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates. Patients and Methods Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib. Results CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall. Conclusion This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.

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