scholarly journals Approach to the Adult Acute Lymphoblastic Leukemia Patient

2019 ◽  
Vol 8 (8) ◽  
pp. 1175 ◽  
Author(s):  
Valentina Sas ◽  
Vlad Moisoiu ◽  
Patric Teodorescu ◽  
Sebastian Tranca ◽  
Laura Pop ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
High Risk Patient ◽  
Late Relapse ◽  
Published Data ◽  
Hematopoietic Stem

During recent decades, understanding of the molecular mechanisms of acute lymphoblastic leukemia (ALL) has improved considerably, resulting in better risk stratification of patients and increased survival rates. Age, white blood cell count (WBC), and specific genetic abnormalities are the most important factors that define risk groups for ALL. State-of-the-art diagnosis of ALL requires cytological and cytogenetical analyses, as well as flow cytometry and high-throughput sequencing assays. An important aspect in the diagnostic characterization of patients with ALL is the identification of the Philadelphia (Ph) chromosome, which warrants the addition of tyrosine kinase inhibitors (TKI) to the chemotherapy backbone. Data that support the benefit of hematopoietic stem cell transplantation (HSCT) in high risk patient subsets or in late relapse patients are still questioned and have yet to be determined conclusive. This article presents the newly published data in ALL workup and treatment, putting it into perspective for the attending physician in hematology and oncology.

Treatment Selection for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors

Chemotherapy ◽  
2019 ◽  
Vol 64 (2) ◽  
pp. 81-93 ◽  
Author(s):  
Yingying Ma ◽  
Quanchao Zhang ◽  
Peiyan Kong ◽  
Jingkang Xiong ◽  
Xi Zhang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Molecular Response ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Philadelphia Chromosome Positive

With the advent of tyrosine kinase inhibitors (TKIs), the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has entered a new era. The efficacy of TKIs compared with other ALL treatment options is emphasized by a rapid increase in the number of TKI clinical trials. Subsequently, the use of traditional approaches, such as combined chemotherapy and even allogeneic hematopoietic stem cell transplantation (allo-HSCT), for the treatment of ALL is being challenged in the clinic. In light of the increased use of TKIs in the clinic, several questions have been raised. First, is it necessary to use intensive chemotherapy during the induction course of therapy to achieve a minimal residual disease (MRD)-negative status? Must a patient reach a complete molecular response/major molecular response before receiving allo-HSCT? Does MRD status affect long-term survival after allo-HSCT? Is auto-HSCT an appropriate alternative for allo-HSCT in those Ph+ ALL patients who lack suitable donors? Here, we review the recent literature in an attempt to summarize the current status of TKI usage in the clinic, including several new therapeutic approaches, provide answers for the above questions, and speculate on the future direction of TKI utilization for the treatment of Ph+ ALL patients.

scholarly journals How I treat relapsed acute lymphoblastic leukemia in the pediatric population

Blood ◽  
2020 ◽  
Vol 136 (16) ◽  
pp. 1803-1812 ◽  
Author(s):  
Stephen P. Hunger ◽  
Elizabeth A. Raetz
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Population ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Survival Rates ◽  
Treatment Decision ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
The Past

Abstract Relapsed acute lymphoblastic leukemia (ALL) has remained challenging to treat in children, with survival rates lagging well behind those observed at initial diagnosis. Although there have been some improvements in outcomes over the past few decades, only ∼50% of children with first relapse of ALL survive long term, and outcomes are much worse with second or later relapses. Recurrences that occur within 3 years of diagnosis and any T-ALL relapses are particularly difficult to salvage. Until recently, treatment options were limited to intensive cytotoxic chemotherapy with or without site-directed radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). In the past decade, several promising immunotherapeutics have been developed, changing the treatment landscape for children with relapsed ALL. Current research in this field is focusing on how to best incorporate immunotherapeutics into salvage regimens and investigate long-term survival and side effects, and when these might replace HSCT. As more knowledge is gained about the biology of relapse through comprehensive genomic profiling, incorporation of molecularly targeted therapies is another area of active investigation. These advances in treatment offer real promise for less toxic and more effective therapy for children with relapsed ALL, and we present several cases highlighting contemporary treatment decision-making.

scholarly journals Tyrosine Kinase Inhibitors and Reduced-Dose Chemotherapy for Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
chunping wu ◽  
mengting zeng ◽  
yuanzhong chen ◽  
yong wu
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Philadelphia Chromosome ◽  
Standard Chemotherapy ◽  
Chemotherapy Group ◽  
Reduced Dose

Abstract Purpose: To compare the outcomes of tyrosine kinase inhibitors in combination with reduced-dose chemotherapy with those of standard induction chemotherapy and to compare the outcomes between TKIs with chemotherapy regimen and transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia Methods: We retrospectively reviewed all patients treated with tyrosine kinase inhibitors in combination with chemotherapy. These patients were divided into the TKIs with reduced-dose chemotherapy group (62 patients) and the TKIs with standard chemotherapy group (143 patients). In further treatment, patients were divided into the transplant group (55 patients) and the non-transplant group (143 patients).Results: The complete remission rate (88.7% vs 83.9%, P=0.372) and early mortality rate (3.2% vs 3.5%, P=0.922) were similar between the TKIs with reduced-dose chemotherapy group and the TKIs with standard chemotherapy group. The proportions of lung infection (P=0.047) and bloodstream infection (P=0.024) and the proportion of patients with >21 days of hospitalization (P<0.001), on >4 types of antibiotics (P=0.003), and on restrictive tigecycline and/or polymyxin (P=0.031) were higher in the standard chemotherapy group than in the TKIs with reduced-dose chemotherapy group. For cost analysis, the total costs and antimicrobial costs were higher in the standard chemotherapy group than in the TKIs with reduced-dose chemotherapy group. The 3-year overall survival rates and 3-year disease-free survival rates were significantly better in the transplant group than in the non-transplant group. Conclusion: An induction regimen combining TKIs with reduced-dose chemotherapy and transplantation in first CR remains a good option for patients with Ph+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.

scholarly journals Acute lymphoblastic leukemia in adults

2011 ◽  
Vol 3 (2s) ◽  
pp. 1 ◽  
Author(s):  
Josep-Maria Ribera
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
New Drugs ◽  
Therapeutic Modality ◽  
Neoplastic Disease ◽  
Hematopoietic Stem ◽  
Therapeutic Modalities ◽  
Number Of Patients

Acute lymphoblastic leukemia (ALL) is the most frequent neoplastic disease in children, being a rare disease in adults. Many of the advances in pediatric ALL have been through modifications in the doses and schedules of available agents as opposed to the introduction of new compounds. In recent years some improvements in the outcome of ALL in adults have occurred. Application of pediatric regimens to young and middle-aged adults shows promise to improve outcome. Advances in the supportive care of patients undergoing allogeneic stem cell transplantation (SCT), the use of alternative sources of hematopoietic stem cells and the use of reduced-intensity conditioning regimens will expand the number of patients who can benefit from this therapeutic modality. The evaluation of minimal residual disease will further stratify risk classification and redefine the role of therapeutic modalities such as SCT or biologic agents. New drugs such as thyrosin kinase inhibitors or monoclonal antibodies have led to incremental improvements in outcome. Advances in the genetic and epigenetic mechanisms of the disease provide hope that targeted therapies can more effectively treat the disease with less toxicity.

Chemotherapy resistance in acute lymphoblastic leukemia requires hERG1 channels and is overcome by hERG1 blockers

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 902-914 ◽  
Author(s):  
Serena Pillozzi ◽  
Marika Masselli ◽  
Emanuele De Lorenzo ◽  
Benedetta Accordi ◽  
Emanuele Cilia ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chemokine Receptor ◽  
Molecular Mechanisms ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Chemotherapy Resistance ◽  
Leukemic Cells ◽  
Channel Blockers ◽  
Integrin Subunit ◽  
Signaling Complex

Abstract Bone marrow mesenchymal cells (MSCs) can protect leukemic cells from chemotherapy, thus increasing their survival rate. We studied the potential molecular mechanisms underlying this effect in acute lymphoblastic leukemia (ALL) cells. Coculture of ALL cells with MSCs induced on the lymphoblast plasma membrane the expression of a signaling complex formed by hERG1 (human ether-à-go-go-related gene 1) channels, the β1-integrin subunit, and the chemokine receptor CXC chemokine receptor-4. The assembly of such a protein complex activated both the extracellular signal-related kinase 1/2 (ERK1/2) and the phosphoinositide 3-kinase (PI3K)/Akt prosurvival signaling pathways. At the same time, ALL cells became markedly resistant to chemotherapy-induced apoptosis. hERG1 channel function appeared to be important for both the initiation of prosurvival signals and the development of drug resistance, because specific channel blockers decreased the protective effect of MSCs. NOD/SCID mice engrafted with ALL cells and treated with channel blockers showed reduced leukemic infiltration and had higher survival rates. Moreover, hERG1 blockade enhanced the therapeutic effect produced by corticosteroids. Our findings provide a rationale for clinical testing of hERG1 blockers in the context of antileukemic therapy for patients with ALL.

scholarly journals How I treat acute lymphoblastic leukemia in older adolescents and young adults

Blood ◽  
2015 ◽  
Vol 125 (24) ◽  
pp. 3702-3710 ◽  
Author(s):  
Emily Curran ◽  
Wendy Stock
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Survival Rates ◽  
Age Groups ◽  
Disease Free Survival ◽  
Current Approach ◽  
Adolescent And Young Adult

Abstract At the intersection between children and older adults, the care of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) poses unique challenges and issues beyond those faced by other age groups. Although the survival of AYA patients is inferior to younger children, growing evidence suggests that AYA patients have improved outcomes, with disease-free survival rates of 60% to 70%, when treated with pediatric-based approaches. A holistic approach, incorporating a multidisciplinary team, is a key component of successful treatment of these AYA patients. With the appropriate support and management of toxicities during and following treatment, these regimens are well tolerated in the AYA population. Even with the significant progress that has been made during the last decade, patients with persistence of minimal residual disease (MRD) during intensive therapy still have a poor prognosis. With new insights into disease pathogenesis in AYA ALL and the availability of disease-specific kinase inhibitors and novel targeted antibodies, future studies will focus on individualized therapy to eradicate MRD and result in further improvements in survival. This case-based review will discuss the biology, pharmacology, and psychosocial aspects of AYA patients with ALL, highlighting our current approach to the management of these unique patients.

scholarly journals ROLE OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014065 ◽  
Author(s):  
Federico Lussana ◽  
Alessandro Rambaldi
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Consolidation Therapy ◽  
Hematopoietic Stem ◽  
Risk Class

Adult acute lymphoblastic leukemia (ALL) is a heterogeneous disease, due to the expression of different biological and clinical risk factors, for which allogeneic stem cell transplantation (alloHSCT) is an effective consolidation therapy. The non-relapse mortality of alloHSCT remains significantly higher compared with that of conventional chemotherapy; therefore, one of the main challenges in the care of ALL is to establish a more precise prognostic definition to select patients who could take advantage from an alloHSCT. Currently, the use of minimal residual disease following induction and early consolidation therapy has improved the prognostic accuracy in defining ALL risk class. In Philadelphia-positive ALL, the introduction of tyrosine kinase inhibitors pre and post alloHSCT appears to improve outcomes significantly and, in the absence of specifically designed clinical trials, alloHSCT remains the most effective post- remission therapy. Nowadays, alloHSCT can be performed according to different modalities encompassing the use of different conditioning regimens, as well as different donors and stem cell source, with a significant accessibility to transplant.

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