The Treatment of Adults with Acute Lymphoblastic Leukemia

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 381-389 ◽  
Author(s):  
Adele Fielding
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Evidence Base ◽  
Current Evidence ◽  
Disease Biology ◽  
Current Evidence Base ◽  
Low Incidence ◽  
Treat All

Abstract Despite the relatively low incidence of acute lymphoblastic leukemia (ALL) in adults, large national and international collaborations have recently improved our understanding of how to treat ALL in adults. This article documents and examines the current evidence base for a “state of the art” therapy in both Philadelphia chromosome–negative and –positive adult ALL. The article comments upon areas of therapeutic debate, such as the role of bone marrow transplantation. In particular, the controversial subject of whether the superior outcome seen in younger patients is predicated on disease biology or therapeutic strategy is examined closely. Promising approaches under development are also discussed.

scholarly journals Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial

2018 ◽  
Vol 36 (24) ◽  
pp. 2514-2523 ◽  
Author(s):  
Françoise Huguet ◽  
Sylvie Chevret ◽  
Thibaut Leguay ◽  
Xavier Thomas ◽  
Nicolas Boissel ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Standard Dose ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Treatment Phase ◽  
Free Survival ◽  
Treatment Tolerance ◽  
To Receive

Purpose To evaluate randomly the role of hyperfractionated cyclophosphamide (hyper-C) dose intensification in adults with newly diagnosed Philadelphia chromosome–negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol and to determine the upper age limit for treatment tolerability in this context. Patients and Methods A total of 787 evaluable patients (B/T lineage, 525 and 262, respectively; median age, 36.1 years) were randomly assigned to receive a standard dose of cyclophosphamide or hyper-C during first induction and late intensification. Compliance with chemotherapy was assessed by median doses actually received during each treatment phase by patients potentially exposed to the full planned doses. Results Overall complete remission (CR) rate was 91.9%. With a median follow-up of 5.2 years, the 5-year rate of event-free survival (EFS) and overall survival (OS) was 52.2% (95% CI, 48.5% to 55.7%) and 58.5% (95% CI, 54.8% to 61.9%), respectively. Randomization to the hyper-C arm did not increase the CR rate or prolong EFS or OS. As a result of worse treatment tolerance, advanced age continuously affected CR rate, EFS, and OS, with 55 years as the best age cutoff. At 5 years, EFS was 55.7% (95% CI, 51.8% to 59.4%) for patients younger than 55 years of age versus 25.8% (95% CI, 19.9% to 35.6%) in older patients (hazard ratio, 2.16; P < .001). Patients ≥ 55 years of age, in whom a lower compliance to the whole planned chemotherapy was observed, benefited significantly from hyper-C, whereas younger patients did not. Conclusion No significant benefit was associated with the introduction of a hyper-C sequence into a frontline pediatric-like adult acute lymphoblastic leukemia therapy. Overall, tolerability of an intensive pediatric-derived treatment was poor in patients ≥ 55 years of age.

The Effect of Gender on Women-led Small Enterprises: The Case of India

2013 ◽  
Vol 2 (1) ◽  
pp. 61-75
Author(s):  
Debasree Das Gupta
Keyword(s):  
Gender Gap ◽  
Institutional Environment ◽  
State Level ◽  
Evidence Base ◽  
Current Evidence ◽  
Economic Activities ◽  
Related Factors ◽  
Current Evidence Base ◽  
Entrepreneurial Activities

The importance of women-led enterprises for any country’s economic growth and competitiveness is well established. According to a 2009 study, in India female-run enterprises in recent years have performed significantly better than other enterprises in terms of productivity and export percentages. However, gender gap in entrepreneurial initiatives in India is among the highest in the world. Although accepted as crucial, the role of public policy towards addressing these barriers is under-researched in the entrepreneurship literature. Further, the current evidence base on state-level predictors of female enterprises is scant. The aim of this study is to highlight these gaps. In doing so, the focus is on interpreting the role of gender correlates—fertility, female educational attainment and female economic activities—in facilitating or hindering women-led enterprises. Indeed, previous studies have identified gender-related factors to have the greatest impact on women’s choice in not taking up entrepreneurial activities. An empirical regression analysis and a qualitative review of the institutional environment are conducted. The findings presented in this study indicate the need for a realignment of policy focus towards addressing gender barriers and developing managerial skills, in addition to technical skills, of women entrepreneurs.

scholarly journals Interventions for challenging behaviour in intellectual disability

2014 ◽  
Vol 20 (3) ◽  
pp. 184-192 ◽  
Author(s):  
Afia Ali ◽  
Jessica Blickwedel ◽  
Angela Hassiotis
Keyword(s):  
Intellectual Disability ◽  
Evidence Base ◽  
Current Evidence ◽  
List Type ◽  
Challenging Behaviour ◽  
Pharmacological Treatments ◽  
Current Evidence Base ◽  
The Individual

SummaryChallenging behaviour is common in intellectual disability but it is difficult to diagnose and manage. It can adversely affect the quality of life of the individual and cause the breakdown of community placements, resulting in hospital admission. This article discusses the aetiology of challenging behaviour (including the complex relationship with mental illness), diagnostic problems, the current evidence base in relation to psychosocial and pharmacological treatments, and service delivery.LEARNING OBJECTIVES•Understand the aetiological basis of challenging behaviour.•Understand the role of functional analysis.•Appreciate the evidence base in relation to the psychological and pharmacological treatment of challenging behaviour.

scholarly journals IKZF1 deletions in pediatric acute lymphoblastic leukemia: still a poor prognostic marker?

Blood ◽  
2020 ◽  
Vol 135 (4) ◽  
pp. 252-260 ◽  
Author(s):  
Martin Stanulla ◽  
Hélène Cavé ◽  
Anthony V. Moorman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Perceived Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
Response To Treatment ◽  
Primary Therapy ◽  
Disease Biology ◽  
Pediatric All ◽  
Shed Light

Abstract 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.

scholarly journals The role of stem cell transplantation in the management of Philadelphia chromosome-positive acute lymphoblastic leukemia

2018 ◽  
Vol 9 (12) ◽  
pp. 357-368 ◽  
Author(s):  
Jose-Maria Ribera ◽  
Jordi Ribera ◽  
Eulalia Genescà
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Molecular Response ◽  
Hematopoietic Stem ◽  
Philadelphia Chromosome Positive

The concurrent administration of tyrosine kinase inhibitors (TKIs) with standard chemotherapy together with allogeneic hematopoietic stem cell transplantation (alloHSCT) has improved the outcome of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Although to date, no study has shown alloHSCT to be inferior to chemotherapy plus TKIs in any subgroup of adult Ph+ ALL, there is some evidence suggesting no additional benefit of alloHSCT in patients with deep molecular responses to intensive chemotherapy with a second-generation, and especially, third-generation TKI. As none of these positive and negative studies are controlled, randomized trials are needed to fully define the role of alloHSCT in Ph+ ALL, especially in those with deep molecular response. However, if studies combining TKIs with new approaches such as immunotherapy lead to durable responses, alloHSCT in the first complete remission could be avoided in the near future in the majority of patients with Ph+ ALL.

How I treat Philadelphia chromosome–positive acute lymphoblastic leukemia

Blood ◽  
2010 ◽  
Vol 116 (18) ◽  
pp. 3409-3417 ◽  
Author(s):  
Adele K. Fielding
Keyword(s):  
Clinical Trials ◽  
Acute Lymphoblastic Leukemia ◽  
Randomized Clinical Trials ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Current Evidence ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Treatment Choices

AbstractThe Philadelphia chromosome is present in approximately 20% to 30% of adults with acute lymphoblastic leukemia (ALL). The poor prognosis of this relatively uncommon acute leukemia has led to the rapid adoption of treatment strategies such as unrelated donor hematopoietic stem cell transplant and tyrosine kinase inhibitors into clinical practice, despite a relative paucity of randomized clinical trials. Recently, there has been a surge of interest in the underlying biology of ALL. In combination with an accumulation of more mature clinical study data in Philadelphia-positive ALL, it is increasingly possible to make more rational and informed treatment choices for patients of all ages. In this article, I review available data and indicate how I personally interpret current evidence to make pragmatic treatment choices with my patients, outside of clinical trials. My strongest recommendation is that all physicians who are treating this rare disease actively seek appropriate clinical trials for their patients wherever possible.

scholarly journals Role of Autophagy and Apoptosis in Acute Lymphoblastic Leukemia

2021 ◽  
Vol 28 ◽  
pp. 107327482110191
Author(s):  
Fang-Liang Huang ◽  
Sheng-Jie Yu ◽  
Chia-Ling Li
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Intracellular Signaling ◽  
Lymphoblastic Leukemia ◽  
New Drugs ◽  
Apoptosis Pathways ◽  
Treat All ◽  
Differentiation And Proliferation

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease characterized by an excessive number of immature lymphocytes, including immature precursors of both B- and T cells. ALL affects children more often than adults. Immature lymphocytes lead to arrested differentiation and proliferation of cells. Its conventional treatments involve medication with dexamethasone, vincristine, and other anticancer drugs. Although the current first-line drugs can achieve effective treatment, they still cannot prevent the recurrence of some patients with ALL. Treatments have high risk of recurrence especially after the first remission. Currently, novel therapies to treat ALL are in need. Autophagy and apoptosis play important roles in regulating cancer development. Autophagy involves degradation of proteins and organelles, and apoptosis leads to cell death. These phenomena are crucial in cancer progression. Past studies reported that many potential anticancer agents regulate intracellular signaling pathways. Methods: The authors discuss the recent research findings on the role of autophagy and apoptosis in ALL. Results: The autophagy and apoptosis are widely used in the treatment of ALL. Most studies showed that many agents regulate autophagy and apoptosis in ALL cell models, clinical trials, and ALL animal models. Conclusions: In summary, activating autophagy and apoptosis pathways are the main strategies for ALL treatments. For ALL, combining new drugs with traditional chemotherapy and glucocorticoids treatments can achieve the greatest therapeutic effect by activating autophagy and apoptosis.

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