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 Personalized therapy in pediatric high-risk B-cell acute lymphoblastic leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062072092757 ◽  
Author(s):  
Seth E. Karol ◽  
Ching-Hon Pui
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Risk Patients ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Disease Stratification ◽  
Cure Rates ◽  
Minimal Residual

Although cure rates for pediatric acute lymphoblastic leukemia (ALL) have now risen to more than 90%, subsets of patients with high-risk features continue to experience high rates of treatment failure and relapse. Recent work in minimal residual disease stratification and leukemia genomics have increased the ability to identify and classify these high-risk patients. In this review, we discuss this work to identify and classify patients with high-risk ALL. Novel therapeutics, which may have the potential to improve outcomes for these patients, are also discussed.

Biallelic loss ofCDKN2Ais associated with poor response to treatment in pediatric acute lymphoblastic leukemia

2016 ◽  
Vol 58 (5) ◽  
pp. 1162-1171 ◽  
Author(s):  
Marcin Braun ◽  
Agata Pastorczak ◽  
Wojciech Fendler ◽  
Joanna Madzio ◽  
Bartlomiej Tomasik ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Response To Treatment ◽  
Pediatric Acute Lymphoblastic Leukemia

scholarly journals Use of Minimal Residual Disease Assessment to Redefine Induction Failure in Pediatric Acute Lymphoblastic Leukemia

2017 ◽  
Vol 35 (6) ◽  
pp. 660-667 ◽  
Author(s):  
David O’Connor ◽  
Anthony V. Moorman ◽  
Rachel Wade ◽  
Jeremy Hancock ◽  
Ronald M.R. Tan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Chromosomal Abnormalities ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Assessment ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Real Time Quantitative Pcr ◽  
Induction Failure ◽  
Minimal Residual

Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in the identification and stratification of induction failure in patients with pediatric acute lymphoblastic leukemia (ALL) and to identify genetic abnormalities that drive disease in these patients. Patients and Methods Analysis included 3,113 patients who were treated in the Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 and 2011. MRD was measured by using standardized real-time quantitative PCR. Median follow-up was 5 years 9 months. Results Fifty-nine patients (1.9%) had morphologic induction failure with 5-year event-free survival (EFS) of 50.7% (95% CI, 37.4 to 64.0) and 5-year overall survival of 57.7% (95% CI, 44.2 to 71.2). Of these, a small proportion of patients with M2 marrow (6 of 44) and a low EOI MRD level (< 0.01%) had 5-year EFS of 100%. Conversely, among patients with morphologic remission 2.3% (61 of 2,633) had high MRD (≥ 5%) and 5-year EFS of 47.0% (95% CI, 32.9 to 61.1), which was similar to those with morphologic induction failure. Redefining induction failure to include morphologic induction failure and/or MRD ≥ 5% identified 3.9% (120 of 3,133 patients) of the trial cohort with 5-year EFS of 48.0% (95% CI, 39.3 to 58.6). Induction failure (morphologic or MRD ≥ 5%) occurred most frequently in T-ALL (10.1%; 39 of 386 T-ALL cases) and B-other ALL, that is, lacking established chromosomal abnormalities (5.6%; 43 of 772 B-other cases). Genetic testing within the B-other group revealed the presence of PDGFRB gene fusions, particularly EBF1-PDGFRB, in almost one third of B-other ALL cases. Conclusion Integration of EOI MRD level with morphology identifies induction failure more precisely than morphology alone. Prevalence of EBF1-PDGFRB fusions in this group highlights the importance of genetic screening to identify abnormalities that may be targets for novel agents.

scholarly journals T-cell acute lymphoblastic leukemia

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 580-588 ◽  
Author(s):  
Elizabeth A. Raetz ◽  
David T. Teachey
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Disease Response ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Relapsed Disease ◽  
Modern Genomic

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included. Recent insights into T-ALL biology, using modern genomic techniques, have identified a number of recurrent lesions that can be grouped into several targetable pathways, including Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK. With contemporary chemotherapy, outcomes for de novo T-ALL have steadily improved and now approach those observed in B-ALL, with approximately 85% 5-year event-free survival. Unfortunately, salvage has remained poor, with less than 25% event-free and overall survival rates for relapsed disease. Thus, current efforts are focused on preventing relapse by augmenting therapy for high-risk patients, sparing toxicity in favorable subsets and developing new approaches for the treatment of recurrent disease.

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.

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