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Background/Objectives: Relapsed B-cell acute lymphoblastic leukemia (B-ALL) remains an unresolved matter of concern regarding adverse outcomes. This case study aimed to evaluate the effectiveness of blinatumomab, with or without door lymphocyte infusion (DLI), in treating measurable residual disease (MRD)-positive B-ALL. Methods: All patients who received blinatumomab salvage therapy were included in this study. Eleven patients were included in the study. All patients were evaluated for MRD-negativity. Results: Before starting blinatumomab therapy, seven patients tested positive for MRD, three tested negative, and one had refractory disease. Hematopoietic cell transplantation (HCT) was reserved for five patients with persistent MRD. Six patients became MRD-negative and subsequent HCT was not performed. Only two patients relapsed; one patient died of relapse, and the other one received carfilzomib-based therapy and was MRD-negative thereafter. Nine patients were MRD-negative at a median follow-up of 28 months (15–52 months). Two of three MRD-positive post-transplant patients remained in complete molecular remission after preemptive DLI at the last follow-up date. In the first salvage, blinatumomab may achieve complete remission and bridging to HCT in pediatric patients with end-of-induction MRD-positive B-cell precursor ALL. Conclusions: The decision on how to treat post-transplant relapse continues to affect survival outcomes. Blinatumomab combined with DLI may extend the armamentarium of release options for high-risk pediatric patients. This approach is encouraging for high-risk ALL patients who are MRD-positive post-transplantation. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is an essential part of therapy in the treatment of acute lymphoblastic leukemia (ALL) in children, and inferior intellectual outcomes have been reported in children who are leukemia survivors. Although several studies have demonstrated that the interaction between gut microbiota changes and the brain plays a vital role in the pathogenesis of chemotherapy-induced brain injury, preexisting studies on the effect of MTX on gut microbiota changes focused on gastrointestinal toxicity only. Based on our previous studies, which revealed that MTX treatment resulted in inferior neurocognitive function in developing young rats, we built a young rat model mimicking MTX treatment in a child ALL protocol, trying to investigate the interactions between the gut and brain in response to MTX treatment. We found an association between gut microbiota changes and neurogenesis/repair processes in response to MTX treatment, which suggest that MTX treatment results in gut dysbiosis, which is considered to be related to MTX neurotoxicity through an alteration in gut–brain axis communication. [ABSTRACT FROM AUTHOR]

Summary: This study investigates the potential utility of IKZF1 deletion as an additional high‐risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD‐guided TPOG‐ALL‐2013 protocol using 412 newly diagnosed B‐ALL patients aged 1–18. IKZF1 status was determined using multiplex ligation‐dependent probe amplification. IKZF1 deletions, when co‐occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B‐ALL. IKZF1plus was observed in 4.1% of Philadelphia‐negative ALL, with a significantly lower 5‐year event‐free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild‐type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high‐risk patients with IKZF1plus exhibited the worst outcomes in event‐free survival (42.0%), relapse‐free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia‐negative B‐ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment. [ABSTRACT FROM AUTHOR]

With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity. [ABSTRACT FROM AUTHOR]

Glucocorticoids play a pivotal role in therapeutic protocols in acute lymphoblastic leukemia (ALL) treatment. Systemic steroids are known to be less likely to elevate the intraocular pressure when compared to topical administration, and reports addressing hypertensive ocular response in the Asian pediatric ALL population are currently limited. We report a case of a nine-year-old girl with acute lymphoblastic leukemia (ALL) who was found to have highly elevated intraocular pressure (IOP) during maintenance treatment when taking oral dexamethasone (6 mg/m2/day). Her IOP increased on day 5 after taking dexamethasone, reached a peak on day 7 or 8, and returned back to baseline on day 13 before anti-glaucoma medications were used. Thus, we prescribed IOP-lowering agents for 10 consecutive days starting on the day oral dexamethasone was administered, and observed that not only did the peak levels lower remarkably, but the IOP levels returned to baseline more rapidly as well. [ABSTRACT FROM AUTHOR]

Background/purpose: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear.Methods: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry.Results: MRD results were concordant in 91 of the 108 paired samples (84.2%; K=0.690); 49 samples were MRD-negative while 42 were MRD-positive by both methods, with < 1 log difference in positive MRD estimates in 39 samples (92.9%). Of the 17 discordant samples, 16 were MRD-positive by RQ-PCR but MRD-negative by flow cytometry; the opposite was true in one sample. Kappa value/concordance was 0.690/85.0% (n = 60) for ETV6-RUNX1, 0.842/93.3% (n = 15) for TCF3-PBX1, and 0.535/78.8% (n = 33) for BCR-ABL1. Specific immunophenotypic abnormalities were more prevalent in each genetic subgroup, such as CD38 underexpression, CD58 overexpression, and CD34 overexpression in ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1, respectively.Conclusion: In most follow-up samples, MRD estimates by two methods are in agreement, especially in patients with TCF3-PBX1. [ABSTRACT FROM AUTHOR]

Abstract: Minimal residual disease (MRD) in 56 children with acute lymphoblastic leukemia (ALL) was quantified simultaneously by flow cytometry and by RQ-PCR of WT1 transcripts. Six patients failed remission induction, all had detectable MRD by flow cytometry, and two had undetectable MRD by WT1 assay. Among 41 patients, who achieved remission and had overexpression of WT1 transcripts at diagnosis, the two techniques gave concordant MRD results in 26 and discordant MRD results in 15. Nine patients did not show overexpression of WT1 at diagnosis. Our results indicate that RQ-PCR measurements of WT1 may be of limited value for monitoring MRD in childhood ALL. [Copyright &y& Elsevier]

With the improvement of the survival rates in children acute lymphoblastic leukemia (ALL), some children ALL survivors show impaired cognitive function. Methotrexate (MTX), an essential component in ALL treatment, has been reported to be related to neurologic sequelae and to increased oxidative stress through its interactions with enzymes in the folate pathway. Asymmetric dimethylarginine (ADMA) is the main endogenous inhibitor of nitric oxide synthase, and increased ADMA may result from increased oxidants. Melatonin is an antioxidant; however, its role in MTX neuropathy is not well studied. We developed a rat model mimicking child ALL treatment to explore peripheral and central homocysteine and ADMA regulation after MTX and found potential treatment choice. Preweaning male Sprague-Dawley rats were used in this study. Experiment 1 evaluated spatial performance in rats with intrathecal (IT) MTX, intraperitoneal (IP) MTX, or combined IT and IP MTX, protocols mimicking ALL treatment in children. Experiment 2 focused on rats with combined IT and IP MTX, evaluating spatial performance and plasma and dorsal hippocampal homocysteine and ADMA levels, their regulation, and the protective effect of melatonin. Combined IT and IP MTX treatment caused in spatial deficits in developing rats, and melatonin restored the spatial performance. Alterations in peripheral and central homocysteine and ADMA concentrations and their regulation were found and could be alleviated by melatonin treatment. Combined IP and IT MTX treatment caused spatial deficits in developing rats. Melatonin could restore spatial performance through alleviating the effects on the imbalance of oxidative stress. [ABSTRACT FROM AUTHOR]