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This review focuses on asparaginase, a key component of childhood acute lymphoblastic leukaemia (ALL) treatment since the 1970s. This review evaluates how much asparaginase is needed for optimal outcome in childhood ALL. We provide an overview of asparaginase dose intensity, i.e. duration of total cumulative exposure in weeks and level of exposure reflected by dose and/or asparaginase activity level, and the corresponding outcome. We systematically searched papers published between January 1990 and March 2021 in the PubMed and MEDLINE databases and included 20 papers. The level and duration of exposure were based on the pharmacokinetic profile of the drug and the assumption that trough asparaginase activity levels of ≥100 IU/L should be achieved for complete l -asparagine depletion. The statistical meta-analysis of outcomes was not performed because different outcome measures were used. The level of exposure was not associated with the outcome as long as therapeutic asparaginase activity levels of ≥100 IU/L were reached. Conflicting results were found in the randomised controlled trials, but all truncation studies showed that the duration of exposure (expressed as weeks of l -asparagine depletion) does affect the outcome; however, no clear cutoff for optimal exposure duration was determined. Optimal exposure duration will also depend on immunophenotype, (cyto)genetic subgroups, risk group stratification and backbone therapy. • This review provides a detailed overview of asparaginase therapy in peadiatric ALL. • Truncation studies show that the duration of asparaginase exposure affects the outcome. • No clear cutoff for the optimal duration of asparaginase exposure was determined. • Exposure level (expected asparaginase levels ≥100IU/L) was not associated with the outcome. [ABSTRACT FROM AUTHOR]

Background: This study was carried out to determine the frequency of CD34 positivity in acute lymphoblastic leukaemia (B-ALL) in our population and to report its association with the clinicopathological profile at the time of diagnosis. Methods: The cross-sectional study was conducted at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan, from March 2020 till December 2020.Newly diagnosed patients were selected, from both genders and all age groups. Relevant history and findings of physical examination were recorded. Immunohistochemistry was done on trephine biopsy and molecular studies were carried on bone marrow aspirates or peripheral blood samples. Results: Out of 105 patients enrolled, 67 (63.8%) were males, with a male to female ratio (M: F) 1.8:1. Of the total patients, 62 (59.04%) were above 15 years of age. CD34 was expressed in 73 (69.5%) cases. Lymphadenopathy, splenomegaly, and hepatomegaly were separately noted in context to CD 34 expression in 22 (66.6%), 24 (64.8%), and 14 (58.3%) patients, respectively. CNS disease was seen in a total of 3(2.75%) subjects, in which 2 (66.6%) of the patients had CD34 expression. Total 81 patients in our study fall into the high-risk group out of which CD 34 expression was seen in 58(71.6%) subjects. Cytogenetic analysis, BCR-ABL p190, and MLL gene rearrangement were investigated in all participants. Cytogenetic analysis revealed an abnormality in 20 (19%) cases out of which 13 (17.8%) cases were from CD34 positive group. Conclusion: Our study reported CD34 expression in more than two-thirds of cases. High-risk disease was significantly associated with CD34 expression. [ABSTRACT FROM AUTHOR]

Leukaemia is diagnosed conventionally by observing the peripheral blood and bone marrow smear using a microscope and with the help of advanced laboratory tests. Image processing-based methods, which are simple, fast, and cheap, can be used to detect and classify leukemic cells by processing and analysing images of microscopic smear. The proposed study aims to classify Acute Lymphoblastic Leukaemia (ALL) by Deep Learning (DL) based techniques. The study used Deep Convolutional Neural Networks (DNN s) to classify ALL according to WHO classification scheme without using any image segmentation and feature extraction that involves intense computations. Images from an online image bank of American Society of Haematology (ASH) were used for the classification. A classification accuracy of 94.12% is achieved by the study in isolating the B-cell and T-cell ALL images using a pretrained CNN AlexNet as well as LeukNet , a custom-made deep learning network designed by the proposed work. The study also compared the classification performances using three different training algorithms. The paper detailed the use of DNNs to classify ALL, without using any image segmentation and feature extraction techniques. Classification of ALL into subtypes according to the WHO classification scheme using image processing techniques is not available in literature to the best of the knowledge of the authors. The present study considered the classification of ALL only, and detection of other types of leukemic images can be attempted in future research. • Deep Learning based classification of ALL. • Classification of ALL based on WHO scheme. • ALL is classified into B – cell lymphoblasts and T – cell lymphoblasts. • Use of Convolutional Neural Networks (CNN) for leukaemia classification. • Leukaemia classification without image segmentation and feature extraction. [ABSTRACT FROM AUTHOR]

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The article discusses a study which investigated the association between pharmacogenetics and neurotoxicity in children with acute lymphoblastic leukemia (ALL). The epidemiological study involved patients diagnosed with ALL between 1991 and 2015 who were treated at Texas Children's Cancer Center in Houston, Texas. Retrospective analysis of treatment and toxicity data was based on information from electronic medical records. The limitations of the study are also cited.

In this age of digital microscopy, image processing, statistical analysis, categorization, and systems for decision-making have become essential tools for medical diagnostics research. By visualizing and analyzing images, clinicians can identify anomalies in intracellular structure. Leukemia is a cancerous condition marked by an unregulated increase in aberrant white blood cells (WBCs). Recognizing acute leukemia tumor cells in blood smear images (BSI) is a challenging assignment. Image segmentation is regarded as the most significant step in the automated identification of this disease. The innovative concavity-based segmentation algorithm is employed in this study to segment WBC in sub-images from the ALLIDB2 database. The concave endpoints and elliptical features are used in the segmentation step of convex-shaped cell images. The procedure involves the extraction of contour evidence, which detects the visible section of each object, and contour estimation, which corresponds to the final object's contours. Following the identification of the cells and their internal structure by concavity-based segmentation, the cells are categorized based on their morphological and statistical features. The method was evaluated using a public dataset meant to test classification and segmentation approaches. The statistical tool SPSS is used to independently check the significance of derived features. For classification, significant features are passed into machine learning techniques such as support vector machines (SVM), k-nearest neighbor (KNN), neural networks (NN), decision trees (DT), and Nave Bayes (NB). With an AUC of 98.9% and a total accuracy of 95%, the neural network model performed better. We advocate using the neural network model to identify acute leukemia cells based on its accuracy. [ABSTRACT FROM AUTHOR]

A seven-year-old girl presented with pain in multiple joints and constitutional symptoms over a period of four months. There were no significant clinical findings apart from joint tenderness. Blood test results did not indicate any specific pathology and initial radiology imaging was normal. Subsequent careful examination of her X-ray images led to an MRI of her left knee, which revealed acute osteonecrotic changes. A following whole-body MRI examination demonstrated multifocal bony lesions. Bone marrow examination conclusively diagnosed acute lymphoblastic leukaemia (ALL). Acute osteonecrosis has classically been described as a complication of treatment in children with ALL and has not been recognised as a presenting feature until recently. [ABSTRACT FROM AUTHOR]

Summary: Blinatumomab with subsequent haematopoietic stem cell transplantation was applied in 13 infants with acute lymphoblastic leukaemia (ALL). Eight patients were treated in first remission due to slow clearance of minimal residual disease (MRD); one for MRD‐reappearance after long MRD negativity, one for primary refractory disease and three during relapse treatment. In slow MRD responders, complete MRD response was achieved prior to transplantation, with an 18‐month event‐free survival of 75%. In contrast, only one of five patients with relapsed/refractory ALL is still in complete remission. These data provide a basis for future studies of immunotherapy in very high‐risk infant ALL. [ABSTRACT FROM AUTHOR]

The objective of this work is to create a diagnostic tool for the early diagnosis of leukaemia which is a serious type of cancer affecting bones and blood. Acute lymphoblastic leukemia (ALL) is the most dangerous form of leukemia. Doctors diagnose it by blood samples under powerful microscopes with enhanced lenses which can be slow and is sometimes affected by disagreements among experts. Therefore, the purpose of this work was to create a profound diagnostic tool for the early diagnosis of leukaemia. We proposes an Optimized Light Weight CNN to detect ALL at the early stage. Fragmentation and classification based on preprocessing are the two main components of the suggested method. Artificial images are created during the segmentation process and then tamed by chromatic modification. The proposed model is used to extract the best deep features from every blood smear image to predict the presence of ALL. The work was tested by two lymphoblastic leukaemia image databases (ALL_IDB1 and ALL_ IDB2). Deep-learning (DL) models-based segmentation and classification techniques have recently been introduced for detecting ALL; however they still have certain drawbacks. The proposed approach was assessed with few DL parameters like accuracy, F1 score, precision, recall and Area under the curve. In comparison to the most recent research studies already published; the suggested strategy produced exceptional classification accuracy as 99.56%, F1 score as 99.53%. [ABSTRACT FROM AUTHOR]

The potential of Sphagnum sericeum moss extracts as an alternative treatment for childhood acute Lymphoblastic leukaemia (ALL) was investigated in this study. Aqueous, methanol, and chloroform Sphagnum sericeum extracts were analyzed for phytochemical composition and cytotoxic effects on T-cell ALL lines (Jurkat and CCL-119). Results show that the S. sericeum aqueous extract (SSAE) yielded the highest percentage, followed by the methanol extract (SSME) and the chloroform extract (SSCE). Phytochemical analysis identified alkaloids, glycosides, and terpenoids in all extracts. SSME demonstrated significant cytotoxicity towards ALL cells, with the lowest IC50 values observed at 72 hours. Notably, SSME induced morphological changes, including blebbing and cell fragmentation after 6 h, indicative of apoptosis and cell destruction. These findings suggest SSME's potential as a natural agent for treating paediatric ALL, offering a novel approach in cancer research and contributing insights into the phytochemical compounds and cytotoxic effects of S. sericeum extracts on T-ALL cell lines. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Caring for children with ALL is an uncommon experience for parents without medical training. They urgently need professional assistance when their children are recovering at home. This paper documents the process of developing an Android application (app) "Care Assistant" for family caregivers of children with ALL. Key informant interviews and focus group studies were used before programming the app. The key informants and focus group members included: caregivers of children with ALL, cancer care physicians and nurses, and software engineers. We found several major challenges faced by caregivers: limited access to evidence-based clinic information, lack of financial and social assistance, deficient communications with doctors or nurses, lack of disease-related knowledge, and inconvenience of tracking treatments and testing results. This feedback was used to develop "Care Assistant". This app has eight modules: personal information, treatment tracking, family care, financial and social assistance, knowledge centre, self-assessment questionnaires, interactive platform, and reminders. We have also developed a web-based administration portal to manage the app. The usability and effectiveness of "Care Assistant" will be evaluated in future studies. [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death in the paediatric population after injuries. 3--10% of them are multiple primary malignant neoplasms, which are a huge problem both in diagnosis and treatment. We present a case of a boy, nearly 2 years old, with synchronous coexistence of T-cell acute lymphoblastic leukaemia and Langerhans cell histiocytosis. During the M AIEOP BFM ALL 2017 Protocol, the patient suffered an injury to the right elbow joint. Despite the limb being provided with a plaster cast and orthopaedic intervention, local improvement was not achieved. The obtained result of the histopathological examination revealed a disseminated aggressive form of histiocytosis affecting the skeletal system and lungs. In the presence of non-specific symptoms for the diagnosed cancer, one should be vigilant and suspect the coexistence of another proliferative process, which may cause no improvement despite proper therapeutic management. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukaemia (ALL) is the most common malignancy among children. It originates from over-proliferating immature lymphoid cells called lymphoblasts. Modern genetic studies have shown that the aetiology of ALL is correlated with numerous chromosomal aberrations, including activating mutation of the JAK/STAT pathway. This pathway is responsible for regulating the transmission of signals from extracellular cytokines to the nucleus of cells, regulating their growth, differentiation and immune response. With proper patient diagnosis, it is possible to correctly classify the genetic subtypes of ALL, allowing more effective therapies to be introduced. The following study presents the importance of genetic diagnosis for the treatment of a paediatric patient with ALL with the above mutation in the genome. [ABSTRACT FROM AUTHOR]

The Philadelphia (Ph) chromosome results from the formation of breakpoint cluster region (BCR)-Abelson 1 (ABL1) fusion gene (BCR-ABL1). The most common type of adult acute lymphoblastic leukaemia (ALL) is Ph chromosome-positive (Ph+); Ph+ ALL has an incidence of 25%∼30%. Several types of BCR-ABL1 fusion transcripts have been reported, including e1a2, e13a2 and e14a2. In addition, some rare BCR-ABL1 transcripts, such as e1a3, have been reported in chronic myeloid leukaemia. However, until now, the presence of e1a3 BCR-ABL1 fusion transcripts has only been reported in a few cases of ALL. In this study, a rare e1a3 BCR-ABL1 fusion transcript was found in a patient diagnosed with Ph+ ALL. However, the patient also suffered from severe agranulocytosis with pulmonary infection and died after being transferred to the intensive care unit before the significance of the presence of e1a3 BCR-ABL1 fusion transcript could be determined. In conclusion, e1a3 BCR-ABL1 fusion transcripts related to Ph+ ALL cases need to be better identified, and appropriate treatment strategies must be designed for such cases. [ABSTRACT FROM AUTHOR]

Abstract: Quality of life (QOL) in children with acute lymphoblastic leukaemia (ALL) is now considered an important outcome measure of treatment for this disease. The aim of this paper is to systematically review studies on QOL in children during treatment for ALL with consideration to methodological details and quality of studies, empirical findings on QOL as reported by children and parents, and whether children and parents differ in their reports on QOL. Searches were conducted in biomedical, psychological and behavioural science databases. Six papers met inclusion criteria for review: 4 cross-sectional studies and 2 qualitative studies. There was little consistency in how QOL was measured or qualitatively assessed across studies. The quality of most studies was limited by small sample sizes and cross-sectional designs. Children''s reports on QOL were represented in 3 studies and discrepancies were found between children''s and parent''s accounts of QOL. There is a need for ongoing research on QOL in children with ALL that use longitudinal designs, large sample sizes, and child reports of QOL. There is a need for theoretical development of the concept of QOL through concept analysis, grounded theory research and empirical validation of developing theory of QOL. Theoretical development of the concept of QOL will contribute to greater clarification of what is meant by QOL than currently exists which in turn has the potential to advance the methodology of measuring this concept in children. [Copyright &y& Elsevier]

Background Treatment of childhood cancer occurs over a 2- to 3-year period, with initial intense phases of chemotherapy followed by less severe treatment periods. From first diagnosis, families are encouraged by healthcare professionals (following government guidelines) to try to maintain a normal life. The aim of this paper is to contribute to our understanding of how ‘normal’ family life is compromised from the perspective of the families themselves during this period of extreme stress and concern for the health and well-being of their child. Methods This study was longitudinal and involved a cross section of 32 mothers of children recently diagnosed with acute lymphoblastic leukaemia (ALL) currently participating in the Medical Research Council ALL-97 randomized control trial. Mothers were interviewed at three time points (3–4 months post diagnosis, 15 and 27 months) using a semi-structured format with open-ended questions. A qualitative methodology was employed to analyse interview data using Thematic analysis. Results Mothers reported understanding the importance of achieving normal life, but described how this was difficult to realize. At first interview, mothers were optimistic that they could achieve the ‘normal life’ as advised by healthcare workers. At 12 and 24 months, although all mothers reported that life was not back to normal, there were differences in how they perceived this lack of normality. Whereas some families experienced frustration and disappointment, others had adjusted and managed to accept the new order. Conclusions Families felt encouraged on diagnosis to be told that despite the severity of the disease and treatment regime, a normal life was possible and should be pursued. Our findings indicate that over time, more concrete information is needed to guide parents through the treatment process in order to help them achieve this. [ABSTRACT FROM AUTHOR]

ABSTRACT Paediatric acute lymphoblastic leukaemia (ALL) has provided a landmark in cancer therapy as the first disseminated and otherwise lethal malignancy to be curable in the majority of patients. Although the success rate is high, this benefit is achieved through a long, invasive and very arduous treatment process. The experience of undergoing such intensive treatments affects not only the child, but the entire family. To date, however, psychosocial research is only beginning to describe the depth and breadth of the impact on families of this experience. This paper presents findings from a recent qualitative study of families coping with the initial stage (induction remission) of treatment for childhood ALL. The findings indicate that the experience is so profoundly disturbing and disruptive that it challenges the families' sense of normalcy and stability. These findings provide evidence of significant hardship and stress, with the consequent indication of the need for social work support. Above all, such families need to hear the comforting message from social workers that what they are experiencing is normal under the circumstances. Along with practical assistance, they need reassurance about the intensity of feelings they will experience and an affirmation of the difficulty of the challenges they face. [ABSTRACT FROM AUTHOR]

Rearrangements of the T-cell receptor (TCR) and immunoglobulin genes are considered as useful clonal markers in lymphoproliferative disorders of B- and T-cell lineage, and are frequently used for the detection of minimal residual disease (MRD). In this paper, we report on the unexpected results of an extensive analysis of TCR-δ chain gene rearrangement frequencies and patterns in leukaemic bone marrow DNA samples collected from 438 children with initial (n = 112) or relapsed (n = 326) acute lymphoblastic leukaemia (ALL). By applying a previously described multiplex polymerase chain reaction, the overall incidence of non-deleted TCR-δ gene rearrangements in ALL was 47% (206/438), 52% in initial ALL (58/112) and 45% in relapsed ALL (148/326). As expected, the majority of B-cell precursor (BCP) ALL had incomplete Vδ2-Dδ3 or Dδ2-Dδ3 TCR-δ gene rearrangements, whereas most T-ALL showed complete rearrangements of the TCR-δ gene locus (Vδ1-Jδ1, Vδ2-Jδ1, Vδ3-Jδ1). However, unexpectedly, 5/206 rearranged TCR-δ alleles in BCP-ALL showed a complete Vδ-(Dδ)-Jδ gene rearrangement pattern, and 3/31 T-ALL had an incomplete recombination. Theoretically, complete TCR-δ gene rearrangements should not occur in cells other than T-lymphocytes and have only been reported once previously in BCP-ALL. The data contribute to the discussion about the reliable screening for clonal markers in ALL. [ABSTRACT FROM AUTHOR]

Summary: Blinatumomab is the first bi‐specific T‐cell engager approved for relapsed or refractory B‐cell precursor acute lymphoblastic leukaemia (B‐ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty‐nine patients with B‐ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T‐cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T‐cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T‐cell subsets showed a broader post‐treatment subversion, including the modulation of markers associated with a T‐cell‐exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting. [ABSTRACT FROM AUTHOR]

Chemotherapy‐induced mucositis increases the risk of blood stream infections (BSI) due to translocation of bacteria across the intestinal epithelium. Our study investigated if quantitative measures of intestinal mucositis severity, including plasma citrulline (a marker of functional enterocytes) and CCL20 (an intestinal immune homeostatic chemokine), could identify patients at risk of BSI. A total of 106 children with ALL undergoing induction treatment (NOPHO ALL 2008) were included and information regarding BSI episodes was collected from the patients' medical records. Twenty‐seven patients (25%) developed BSI during induction. Patients with BSI had a larger decrease in citrulline after chemotherapy than patients without BSI, and nearly all BSI episodes (25/27) occurred in the group of patients exhibiting a drop in citrulline (OR = 6.4 [95% CI: 1.4‐29.3], P =.008). Patients who developed BSI had higher plasma CCL20 levels on days 8, 15 and 22 than patients without BSI (all P <.05), and elevated CCL20 levels on day 8 increased the risk of subsequent BSI (OR = 1.57 [1.11‐2.22] per doubling of CCL20 level, P =.01) in a multivariable logistic regression analysis. These findings suggest that children with ALL who develop BSI during chemotherapy are characterised by more severe intestinal mucositis, as measured by plasma citrulline and CCL20. These markers may be useful in early risk stratification to guide treatment decisions. [ABSTRACT FROM AUTHOR]

Objectives: The study aims to assess the proportion and magnitude of chemotherapy-induced peripheral neuropathy (CIPN) and other common complications reported in children with acute lymphoblastic leukaemia (ALL)/ acute lymphoblastic lymphoma (LBL) undergoing chemotherapy. Material and Methods: The study included children between 5 and 18 years old with ALL/LBL undergoing chemotherapy in Tertiary Care Hospitals, Mangalore. The study was conducted using various instruments, including paediatric-modified total neuropathy scale for CIPN, handheld dynamometer for muscle strength, bioimpedance analyser for muscle mass, timed up-and-go test for physical performance, and national comprehensive cancer network (NCCN) guidelines for scoring cancer-related fatigue at 3-time points. The collected data were analysed by IBM Statistical Package for the Social Sciences version 29 using Z-scores with standard deviation for distinct ALL/LBL types. In addition, the Paired t-test compared the baseline outcome to the 3rd and 6th time points. Results: The study evaluated 25 children with ALL undergoing chemotherapy based on the UKALL 2003 protocol during their maintenance phase. The study found that 25 children experienced CIPN, with changes in sensory and pin sensibility scores at 3 and 6 months. The study found a significant change in handgrip strength, body mass index, and muscle mass at 3 months, with no significant change in physical performance over time. Fatigue scores increased from baseline to 3 months, with significant changes observed for the 7-12 years age group at 3 months but not for the 5-6 years age group at 6 months. Conclusion: Children with ALL/LBL undergoing chemotherapy experience CIPN and other side effects such as sarcopenia and fatigue. The study highlights the potential benefits of physiotherapy interventions and supportive care strategies aimed at managing the adverse effects of chemotherapy in children with ALL/LBL. [ABSTRACT FROM AUTHOR]

Summary: To avoid toxicity, patients with inherited intolerance to thiopurines require major dose reductions of six mercaptopurine (6MP) for acute lymphoblastic leukaemia (ALL) maintenance treatment. Germline variants in the NUDT15 gene are emerging as the most common cause of 6MP intolerance in East Asian populations. New approaches are being developed to identify susceptibility to 6MP toxicity in order to appropriately tailor dosing schedules for at‐risk patients. Commentary on: Tanaka et al. Prominence of NUDT15 genetic variation associated with 6‐mercaptopurine tolerance in a genome‐wide association study of Japanese children with acute lymphoblastic leukaemia. Br J Haematol 2022;199:260‐269 and Yoshida et al. Low NUDT15 expression levels due to biallelic NUDT15 variants and 6‐mercaptopurine intolerance. Br J Haematol 2022;199:270‐276. [ABSTRACT FROM AUTHOR]

Hypothyroidism as a long‐term complication in cancer survivors has been an issue, but few studies have focused on changes in thyroid hormone levels during chemotherapy for leukaemia. This retrospective study was conducted to assess the characteristics of children with acute lymphoblastic leukaemia (ALL) and hypothyroidism during induction chemotherapy and to investigate the prognostic value of hypothyroidism in ALL. Patients with a detailed thyroid hormone profile at ALL diagnosis were enrolled. Hypothyroidism was defined as low serum levels of free tetraiodothyronine (FT4) and/or free triiodothyronine (FT3). The Kaplan‐Meier method was used to create survival curves, and multivariate Cox regression analysis was used to screen prognostic factors associated with progression‐free survival (PFS) and overall survival (OS). There were 276 children eligible for the study, and 184 patients (66.67%) were diagnosed with hypothyroidism, including 90 cases (48.91%) with functional central hypothyroidism and 82 cases (44.57%) with low T3 syndrome. Hypothyroidism was correlated with the dosages of L‐Asparaginase (L‐Asp) (P =.004) and glucocorticoids (P =.010), central nervous system (CNS) status (P =.012), number of severe infections (grade 3, 4 or 5) (P =.026) and serum albumin level (P =.032). Hypothyroidism was an independent prognostic factor for PFS in ALL children (P =.024, 95% CI: 1.1‐4.1). We conclude that hypothyroidism is commonly present in ALL children during induction remission, which is related to chemotherapy drugs and severe infections. Hypothyroidism was a predictor of poor prognosis in childhood ALL. [ABSTRACT FROM AUTHOR]

Autologous haematopoietic stem cell transplantation (auto‐HSCT) as a treatment for B‐cell acute lymphoblastic leukaemia (B‐ALL) has been rigorously debated in recent years. We retrospectively analysed the outcomes of 355 adult patients with B‐ALL in first complete remission who had received auto‐HSCT or allogeneic HSCT (allo‐HSCT) in our centre. The treatment efficacy was evaluated from a model stratified on the risk classification and minimal residue disease (MRD) status after three chemotherapy cycles. Auto‐HSCT demonstrated comparable 3‐year overall survival (OS) (72.7% vs. 68.5%, p = 0.441) and leukaemia‐free survival rates (62.8% vs. 56.1%, p = 0.383) compared to allo‐HSCT for patients with negative MRD, while the advantage of lower non‐relapse mortality (1.5% vs. 25.1%, p < 0.001) was offset by a higher cumulative incidence of relapse (CIR) rates (35.7% vs. 18.9%, p = 0.018), especially in high‐risk patients. For patients at high risk and with positive MRD, there was a lower trend of 3‐year OS (50.0% vs. 66.0%, p = 0.078) and significantly higher CIR rates (71.4% vs. 39.1%, p = 0.018) in auto‐HSCT. However, no significant interaction was observed in the tests. In conclusion, auto‐HSCT appears to be an attractive treatment for patients with negative MRD after three chemotherapy cycles. For MRD‐positive patients, allo‐HSCT may be a more effective treatment. [ABSTRACT FROM AUTHOR]

The therapy of children with acute lymphoblastic leukemia (ALL) in limited resource geospaces is challenging and must balance safety, efficacy, availability, and affordability. We modified the control arm of the St. Jude Total XI protocol for outpatient delivery including once-weekly daunorubicin and vincristine in initial therapy, postponing intrathecal chemotherapy until day 22, prophylactic oral antibiotics/antimycotics, use of generic drugs, and no central nervous system (CNS) radiation. Data were interrogated from 104 consecutive children =12 years (median, 6 years [interquartile range (IQR), 3, 9 years]. All therapies were given in an outpatient setting in 72 children. Median follow-up is 56 months (IQR 20, 126 months). A total of 88 children achieved a hematological complete remission. Median event-free survival (EFS) is 87 months [95% confidence interval (CI), 39, 60], 7.6 years in low-risk children (3.4, 8 years) whereas 2.5 years (1, 10 years) in high-risk children. The 5-year cumulative incidence of relapse (CIR) is 28% (18, 35%), 26% (14, 37%) in low-risk children and 35% (14, 52%) in high-risk children. Median survival for all subjects is not reached but must exceed 5 years. A total of 36 children relapsed at a median of 12 months (5, 23 months). Outcomes were comparable to those reported in the control arm of the Total Therapy XI study, but inferior to current treatment protocols in highincome countries. The average cost of the first 2 years of therapy was $28,500 USD compared with an average cost of approximately $150,000 USD in the US, an 80% saving. In conclusion, using an outpatient-based modification of the St. Jude Total XI protocol, we obtained good results with relatively few hospitalizations or adverse events and at a substantial saving. This model can be applied in other resource-poor geospaces. [ABSTRACT FROM AUTHOR]

Summary: Asparaginase is an essential drug for acute lymphoblastic leukaemia (ALL) treatment, but has several side effects, and its discontinuation often compromises patient outcomes. In the prospective Japan Association of Childhood Leukaemia Study ALL‐02 protocol, two major changes were made: (1) additional chemotherapies to compensate for the reduction of treatment intensity when asparaginase was discontinued and (2) more intensive concomitant corticosteroid administration, relative to our previous ALL‐97 protocol. In ALL‐02 study, 1192 patients were included and L‐asparaginase was discontinued for 88 (7.4%). Discontinuation due to allergy was markedly decreased relative to the ALL‐97 protocol (2.3% vs 15.4%). Event‐free survival (EFS) among patients with T‐ALL was compromised when L‐asparaginase was discontinued, as well as among patients with high‐risk B‐cell ALL, especially when discontinued before maintenance therapy. Moreover, multivariate analysis identified discontinuation of L‐asparaginase as an independent poor prognostic factor for EFS. In the current study, additional chemotherapies failed to fully compensate for L‐asparaginase discontinuation, illustrating the difficulty of replacing asparaginase with other classes of drugs, although this study was not designed to evaluate the effect of these modifications. Concomitant intensive corticosteroid treatment may help to reduce allergy to asparaginase. These results will assist in further optimization of asparaginase use. [ABSTRACT FROM AUTHOR]