Search

Abstract: Ovarian hyperstimulation syndrome (OHSS) is characterized by cystic enlargement of the ovaries and a fluid retention. This syndrome is sometimes caused after in vitro fertilization. We treated a 37-year-old woman with OHSS after in vitro fertilization, coincidentally complicated with acute lymphoblastic leukemia. Her clinical course of acute lymphoblastic leukemia was aggressive with the manifestation of OHSS, such as massive pleural effusion and massive ascites. The leukemic cells broadly infiltrated to the peritoneum, ovary, central spine fluid, and pleura. We speculated that this hyperpermeability of leukemic cells could be associated with the cytokine milieu caused by OHSS., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: This study aimed to develop highly precise radiomics and deep learning models to accurately detect acute lymphoblastic leukemia (ALL) using a T1WI image., Materials and Methods: A total of 604 brain magnetic resonance data of ALL group and normal children (NC) group. Two radiologists independently retrieved radiomics features after manually delineating the area of interest along the clivus at the median sagittal position of T1WI. According to the 9:1 ratio, all samples were randomly divided into the training cohort and the testing cohort. support vector machine was then used to classify the radiomics model using the features that had a correlation coefficient of greater than 0.99 in the training cohort. The Efficientnet-B3 network model received the training set images to create a deep learning model. The sensitivity, specificity, and area under the ROC curve were calculated in order to evaluate the diagnostic efficacy of the different models after the validation of two aforementioned models in the testing cohort., Results: The deep learning model had a higher AUC value of 0.981 than the radiomics model's value of 0.962 in the testing cohort. Delong's test showed no statistical difference between the two models (P>0.05). The accuracy/sensitivity/specificity/negative predictive value/positive predictive value achieved 0.9180/0.9565/0.8947/0.9714/0.8462 for the radiomics model and 0.9344/0.8696/0.9737/0.9250/0.9524 for deep learning model., Conclusions: The deep learning and radiomics models showed high AUC values in the training and test cohorts. They also exhibited good diagnostic efficacy for predicting ALL., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Children with acute lymphoblastic leukaemia (ALL) are at risk for obesity and cardiometabolic diseases. To gain insight into body composition changes among children with ALL, we assessed quantitative computed tomography (QCT) data for specific body compartments (subcutaneous adipose tissue [SAT], visceral adipose tissue [VAT], total adipose tissue [TAT], lean tissue [LT], LT/TAT and VAT/SAT at lumbar vertebrae L1 and L2) at diagnosis and at off-therapy for 189 children with ALL and evaluated associations between body mass index (BMI) Z-score and clinical characteristics. BMI Z-score correlated positively with SAT, VAT and TAT and negatively with LT/TAT and VAT/SAT. At off-therapy, BMI Z-score, SAT, VAT and TAT values were higher than at diagnosis, but LT, LT/TAT and VAT/SAT were lower. Patients aged ≥10 years at diagnosis had higher SAT, VAT and TAT and lower LT and LT/TAT than patients aged 2.0-9.9 years. Female patients had lower LT and LT/TAT than male patients. Black patients had less VAT than White patients. QCT analysis showed increases in adipose tissue and decreases in LT during ALL therapy when BMI Z-scores increased. Early dietary and physical therapy interventions should be considered, particularly for patients at risk for obesity., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

The timely diagnosis of acute lymphoblastic leukemia (ALL) is of paramount importance for enhancing the treatment efficacy and the survival rates of patients. In this study, we seek to introduce an ensemble-ALL model for the image classification of ALL, with the goal of enhancing early diagnostic capabilities and streamlining the diagnostic and treatment processes for medical practitioners. In this study, a publicly available dataset is partitioned into training, validation, and test sets. A diverse set of convolutional neural networks, including InceptionV3, EfficientNetB4, ResNet50, CONV_POOL-CNN, ALL-CNN, Network in Network, and AlexNet, are employed for training. The top-performing four individual models are meticulously chosen and integrated with the squeeze-and-excitation (SE) module. Furthermore, the two most effective SE-embedded models are harmoniously combined to create the proposed ensemble-ALL model. This model leverages the Bayesian optimization algorithm to enhance its performance. The proposed ensemble-ALL model attains remarkable accuracy, precision, recall, F1-score, and kappa scores, registering at 96.26, 96.26, 96.26, 96.25, and 91.36%, respectively. These results surpass the benchmarks set by state-of-the-art studies in the realm of ALL image classification. This model represents a valuable contribution to the field of medical image recognition, particularly in the diagnosis of acute lymphoblastic leukemia, and it offers the potential to enhance the efficiency and accuracy of medical professionals in the diagnostic and treatment processes.

The characterization of cardiac mechanical properties may contribute to better understanding of doxorubicin-induced cardiotoxicity. Our study aims to investigate the relationship between cardiac mechanical properties, T1 and T2 relaxation times and partition coefficient. Fifty childhood acute lymphoblastic leukemia survivors underwent a cardiac magnetic resonance (CMR) at rest on a 3T MRI system and included a standard ECG-gated 3(3)3(3)5 MOLLI sequence for T1 mapping and an ECG-gated T2-prepared TrueFISP sequence for T2 mapping. Partition coefficient, ejection fraction, end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated. CircAdapt model was used to study cardiac mechanical performance (left ventricle stiffness (LVS), contractility (LVC) and pressure (Pmin and Pmax), cardiac work efficiency (CWE) and ventricular arterial coupling). In the whole cohort, our results showed that LVC (R 2  = 69.2%, r = 0.83), Pmin (R 2  = 62.9%, r = 0.79) and Pmax can be predicted by significant CMR parameters, while T1 (R 2  = 23.2%, r = 0.48) and partition coefficient (R 2  = 13.8%, r = 0.37) can be predicted by significant cardiac mechanical properties. In SR group LVS (R 2  = 94.8%, r = 0.97), LVC (R 2  = 93.7%, r = 0.96) and Pmin (R 2  = 90.6%, r = 0.95) can be predicted by significant cardiac mechanical properties, while in HR + DEX group CWE (R 2  = 49.8%, r = 0.70) can be predicted by significant cardiac mechanical properties. Partition coefficient (R 2  = 72.6%, r = 0.85) can be predicted by significant CMR parameters in SR group. Early characterization of cardiac mechanical properties from CMR parameters has the potential to early detect doxorubicin-induced cardiotoxicity., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

A 2-year-old boy presented with left periorbital edema, proptosis, hyperglobus and esotropia. Imaging revealed an inferotemporal orbital mass with adjacent bony erosion. Histological evaluation of an orbital biopsy revealed B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/BLL). The patient was subsequently treated with chemotherapy. Although orbital involvement in acute myelogenous leukemia has been well-described, orbital manifestations of B-ALL/BLL are uncommon, with only a limited number of previous reports in the literature.

The purpose of this study is to observe the changes of cortical morphological characteristics and their potential contribution to cognitive function in ALL survivors by using surface-based morphometry (SBM). Using SBM analysis, we calculated and compared group differences in cortical thickness, sulcal depth, gyrification, and fractal dimension of the cerebral cortex between 18 pediatric ALL survivors treated on chemotherapy-only protocols and off treatment within 2 years, and 18 healthy controls (HCs) with two-sample t-tests [P < 0.05, family-wise error (FWE) corrected]. Relationships between abnormal cortical characteristic values and cognitive function parameters were investigated with partial correlation analysis, taking age as a covariate. We found decreased cortical thickness mainly located in the prefrontal and temporal region, and increased sulcal depth in left rostral middle frontal cortex and left pars orbitalis in the ALL survivors compared to HCs. There were no statistically significant differences in the gyrification and fractal dimension between the two groups. In ALL survivors, cortical thickness and sulcal depth of above areas values revealed no significant correlation with the cognitive function parameters. In conclusion, pediatric ALL survivors show decreased cortical thickness in prefrontal and temporal regions, and increased sulcal depth in prefrontal region. These results suggest that SBM-based approach can be used to assess changes of cortical morphological characteristics in pediatric ALL survivors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: During treatment for acute lymphoblastic leukaemia (ALL), children are prone to musculoskeletal deterioration. However, non-invasive tools to measure muscle mass and intramuscular alterations are limited. In this study we explored the feasibility of muscle ultrasound in children with ALL. Additionally, we analysed whether automated ultrasound outcomes of muscle size and intramuscular fat infiltration (IMAT) were associated with appendicular skeletal muscle mass (ASMM), muscle strength and physical performance., Methods: Children with ALL, aged 3-18 years were included during maintenance therapy. Bilateral images of the rectus femoris muscle were captured using a portable linear array transducer connected to a tablet. Subsequently, an automated image annotation software (MuscleSound) was used to estimate cross-sectional area, muscle thickness and IMAT. Feasibility was assessed using acceptance (percentage of children approached who were enrolled), practicality (percentage of children that completed the ultrasound measurement after enrolment) and implementation (percentage of children that had sufficient imaging to be processed and analysed by the software). Assessments of ASMM by bioimpedance analysis, muscle strength using handheld dynamometry and timed physical performance tests were administered at the same visit. Multivariable linear models were estimated to study the associations between muscle ultrasound outcomes and ASMM, strength and physical performance, adjusted for sex, age, body mass index and ALL treatment week., Results: Muscle ultrasound was performed in 60 out of 73 invited patients (76.9%), of which 37 were boys (61.7%), and median age was 6.1 years (range: 3-18.8 years). The acceptance was 98.7%, practicality 77.9% and implementation was 100%. Patients who refused the examination (n = 13) were younger (median: 3.6, range: 3-11.2 years) compared with the 60 examined children (P = 0.0009). In multivariable models, cross-sectional area was associated with ASMM (β = 0.49 Z-score, 95% confidence interval [CI]:0.3,2.4), knee-extension strength (β = 16.9 Newton [N], 95% CI: 4.8, 28.9), walking performance (β = -0.46 s, 95% CI: -0.75, -0.18) and rising from the floor (β = -1.07 s, 95% CI: -1.71, -0.42). Muscle thickness was associated with ASMM (β = 0.14 Z-score, 95% CI: 0.04, 0.24), knee-extension strength (β = 4.73 N, 95% CI: 0.99, 8.47), walking performance (β = -0.13 s, 95% CI: -0.22, -0.04) and rising from the floor (β = -0.28 s, 95% CI: -0.48, -0.08). IMAT was associated with knee-extension strength (β = -6.84 N, 95% CI: -12.26, -1.41), walking performance (β = 0.2 s, 95% CI: 0.08, 0.32) and rising from the floor (β = 0.54 s, 95% CI: 0.27, 0.8). None of the muscle ultrasound outcomes was associated with handgrip strength., Conclusions: Portable muscle ultrasound appears a feasible and useful tool to measure muscle size and intramuscular alterations in children with ALL. Validation studies using magnetic resonance imaging (gold standard) are necessary to confirm accuracy in paediatric populations., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Haematological diseases with pancreatic masses as the first symptom are clinically rare but should not be ignored. This case report describes a 60-year-old female patient with acute leukaemia that had a pancreatic mass as her first symptom. The patient was admitted and elastography combined with endoscopic ultrasound (EUS) guided fine needle aspiration biopsy (EUS-FNA) was used for diagnosis, treatment planning and determination of prognosis. The site selected for the EUS-FNA puncture was the caudal section of the pancreatic body and the posterior wall of the gastric body was used as the puncture point. The elastography view of the head of the pancreas was blue/green with predominant blue colour. A 19 G puncture needle with a slow-draw core and two stitches of micro-negative pressure were used. Cytology detected heterotypic cells, pancreatic puncture histopathology, the presence of pancreatic alveolar structures and heterotypic tumour cells in the interstitium. Immunohistochemistry of the pancreatic puncture tissue showed B-cell lymphoblast-derived tumours and bone marrow puncture indicated acute lymphoblastic leukaemia. The patient was diagnosed with acute lymphoblastic leukaemia invading the pancreas and was treated with chemotherapy. After treatment, her condition was stable. Follow-up is ongoing and there have been no signs of tumour recurrence or metastasis.

We herein report a case of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) that was incidentally detected by fluorodeoxyglucose-positron emission tomography ( 18 F-FDG PET)/computed tomography (CT) at a health checkup. At that time, the findings of a physical examination and blood tests were all normal, except for the diffuse bone marrow uptake (maximum standardized uptake value: 6.3). One month later, when the blood counts remained in the normal ranges, a bone marrow examination confirmed the diagnosis of Ph-ALL. Although a diffuse bone marrow uptake of 18 F-FDG is observed in some benign conditions, physicians should also consider the possibility of hematological malignancies, including acute leukemia, even when that is the only abnormal finding.

We evaluated outcomes of 18 patients with isolated extramedullary disease (iEMD) relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with the CD19-directed CAR T cells ARI-0001 in two centers (adult and pediatric), including patients treated in the CART19-BE-01 trial and the consecutive compassionate use program. iEMD was detected by PET-CT in 78% (14/18), and/or by cerebrospinal fluid analysis in 28% (5/18). Patients received cyclophosphamide and fludarabine followed by 1 × 10 6 ARI-0001 cells/kg, initially as a single dose (first patient) and later split into three fractions (10%, 30%, and 60%). Cytokine release syndrome (CRS) occurred in 50% (9/18) of patients, with no cases of grade ≥3 CRS, and 1 case (6%) of grade 1 neurotoxicity. Tocilizumab was used in 6% of patients (1/18). Procedure-related mortality was 0% at 2 years. Objective responses were seen in 94% (95% confidence interval [CI]: 73%-99%) of patients, with complete responses (CR) seen in 78% (95% CI: 52%-94%) of them. Progression-free and overall survival were 49% (95% CI: 30%-79%) and 61% (95% CI: 40%-92%) at 2 years. In conclusion, the use of ARI-0001 cells in patients with R/R ALL and iEMD was associated with a safety and efficacy profile that is comparable with what is observed in patients with marrow involvement and in line with other CART19 products., (© 2022 Wiley Periodicals LLC.)

Purpose: Recent initial findings suggest that radiation therapy improves blood perfusion and cellular chemotherapy uptake in mice with leukemia. However, the ability of radiation therapy to influence drug accumulation in the extracellular bone marrow tissue is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton microscopy (L-QMPM) to characterize the bone marrow vasculature (BMV) and drug accumulation in the extracellular bone marrow tissue before and after radiation therapy in mice bearing leukemia., Methods and Materials: We developed a longitudinal window implant for L-QMPM imaging of the calvarium BMV before, 2 days after, and 5 days after total body irradiation (TBI). Live time-lapsed images of a fluorescent drug surrogate were used to obtain measurements, including tissue wash-in slope (WIS tissue ) to measure extracellular drug accumulation. We performed L-QMPM imaging on healthy C57BL/6 (WT) mice, as well as mice bearing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)., Results: Implants had no effects on calvarium dose, and parameters for wild-type untreated mice were stable during imaging. We observed decreased vessel diameter, vessel blood flow, and WIS tissue with the onset of AML and ALL. Two to 10 Gy TBI increased WIS tissue and vessel diameter 2 days after radiation therapy in all 3 groups of mice and increased single-vessel blood flow in mice bearing ALL and AML. Increased WIS tissue was observed 5 days after 10 Gy TBI or 4 Gy split-dose TBI (2 treatments of 2 Gy spaced 3 days apart)., Conclusions: L-QMPM provides stable functional assessments of the BMV. Nonmyeloablative and myeloablative TBI increases extracellular drug accumulation in the leukemic bone marrow 2 to 5 days posttreatment, likely through improved blood perfusion and drug exchange from the BMV to the extravascular tissue. Our data show that neo-adjuvant TBI at doses from 2 Gy to 10 Gy conditions the BMV to improve drug transport to the bone marrow., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Iris involvement by acute lymphoblastic leukemia is a very rare primary leukemic infiltration. Blurred vision, conjunctival injection, anterior chamber reaction, pseudohypopyon, thickening of the iris stroma, change in iris shape and color are common clinical signs in leukemic iris infiltration. There is no optimal treatment. Radiotherapy, systemic chemotherapy (high-dose of methotrexate and/or high-dose cytarabine), topical and systemic corticosteroids have been reported as treatment modalities. Herein we present anterior segment optical coherence tomography findings in a 21-years-old, male, diffuse B-cell Acute Lymphoblastic Leukemia (ALL) patient who has a leukemic iris infiltration in his left eye that was successfully treated with intravitreal methotrexate., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Childhood acute lymphoblastic leukemia (ALL) is associated with cognitive impairment in adulthood. Cognitive interference processing and its correlated functional magnetic resonance imaging (fMRI) activity in the brain have not yet been studied in this patient group., Material: Twenty-six adult childhood ALL survivors (median [interquartile range {IQR}] age, 40.0 [37.0-42.3] years) were investigated at median age (IQR), 35.0 (32.0-37.0) years after treatment with intrathecal and intravenous chemotherapy as well as cranial radiotherapy (24 Gy) and compared with 26 matched controls (median [IQR] age, 37.5 [33.0-41.5] years)., Methods: Cognitive interference processing was investigated in terms of behavioral performance (response times [ms] and accuracy performance [%]) and fMRI activity in the cingulo-fronto-parietal (CFP) attention network as well as other parts of the brain using the multisource interference task (MSIT)., Results: ALL survivors had longer response times and reduced accuracy performance during cognitive interference processing (median [IQR] interference effect, 371.9 [314.7-453.3] ms and 6.7 [4.2-14.7]%, respectively) comparedwith controls (303.7 [275.0-376.7] ms and 2.3 [1.6-4.3]%, respectively), but did not exhibit altered fMRI activity in the CFP attention network or elsewhere in the brain., Conclusion: Adult childhood ALL survivors demonstrated impaired behavioral performance but no altered fMRI activity when performing cognitive interference processing when compared with controls. The results can be used to better characterize this patient group and to optimize follow-up care and support for these individuals.

Acute leukemia is typically diagnosed from presenting features related to hematological symptoms, but certain patients present with prominent musculoskeletal pain without signs of hematological abnormality. We reviewed the medical records of 58 children diagnosed with acute lymphoblastic leukemia (ALL) at our hospital to evaluate initial features. Forty six of these patients had hematological symptoms, anemia, or hemorrhage (Group H), while 12 patients had prominent musculoskeletal pain without hematological symptoms (Group P). Diagnosis of leukemia took significantly more time for those 12 patients (Group H, 17.1 days; Group P, 48.5 days). In three of the 12 patients in Group P, localized abnormal imaging findings and unremarkable blood test results led to initial diagnoses of chronic recurrent multifocal osteomyelitis, bone fracture, and septic osteomyelitis. However, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) revealed multiple intense bone foci or systemic bone marrow uptake, leading to the diagnosis of ALL. A review of 18F-FDG-PET results from 23 patients with ALL who underwent a PET scan (Group H, n = 15; Group P, n = 8) showed multiple bone foci or systemic bone marrow uptake in all cases. In conclusion, lack of hematological symptoms in ALL patients can delay diagnosis, and 18F-FDG-PET is useful for diagnosing leukemia in such cases., (© 2021. Japanese Society of Hematology.)

Background: Loss of bone mineral is a common concomitant of the treatment of acute lymphoblastic leukemia (ALL) due mainly to chemotherapy, especially with corticosteroids. Osteopenia/osteoporosis may be encountered long into survivorship. Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry is limited to two-dimensionality and cannot distinguish trabecular from cortical bone., Methods: A sample of 74 subjects, ages 13.5-38.3 years more than 10 years from diagnosis, underwent peripheral quantitative computed tomography (pQCT) at metaphyseal (trabecular bone) and diaphyseal (cortical bone) sites in the radius and tibia. pQCT provides three-dimensional assessment of bone geometry, density, and architecture., Results: Average values in multiple metrics were similar to those in healthy individuals, but deficits in both trabecular and cortical bones were revealed by lower Z scores using an ethnically comparable sample of healthy individuals. Connectivity, a measure of bone architecture and a surrogate measure of bone strength, was lower in females than males. Survivors of standard-risk ALL had greater connectivity in and more compact trabecular bone than high-risk survivors who had received more intensive osteotoxic chemotherapy. There were no statistically significant differences in any of the metrics at any of the sites between subjects who had or had not a history of fracture, cranial irradiation, or use of a bisphosphonate., Conclusions: These long-term survivors of ALL have somewhat compromised bone health, but data in comparable healthy populations are limited. Longitudinal studies in larger and more ethnically diverse cohorts will provide greater insight into bone health in this vulnerable population., (© 2021 Wiley Periodicals LLC.)

Acute lymphoblastic leukemia is the most frequent cancer in children: it represents 80% of leukemias and about 24% of all neoplasms diagnosed between 0 and 14 years. Acute lymphoblastic leukemia mainly affects children between 2 and 5 years old and in this age group the incidence is about 80-90 cases per million per year. In acute lymphoblastic leukemia, cancer cells multiply rapidly and accumulate in the bone marrow and subsequently invade the blood. However, at the time of diagnosis, leukemia rarely occurs outside the bone marrow or blood vessels and the extramedullary involvement happens mostly in patients with refractory or relapsing disease. In this article, we report an unusual clinical presentation of acute B cell lymphoblastic leukemia with intestinal and ovarian localizations in a 5-year-old girl., (© 2020. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Abstract: Primary osseous B-lymphoblastic lymphoma/leukemia is very rare, especially multiple bones involved. Herein, we reported the bone scintigraphy findings in a 16-year-old adolescent boy with a 20-day history of right thigh pain caused by B-lymphoblastic lymphoma/leukemia. Multiple abnormal MDP-avid foci were noted on 99mTc-MDP bone scintigraphy. Interestingly, the CT images of corresponding lesions were unrevealing. Finally, the B-lymphoblastic lymphoma/leukemia was confirmed by pathology and immunohistochemistry., Competing Interests: Conflicts of interest and sources of funding: The author declares that there are no conflicts of interest. This article was partially funded by Natural Science Foundation of Hebei Province (H2020206422)., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Bone marrow necrosis (BMN) is a rare but important complication of hematological malignancies. We report the case of a 52-year-old male patient with a recurrence of acute lymphoblastic leukemia (ALL) accompanied by BMN. After re-induction therapy, bone marrow aspiration (BMA) and biopsy from the iliac bone showed necrotic cells and eosinophilic debris, respectively. Magnetic resonance imaging (MRI) showed heterogeneous signals in the bilateral iliac bone, possibly reflecting various stages of BMN. BMA from the sternum eventually revealed the recurrence of ALL after a few weeks. Comprehensive assessments, including MRI and repeated bone marrow tests, are required when evaluating the underlying hematological malignancies of patients with BMN.

This report describes a patient who had acute lymphocytic leukemia with exudative retinal detachment (RD), which mimicked Vogt-Koyanagi-Harada disease (VKH). A 61-year-old woman presented with painless loss of vision in the left eye. Fundus examination revealed RD in her left eye. B-scan ultrasonography confirmed localized RD and choroidal thickening. Fundus fluorescein angiography revealed stippled pinpoint hyperfluorescence in the upper macula. One week later, reduced visual acuity was noted in the right eye. B-scan ultrasonography and optical coherence tomography revealed serous RD in both eyes. A provisional diagnosis of VKH was made. However, subsequent hematologic analysis detected an extremely high leukocyte count. Elevated numbers of leukocytes and tumor cells were found in cerebrospinal fluid. Bone marrow biopsy revealed 77% primary atypical blood cells, 89% of which were immature lymphocytes. The patient was subsequently diagnosed with acute lymphocytic leukemia and transferred to the Department of Hematology. However, the patient and her family refused chemotherapy; she eventually died. Our findings suggest that exudative RD, similar to VKH, could be a sign of leukemia. Pinpoint hyperfluorescence leakage is important for differential diagnosis, particularly with respect to VKH.

Objectives: The most common form of pediatric cancer is acute lymphoblastic leukemia (ALL). Magnetic resonance (MR) neuroimaging studies have revealed leukoencephalopathy (LE) in pediatric ALL, but the impact of LE on long-term neurocognitive performance remains unknown. This study aims to objectively characterize the prevalence, extent, and intensity of LE, and their association with later neurocognitive performance., Materials and Methods: Pediatric patients (N = 377) treated for ALL without irradiation underwent MR neuroimaging at 4 time points throughout therapy (end of remission induction [MR1], end of consolidation [MR2], and week 31 [MR3] and week 120 [end therapy, MR4] of continuation treatment) and neurocognitive evaluations at the end of therapy and 2 years later. Generalized estimation equation models with logit link were developed to explore the association between LE prevalence and extent with time points throughout therapy, age at diagnosis (≤5 years or >5 years), treatment risk arm (low risk or standard/high risk), and sex. General linear models were also developed to investigate the association between neuroimaging metrics during treatment and neurocognitive performance at 2-year follow-up., Results: The prevalence of LE was greatest (22.8%, 74/324) after consolidation therapy. The prevalence of LE increased at MR2 relative to MR1 regardless of treatment risk arm (both P's < 0.001), age group (both P's < 0.001), or sex (male, P < 0.001; female, P = 0.013). The extent of white matter affected also increased at MR2 relative to MR1 regardless of treatment risk arm (standard/high risk, P < 0.001; low risk, P = 0.004), age group (both P's < 0.001), or sex (male, P < 0.001; female, P = 0.001). Quantitative relaxation rates were significantly longer in LE compared with that in normal-appearing white matter in the same examination (T1, P < 0.001; T2, P < 0.001). The LE prevalence early in therapy was associated with increased parent ratings of conduct problems (P = 0.039) and learning difficulties (P = 0.036) at 2-year follow-up compared with that at the end of therapy. A greater extent of LE early in therapy was associated with decreasing performance on a measure of processing speed (P = 0.003) from the end of therapy to 2-year follow-up. A larger extent of LE at the end of therapy was associated with decreased performance in reading (P = 0.004), spelling (P = 0.003), and mathematics (P = 0.019) at 2-year follow-up and increasing problems with attention (omissions, P = 0.045; β, P = 0.015) and memory (list A total recall, P = 0.010) at 2-year follow-up compared with that at the end of therapy., Conclusions: In this large cohort of pediatric patients treated for ALL without irradiation, asymptomatic LE during therapy can be seen in almost a quarter of patients, involves as much as 10% of the white matter volume, and is associated with decreasing neurocognitive performance, increasing parent reports of conduct problems, and learning difficulties in survivors., Competing Interests: Conflicts of interest and sources of funding: This study was funded by R01 CA090246 and Cancer Center Support Grant P30 CA21765 from the National Cancer Institute and by American Lebanese Syrian Associated Charities. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors had no other conflicts of interest to declare., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: In the present study, we mainly aimed to evaluate the prognostic value of 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]F-FDG) positron emission tomography (PET)/computed tomography (CT) after allogeneic stem cell transplantation (allo-SCT) in lymphoblastic lymphoma (LBL) patients using Deauville Scores (DS). Materials and Methods: A total of 63 LBL patients who benefited from 18 F-FDG PET-CT after allo-SCT in our institution between April 2010 and August 2020 were enrolled in this retrospective study. These above-mentioned patients were divided into two groups based on the Deauville criteria. Diagnostic efficiency of 18 F-FDG PET/CT and integrated CT in detecting lymphoma were calculated. Consistencies were evaluated by comparing 18F-FDG PET/CT and integrated CT results through kappa coefficient. Kaplan-Meier method was used in survival analysis, and the log-rank method was adopted in comparisons. Prognostic factor analysis was performed by the Cox regression model. Results: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy of post-SCT 18 F-FDG PET-CT were 100%(12/12), 92.2%(47/51), 75.0%(12/16), 100%(47/47) and 93.7%(59/63). The consistency of 18F-FDG PET-CT and integrated CT was moderate(Kappa = .702，P < .001). Positive post-SCT 18F-FDG PET-CT was associated with lower progression-free survival (PFS) but not overall survival (OS) (p = .000 and p = .056, respectively). The 3-year PFS of the PET-positive group and PET-negative group was 18.8% and 70.2%, respectively. Multivariate analysis showed that post-SCT PET-CT findings was an independent prognostic factor for PFS (p = .000; HR, 3.957; 95%CI, 1.839-8.514). Other factors independently affecting PFS were sex (p = .018; HR, 2.588; 95% CI, 1.181 - 5.670) and lactate dehydrogenase (LDH) (p = .005; HR, 3.246; 95% CI, 1.419 - 7.426). However, none of the above-mentioned factors were associated with OS. Conclusions: Collectively, we found that 18F-FDG PET-CT after allo-SCT was a strong indicator for PFS, but not OS, which might provide important evidence for the selection of subsequent treatment regimen for LBL patients. Trial registration number: ChiCTR2100046709.

Growth arrest at the secondary growth plate, also known as the acrophysis, is a rare phenomenon with only very few known published case reports. We report on a case of formation of ghost secondary ossification centers at the acrophyses of the knee joint in a 14-year-old female, who survived early childhood acute lymphoblastic leukemia. The patient suffered from severe side effects from both disease and subsequent treatment strategies with a 10-month immobilization period as a consequence at the age of 3 years. The ghost secondary ossification centers were encountered on radiographs and MRI 10 years later, when she presented for evaluation of chronic pain in her left knee related to sports activities, due to a meniscal cyst. Awareness of this phenomenon is nevertheless important, because it seems that endochondral bone growth recovery at the acrophyses might be different from recovery in physes, because we found no concomitant sequelae of growth arrest in the metaphyses.

Purpose: The study was aimed at assessing renal functions of children with acute lymphoblastic leukemia (ALL) after induction therapy by 99m Tc-DTPA renal dynamic imaging Gates method (GFR Gates ) and investigating whether renal function after induction therapy will affect the occurrence of high-dose methotrexate- (HDMTX-) induced acute kidney injury (AKI)., Methods: Children with newly diagnosed ALL were enrolled. Renal functions before the administration of HDMTX were assessed by estimated glomerular filtration rate (eGFR) and GFR Gates , respectively, before the first cycle of HDMTX after induction therapy. The areas under the ROC curve were used to assess covariates' ability to predict HDMTX-induced AKI., Results: 102 children with ALL were included in the study. A stepwise backward binary logistic regression showed that only standardized GFR Gates was an independent risk factor for HDMTX-induced AKI ( p = 0.018, odds ratio 0.985, 95% CI 0.972-0.997). The area under the ROC of standardized GFR Gates was 0.679 ( p = 0.012, 95% CI 0.554-0.804)., Conclusion: Standardized GFR Gates showed that the normal renal function of children is not enough to be used as a cutoff point to predict HDMTX-induced AKI in ALL children receiving HDMTX. More attention and supportive care should be given to the children with standardized GFR Gates lower than the cutoff value to avoid the HDMTX-induced AKI., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2020 Lidan Wang et al.)

Background: Osteonecrosis is a debilitating complication in children and adolescents with acute lymphoblastic leukemia or acute lymphoblastic lymphoma (LLy). An objective screening test to identify patients at risk for symptomatic, extensive joint involvement will help manage osteonecrosis., Methods: We performed a prospective, longitudinal pilot study with whole-joint magnetic resonance imaging (MRI) of shoulders, elbows, hips, knees, ankles, and hindfeet to evaluate the incidence and timing of osteonecrosis involving multiple joints in 15 patients with LLy aged 9-21 years at diagnosis., Results: Osteonecrosis affecting ≥30% of the epiphysis occurred in eight of 15 patients, with a high prevalence in hips (12 of 26 examined [46%]) and knees (10 of 26 [38%]) post reinduction I and in shoulders (seven of 20 [35%]) post reinduction II. Most osteonecrotic hips and knees with ≥30% epiphyseal involvement became symptomatic and/or underwent surgery (100% and 82%, respectively). All eight patients with ≥30% epiphyseal involvement had multijoint involvement. Seven of these patients had hip or knee osteonecrosis by the end of remission induction, and only these patients developed osteonecrosis that became symptomatic and/or underwent surgery in their hips, knees, shoulders, ankles, and/or feet; all of these joints were associated with epiphyseal abnormalities on post reinduction I imaging., Conclusions: MRI screening in adolescent patients with LLy revealed osteonecrosis in multiple joints. Initial screening with hip and knee MRI at the end of induction may identify susceptible patients who could benefit from referrals to subspecialties, more extensive follow-up imaging of other joints, and early medical and surgical interventions., (© 2020 Wiley Periodicals, Inc.)

Drug resistance is an obstacle in the therapy of acute lymphoblastic leukemia (ALL). Whether the physical properties such as the motility of the cells contribute to the survival of ALL cells after drug treatment has recently been of increasing interest, as they could potentially allow the metastasis of solid tumor cells and the migration of leukemia cells. We hypothesized that chemotherapeutic treatment may alter these physical cellular properties. To investigate the motility of chemotherapeutics-treated B-cell ALL (B-ALL) cells, patient-derived B-ALL cells were treated with chemotherapy for 7 days and left for 12 h without chemotherapeutic treatment. Two parameters of motility were studied, velocity and migration distance, using a time-lapse imaging system. The study revealed that compared to non-chemotherapeutically treated B-ALL cells, B-ALL cells that survived chemotherapy treatment after 7 days showed reduced motility. We had previously shown that Tysabri and P5G10, antibodies against the adhesion molecules integrins α4 and α6, respectively, may overcome drug resistance mediated through leukemia cell adhesion to bone marrow stromal cells. Therefore, we tested the effect of integrin α4 or α6 blockade on the motility of chemotherapeutics-treated ALL cells. Only integrin α4 blockade decreased the motility and velocity of two chemotherapeutics-treated ALL cell lines. Interestingly, integrin α6 blockade did not affect the velocity of chemoresistant ALL cells. This study explores the physical properties of the movements of chemoresistant B-ALL cells and highlights a potential link to integrins. Further studies to investigate the underlying mechanism are warranted.

Acute lymphoblastic leukemia (ALL) is a pervasive pediatric white blood cell cancer across the globe. With the popularity of convolutional neural networks (CNNs), computer-aided diagnosis of cancer has attracted considerable attention. Such tools are easily deployable and are cost-effective. Hence, these can enable extensive coverage of cancer diagnostic facilities. However, the development of such a tool for ALL cancer was challenging so far due to the non-availability of a large training dataset. The visual similarity between the malignant and normal cells adds to the complexity of the problem. This paper discusses the recent release of a large dataset and presents a novel deep learning architecture for the classification of cell images of ALL cancer. The proposed architecture, namely, SDCT-AuxNet θ is a 2-module framework that utilizes a compact CNN as the main classifier in one module and a Kernel SVM as the auxiliary classifier in the other one. While CNN classifier uses features through bilinear-pooling, spectral-averaged features are used by the auxiliary classifier. Further, this CNN is trained on the stain deconvolved quantity images in the optical density domain instead of the conventional RGB images. A novel test strategy is proposed that exploits both the classifiers for decision making using the confidence scores of their predicted class labels. Elaborate experiments have been carried out on our recently released public dataset of 15114 images of ALL cancer and healthy cells to establish the validity of the proposed methodology that is also robust to subject-level variability. A weighted F1 score of 94.8% is obtained that is best so far on this challenging dataset., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: This article reports a study of cell mechanics in patient-derived (primary) B-cell acute lymphocytic leukemia (ALL) cells treated with antibodies against integrins. Leukemia cell adhesion to stromal cells mediates chemotherapeutic drug resistance, also known as cell adhesion-mediated chemotherapeutic drug resistance. We have previously shown that antibodies against integrin α 4 and α 6 adhesion molecules can de-adhere ALL cells from stromal cells or counter-receptors. Because drug-resistant cells are more deformable, as evaluated by single-beam acoustic tweezers, we hypothesized that changes in cell mechanics might contribute to the de-adhesive effect of integrin-targeting antibodies., Methods: In this study, the deformability of primary pre-B ALL cells was evaluated by single-beam acoustic tweezers after treatments with the de-adhering antibody Tysabri or P5G10 against integrin α 4 and α 6 adhesion molecules., Results: We demonstrated that primary ALL cells treated with P5G10 expressed decreased deformability compared with immunoglobulin G 1 -treated control cells (P < .05). Tysabri did not show an effect on deformability (P > .05)., Conclusions: These results suggest that decreased deformability is associated with an integrin α 6 blockade. Further assessments of the functional roles of deformability and integrin blockades in B-ALL cell drug resistance and deformability, respectively, are necessary., (© 2019 by the American Institute of Ultrasound in Medicine.)

Objectives: Neuroimaging studies of acute lymphoblastic leukemia (ALL) during chemotherapy treatment have shown alterations in structure, function, and connectivity in several brain regions, suggesting neurobiological impairment that might influence the large-scale brain network. This study aimed to detect the alterations in the topological organization of structural covariance networks of ALL patients., Methods: This study included 28 ALL patients undergoing chemotherapy and 20 matched healthy controls. We calculated the gray matter volume of 90 brain regions based on an automated anatomical labeling template and applied graph theoretical analysis to compare the topological parameters of the gray matter structural networks between the two groups., Results: The results demonstrated that both the ALL and healthy control groups exhibited a small-world topology across the range of densities. Compared to healthy controls, ALL patients had less highly interactive nodes and a reduced degree/betweenness in temporal regions, which may contribute to impaired memory and executive functions in these patients., Conclusion: These results reveal that ALL patients undergoing chemotherapy treatment may have decreased regional connectivity and reduced efficiency of their structural covariance network. This is the first report of anomalous large-scale gray matter structural networks in ALL patients undergoing chemotherapy treatment and provides new insights regarding the neurobiological mechanisms underlying the chemo-brain network., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Therapies for pediatric ALL have improved such that more than 80% of patients survive to 5 years post-therapy, and most survive to adulthood. These ALL patients experience long-term side effects that permanently affect their quality of life, with bone loss and reduced longitudinal growth being the most common skeletal complications. To determine the effects of the chemotherapeutic agents used in ALL induction therapy on bone density and longitudinal growth in mice, we treated juvenile mice with doxorubicin, dexamethasone, vincristine, l-asparaginase, or combination therapy. At adulthood, mice were culled and bones collected and scanned by micro-computed tomography (micro-CT). Mice that received doxorubicin and combination therapy exhibited reduced longitudinal growth and significant reductions in trabecular bone volume, trabecular thickness, and trabecular number, with increased trabecular separation. Mean cortical thickness, cortical area, marrow area, endocortical perimeter, and polar moment of inertia were significantly reduced by doxorubicin and combination therapy. Vincristine treatment significantly decreased trabecular bone volume, trabecular number, and increased trabecular separation but had no effects on cortical bone. Dexamethasone treatment increased trabecular bone separation, cortical marrow area, and cortical bone periosteal perimeter. Mice treated with l-asparaginase did not have any bone phenotypes. In conclusion, these data indicate that the majority of the chemotherapy agents used in induction therapy for pediatric ALL have long-term effects on bone in mice. A single dose of doxorubicin in juvenile mice was sufficient to cause the majority of the bone phenotypes, with combination therapy intensifying these effects., (Copyright © 2020 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Background: Survivors of childhood leukemia/lymphoma are at increased risk for reduced bone mineral density (BMD). The authors sought to determine the frequency of reduced BMD detected by off-therapy surveillance, factors associated with reduced BMD, and the association of reduced BMD with fractures., Methods: This cross-sectional study included childhood leukemia/lymphoma survivors attending 2 survivorship clinics who received guideline-recommended BMD surveillance ≥2 years post-therapy with dual-energy x-ray absorptiometry (from January 1, 2004 to August 31, 2016). Lumbar spine BMD z-scores were height-for-age-adjusted. Low and very low BMD were >1 SD and >2 SDs below norms, respectively. Treatment, chronic conditions, and fractures were abstracted from medical records. Logistic regression was used to examine the association of low BMD with patient/treatment factors and fractures., Results: In total, 542 patients (51.5% female) with a mean age of 15.5 years (range, 4.4-52.2 years) who were 6 years post-therapy (range, 2.0-35.1 years) were evaluated, including 116 who reported post-therapy fractures. Lumbar spine low BMD was identified in 17.2% of survivors, and very low BMD was identified in 3.5% of survivors, but frequencies varied considerably between subgroups; 10.8% of survivors aged 15 to 19 years at diagnosis had very low BMD. In multivariable analyses, older age at diagnosis, white race, and being underweight were significantly associated with low BMD. Survivors with low BMD had greater odds of nondigit fractures (odds ratio, 2.2; 95% CI, 1.3-3.7) and specifically long-bone fractures (odds ratio, 2.7; 95% CI, 1.5-4.7)., Conclusions: In this study of childhood leukemia/lymphoma survivors undergoing guideline-recommended dual-energy x-ray absorptiometry surveillance, patients who were older at diagnosis, white, and underweight were at the highest risk for lumbar spine low BMD. Low BMD was associated with a greater risk of fractures, emphasizing the clinical importance of surveillance., (© 2019 American Cancer Society.)

In this paper, we propose a novel and efficient method for detecting and quantifying red and white blood cells from microscopic blood images. Laboratory tests that use a cell counter or a flow cytometer can perform a complete blood count (CBC) rapidly. Nonetheless, a manual blood smear inspection is still needed, both to have a human check on the counter results and to monitor patients under therapy. Moreover, it allows for describing the cells' appearance as well as any abnormalities. However, manual analysis is lengthy and repetitive, and its result can be subjective and error-prone. In contrast, by using image processing techniques, the proposed system is entirely automated. The main effort is devoted to both achieving high accuracy and finding a way to overcome the typical differences in the condition of blood smear images that computer-aided methods encounter. It is based on the Edge Boxes method, which is considered a state-of-art region proposal approach. By incorporating knowledge-based constraints into the detection process using Edge Boxes, we can find cell proposals rapidly and efficiently. We tested the proposed approach on the Acute Lymphoblastic Leukaemia Image Database (ALL-IDB), a well-known public dataset proposed for leukaemia detection, and the Malaria Parasite Image Database (MP-IDB), a recently proposed dataset for malaria detection. Experimental results were excellent in both cases, outperforming the state-of-the-art on ALL-IDB and creating a strong baseline on MP-IDB, demonstrating that the proposed method can work well on different datasets and different types of images., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Treatments against ALL might lead to later cognitive effects and alterations in brain structure in survivors but to the authors' knowledge the observed variability in the severity of neurocognitive deficits is not fully understood. The objective of the current study was to investigate abnormalities in visual short-term memory (VSTM) brain activation in survivors of childhood ALL using magnetoencephalography., Methods: A VSTM task was completed by 40 survivors of ALL and 26 controls. VSTM capacity (Cowan K) and brain activation were assessed during the retention period of the task (400-1400 milliseconds) using a standard minimum norm source localization method., Results: Performance (Cowan K) was found to be similar between survivors of ALL and controls. Atypical brain activation was found in survivors of ALL during the task, including overactivation of regions usually involved in VSTM (lateral occipital, precentral gyrus, and postcentral gyrus), recruitment of regions that typically are not involved in VSTM (superior/middle temporal gyrus and supramarginal gyrus), and lower activation of frontal brain regions (inferior frontal gyrus). These patterns of activation were modulated by the age at the time of cancer onset (P = .01) because activity was found to be reduced in participants who were younger at diagnosis., Conclusions: The results of the current study suggest a pattern of neural inefficiency and compensatory activity during VSTM in survivors of ALL., (© 2019 American Cancer Society.)

Background and Objective: Due to the development in digital microscopic imaging, image processing and classification has become an interesting area for diagnostic research. Various techniques are available in the literature for the detection of Acute Lymphocytic Leukemia from the single cell blood smear images. The purpose of this work is to develop an effective method for leukemia detection., Methods: This work has developed deep learning based leukemia detection module from the blood smear images. Here, the detection scheme carries out pre-processing, segmentation, feature extraction and classification. The segmentation is done by the proposed Mutual Information (MI) based hybrid model, which combines the segmentation results of the active contour model and fuzzy C means algorithm. Then, from the segmented images, the statistical and the Local Directional Pattern (LDP) features are extracted and provided to the proposed Chronological Sine Cosine Algorithm (SCA) based Deep CNN classifier for the classification., Results: For the experimentation, the blood smear images are considered from the AA-IDB2 database and evaluated based on metrics, such as True Positive Rate (TPR), True Negative Rate (TNR), and accuracy. Simulation results reveal that the proposed Chronological SCA based Deep CNN classifier has the accuracy of 98.7%., Conclusions: The performance of the proposed Chronological SCA-based Deep CNN classifier is compared with the state-of-the-art methods. The analysis shows that the proposed classifier has comparatively improved performance and determines the leukemia from the blood smear images., (Copyright © 2019. Published by Elsevier B.V.)

Asparaginase (ASP) and steroids are a main part of treatment for ALL, in both front-line and relapse setting. It is known, that ASP can cause several toxicities such as hypersensitivity, pancreatitis, as well as severe lipid and coagulation disturbances. Administered steroids can result in diabetes, obesity, hyponatremia and also mild hyperlipemia, which can intensify side effects of asparaginase. When triglyceride elevation is greater than 1000 mg/dl, the risk of pancreatitis is significantly increased. We report two patients who were hospitalized in Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin in Poland and developed severe hypertriglyceridemia after receiving asparaginase and steroid therapy for acute lymphoblastic leukemia. These patients were treated using plasmapheresis. This procedure was performed with a venous catheter in the femoral vein and 5% albumin or fresh frozen plasma as the replacement fluid. We analysed the laboratory and clinical data of these children. Plasmapheresis was well tolerated in both cases and a decrease of hypertriglyceridemia was quickly observed. However, the girl developed pancreatitis. In our opinion, plasmapheresis appears to be safe and effective in reducing hypertriglyceridemia. We could recommend that this procedure should be performed early, as soon as the triglyceride level is above 1000 mg/dl, in order to prevent severe complications. Patients should continue chemotherapy without ASP. It is important to regularly monitor of the lipid profile, pancreatic enzymes and coagulation during ASP and steroids therapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Intussusception, which is common in pediatric patients but rare in adults with leukemia, usually presents with an intralumenal lesion as a lead point in adults., Case Report: We herein report the case of a 38-year-old female who developed right lower quadrant abdominal pain and fever on day 16 of chemotherapy. Abdominal computed tomography showed ileocecal intussusception. The patient underwent surgery, and the definitive pathological diagnosis was typhlitis leading to intussusception. Albeit very rare in adults, typhlitis-induced intussusception should be suspected in those with leukemia presenting with abdominal pain.

PSMA PET/CT is known to show uptake in various benign and malignant processes. The following PSMA PET/CT was performed for prostate carcinoma staging (Gleason 3 + 4 left apex; PSA 5.8). It shows incidental diffuse PSMA marrow uptake, not typical for prostate metastatic disease. No treatment had been commenced at the time of the scan. Serology and bone marrow biopsy showed B-cell acute lymphocytic leukemia. Focal PSMA uptake in the right ischium was correlated with a T1 hypointense lesion on a previous MRI and was convincing for a skeletal metastasis. Alternative diagnoses in diffuse skeletal PSMA uptake need therefore to be considered.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.