Accurate prediction of breast cancer (BC) response to neoadjuvant chemotherapy (NAC) is critical for tailoring treatment strategies and improving patient outcomes. This study introduces a novel deep learning-based framework that integrates multi-parametric magnetic resonance imaging (MRI) (i.e., T1, T2, STIR, and DWI), along with clinical and molecular subtype markers, to classify tumor response into pathological complete response (pCR), partial response (PR), and stable disease (SD). First, tumor regions are delineated across MRI modalities and then modeled using a translation-invariant Markov-Gibbs random field (MGRF) with analytical parameter estimation to capture modality-specific spatial appearance patterns correlated with NAC response. Subsequently, diffusion-weighted MRI is processed to generate apparent diffusion coefficient (ADC) maps, offering quantitative assessment of intratumoral water diffusion and cellularity. Afterward, an adaptive rescaling module (ARM) is proposed to adjust spatial resolution and project volumetric inputs into 2D, enabling compatibility with pretrained convolutional networks. Finally, a customized SEResNet architecture, augmented with Squeeze-and-Excitation (SE) blocks, is introduced to extract modality-specific features which are then fused with clinical and molecular subtypes descriptors for final classification. Evaluated on a cohort of 109 BC patients using leave-one-subject-out (LOSO) cross-validation method, the system achieved an accuracy of 96.33%, a precision of 96.51%, a recall of 96.33%, an F1-score of 96.23%, and a Cohen’s kappa of 94.08%, outperforming its individual components, various pretrained deep learning models, and a state-of-the-art method. These results underscore the value of integrating the appearance model, functional (i.e., ADC) model, adaptive rescaling module, SE blocks, and clinical and molecular subtype markers for the precise prediction of NAC outcomes.

A precise computer-aided diagnosis (CAD) system is introduced to predict two different tumor responses to neoadjuvant chemotherapy (NAC) by studying the correlation between radiological and clinical markers, and treatment response: complete response and stable disease. Predicting the NAC response assists physicians in managing the treatment plan effectively and reduces unnecessary use of NAC. First, the breast tumor is delineated from MRI modalities. Then, the proposed system extracts functional features, including the apparent diffusion coefficient (ADC), from diffusion-weighted imaging (DWI), and 2nd-order texture features, such as gray-level co-occurrence matrix (GLCM) and gray-level run length matrix (GLRLM), from various MRI modalities. Afterward, statistical features are extracted from these matrices. Moreover, ADC features are represented statistically using percentiles with 2% intervals. Subsequently, a feature selection approach, namely the genetic algorithm (GA), is employed for each fused features individually (i.e., ADC, GLCM, and GLRLM) to extract the most relevant features. The resulting feature set undergoes a multi-stage feature generation system, introducing new features (i.e., probabilities), which are fused with its input and clinical markers and are then fed into a lightGBM classifier for final prediction. Our system was evaluated on 54 patients using leave-one-subject-out (LOSO) cross-validation, achieving a sensitivity of 89.89%, a specificity of 89.29%, and an accuracy of 89.09%, emphasizing the promise of our system in predicting breast tumor response to NAC.

Context The etiology of AML is unknown, although “secondary” AML includes either therapy-related AML or an evolution from myelodysplastic syndrome or myeloproliferative neoplasms. Typically, AML is de novo. Evolution of AML is a multistep process with many mechanisms for leukemic transformation. ITP is not one of them. Objective We report a case of 2 possible scenarios where ITP ended up as AML or AML presented as ITP. Thrombocytopenia preceding AML for months without any suspicious presentation is rarely reported. Design An ongoing observational study, originating in February 2024. Setting Hematology Unit, Oncology Center, Mansoura University, Egypt. Patient A 49-year-old woman presented with ITP and received corticosteroid therapy. Three months later, she developed AML. Interventions The patient presented with easy fatigability and history of heavy menstruation the preceding year. There were no constitutional symptoms. Examination revealed only pallor. The initial full blood count (FBC) showed total leucocytic count (TLC) of 5500/mm3 with normal differential leucocytic count (DLC), hemoglobin 5.3 gm/dL, MCV 73 fL, platelet count 30,000/mm3. All causes for secondary ITP were excluded. Abdominal ultrasound was normal except for fundal fibroid. Serum ferritin was 10.8 ng/mL and direct Coombs test was negative. Bone marrow aspiration (BMA) was not requested as there was no indication at diagnosis. Main Outcome Measures Diagnosis of ITP was established by exclusion. Treatment was started with oral prednisolone at 60 mg daily and oral iron therapy. After 1 month, platelet count increased to 70,000/mm3 hemoglobin to 6.5 gm/dL, and she continued on the same medication. Results After about 3 months of therapy, she presented with mild epistaxis. Her FBC showed a TLC of 87,000/mm3 hemoglobin of 8.1 gm/dL, MCV of 83 fL, and platelet count of 5000/mm3. Examination showed moderate splenomegaly and multiple ecchymosis over the whole body. DLC showed 62% blasts. BMA showed no dysplastic features. Flow cytometry result was AML (M1-M2) with aberrant expression of CD4, CD99. She was started on 7+3 regimen on May 22, 2024. Conclusions This report emphasizes the importance of close monitoring and better diagnostic procedures including BMA for all ITP cases even if there are no atypical clinical or hematological features at diagnosis.

Analytes within liquid biopsies have emerged as promising alternatives to traditional tissue biopsies for various malignancies, including lymphomas. This review explores the clinical applications of one such liquid biopsy analyte, circulating tumor DNA (ctDNA) in different types of lymphoma, focusing on its role in diagnosis, disease monitoring, and relapse detection. Advancements in next-generation sequencing (NGS) and machine learning have enhanced ctDNA analysis, offering a multi-omic approach to understanding tumor genetics. In lymphoma, ctDNA provides insights into tumor heterogeneity, aids in genetic profiling, and predicts treatment response. Recent studies demonstrate the prognostic value of ctDNA and its potential to improve patient outcomes by facilitating early disease detection and personalized treatment strategies Despite these advancements, challenges remain in optimizing sample collection, processing, assay sensitivity, and overall consensus workflows in order to facilitate integration into routine clinical practice.

The primary objective of this paper is to develop a machine learning-based approach capable of predicting the treatment response of neoadjuvant chemotherapy (NAC) to enhance breast cancer treatment management. The proposed system aims to predict NAC outcomes across three categories: pathological complete response (CR), partial response (PR), and stable disease (SD), by analyzing multimodal magnetic resonance images with clinical and molecular subtype markers. To ensure the comprehensiveness of our system design, texture radiomics were extracted from T1, T2, and STIR MRI modalities, along with functional radiomics from diffusion-weighted MRI at various b-values. The main rationale behind employing multiple b-values in collecting DW-MRI is to effectively capture the complexities of blood diffusion within the tumor microstructure. The proposed system comprises several key steps: (i) extracting texture and functional radiomics from T1, T2, STIR MRI, and DW-MRI data; (ii) identifying the most significant radiomics correlated with NAC treatment using a genetic algorithm; (iii) initially predicting the PR from alternative treatment responses utilizing the extracted textures and functional radiomics; and (iv) subsequently integrating clinical and molecular subtype markers with imaging radiomics to differentiate between CR and SD. Our proposed system is trained and validated through the utilization of a leave-one-subject-out (LOSO) cross-validation approach on various MRI scans from 109 subjects, of whom 27 had complete responses, 54 had partial responses, and 28 had no responses. The performance of the proposed system was assessed through the utilization of Cohen’s Kappa and accuracy metrics, achieving 81.31% and 88.07%, respectively. Our various experiments showed that integrating clinical and molecular subtype markers with radiomics highlights the proposed system’s efficiency in evaluating the tumor’s response to NAC efficiently, outperforming predictions based solely on individual radiomics.INDEX TERMS Breast cancer, neoadjuvant chemotherapy, MRI, DW-MRI, radiomics, tumor clinical markers, machine learning, treatment response prediction.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma and is characterized by heterogeneity in biology and clinical behavior. Mutations in the myeloid differentiation primary response 88 (MYD88) are found in different lymphoproliferative disorders and are associated with variable clinical and prognostic impact. Aim To investigate the frequency of MYD88 L265P mutation and its clinical impact in a cohort of Egyptian DLBCL patients. Methods FFPE lymph node samples from 87 DLBCL patients (46 males / 41 females; median age, 58 years) were included and analyzed for MYD88 L265P by an allele-specific PCR. Results MYD88 L265P mutations were found in 52 patients (59.8%) out of 87 DLBCL cases. Patients with L265 mutation were significantly younger than non-mutated patients (p = 0.022). None of the patients with the L265P mutation showed a significant association with the clinical parameters of DLBCL. Interestingly, MYD88 L265 mutated patients were found to be significantly correlated with HCV infection (p = 0.037). The median follow-up time across the entire cohort was 26 months. Univariate analysis showed that overall survival (OS) was affected by gender, LDH level, and CNS-IPI scoring (p = 0.048, 0.008, and 0.046, respectively), while disease-free survival (DFS) was affected by B symptoms and LDH level (p = < 0.000 and 0.02, respectively). However, the MYD88 mutation status and other prognostic factors showed no association with OS or DFS. Conclusions Our findings indicate a high frequency of MYD88 L265P mutations in our study population and not associated with prognostic markers or the outcome of the disease.

Background Engraftment syndrome (ES) encompasses a spectrum of clinical manifestations linked to neutrophil recovery following hematopoietic stem cell transplantation (HSCT). Prominent findings include non-infectious fever, rash, pulmonary infiltration, or edema, closely impacting HSCT outcomes. Aim This study aimed to evaluate the safety and efficacy of corticosteroid prophylaxis in preventing the incidence and severity of ES following autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Method A cohort of 26 patients with MM from the bone marrow transplantation (BMT) unit at the Oncology Center, Mansoura University, Egypt, were assessed from June 2022 to June 2023. Patients received dexamethasone 4 mg twice daily (D+9 to D+13) following stem cell infusion. Evaluation parameters included time to neutrophil recovery, ES signs and symptoms, and duration of hospital admission. Results The study enrolled 26 patients with MM (69.2% males, 30.8% females) with a median age of 52 years (34-67 years). The majority (84%) were transplanted with very good partial response or better, while 15.4% were in partial response. Febrile neutropenia was observed in 14 patients (53%). Treatment was discontinued in one patient (3.9%) due to uncontrolled diabetes mellitus. Two patients (7.9%) experienced a mild form of symptoms possibly attributable to ES, including diarrhea and skin rash. No instances of early mortality were recorded. Median time to engraftment was 10 days (9-15 days), and median duration of hospital stay was 17 days (12-30 days). Summary and Conclusions The prophylactic utilization of dexamethasone is correlated with a low incidence and reduced severity of ES, coupled with a favorable safety profile.

BACKGROUND:Activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic active B-cell receptor signaling and a constitutive activation of the NF-KB pathway. MYD88 L265P mutation occurs as a driving force of NF-KB overactivity in ABC-DLBCL. Nonetheless, in cases of DLBCL, the MYD88 L265P mutation has not yet been investigated in association with the tumour necrosis factor alpha induced protein3 (TNFAIP3) mutation.OBJECTIVE:To investigate the frequency of MYD88 and TNFAIP3 mutations in DLBCL and their association to the clinico-hematological profile.MATERIAL AND METHODS:We used real-time polymerase chain reaction in order to search for MYD88 L265P and TNFAIP3 mutations in 100 DLBCL patients.RESULTS:MYD88 L265P In 20% of cases, the CT heterozygous genotype was discovered.  CT heterozygous genotype was more common in ABC type, stage IV, greater IPI groups, extra-nodal infiltration, and BM infiltration. It was also linked to a shorter OS. TNFAIP3 mutation GA heterozygous genotype was detected in 18% of the patients, with ABC-DLBCL subtype accounting for 77.8%. The GA heterozygous genotype was usually related with stage IV, extranodal infiltration, and a reduced life expectancy.CONCLUSION:MYD88 L265P and to lesser extent TNFAIP3 mutations are major mutations in ABC- DLBCL and may be predictive factors for poor OS in ABC- DLBCL patients.

S316chemotherapy regimen.In Latin America and Colombia, there are no studies evaluating the possible associations of CGA with outcomes in patients with AML.Objective: To evaluate the association between CGA and clinical outcomes in patients with AML in a university hospital in Colombia.Design: Retrospective cohort study conducted between June 1, 2013, and December 31, 2021.All patients were followed for at least one year after AML diagnosis.Setting: Referral center caring for adult patients with AML.Patients or Other Participants: Patients aged 60 years or older (60+) with a diagnosis of AML and CGA were included.Interventions: Patients in the study underwent CGA.Univariate and bivariate analyses were performed to describe the study population and determine the possible association of the CGA scales with outcome measures.Main Outcome Measures: Overall survival, event-free survival, toxicity, and complete remission after induction chemotherapy.Results: Seventy-seven patients 60+ were included.The median age was 71 years (IQR:64-79), 53.2% were men, and 55.8% (n=43) had ECOG < 2. In line with the Frail Scale, 54.5% (n=42) and 32.5% (n=25%) were pre-frail and frail, respectively.Pre-frailty and frailty according to the Frail Scale were associated with shorter overall survival (HR 1.6, 95%CI 1.05-2.55).Mild dependence according to the Lawton scale reduced the probability of complete remission after induction chemotherapy by 56% (RR 0.4, 95%CI 0.20-0.96).CGA was not associated with event-free survival or toxicity.Conclusions: Frailty or pre-frailty according to the Frail scale in adults 60+ with a diagnosis of AML was associated with a shorter overall survival at one year.Furthermore, this is the first analytical observational study in the literature to describe a statistically significant association between the Frail score and overall survival in elderly patients with a diagnosis of AML.

Topic: 22. Stem cell transplantation - Clinical Background: Autologous bone marrow transplantation (ABMT) is the cornerstone of many hematological disorders. HCV-infected patients who undergo ABMT are at risk for a variety of HCV infection-related complications. Furthermore, acute exacerbation may occur during and after transplantation. Hence, the need for studies on the impact of HCV on ABMT is imperative. Aims: The primary objective of this study is to determine the outcome of HCV patients with hematological malignancies after ABMT, including toxicity and disease-free survival (DFS). The secondary objective is to identify if there is a difference in overall survival (OS) between HCV-positive and negative patients after ABMT. Methods: This is a retrospective study that included 100 HCV positive patients with hematological malignancies (lymphoma and myeloma) who received ABMT compared to cross matched 100 HCV negative patients based on age, gender, and disease status at transplant. They were attending the outpatient clinics for follow up in Nasser Institute and Sheikh Zayed Specialized Hospital, Egypt. Acute exacerbation of chronic HCV infection is defined as ≥ 3-fold increase in basal ALT level without recent history of blood transfusion, infection, hepatic infiltration, or use of hepatotoxic drugs. Results: This study showed that the mean age of patients was 44.5 (± 12.5) years. They were 154 males and 46 females. The most common reasons for ABMT were multiple myeloma (40%), non-hodgkin lymphoma (33.5%), and hodgkin lymphoma (26.5%). There was a significant increase in the frequency of NHL among the HCV-positive group (p 0.007). Pre-transplant AST and ALT levels were significantly higher in the HCV-positive group than in the HCV-negative group (p 0.001 and 0.001, respectively). There were significant differences in the post-transplant outcome regarding serum bilirubin level and the incidence of acute exacerbation between the HCV- positive and HCV- negative study groups (p 0.044 and 0.049, respectively). The HCV-positive group received a significantly higher number of platelet units transfusion than those in the HCV-negative group (p 0.001). The median duration of hospital stay was significantly prolonged in the HCV-positive group compared to the HCV-negative group (p 0.024). DFS was significantly shorter in HCV-infected individuals (p 0.048), while OS was comparable between both groups (P 0.259). Summary/Conclusion: We concluded that, while the HCV-negative arm had a better result than the positive arm, HCV positivity is not a contraindication to ABMT. Keywords: Hepatitis C virus, Multiple myeloma, Autologous bone marrow transplant, Lymphoma

Background: Activation of pathway of nuclear factor kappaB (NF-κB) which is caused by genetic alterations has been reported in B cell lymphoma.A20 gene is considered main regulator component of NF-κB signaling.Its function is mainly suppression of this pathway.Deletions and/or mutations in A20 gene cause inactivation of this pathway which were found in various hematologic malignancies.Objective: The current study aims to determine the prevalence of A20 gene mutations and their relationship with the clinical and laboratory profile in diffuse large B-cell lymphoma (DLBCL).Patients and methods: A total 100 DLBCL patients were investigated for A20 gene mutation by real time polymerase chain reaction.Results: A20 gene mutation GA mutant genotype was found in 18% of the patients, where 77.8% of them were ABC-DLBCL subtypes.GA heterozygous genotype was frequently associated with stage IV and extra-nodal infiltration, and shorter overall survival (OS). Conclusion:Our study suggests a role of A20 gene mutation in DLBCL pathogenesis as well as its prognosis.

Activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic active B-cell receptor signaling and a constitutive activation of the nuclear factor kappa B (NF-KB) pathway. As a driving force of NF-KB overactivity, myeloid differentiation primary response gene 88 (MYD88) L265P mutation occurs in ABC-DLBCL. However, the MYD88 L265P mutation has not yet been studied with tumor necrosis factor alpha induced protein3 (TNFAIP3) mutation in DLBCL cases

The Wnt pathway is aberrantly activated in chronic lymphocytic leukemia (CLL) and contributes to the antiapoptotic and mitogenic characteristics of CLL cells. Lymphoid enhancer-binding factor‑1 (LEF1) acts as a mediator and key transcription factor of the Wnt/β-catenin pathway. LEF1 helps to regulate important genes involved in tumor cell death mechanisms. To analyze the expression levels of Wnt signaling pathway member (WNT3) and its key mediator LEF1 in Egyptian CLL patients and to detect the potential use of these genes as markers of CLL outcome. We quantified the expression levels of Wnt3 and LEF1 in peripheral blood mononuclear cells of 30 untreated CLL and 19 healthy controls by qRT-PCR (quantitative real time polymerase chain reaction). Our study demonstrated significant upregulation of both Wnt3 and LEF1 in CLL (P < 0.0001). WNT3 and LEF1 were significantly decreased in CLL patients with ECOG performance 2 and 3 than those with 0 and 1 (p = 0.023 and 0.007, respectively). CLL patients with 17p deletion express significantly low LEF1 (p = 0.033). Low levels of WNT3 and LEF1 expression indicated a shorter overall survival (P = 0.007, 0.005, respectively). The predictive power of WNT3 and LEF1 expression showed good discrimination of CLL patients from controls (AUC >0.9). Upregulation of WNT3 and LEF1 could be used as helpful and specific markers to distinguish our CLL patients. Low WNT3 and LEF1 expression is associated with shortened survival in CLL patients. These results indicate that WNT3 and LEF1 represent an attractive therapeutic target for future therapies in Egyptian CLL patients.