BACKGROUND/AIM The Philadelphia chromosome is found in 30% of acute lymphoblastic leukemia (ALL) patients, a distinct ALL subgroup where the BCR-ABL fusion gene is associated with poor prognosis. Treatment with tyrosine kinase inhibitors (TKIs) often induces complete remission and these patients subsequently undergo an autologous stem cell transplantation (ASCT). However, 20% of subjects experience a relapse associated with the selection of point-mutations in the BCR-ABL kinase domain. We report the clinical evolution of a Philadelphia-positive ALL patient co-expressing the e1a2 and e14a2 BCR-ABL transcript at diagnosis. MATERIALS AND METHODS Multiplex reverse transcriptase (RT)-PCR was used to detect BCR-ABL transcripts and their levels were measured by quantitative Real Time PCR. Clonal sequencing and next-generation sequencing (NGS) were used to identify mutations. RESULTS Although the patient underwent ASCT following treatment with multiple TKIs, he relapsed twice. The first time he exhibited the e1a2 transcript and the second time he presented only the e14a2 variant. Mutation analysis, performed by clonal sequencing and NGS, detected two alterations after the first relapse and a single mutation at the time of the second relapse. CONCLUSION The observed shift from the e1a2 to the e14a2 variant and the selection of TKI-resistant clones heavily contributed to the fatal evolution of the disease.

B-ALL Relapses After Autologous Stem Cell Transplantation Associated With a Shift from e1a2 to e14a2 BCR-ABL Transcripts: A Case Report.

Abstract Background In recent years, the research on the relationship between sarcopenia before and after the treatment of esophageal cancer, as well as its impact on prognosis of esophageal cancer, has increased rapidly, which has aroused people’s attention to the disease of patients with esophageal cancer complicated with sarcopenia. This review examines the prevalence of sarcopenia in patients with esophageal cancer, as well as the relationship between sarcopenia (before and after surgery or chemotherapy) and prognosis in patients with esophageal cancer. Moreover, we summarized the potential pathogenesis of sarcopenia and pharmacologic and non-pharmacologic therapies. Methods A narrative review was performed in PubMed and Web of Science using the keywords (“esophageal cancer” or “esophageal neoplasm” or “neoplasm, esophageal” or “esophagus neoplasm” or “esophagus neoplasms” or “neoplasm, esophagus” or “neoplasms, esophagus” or “neoplasms, esophageal” or “cancer of esophagus” or “cancer of the esophagus” or “esophagus cancer” or “cancer, esophagus” or “cancers, esophagus” or “esophagus cancers” or “esophageal cancer” or “cancer, esophageal” or “cancers, esophageal” or “esophageal cancers”) and (“sarcopenia” or “muscular atrophy” or “aging” or “senescence” or “biological aging” or “aging, biological” or “atrophies, muscular” or “atrophy, muscular” or “muscular atrophies” or “atrophy, muscle” or “atrophies, muscle” or “muscle atrophies”). Studies reporting relationship between sarcopenia and esophageal cancer were analyzed. Results The results of the review suggest that the average prevalence of sarcopenia in esophageal cancer was 46.3% ± 19.6% ranging from 14.4 to 81% and sarcopenia can be an important predictor of poor prognosis in patients with esophageal cancer. Patients with esophageal cancer can suffer from sarcopenia due to their nutritional deficiencies, reduced physical activity, chemotherapy, and the effects of certain inflammatory factors and pathways. When classic diagnostic values for sarcopenia such as skeletal muscle index (SMI) are not available clinically, it is also feasible to predict esophageal cancer prognosis using simpler metrics, such as calf circumference (CC), five-count sit-up test (5-CST), and six-minute walk distance (6MWD). Conclusions Identifying the potential mechanism of sarcopenia in patients with esophageal cancer and implementing appropriate interventions may hold the key to improving the prognosis of these patients. 

Correlation between sarcopenia and esophageal cancer: a narrative review

In Pakistan the disease burden of Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) is quite high, yet there is a lack of scientific evidence regarding the spectrum of BCR-ABL rearrangement variants in CML and ALL. Knowing about BCR-ABL rearrangement is important in determining the prognosis and treatment strategy of disease at the time of diagnosis. This study included a total of 685 patients, out of which there were 644 CML patients and 41 ALL patients, from October 2016-July 2019. From the CML group, 270 patients were reported to have the BCR-ABL1 transcript, from which 50% were males. Whereas in the ALL group, 35 patients were reported to have the BCR-ABL1 transcript out of which 65.7% were males. Proportions of BCR-ABL transcript type differed between the two groups, with b3a2 (63.3%) and b2a2 (34.8%) transcript types having the highest frequency in CML patients, whereas e1a2 (77.1%) and b3a2 (11.3%) transcript types were found to have the highest frequency in ALL patients. Our data shows transcript genotypes in CML and ALL patients in an Asian population, which may be useful to guide the clinical management and assess prognosis. Since the majority of our CML population had the b3a2 transcript, they have a better prognosis and treatment response.

/pdf/molecular-epidemiology-of-bcr-abl-rearrangement-variants-in-4zcqoz0q1e.pdf

Molecular Epidemiology of BCR-ABL Rearrangement Variants in Chronic Myeloid Leukemia and Acute Lymphocytic Leukemia from Major Institute of Pakista

Preoperative laboratory data indicators significantly affect the prognosis of a variety of tumors. Nevertheless, the combined effect of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) on overall survival (OS) in patients with esophageal carcinoma remains unclear. Thus, we examined these associations among patients with postoperative staged T3N0M0 esophageal carcinoma. The data of 246 patients with postoperative staged T3N0M0 esophageal carcinoma from January 1, 2010, to December 31, 2022, were retrospectively analyzed. OS was measured from the date of pathological diagnosis until either death or the last follow-up. The Kaplan-Meier method and multivariate Cox regression model were used to analyze the relationship between neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Platelet-to-lymphocyte ratio (LMR), SII, PNI, and OS. The predictive value of SII and PNI as a combined index was analyzed by the receiver operating characteristic curve (ROC). A total of 246 patients aged 65.5 ± 7.4 years were included in this study and 181 (73.6%) were male. The univariate analysis revealed that differentiation, vessel involvement, postoperative treatment, NLR, SII, PLR, LMR, PNI were predictors of OS (P < .05). After adjusted for potential confounds, multivariate Cox regression analysis showed that the differentiation, SII, PNI, and postoperative treatment were independent prognostic factors correlated with OS in patients with postoperative staged T3N0M0 esophageal carcinoma (P < .05). SII and PNI, as a combined indicator, have a higher predictive value for OS. The NLR, SII, PLR, LMR, and PNI could all be used as independent predictors of OS in patients with postoperative staged T3N0M0 esophageal carcinoma. The combination of SII and PNI can significantly improve the accuracy of prediction. 

The prognostic value of preoperative laboratory data indicators in patients with esophageal carcinoma: An observational study

<title>Abstract</title> <bold>Introduction</bold> The efficacy of immune checkpoint inhibitors (ICIs) for advanced esophageal squamous cell carcinoma (ESCC) remains suboptimal. This study aims to construct and validate a clinically accessible model to better identify populations that may potentially benefit from ICIs. <bold>Methods</bold> This study enrolled advanced ESCC patients treated with ICIs at Peking University Cancer Hospital from January 14, 2016, to January 26, 2024, forming the training cohort. Combined positive score (CPS) was recorded to evaluate the predictive value of programmed cell death ligand-1 (PD-L1). Baseline clinical characteristics and laboratory test results were identified as predictors through a 2-phase selection based on Cox proportional hazard regression and minimization of Akaike information criterion (AIC). The prediction model was internally validated using bootstrapping and externally validated in patients from Harbin Medical University Cancer Hospital between January 10, 2019, and July 6, 2022. <bold>Results</bold> A total of 430 patients from Peking University Cancer Hospital and 184 patients from Harbin Medical University Cancer Hospital were ultimately enrolled. PD-L1 expression failed to discriminate survival outcomes (HR=0.94, 95% CI: 0.74-1.19, <italic>P = .6</italic>). The final model incorporates 10 variables: stage, bone metastasis, line of therapy, treatment, lactate dehydrogenase, carcinoembryonic antigen, carbohydrate antigen 199, lymphocyte count, prognostic nutritional index, and systemic immune-inflammation index. The C-index was 0.725 (95%CI: 0.694-0.756) in the training cohort, 0.722 (95%CI: 0.688-0.751) after bootstrapping, and 0.691 (95%CI: 0.650-0.733) in the external validation cohort, outperforming PD-L1 in prognostic prediction and risk stratification. An interactive online prediction tool (https://escc-survival.shinyapps.io/shiny_app/) was subsequently developed. <bold>Conclusions</bold> This is the first model for individualized survival prediction in advanced ESCC patients treated with ICIs based on large-scale, high-quality real-world data, potentially guiding clinical decision-making and optimize treatment strategies. 

An integrated prognosis prediction model based on real-word clinical characteristics for immunotherapy in advanced esophageal squamous cell carcinoma

Nutritional indicators have been implicated in the survival outcomes of various malignant tumors. However, there are few studies on the association between nutritional indicators and immunotherapy for esophageal cancer. The present study aimed to explore the value of nutritional indicators with regard to the survival outcomes in patients with metastatic esophageal squamous cell carcinoma (ESCC) treated with camrelizumab. A retrospective cohort analysis of 158 metastatic ESCC patients treated with camrelizumab in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University (Xinghua, China) between September 2019 and July 2022 was conducted. A receiver operating characteristic curve was used to determine the optimal cut-off values of prognostic nutritional index (PNI) and albumin (ALB). The cut-off value for body mass index (BMI) was set at the normal lower limit (18.5 kg/m2). Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and the differences in PFS or OS between groups were compared using the log-rank test. The prognostic value of each variable was analyzed based on the univariate and multivariate Cox proportional hazards regression models. The optimal cutoff values of PNI, ALB and BMI were 41.35, 36.8 g/l and 18.5 kg/m2, respectively. Lower PNI, ALB and BMI were closely associated with shorter PFS [hazard ratio (HR) for PNI, 3.599; P<0.001; HR for ALB, 4.148; P<0.001; HR for BMI, 5.623; P<0.001) and OS (HR for PNI, 7.605; P<0.001; HR for ALB, 7.852; P<0.001; HR for BMI, 7.915; P<0.001) times. Univariate and multivariate Cox regression analyses indicated that lower PNI, ALB and BMI were independent risk factors of PFS and OS in patients with metastatic ESCC receiving camrelizumab treatment. In conclusion, PNI, ALB and BMI are promising predictive indicators to assess the survival outcomes in patients with metastatic ESCC treated with camrelizumab. Moreover, PNI, ALB and BMI may have prognostic significance in these patients.

/pdf/predictive-value-of-nutritional-indicators-with-regard-to-3iwuxwbq.pdf

Predictive value of nutritional indicators with regard to the survival outcomes in patients with metastatic esophageal squamous cell carcinoma treated with camrelizumab

nosed with acute B lymphoblastic leukemia (B-ALL) according to the MICM criteria in a university hospital. A complete blood count showed the following: hemoglobin 8.77 g/dl, white blood cell count 94.4 ! 10 9 /l, and platelet count 15.4 ! 10 9 /l. A bone marrow aspirate showed active hyperplasia and a blast cell count of 87.6%. The peroxidase was negative. The immunophenotype of the leukemic blasts analyzed by flow cytometry was as high as those typical of B-ALL, with CD9+ (98.8%), CD10+ (98.7%), CD19+ (92.2%), CD20+ (70%), CyCD7a+ (99.8%), and HLA-DR+ (97.5%). Cytogenetic analysis showed the karyotype as 46,XX,t(9; 22)(q34;q11)[9]/46,XX[1]. The patient was treated with a standard VCDP chemotherapy plan (vindesine 3 mg, days 1, 8, 15, and 22; daunomycin 60 mg, days 1 and 8; cyclophosphamide 800 mg, days 1 and 15, and prednisone 60 mg, days 1–14) and was sensitive to this treatment. Laboratory examinations showed that the total leukocyte count was reduced to 2.71 ! 10 9 /l. Due to the fact that the patient was affected with fever, hemoculture was adopted and Escherichia coli bacteremia was observed 1 week later. On the 13th day after treatment, bone marrow aspiration showed that the leukemia blast cells decreased to 1.5%. After the first induced chemotherapy, the patient achieved complete remission and continued extramural treatment with imatinib at 400 mg/day. During subsequent treatment The Philadelphia (Ph) chromosome arises from the reciprocal translocation t(9; 22)(q34;q11), resulting in the juxtaposition of the ABL gene at 9q34 to the BCR gene at 22q11, which generates the chimeric gene BCR-ABL. The fusion gene is found in more than 95% of patients with chronic myelogenous leukemia (CML), and in 10–20% of adults and 2–5% of children with acute lymphoblastic leukemia (ALL) [1] . It is rarely seen in acute myelogenous leukemia (AML) [2] . At the genomic level, three different breakpoint cluster regions in the BCR gene (Mbcr , mbcr , and bcr ) have been reported [1] , which generate commonly different transcripts and somewhat different proteins, b2a2 (p210), b3a2 (p210), e1a2 (p190), and c3a2 (p230) [3] . The b3a2 or b2a2 fusion transcripts are found in 83–90.4% of patients with CML [4, 5] . In addition, e1a2 is present in 60–75% of patients with Ph-positive ALL [6, 7] and only 1% of patients with CML [8] . In recent years, the e1a2 (p190) transcript has been constantly reported to coexist with b2a2 or b3a2 (p210) in patients with Ph-positive ALL and CML [5, 9–11] . The coexpression of three or more types of fusion transcripts is occasionally reported only in CML patients [4, 5] . In this study, a rare Ph-positive ALL patient who coexpresses b3a2 (p210), e1a2 (p190), and a novel variant of the e1a2 transcript is reported upon. In September 2009, a 62-year-old female who presented with a 3-week history of fatigue and fever was diagReceived: September 21, 2011 Accepted after revision: March 16, 2012 Published online: June 30, 2012

Acute lymphoblastic leukemia expressing b3a2 (p210), e1a2 (p190), and variant e1a2 BCR-ABL transcripts: a case report and review of the literature.

3039 – oxidized 5-methylcytosine modulates synthetic lethality to poly-adp-ribose polymerase inhibitors in acute myeloid leukemia

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Predictive value of nutritional indicators with regard to the survival outcomes in patients with metastatic esophageal squamous cell carcinoma treated with camrelizumab

Acute lymphoblastic leukemia expressing b3a2 (p210), e1a2 (p190), and variant e1a2 BCR-ABL transcripts: a case report and review of the literature.

3039 – oxidized 5-methylcytosine modulates synthetic lethality to poly-adp-ribose polymerase inhibitors in acute myeloid leukemia