ImmunoPET imaging of hematological malignancies: From preclinical promise to clinical reality

Immuno-positron emission tomography (immunoPET) imaging is a paradigm-shifting imaging technique for whole-body and all-lesion tumor detection, based on the combined specificity of tumor-targeting vectors [e.g., monoclonal antibodies (mAbs), nanobodies, and bispecific antibodies] and the sensitivity of PET imaging. By noninvasively, comprehensively, and serially revealing heterogeneous tumor antigen expression, immunoPET imaging is gradually improving the theranostic prospects for hematological malignancies. In this review, we summarize the available literature regarding immunoPET in imaging hematological malignancies. We also highlight the pros and cons of current conjugation strategies, and modular chemistry that can be leveraged to develop novel immunoPET probes for hematological malignancies. Lastly, we discuss the use of immunoPET imaging in guiding antibody drug development.     

Risk of Acute Lymphoblastic Leukemia: Results of a Case-Control Study

Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Differentenvironmental factors might be effective in the occurrence of this malignancy during childhood. The aim of this studywas to find environmental risk factors in childhood ALL in Hamadan, Iran. Methods: This case-control study wasdone in 2015-2018 on 125 children younger than 15 years of age suffering from ALL. Patients were matched with130 controls with respect to age, gender, and residence location. The identification of risk factors for ALL was soughtbased on the comparison of studied variables between case and control individuals. Results: A statistically significantincreased risk for ALL was found with regard to type of delivery (OR: 0.43, 95% CI: 0.20 - 0.92, p˂0.02), childcare(OR: 4.58, 95% CI: 0.95 - 22.20, p˂0.04), birth weight (OR: 1.44, 95% CI: 1.53 - 2.21, p˂0.006), father’s educationlevel (OR: 2.67, 95% CI: 1.10 - 6.45, p˂0.02), and father’s job (OR: 0.2 95% CI: 0.08 - 0.51, p˂0.001). Also observedwere increased odds for ALL regarding male gender, mother’s high education level, mother’s freelance job, and mediumor high family income. No association with ALL incidence was observed for age, gender, breastfeeding, mother’s ageat pregnancy, malignancy in first- or second-degree relatives, or mother’s use of hair dye during pregnancy (p> 0.05).Conclusion: This study showed that father’s education level, father’s job, delivery type, birth weight, and childcarecan play a role in the incidence of childhood ALL.     

Altitude exposure as a training & iron overload management strategy post leukemia

ObjectivesTo examine iron stores, hemoglobin mass, and performance before, during and after intermittent altitude exposure in a professional male rugby player experiencing iron overload following blood transfusions for treatment for acute myeloid leukemia.DesignLongitudinal, repeated measures, single case-study.MethodsThe player was followed prior to (control), and during (study), an in-season block of altitude training. During the control period two venesections were performed for a total of 750 mL of blood removal. Internal and external training load, match statistics, blood volume, plasma volume, haemoglobin mass, serum ferritin and reticulocyte count were monitored throughout.ResultsDuring the control period serum ferritin declined following the two venesections (∼51%) as did haemoglobin mass (∼2%), reticulocyte count remained stable. During the study period serum ferritin further declined (∼30%), however haemoglobin mass and reticulocyte count increased (∼4% and ∼14% respectively). Internal training load for the control and study period was similar, however external training load was lower in the study period. Match statistics were not favourable for the player during the control period, however they improved during the study period.ConclusionsThis case supports the theory that individuals with elevated iron availability are well placed to achieve increases in haemoglobin mass. Furthermore, although therapeutic venesections may still be required to manage iron overload, the addition of altitude exposure may be a method to assist in reducing total body iron by means of mobilising available (excessive) iron to incorporate into haemoglobin. Altitude exposure did not hinder the players’ performance. Further research is encouraged.     

The pharmacological management of hairy cell leukemia

ABSTRACT

Introduction

Hairy cell leukemia (HCL) is a B-cell lymphoid malignancy that accounts for approximately 2% of all leukemias. Treatment with purine nucleoside analogs (PNA) results in a high response rate and remains the standard of care. Long term follow-up shows that most patients relapse and require retreatment. Newer combination strategies and agents have emerged to try to reduce the relapse rate and to address cases of PNA refractoriness.     

Analyzing Survival Rate of Leukemia Patients Applying Long Term Exponential Model

Background: Making progressin treatment of all branches of cancers has increasedthe percent of patients that never experience the event of interest. These cases are called immune or cure and models for handling the data included cure fraction rate, are referred to as cure model or long-term survival models. Methods:The data for this historical cohort study, were collected from leukemia patients diagnosed between 2007 to 2014 and followed up until 2016 in Taleghani hospital and received BMT (Bone Marrow Transplant). Some data had to be excluded because of incomplete information. Using recorded files mostly and phone calls rarely, were made to confirm whether the patients were still alive or not. Death due to leukemia was regarded as interested event. Analysis were performed by R version 3.4.1and Stata version 14. Results: Number of recurrents after receiving BMT, pre-transplant Hb and age at diagnosis were found as significant prognostics of survival time. HD patients had the highest 5-years overall survival in category of diagnosis type with 81.3%. Cure fraction was estimated to be 64.1%. Conclusion: According to high percentage of censoring, using long-term model had better fit.     

白念珠菌对人急性单核细胞白血病细胞系产生肿瘤坏死因子α、活化信号分子p38MAPK 的影响

目的：探讨白念珠菌对人急性单核细胞白血病细胞系（THP-1细胞系）分泌肿瘤坏死因子α（TNF-α）和细胞内信号分子 p38丝裂原活化蛋白激酶（MAPK）激活的影响。方法实时荧光定量 PCR 分析105、106 CFU/ml 灭活白念珠菌及阳性刺激物脂多糖刺激 THP-1细胞1、3、6 h 后 TNF-α mRNA 表达水平变化。40μg/L 地塞米松预先与 THP-1细胞共培养30 min 后，再用106 CFU/ml 白念珠菌、脂多糖刺激6 h 后检测TNF-α mRNA 表达水平。酶联免疫吸附法检测白念珠菌刺激 THP-1细胞24 h 后 TNF-α分泌量。免疫印迹法分析白念珠菌体外作用 THP-1细胞30 min、1 h 后 p38MAPK 和磷酸化 p38MAPK 的水平。结果105 CFU/ml 白念珠菌、106 CFU/ml 白念珠菌、脂多糖刺激 THP-1细胞组以及空白对照组 TNF-α mRNA 表达水平差异有统计学意义（F =110.98，P <0.001）；白念珠菌刺激1、3、6 h 之间差异也有统计学意义（F =701.680，P <0.001），随培养时间延长，THP-1细胞 TNF-α mRNA 水平增高，呈时间依赖效应。106 CFU/ml 白念珠菌刺激 THP-1细胞后24 h，TNF-α蛋白水平（6385.70±533.99 ng/L）较空白对照组（147.10±0.53 ng/L）明显升高，差异有统计学意义（P <0.01）。106 CFU/ml 白念珠菌作用于 THP-1细胞30、60 min 后磷酸化 p38MAPK 蛋白水平也明显升高。40μg/L地塞米松预先与 THP-1细胞共培养30 min 后，再以106 CFU/ml 白念珠菌刺激6 h 后 TNF-α mRNA 表达水平（3.77±0.62）较未用地塞米松组（208.50±10.50）明显降低，地塞米松可阻断白念珠菌上调 TNF-α mRNA 水平。结论人 THP-1细胞体外与白念珠菌作用后激活信号分子 p38MAPK 并分泌 TNF-α，参与抗念珠菌感染固有免疫反应。