Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies,an in-depth review

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.     

Exploratory Study of Apparent Diffusion Coefficient Histogram Metrics in Assessing Pancreatic Malignancy

PurposeTo evaluate whole-lesion 3D-histogram apparent diffusion coefficient (ADC) metrics for assessment of pancreatic malignancy.MethodsForty-two pancreatic malignancies (36 pancreatic adenocarcinoma [PDAC], 6 pancreatic neuroendocrine [PanNET]) underwent abdominal magnetic resonance imaging (MRI) with diffusion-weighted imaging before endoscopic ultrasound biopsy or surgical resection. Two radiologists independently placed 3D volumes of interest to derive whole-lesion histogram ADC metrics. Mann-Whitney tests and receiver operating characteristic analyses were used to assess metrics’ diagnostic performance for lesion histology, T-stage, N-stage, and grade.ResultsWhole-lesion ADC histogram metrics lower in PDACs than PanNETs for both readers (P ≤ .026) were mean ADC (area under the curve [AUC] = 0.787-0.792), mean of the bottom 10th percentile (mean_0-10) (AUC = 0.787-0.880), mean of the 10th-25th percentile (mean_10-25) (AUC = 0.884-0.917) and mean of the 25th-50th percentile (mean_25-50) (AUC = 0.829-0.829). For mean_10-25 (metric with highest AUC for identifying PDAC), for reader 1 a threshold > 0.94 × 10^?3 mm²/s achieved sensitivity 94% and specificity 83%, and for reader 2 a threshold > 0.82 achieved sensitivity 97% and specificity 67%. Metrics lower in nodal status ≥ N₁ than N₀ for both readers (P ≤ .043) were mean_0-10 (AUC = 0.789-0.822) and mean_10-25 (AUC = 0.800-0.822). For mean_10-25 (metric with highest AUC for identifying N₀), for reader 1 a threshold <1.17 achieved sensitivity 87% and specificity 67%, and for reader 2 a threshold <1.04 achieved sensitivity 87% and specificity 83%. No metric was associated with T-stage (P > .195) or grade (P > .215).ConclusionVolumetric ADC histogram metrics may serve as non-invasive biomarkers of pancreatic malignancy. Mean_10-25 outperformed standard mean for lesion histology and nodal status, supporting the role of histogram analysis.     

The diagnostic and prognostic role of liquid-based cytology: are we ready to monitor therapy and resistance?

Here, we evaluate the diagnostic and prognostic role of liquid-based cytology (LBC) in different body lesions, including thyroid, lung, effusions and malignant breast lesions. LBC has gained consensus after being applied to both non-gynecologic and fine-needle aspiration cytology. Although some remain sceptical regarding the diagnostic efficacy of LBC, mainly when used alone, in recent years, good results have been obtained as long as it showed a high diagnostic accuracy. Here, we discuss the additional possibility of storing material for the application of ancillary techniques (immunocytochemistry–molecular analysis) with several diagnostic and prognostic advantages, which may pave the way for the challenging evaluation of both monitoring responses to treatment and resistance to targeted therapies in thyroid, lung, breast carcinoma or malignant effusions. Furthermore, it provides the use of several molecular spots as specific targets for personalized therapy.     

脐血移植治疗37例儿童恶性血液病的临床研究-单中心经验

目的 探讨脐血造血干细胞移植（UCBT）治疗儿童恶性血液病的疗效。方法 回顾性分析接受UCBT 的37 例恶性血液病患儿的临床资料，包括急性淋巴细胞性白血病14 例，急性髓细胞性白血病9 例，幼年粒单细胞白血病5 例，慢性粒细胞白血病和骨髓增生异常综合征各3 例，急性混合型白血病2 例，淋巴肉瘤性白血病1 例。其中34 例非血缘相关，3 例血缘相关。HLA 配型6/6 相合5 例，5/6 相合12 例，4/6 相合11 例，3/6 相合9 例。移植中位年龄5.7 岁，中位体重20 kg。结果 中性粒细胞和血小板植入中位天数分别是12 d 和25 d，植入率分别为95% 和78%。中性粒细胞植入率与CD34+ 细胞数呈正相关（P=0.011）。血小板植入率与CD34+ 细胞数和有核细胞数均有关（分别P=0.001、0.014）。急性移植物抗宿主病（GVHD）的发生率为49%，慢性GVHD 为11%。随访中位时间54 个月，5 年移植相关病死率、总生存率和无病生存率分别为27%、57%和41%。结论 脐血移植是快速获得的造血干细胞来源之一，为恶性疾病患儿争取了治疗时间。     

Transitional cell carcinoma in a patient with X‐linked hyperimmunoglobulin M syndrome

Patients with X‐linked hyperimmunoglobulin M syndrome (XHIGM) have a defective CD40–CD40 ligand system and further immunoglobulin class‐switching. They may present with recurrent infection and malignancy involving the liver, pancreas or biliary tract. We report here a case of poorly differentiated transitional cell carcinoma in a young man with XHIGM even on regular treatment and discuss the possible pathogenesis. Given that the triggering of the CD40–CD40 ligand system has been found to improve tumor immunogenicity in recent studies, future immunotherapy targeting the CD40 ligand for these patients may be feasible to prolong their survival.     

Concurrent mycosis fungoides and intravascular large B-cell lymphoma in a single patient

Mycosis fungoides (MF) is an indolent, uncommon, non-Hodgkin T-cell lymphoma of the skin. It classically presents with patches, plaques, and tumors and may rarely show spread to internal organs or bone marrow. Up to 7.5% of MF patients may be diagnosed with a second malignancy. Intravascular large B-cell lymphoma (IVLBCL) is an exceedingly rare non-Hodgkin B-cell lymphoma characterized by predominant growth of large neoplastic cells in the lumina of blood vessels. This case presents with an unusual confluence of two rare diagnoses, MF and IVLBCL, made more remarkable by the presence of both diagnoses on a single skin biopsy sample.