Utilisation des cathéters centraux insérés par voie périphérique (PICC) en oncohématologie

Peripherally inserted central catheters (PICC) have the advantage of limiting the risk of accidents during installation and are easy to remove. Its use in oncology remains debated because of possible infectious complications. We analyzed 52 PICC in patients with hematological tumor from Nice Hospital. An installation failure was noted in 5.8% of cases. After a follow-up of 15 months, the complication rate was 26.9%, mainly mechanical complications: obstruction (13.5%) or accidental removal (9.6%). The organic complications such as infection or thrombophlebitis represented 3.8%. The median duration was 26 days [2-291]. The longest duration was associated with PICC for chemotherapy (median: 58 days). Frequent blood samples (above: 2 week) were associated with lower duration (median: 23 days). In conclusion, PICC represent a simple and effective alternative to intra-venous central devices in onco-hematology. However, physicians have to focus on short-course treatment.     

Therapeutic leukocytapheresis for improvement in respiratory function in a woman with hyperleukocytosis and mantle cell lymphoma with a circulating small lymphocyte phenotype

Mantle cell lymphoma is an aggressive malignant B‐cell disorder that often presents with a leukemic picture. Circulating lymphoma cell morphology may vary from small round mature‐appearing lymphocytes resembling the lymphocytes of chronic lymphocytic leukemia to large prolymphocytoid or blastoid cells. Rare reports of hyperleukocytosis with leukostasis, treated with leukocytapheresis, are described in patients with prolymphocytoid or blastoid morphology. We report an 88 year old woman with mantle cell lymphoma, hyperleukocytosis (WBC > 400 × 10³/µL) with severe respiratory compromise but without interstitial or alveolar infiltrates on radiograph or computerized tomography of the chest. She was afebrile and had no central nervous system signs. Circulating lymphoma cell morphology was predominantly of the small lymphocyte type. A two‐whole‐blood‐volume leukocytapheresis reduced her WBC from 465 to 221 × 10³/µL in 150 min. Her respiratory rate decreased from 28/min to 18/min and her arterial oxygen saturation (SpO₂) rose from 91% to 97% on 6 L/min of oxygen by nasal cannula. Severe breathlessness before the procedure abated completely by the end of the procedure. Respiratory compromise may occur in mantle cell lymphoma with hyperleukocytosis with a mature lymphoma cell phenotype, even without a clear picture of leukostasis. Although the ultimate survival of the patient depends on treatment with chemotherapy, leukocytapheresis for alleviation of symptoms may be warranted and should be considered. Respiratory status and response to leukocytapheresis should be documented with physiological measurements. J. Clin. Apheresis 31:398–402, 2016. © 2015 Wiley Periodicals, Inc.     

血液疾患骨髓微血管密度的研究

为了探讨血液系统疾病骨髓血管新生的状态及意义，采用改良的乙二醇-甲基丙烯酸酯(GMA)塑料包埋骨髓病理切片和免疫组织化学染色检测贫血、急性髓细胞白血病(AML)、急性淋巴细胞白血病(ALL)、慢性髓细胞白血病(CML)患者的骨髓微血管密度(MVD)。结果显示，初诊的恶性血液病患者在治疗前骨髓MVD明显增加；急性白血病化疗完全缓解后骨髓MVD降至正常水平，未缓解者下降程度小，复发者再次升高至化疗前水平；贫血患者骨髓MVD也比对照组明显增高，但远不如急性白血病骨髓MVD增高的幅度大。结论：骨髓血管新生在急性白血病发生过程中有着重要的作用，抗血管新生治疗可能成为治疗白血病的新策略。     

Survivin在造血系统肿瘤中的研究进展

Survivin是一种新的凋亡抑制蛋白(inhibitor of apoptosisprotein，IAP)，具有细胞周期调控和凋亡抑制双重功能。在多种造血系统肿瘤组织中高表达，与诊断、预后和耐药密切相关。利用survivin致敏的树突状细胞疫苗、survivin反义核酸及Survivin阴性突变体可有效抑制肿瘤细胞生长，为采用生物学策略治疗造血系统肿瘤开辟了新途径.本综述重点阐述了survivin在造血系统肿瘤中的表达，survivin与造血系统肿瘤预后和耐药的关系及survivin在造血系统肿瘤治疗中的应用。     

外周血NK细胞亚群检测在恶性血液病患者中的应用研究

目的探讨外周血自然杀伤细胞(NK)亚群检测在恶性血液病患者中的应用价值。方法选择2014年3月至2016年4月于该院接受治疗的100例恶性血液病患者作为观察组,其中急性期50例,平缓期50例,并在同一时段内选择100例体检健康者作为对照组,比较各组间外周血NK细胞数及亚群的变化。结果急性期白血病及淋巴瘤患者NK细胞绝对数及相对数均远低于对照组,而平缓期白血病及淋巴瘤NK细胞绝对数及相对数高于急性期,差异具有统计学意义(P0.05)。治疗后,白血病及淋巴瘤患者NK细胞绝对数及相对数均高于治疗前,差异具有统计学意义(P0.05)。治疗前,白血病及淋巴瘤患者CD56~(bright)及CD56~(dim)水平与对照组比较差异有统计学意义(P0.05);治疗后,两类患者CD56~(bright)及CD56~(dim)水平明显改善,治疗前比较差异有统计学意义(P0.05)。结论恶性血液病患者外周血NK细胞数量降低,细胞功能受损。NK细胞亚群检测在评价恶性血液病患者预后及疗效方面有一定的指导意义。     

Oncolytic Virus Therapy with HSV-1 for Hematological Malignancies

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单核苷酸多态性与血液学肿瘤的研究进展

单核苷酸多态性(single nucleotide polymorphisms,SNP)是第3代分子遗传标志,SNP决定基因的功能单位和人群遗传变异的内在特征。它反映了个体表型、疾病易感性和对药物、环境因子反应的差异。血液肿瘤是一种多基因遗传病,涉及到多个遗传易感基因的作用。本文就近年来单核苷酸多态性与其在血液肿瘤研究领域(致癌物质代谢酶基因的SNP、DNA修复基因的SNP、癌基因与抑癌基因的SNP、药物代谢相关酶基因的SNP等)的相关进展作一综述。     

Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance study from 2014 to 2019

Immune checkpoint inhibitors (ICIs) have shown remarkable clinical effects in many cancer types. However, ICIs could also induce severe organ system toxicities, including those of the hematological system. The present study aimed to extensively characterize the hematological toxicities of ICIs immunotherapy. Data were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1, 2014, to March 31, 2019. Disproportionality analysis, including information component (IC) and reporting odds ratio (ROR), was used to detect potential disproportionality signal. The lower boundary of the 95% confidence interval of IC (IC₀₂₅) exceeding zero or that of ROR (ROR₀₂₅) exceeding one was considered statistically significant for detecting disproportionality signal. A total of 29 294 335 records were extracted from the database, with 132 573 related to ICIs. Overall, hematological adverse events (AEs) were more frequently reported in ICIs (IC₀₂₅: 0.81; ROR₀₂₅: 1.80). On further analysis, hematological AEs were overreported in female patients (female vs male, ROR₀₂₅: 1.04) and anti-CTLA-4 monotherapy groups (anti-CTLA-4 vs anti-PD-1, ROR₀₂₅: 1.33) and polytherapy groups (polytherapy vs monotherapy, ROR: 1.20, ROR₀₂₅: 1.11). Moreover, class-specific hematological AEs were also detected and differed in unique ICI regimens. Notably, disseminated intravascular coagulation had the highest proportion of death outcomes among the top 10 most frequently reported ICI-associated hematological AEs. Our study shows a high reporting frequency of hematological AEs induced by ICI monotherapy (especially by anti-CTLA-4 therapy) and reinforced by polytherapy. A spectrum of class-specific disproportionality signal was also detected; some were fatal and reported for the first time. The heterogeneous clinical spectrum of hematological toxicities, including the non-negligible proportion of death as reported outcome, are warranted to be reminded by clinicians. Early recognition and management of ICI-related hematological AEs are highly important and further studies are needed to confirm the results of our study.     

Clinical presentation,diagnosis and management of therapy‐related hematological disorders in women with epithelial ovarian cancer treated with chemotherapy and poly‐ADP‐ribose polymerase inhibitors: A single‐center experience

We investigated the occurrence and management of therapy‐related hematological disorders (tr‐HDs) in women with epithelial ovarian cancer (EOC) exposed to poly‐ADP‐ribose polymerase inhibitors (PARPi), after previous chemotherapy. We analyzed 130 consecutive EOC patients treated with PARPi at the European Institute of Oncology, Milan. In line with the literature, overall survival of the entire population was 37% at 5.5 years (89% were advanced stages). Cell blood counts were collected prior to start PARPi, at each new cycle and at monthly intervals. Patients displaying persistent and/or marked hematological abnormalities underwent bone marrow evaluation, with cytogenetic and molecular analysis. Nine patients (6,9%) developed tr‐HDs, after a median 22.8 months of PARPi exposure. Two patients died early and could not be treated. Two patients have no indication for active treatment and are presently under close hematological monitoring. Five patients underwent chemotherapy followed, in three cases, by allogeneic hematopoietic transplantation: three patients are in complete remission of their hematological and gynecological malignancies at 13, 19, and 25 months; the remaining two patients died due to progression of their hematological disease. We show the potential risk of hematological disorders in EOC patients treated with chemotherapy and prolonged PARPi therapy. In our series, tr‐HDs incidence was higher compared to recent reports in large series. Our observations suggest careful monitoring in order to conclusively define, on large series and prolonged follow‐up, the actual risk of tr‐HDs in patients under PARPi. Notably, prompt diagnosis of hematological abnormalities and appropriate management allow achievement of remission from severe hematological complications, at least in most patients.     

程序性死亡受体-1及其配体在血液肿瘤中的研究进展

程序性死亡受体-1(programmed death-1,PD-1)及配体PD-L1为CD28/B7免疫球蛋白超家族负性协同刺激分子成员,在许多肿瘤细胞及其相关细胞表面高表达.近年来免疫治疗成为肿瘤治疗的新热点,其中PD-l及配体PD-L1为靶点的免疫抑制药物在各类肿瘤临床试验中显示出了良好的疗效和安全性.本文将对近年来其在白血病、淋巴瘤等血液系统疾病治疗中的研究现状作一综述,以期为血液系统疾病的治疗提供新的方法.