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Invasive Fungal Rhinosinusitis Due to Co-infection with Mucormycosis and Exserohilum rostratum in a Patient with Acute Lymphoblastic Leukemia. 急性淋巴细胞白血病合并毛霉病和喙状芽孢杆菌感染致侵袭性真菌性鼻窦炎1例。
Pub Date : 2022-06-13 eCollection Date: 2022-06-01 DOI: 10.1007/s44228-022-00009-3
Vera Radici, Eolia Brissot, Suzanne Chartier, Juliette Guitard, Bettina Fabiani, Mara Memoli, Anne Banet, Laurence Heuberger, Simona Lapusan, Sarah Atallah, Ollivier Legrand, Alexis Genthon

Invasive fungal infections remain an important cause of complication and morbidity in the management of acute leukemias. Here we report the case of a 27-year-old patient from French Polynesia who was diagnosed with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia. After induction chemotherapy, she developed rhinosinusitis with extensive bone lysis. The context and clinical presentation quickly made us suspect an invasive mucormycosis infection. However, a multidisciplinary investigation including mass spectrometry techniques also revealed the presence of Exserohilum rostratum, a pathogen member of the genus Exserohilum that is ubiquitous in tropical and subtropical regions but rarely implicated in invasive sinusitis. Antifungal treatment combined with an early surgical approach resulted in a favorable clinical response.

侵袭性真菌感染仍然是急性白血病治疗中并发症和发病率的重要原因。在这里,我们报告一个27岁的病人从法属波利尼西亚谁被诊断为费城染色体阴性b细胞急性淋巴细胞白血病。诱导化疗后,患者出现鼻窦炎伴广泛骨溶解。背景和临床表现很快使我们怀疑是侵袭性毛霉菌感染。然而,一项包括质谱技术在内的多学科研究也发现了枯茎芽孢菌(exserhilum rostratum)的存在,这是枯茎芽孢菌属的一种病原体,普遍存在于热带和亚热带地区,但很少涉及侵入性鼻窦炎。抗真菌治疗结合早期手术方法导致良好的临床反应。
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引用次数: 0
The Use of Bruton Tyrosine Kinase Inhibitors in Waldenström's Macroglobulinemia. 布鲁顿酪氨酸激酶抑制剂在Waldenström巨球蛋白血症中的应用。
Pub Date : 2022-05-23 eCollection Date: 2022-06-01 DOI: 10.1007/s44228-022-00007-5
Obada Ababneh, Hassan Abushukair, Aref Qarqash, Sebawe Syaj, Samer Al Hadidi

The use of Bruton Tyrosine Kinase (BTK) inhibitors in Waldenström's Macroglobulinemia (WM) is evolving. Ibrutinib, a first-generation BTK inhibitor, is currently approved for use in frontline and relapsed/refractory disease. Second-generation BTK inhibitors are being used and studied to improve clinical outcomes and/or safety profile. Zanubrutinib, one such second-generation inhibitor, was recently approved in treatment-naive and refractory/relapsed patients. Here, we review the use of BTK inhibitors in WM in front-line and refractory or relapsed settings. We also highlight common adverse events, the emergence of BTK inhibitors resistance, and future directions of their use.

布鲁顿酪氨酸激酶(BTK)抑制剂在Waldenström大球蛋白血症(WM)中的应用正在不断发展。Ibrutinib是第一代BTK抑制剂,目前已被批准用于一线和复发/难治性疾病。第二代BTK抑制剂正在使用和研究,以改善临床结果和/或安全性。Zanubrutinib,一种这样的第二代抑制剂,最近被批准用于治疗初治和难治性/复发患者。在这里,我们回顾了BTK抑制剂在一线和难治性或复发性WM中的应用。我们还强调了常见的不良事件,BTK抑制剂耐药性的出现,以及它们的未来使用方向。
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引用次数: 1
Safety and Efficacy of Elective Switch from Nilotinib to Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia. 尼洛替尼选择性切换到伊马替尼治疗新诊断的慢性期慢性髓性白血病的安全性和有效性。
Pub Date : 2022-05-12 eCollection Date: 2022-06-01 DOI: 10.1007/s44228-022-00001-x
Ali Ibrahim, Nour Moukalled, Rami Mahfouz, Jean El Cheikh, Ali Bazarbachi, Iman Abou Dalle

The treatment of newly diagnosed chronic phase chronic myeloid leukemia (CML) with nilotinib has resulted in a higher rate of major molecular (MMR) and complete cytogenetic response (CCyR) at 12 months compared to imatinib but at a higher cumulative cost and increased risk of serious adverse events. To maintain long-term efficacy and minimize both toxicity and costs, we aimed at evaluating in a prospective single-center trial the efficacy and safety of a response-directed switch from nilotinib to imatinib after 12 months in patients newly diagnosed with chronic phase CML. Thirteen adult patients were enrolled. Twelve patients started on nilotinib 300 mg twice daily. Eleven patients completed one year of nilotinib and were switched to imatinib 400 mg daily as per protocol. At 3 months, all patients achieved a complete hematologic response, with 7 (58%) patients had early molecular response. At 12 months, all patients achieved CCyR, of whom 5 (42%) and 4 (33%) patients achieved MMR and MR4.5, respectively. Three (27%) patients switched back to nilotinib after 18, 24, and 51 months respectively: 1 patient because of loss of CCyR after 18 months, and 2 patients because of imatinib intolerance. At last follow-up, all patients (n = 12) were alive and in MMR, 6 (50%) of them in continuous MR4.5. These findings suggest that response directed switch from nilotinib to imatinib at 12 months is capable of maintaining long-term response, with manageable side effects. This approach warrants further exploration with larger prospective trials. Clinical trial registration: Clinicaltrials.gov identifier: NCT01316250, https://clinicaltrials.gov/ct2/results?cond=&term=NCT01316250&cntry=&state=&city=&dist=. .

与伊马替尼相比,尼罗替尼治疗新诊断的慢性期慢性髓性白血病(CML)在12个月时的主要分子(MMR)和完全细胞遗传学反应(CCyR)率更高,但累积成本更高,严重不良事件的风险增加。为了保持长期疗效并最小化毒性和成本,我们旨在通过一项前瞻性单中心试验评估新诊断为慢性期CML的患者在12个月后从尼洛替尼转向伊马替尼的疗效和安全性。13名成年患者入组。12名患者开始服用尼罗替尼300毫克,每日两次。11名患者完成了一年的尼罗替尼治疗,并根据治疗方案改为每天400mg伊马替尼。在3个月时,所有患者都获得了完全的血液反应,其中7例(58%)患者有早期分子反应。12个月时,所有患者均达到CCyR,其中5例(42%)和4例(33%)患者分别达到MMR和MR4.5。3例(27%)患者分别在18个月、24个月和51个月后切换回尼罗替尼:1例患者在18个月后CCyR丢失,2例患者因伊马替尼不耐受。最后随访,所有患者(n = 12)存活并处于MMR,其中6例(50%)处于持续MR4.5。这些研究结果表明,在12个月时从尼罗替尼转向伊马替尼能够维持长期反应,副作用可控。这种方法值得进一步探索更大的前瞻性试验。临床试验注册:Clinicaltrials.gov标识符:NCT01316250, https://clinicaltrials.gov/ct2/results?cond=&term=NCT01316250&cntry=&state=&city=&dist=。
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引用次数: 1
Clinical, Morphological and Clonal Progression of VEXAS Syndrome in the Context of Myelodysplasia Treated with Azacytidine. 阿扎胞苷治疗骨髓增生异常伴伴VEXAS综合征的临床、形态学和克隆进展。
Pub Date : 2022-05-12 eCollection Date: 2022-06-01 DOI: 10.1007/s44228-022-00002-w
Marco Manzoni, Alessandro Bosi, Sonia Fabris, Marta Lionetti, Simone Salerio, Anna Chiara Migliorini, Francesca Cavallaro, Kordelia Barbullushi, Nicolò Rampi, Vittorio Montefusco, Maria Grazia Alessio, Antonino Neri, Luca Baldini, Mariarita Sciumè, Elena Tagliaferri, Nicola Fracchiolla, Niccolò Bolli
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引用次数: 5
Selected Domains within a Comprehensive Geriatric Assessment in Older Patients with Non-Hodgkin Lymphoma are Highly Associated with Frailty. 在老年非霍奇金淋巴瘤患者的综合老年评估中选择的领域与虚弱高度相关。
Pub Date : 2022-05-11 eCollection Date: 2022-06-01 DOI: 10.1007/s44228-022-00005-7
María Del Pilar Gamarra Samaniego, Carmelo J Blanquicett, Roger V Araujo Castillo, Julio C Chavez, Brady Ernesto Beltrán Garate

Background: The incidence of Non-Hodgkin Lymphoma (NHL) is increasing, particularly among older patients who tend to have worse outcomes and can be predisposed to increased toxicities and less treatment tolerance. Therefore, a thorough pre-treatment assessment is essential. A comprehensive geriatric assessment (CGA) can be used to evaluate the older patient considering chemotherapy and is the preferred evaluation tool. However, a formal CGA is laborious, complex and time-consuming.

Objectives: To characterize older adults with NHL and determine the CGA variables with the greatest association to frailty in order to propose a more simplified assessment.

Methods: We performed a cross-sectional study using data collected from CGAs in NHL patients > 65 years admitted to our oncology service, from September 2015 to August 2017. Our evaluation parameters included: polypharmacy, a screening tool of older people's prescriptions (STOPP), the Lawton scale, Barthel index, Katz index, gait speed, a Timed Up and Go (TUG) test, a Mini-Mental state examination (MMSE), the Yesavage and Gijon scales, a Mini-nutritional assessment (MNA), a Geriatric Syndromes assessment, and a Cumulative Illness Rating Scale-Geriatric (CIRS-G). The formal CGA was comprised of nine domains; frailty was defined as an impairment in > 2 domains. Each parameter was individually compared with frailty, and the results were used to build different multivariate models using logistic regression analyses to obtain the variables with the highest frailty association.

Results: A total of 253 patients were included. Their median age was 75.4 years (range 65-92), and 62.1% had > 1 impaired domain, with 39.9% considered frail. Bivariate analysis showed strong associations with age > 85 and all the geriatric parameters except for STOPP. Our final multivariate analysis resulted in 5 domains (the use of > 5 medications, a Lawton < 7, TUG > 20, Yesavage > 5, and the presence of at least one geriatric syndrome) being significantly associated with frailty and performing similarly to a CGA.

Conclusion: In our population of older NHL patients, an abbreviated evaluation based of only five domains, polypharmacy, TUG, Lawton scale, Yesavage scale and the presence of at least one geriatric syndrome, had similar performance to a formal CGA in determining frailty.

背景:非霍奇金淋巴瘤(NHL)的发病率正在增加,特别是在老年患者中,他们往往有较差的结局,可能倾向于增加毒性和较低的治疗耐受性。因此,彻底的治疗前评估是必不可少的。综合老年评估(comprehensive geriatric assessment, CGA)可用于评估考虑化疗的老年患者,是首选的评估工具。然而,正式的CGA是费力、复杂和耗时的。目的:分析老年人NHL的特征,确定与衰弱关系最大的CGA变量,以提出更简化的评估方法。方法:我们对2015年9月至2017年8月住院的> 65岁NHL患者的CGAs数据进行了横断面研究。我们的评估参数包括:综合用药、老年人处方筛选工具(STOPP)、Lawton量表、Barthel指数、Katz指数、步态速度、Timed Up and Go (TUG)测试、迷你精神状态检查(MMSE)、Yesavage和Gijon量表、迷你营养评估(MNA)、老年综合征评估和老年累积疾病评定量表(CIRS-G)。正式的CGA由9个域组成;虚弱被定义为2个以上脑域的损伤。将各参数分别与脆弱性进行比较,并利用结果建立不同的多变量模型,采用logistic回归分析,获得脆弱性相关性最高的变量。结果:共纳入253例患者。他们的中位年龄为75.4岁(65-92岁),62.1%的人有> 1个受损域,39.9%的人虚弱。双变量分析显示,与年龄> 85岁和除STOPP外的所有老年参数有很强的相关性。我们最终的多变量分析结果显示,5个领域(使用> 5种药物,Lawton 20, Yesavage > 5,以及至少存在一种老年综合征)与虚弱显着相关,并且表现与CGA相似。结论:在我们的老年NHL患者人群中,仅基于五个域(polypharmacy、TUG、Lawton量表、Yesavage量表和至少存在一种老年综合征)的简化评估在确定衰弱方面与正式的CGA具有相似的效果。
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引用次数: 3
Immunotherapy and Allogeneic Bone Marrow Transplantation in B Acute Lymphoblastic Leukemia: How to Sequence? B 型急性淋巴细胞白血病的免疫疗法和同种异体骨髓移植:如何排序?
Pub Date : 2022-05-11 eCollection Date: 2022-06-01 DOI: 10.1007/s44228-022-00006-6
Anna Komitopoulou, I Baltadakis, I Peristeri, E Goussetis

Long-term disease control is achieved in 80-90% of patients with acute lymphoblastic leukemia of B origin (B-ALL). About half of adult and 10% of pediatric patients develop refractory or relapsed disease, whereas survival after relapse accounts about 10% in adults and 30-50% in children. Allogeneic bone marrow transplantation offers remarkable benefit in cases with unfavorable outcome. Nevertheless, novel immunotherapeutic options have been approved for patients with adverse prognosis. Immunotherapeutic agents, nowadays, are preferred over standard chemotherapy for patients with relapsed or refractory B-ALL The mode of action, efficacy and safety data of immunotherapeutic agents released, indications and sequence of those therapies over the course of treatment, are herein reviewed.

80%-90%的 B 型急性淋巴细胞白血病(B-ALL)患者都能长期控制病情。约有一半的成人患者和10%的儿童患者病情难治或复发,而复发后的存活率成人约为10%,儿童约为30%-50%。同种异体骨髓移植对预后不良的病例有显著疗效。然而,新的免疫治疗方案已被批准用于预后不良的患者。现今,对于复发或难治性 B-ALL 患者,免疫治疗药物是优于标准化疗的首选药物。
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引用次数: 0
Trends in Inpatient Chemotherapy Hospitalizations, Cost and Mortality for Patients with Acute Leukemias and Myeloma. 急性白血病和骨髓瘤患者住院化疗、费用和死亡率的趋势。
Pub Date : 2022-05-11 eCollection Date: 2022-06-01 DOI: 10.1007/s44228-022-00003-9
Kellen Gil, Saqib Abbasi, Kathan Mehta, Brian McClune, Douglas Sborov, Nausheen Ahmed, Al-Ola Abdallah, Siddhartha Ganguly, Joseph McGuirk, Leyla Shune, Ghulam Rehman Mohyuddin
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引用次数: 1
How I Use Measurable Residual Disease in the Clinical Management of Adult Acute Lymphoblastic Leukemia. 如何在成人急性淋巴细胞白血病的临床治疗中使用可测量的残留病。
Pub Date : 2021-11-29 eCollection Date: 2021-12-01 DOI: 10.2991/chi.k.211119.001
Fiona Fernando, Harry Frederick Robertson, Sarah El-Zahab, Jiří Pavlů

Over the last decade the use of measurable residual disease (MRD) diagnostics in adult acute lymphoblastic leukemia (ALL) has expanded from a limited number of study groups in Europe and the United States to a world-wide application. In this review, we summarize the advantages and drawbacks of the current available techniques used for MRD monitoring. Through the use of three representative case studies, we highlight the advances in the use of MRD in clinical decision-making in the management of ALL in adults. We acknowledge discrepancies in MRD monitoring and treatment between different countries, reflecting differing availability, accessibility and affordability.

在过去的十年中,在成人急性淋巴细胞白血病(ALL)中使用可测量残留病(MRD)诊断已经从欧洲和美国的有限研究组扩展到世界范围的应用。在这篇综述中,我们总结了目前可用的MRD监测技术的优点和缺点。通过使用三个代表性的案例研究,我们强调了在成人ALL管理的临床决策中使用MRD的进展。我们承认不同国家在耐药药物监测和治疗方面存在差异,反映了可获得性、可及性和可负担性的差异。
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引用次数: 6
The Management of a Comprehensive Cancer Center during the First Six Months of the COVID-19 Pandemic in the South of France: Lessons from the Paoli-Calmettes Institute's Experience. 法国南部2019冠状病毒病大流行前六个月综合癌症中心的管理:保利-卡尔梅特研究所的经验教训。
Pub Date : 2021-09-27 eCollection Date: 2021-12-01 DOI: 10.2991/chi.k.210919.001
Didier Blaise, Pierre Berger, Djamel Mokart, Jacques Camerlo, Emmanuelle Fougereau, Marc Giovannini, Gilles Houvenaeghel, Olivier Turrini, Christian Chabannon, Gilles Piana, Isabelle Brenot-Rossi, Agnès Tallet, Anthony Gonçalves, Aude Charbonnier, Norbert Vey, Sabrina Grossi, Patrice Viens

During the COVID-19 pandemic, it was rapidly established that cancer patients have an increased risk of developing severe forms of the 2019 coronavirus disease (COVID-19) due to a backlog of cancer diagnostics and immunosuppressive treatments. Cancer centers had to quickly adapt to continue cancer therapies despite the high infection risks and major disruptions in the French healthcare system. We described and analyzed the impact of the pandemic in our institution: management adjustments, COVID-19 infection rates in patients and staff, and impacts on clinical activities and finances during the first wave of the pandemic from March to September 2020. We also compared the results to the clinical activity data from preceding periods. A crisis unit was rapidly created that met 27 times over 66 days, generating numerous changes in hospital protocol. While our area was devastated by the pandemic, the infection rate of our staff and patients remained low (less than 1.5% of all employees). However, the lockdown period was accompanied with a reduction of most clinical activities, leading to decreases of 43%, 36%, 36%, 1%, and 10% in surgery, endoscopy, radiotherapy, and in- and out-patient chemotherapy sessions, respectively, with substantial financial loss. Our report highlights the need for the rapid creation, implementation, and adaptation of new protocols during a pandemic's evolution to prevent disease transmission. Lessons from this situation should provide motivation to better prepare for/limit the dismantling of cancer therapies that can dramatically impact patient care and have deleterious consequences on an institution's financial situation.

在2019冠状病毒病大流行期间,人们迅速确定,由于癌症诊断和免疫抑制治疗积压,癌症患者患严重形式的2019冠状病毒病(COVID-19)的风险增加。癌症中心必须迅速适应持续的癌症治疗,尽管法国医疗保健系统存在高感染风险和重大中断。我们描述并分析了大流行对我们机构的影响:2020年3月至9月第一波大流行期间的管理调整、患者和工作人员的COVID-19感染率以及对临床活动和财务的影响。我们还将结果与前期的临床活动数据进行了比较。急救小组迅速成立,在66天内进行了27次急救,医院规程发生了许多变化。虽然我们的地区受到大流行的破坏,但我们的员工和患者的感染率仍然很低(不到所有员工的1.5%)。然而,封锁期间伴随着大多数临床活动的减少,导致手术、内窥镜检查、放疗和门诊化疗分别减少43%、36%、36%、1%和10%,造成了巨大的经济损失。我们的报告强调,在大流行演变过程中,需要迅速制定、实施和调整新的方案,以预防疾病传播。从这种情况中吸取的教训应该为更好地准备/限制癌症治疗的取消提供动力,这些治疗可能会极大地影响患者的护理,并对机构的财务状况产生有害的后果。
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引用次数: 3
Gastrointestinal Complications after Allogeneic Hematopoietic Stem Cell Transplant: A Multidisciplinary Approach with Early Endoscopic Evaluation. 异基因造血干细胞移植后的胃肠道并发症:早期内镜评估的多学科方法。
Pub Date : 2021-09-23 eCollection Date: 2021-12-01 DOI: 10.2991/chi.k.210826.001
Giuseppe Tarantino, Francesco Saraceni, Giorgia Mancini, Monica Poiani, Luca Maroni, Gaia Goteri, Ilaria Scortechini, Alessandro Fiorentini, Maria Vittoria Dubbini, Francesco Marini, Luigi Daretti, Marco Marzioni, Emanuele Bendia, Antonio Benedetti, Attilio Olivieri

Gastrointestinal complications (GICs) represent the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Differential diagnosis of GICs is of paramount importance since early and reliable identification of graft-versus-host disease (GVHD) is essential for a correct management of the patients. The aim of the present retrospective study was to evaluate the occurrence of GICs after allo-HSCT and to assess the diagnostic performance of a quick endoscopic and histological assessment in the differential diagnosis between GVHD and other GI conditions. Between January 2015 and August 2019, 122 consecutive patients receiving an allo-HSCT were managed by an interdisciplinary team, supported by a dedicated endoscopic service. Clinical, therapeutic, endoscopic and histological data were analyzed for each patient. Collectively, 94 of the patients developed GICs (77%). A moderate-severe mucositis was the most frequent complication, occurring in 79 patients (84%). Acute GI-GVHD was diagnosed in 35 patients (37% of whom with GICs) and 19 of them with a moderate-severe grade. Infective acute colitis developed in eight patients, mainly due to Clostridium difficile (CD) and Cytomegalovirus infections (8.5%). Rectal biopsy showed the highest sensitivity and specificity (80% and 100%, respectively). However, when biopsy procedures were guided by symptoms and performed on apparently intact mucosa, upper histology also provided a high negative predictive value (80%). Our multidisciplinary approach with a quick endoscopic/histologic investigation in the patients receiving an allo-HSCT and who suffered GICs could improve diagnostic and therapeutic management in this challenging setting.

胃肠道并发症(gic)是异体造血干细胞移植(allogenic hematopoietic stem cell transplantation, alloo - hsct)术后发病和死亡的主要原因。GICs的鉴别诊断至关重要,因为早期可靠地识别移植物抗宿主病(GVHD)对于正确治疗患者至关重要。本回顾性研究的目的是评估同种异体造血干细胞移植后GVHD的发生,并评估快速内镜和组织学评估在GVHD和其他胃肠道疾病鉴别诊断中的诊断作用。在2015年1月至2019年8月期间,122名连续接受同种异体造血干细胞移植的患者由一个跨学科团队管理,并由专门的内窥镜服务提供支持。对每位患者的临床、治疗、内镜和组织学资料进行分析。总的来说,94名患者发生了GICs(77%)。中重度粘膜炎是最常见的并发症,发生在79例患者中(84%)。35名患者被诊断为急性GI-GVHD(其中37%为gi患者),其中19名为中重度。8例患者发生感染性急性结肠炎,主要是由于艰难梭菌(CD)和巨细胞病毒感染(8.5%)。直肠活检显示最高的敏感性和特异性(分别为80%和100%)。然而,当活检过程以症状为指导并在表面完整的粘膜上进行时,上部组织学也提供了很高的阴性预测值(80%)。我们采用多学科方法,对接受同种异体造血干细胞移植并患有GICs的患者进行快速内窥镜/组织学检查,可以改善这种具有挑战性的环境下的诊断和治疗管理。
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引用次数: 8
期刊
Clinical Hematology International
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