Management of refractory autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation : current perspectives

Autoimmune hemolytic anemia (AIHA) is increasingly observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a reported incidence between 4% and 6%. The disease is generally severe and refractory to standard therapy, with high mortality, and there are neither defined therapies, nor prospective clinical trials addressing the best treatment. Most of the knowledge on the therapy of AIHAs derives from primary forms, which are highly heterogeneous as well, further complicating the management of post-allo-HSCT forms. The review addresses the risk factors associated with post-allo-AIHA, including unrelated donor, the development of chronic extensive graft-versus-host disease, CMV reactivation, nonmalignant diagnosis pre-HSCT, and alemtuzumab use in conditioning regimens. Regarding therapy, we describe standard treatments, such as corticosteroids, intravenous immunoglobulin, splenectomy, rituximab, cyclophosphamide, and plasma exchange, which have lower response rates than those reported in primary forms. New therapeutic options, including sirolimus, bortezomib, abatacept, daratumumab and complement inhibitors, are promising tools for this detrimental complication occurring after allo-HSCT

Omentum flap as a spacer before carbon ion radiotherapy for gynecological recurrences. A technical note

Re-irradiation of pelvic recurrent gynecological cancer is a challenge due to the proximity of high-radiation-sensitive organs, such as the bowel and the urinary tract. Hadrontherapy for re-irradiation emerges as a safe and effective treatment with a mild rate of morbidity of surrounding normal tissue. To improve the dose to the tumor, a prophylactic displacement of organs at risk is needed, and a multidisciplinary approach is recommended. In this technical note, we report a surgical technique of omentum spacer placement for patients enrolled for carbon ion radiotherapy as re-irradiation for recurrent gynecological tumors. (C) 2022 Societe franc , aise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved

Small Paroxysmal Nocturnal Hemoglobinuria Clones in Autoimmune Hemolytic Anemia: Clinical Implications and Different Cytokine Patterns in Positive and Negative Patients

Autoimmune hemolytic anemia (AIHA) is characterized by immune mediated erythrocytes destruction by autoantibodies with or without complement activation. Additional pathologic mechanisms include cellular cytotoxicity, cytokline dysregulation, and inadequate bone marrow compensation with fibrosis/dyserythropoiesis. The latter resembles that of bone marrow failures, namely aplastic anemia and myelodysplastic syndromes. Paroxysmal nocturnal hemoglobinuria (PNH) clones are increasingly recognized in bone marrow failure syndromes, and their selection and expansion are thought to be mediated by immune mechanisms. In this study, we aimed to evaluate the prevalence of PNH clones in 99 patients with primary AIHA, and their correlations with disease features and outcomes. Moreover, in the attempt to disclose the physiopathology of PNH positivity in AIHA, serum levels of several immunomodulatory cytokines were tested. A PNH clone was found in 37 AIHA patients (37,4%), with a median size of 0.2% on granulocytes (range 0.03\u201385). Two patients showed a large clone (16 and 85%) and were therefore considered as AIHA/PNH association and not included in further analysis. Compared to PNH negative, PNH positive cases displayed a higher hemolytic pattern with adequate bone marrow compensation. AIHA type, response to therapy, complications and outcome were comparable between the two groups. Regarding cytokine levels, IFN-\u3b3 and IL-17 were lower in PNH positive vs. PNH negative AIHAs (0.3 \ub1 0.2 vs. 1.33 \ub1 2.5; 0.15 \ub1 0.3 vs. 3,7 \ub1 9.1, respectively, p = 0.07 for both). In PNH positive AIHAs, IFN-\u3b3 positively correlated with reticulocytes (r = 0.52, p = 0.01) and with the bone marrow responsiveness index (r = 0.69, p = 0.002). Conversely, IL-6 and IL-10 showed the same pattern in PNH positive and PNH negative AIHAs. IL-6 levels and TGF-\u3b2 positively correlated with clone size (r = 0.35, p = 0.007, and r = 0.38, p = 0.05, respectively), as well as with LDH values (r = 0.69, p = 0.0003, and r = 0.34, p = 0.07, respectively). These data suggest testing PNH clones in AIHA since their prevalence is not negligible, and may correlate with a prominent hemolytic pattern, a higher thrombotic risk, and a different therapy indication. PNH testing is particularly advisable in complex cases with inadequate response to AIHA-specific therapy. Cytokine patterns of PNH positive and negative AIHAs may give hints about the pathogenesis of highly hemolytic AIHA

Cancer Rehabilitation and Physical Activity: the “Oncology in Motion” Project

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Knowledge translation in challenging healthcare environments: The PIOPPO experience at the National Centre of Oncological Hadrontherapy (CNAO Foundation).

Knowledge translation is the ability to translate concepts and ideas effectively among different stakeholders, leading to innovation and new knowledge. Translating knowledge is particularly challenging in the healthcare sector, which has been experiencing a shift from a centralized and sequential model of value creation to a more distributed and open model, where various stakeholders (including patients) act as co-creators of the outcome. According to management as well as the medical literature, knowledge translation in healthcare has been mainly seen as the translation of scientific research into clinical practice. However, different types of knowledge translation emerge, such as when multidisciplinary teams need to work together on a joint medical project. In this situation, multiple backgrounds, competencies, skills, and emotional feelings of the different stakeholders are a compelling barrier that prevents the effective transfer and sharing of knowledge. This is why knowledge translation needs a set of enablers to facilitate the transfer, sharing, and creation of new knowledge, innovation, and ideas. This paper investigates such a perspective by analyzing the PIOPPO project from the National Centre of Oncological Hadrontherapy (CNAO Foundation) in Pavia, Italy. The CNAO is one of the few dual-beam Hadrontherapy centres in the world that provides a beam that is able to irradiate patients with protons or carbon ions to treat radioresistant tumours. The PIOPPO project is an experimental phase 2 trial involving preoperative chemotherapy and carbon ion therapy to treat resectable and borderline-resectable pancreatic adenocarcinoma. The stakeholders involved in the PIOPPO trial have different characteristics, both in terms of competencies and emotions. The PIOPPO multidisciplinary team includes highly skilled professionals from several disciplines, which are not all related to medicine (from oncologists to physicists, from biologists to surgeons). Pancreatic cancer patients are also involved while experiencing a challenging personal time. The paper analyses the knowledge translation flows, instruments, and issues among such different stakeholders

Parallel processing in immune networks

In this work we adopt a statistical mechanics approach to investigate basic, systemic features exhibited by adaptive immune systems. The lymphocyte network made by B-cells and T-cells is modeled by a bipartite spin-glass, where, following biological prescriptions, links connecting B-cells and T-cells are sparse. Interestingly, the dilution performed on links is shown to make the system able to orchestrate parallel strategies to fight several pathogens at the same time; this multitasking capability constitutes a remarkable, key property of immune systems as multiple antigens are always present within the host. We also define the stochastic process ruling the temporal evolution of lymphocyte activity, and show its relaxation toward an equilibrium measure allowing statistical mechanics investigations. Analytical results are compared with Monte Carlo simulations and signal-to-noise outcomes showing overall excellent agreement. Finally, within our model, a rationale for the experimentally well-evidenced correlation between lymphocytosis and autoimmunity is achieved; this sheds further light on the systemic features exhibited by immune networks.Comment: 21 pages, 9 figures; to appear in Phys. Rev.

Sexual Health Dysfunction After Radiotherapy for Gynecological Cancer: Role of Physical Rehabilitation Including Pelvic Floor Muscle Training

Introduction: The present study aims to describe: 1. How the side effects of radiotherapy (RT) could impact sexual health in women; 2. The effectiveness of physical rehabilitation including pelvic floor muscle training (PFMT) in the management of sexual dysfunction after RT. Materials and Methods: Search keys on PubMed, Web of Science, Scopus, PEDro, and Cochrane were used to identify studies on women treated with radical or adjuvant RT and/or brachytherapy for gynecological cancers with an emphasis on vulvo-vaginal toxicities and PFMT studies on sexual dysfunction for this group of women. Results: Regarding the first key question, we analyzed 19 studies including a total of 2,739 women who reported vaginal dryness, stenosis, and pain as the most common side effects. Reports of dosimetric risk factors and dose-effect data for vaginal and vulvar post-RT toxicities are scant. Only five studies, including three randomized controlled trials (RCTs), were found to report the effect of PFMT alone or in combination with other treatments. The results showed some evidence for the effect of training modalities including PFMT, but to date, there is insufficient evidence from high-quality studies to draw any conclusion of a possible effect. Conclusions: Gynecological toxicities after RT are common, and their management is challenging. The few data available for a rehabilitative approach on post-actinic vulvo-vaginal side effects are encouraging. Large and well-designed RCTs with the long-term follow-up that investigate the effect of PFMT on vulvo-vaginal tissues and pelvic floor muscle function are needed to provide further guidance for clinical management

Tackling TB in migrants arriving at Europe’s southern border

Over a quarter of the individuals diagnosed with tuberculosis [TB] in the European Union region are born outside of the area and the proportion has been increasing steadily. Italy is a low TB incidence country with over 50% of TB cases in the foreign-born population primarily due to the high numbers of migrants entering the country via land or sea. As a case study to evaluate the value of screening in newly arrived migrants, the EDETECT-TB project in Italy implemented and evaluated active TB screening in the migrant population at first reception centres to ensure early diagnosis to avoid further spread. Based on a cost-effectiveness analysis from a program provider perspective, a decision tree model allowed the assessment of the value for money of case finding by estimating the cost per case of active TB detected compared with the status quo of no screening. The analysis confirmed that early case detection is a cost-effective intervention in areas with migrants arriving from high TB risk settings. Targeted post-arrival early screening of high TB risk vulnerable new entrants to Italy has a potential role in reducing the spread of TB among migrants

Please mind the gap—about equity and access to care in oncology

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