Hemato-oncological Diseases Research Articles

Unmeasurable capillary C-reactive protein as one of the diagnostic clues of severe hematological pathologies in children in primary settings: Case series.

The manuscript aimed to show that an unmeasurable capillary C-reactive protein (CRP) should be a red flag that can indicate a possible severe hematological pathology. The authors present 3 case reports of children with fever examined at the pediatric emergency department. Fever is among the most frequently exhibited symptoms of acute pediatric infectious diseases. However, sometimes fever can be the manifestation of other serious noninfectious diseases. CRP is a marker widely used in clinical pediatric practice to help us evaluate inflammation and possible bacterial infection. All mentioned patients had unmeasurable CRP from capillary blood, even though venous CRP ranged from 14 to 21 mg/L. All of the patients were consequently diagnosed with severe hemato-oncological disease. Possible explanations are that a change in blood viscosity or an elevation of circulating immune complexes in the blood of patients with leukemia leads to malfunctioning immunoturbidimetry measurement. Although these findings are very interesting and could lead to faster recognition of acute leukemia in pediatric clinical practice, further prospective study is needed for their confirmation.

Accuracy of Pancreatic Stone Protein for diagnosis of sepsis in children admitted to pediatric intensive care or high-dependency care: a pilot study

BackgroundPancreatic Stone Protein (PSP) is one of the most promising diagnostic and prognostic markers. The aim of the study was to assess the accuracy of PSP, compared to C-Reactive Protein (CRP), and Procalcitonin (PCT) for sepsis diagnosis in pediatric patients. Furthermore, we explored the correlation of PSP levels with sepsis severity and organ failure measured with PELOD-2 score.MethodsForty pediatric patients were enrolled following admission to pediatric intensive care, high dependency care or pediatric ward. PSP blood levels were measured in Emergency Department (nanofluidic point-of-care immunoassay; abioSCOPE, Abionic SA, Switzerland) on day 1, 2, 3, 5 and 7 from the onset of the clinical signs and symptoms of sepsis or SIRS. Inclusion criteria were: 1) patient age (1 month to 18 years old), 2) signs and symptoms of SIRS, irrespective of association with organ dysfunction. Exclusion criteria were: 1) hemato-oncological diseases and/or immunodeficiencies, 2) pancreatic diseases.ResultsSeptic patients showed higher PSP levels than those with non-infectious systemic inflammation. The optimal cut-off in diagnosis of sepsis for PSP at day 1 was 167 ng/ml resulted in a sensitivity of 59% (95% IC 36%—79%) and a specificity of 83% (95% IC 58%-96%) with an AUC of 0.636 for PSP in comparison to AUC of 0.722 for PCT and 0.503 for C-RP. ROC analysis for outcome (survival versus no survival) has showed AUC 0.814 for PSP; AUC 0.814 for PCT; AUC of 0.657 for C-RP.ConclusionsPSP could distinguish sepsis from non-infectious systemic inflammation; however, our results need to be confirmed in larger pediatric population.

Varicella Zoster Virus-Specific Hyperimmunoglobulin in the Adjuvant Treatment of Immunocompromised Herpes Zoster Patients: A Case Series.

Immunocompromised patients are at increased risk for herpes zoster (HZ)-associated complications. Despite standard therapy with systemic antiviral drugs and analgesics, complications are frequently encountered, including generalization of lesions or persistent neuropathic pain, so-called post-herpetic neuralgia (PHN). Given the scarcity of literature and awareness of therapeutic options to improve patient outcomes, especially for vulnerable patient groups, here we describe a strategy based on early intensification of treatment with a varicella zoster virus-specific hyperimmunoglobulin (VZV-IgG), which is approved in the adjuvant treatment of HZ. For this case series, we selected four cases of HZ in patients with impaired immunity due to hemato-oncologic disease or immunosuppressive treatment who presented with either existing generalized lesions and/or severe pain or with other risk factors for a complicated HZ course such as PHN. They were considered to be representative examples of different patient profiles eligible for intensification of treatment by the addition of VZV-IgG to virostatic therapy. All patients showed a rapid response to combined treatment with VZV-IgG and a virostatic agent. In two patients who had generalized lesions, the formation of new lesions ceased 1 day after VZV-IgG infusion. One patient, with mantle cell lymphoma, achieved complete healing of the lesions 9 days after diagnosis of HZ, a rare occurrence compared to similar cases or cohorts. A patient with HZ in the cervical region showed a good response after a single dose of VZV-IgG. None of the patients developed post-zoster-related complications. Combination therapy of a virostatic agent and VZV-IgG was well tolerated in these four cases. This case series demonstrates highly satisfactory treatment effectiveness and tolerability for VZV-IgG in the adjuvant treatment of immunocompromised HZ patients and supports early intensification of HZ therapy in patients at high risk of severe disease progression.

Safety and usefulness of nebulized liposomal amphotericin B: Systematic scoping review

PurposeInvasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a high concentration of drug delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy. MethodsAccording to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including “inhaled liposomal amphotericin B″, “nebulized liposomal amphotericin B″, or “aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022. ResultsOf the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed. ConclusionIn conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological diseases.

Variable Outcomes of Hepatitis E Infections in Patients with Hemato-Oncologic Diseases

Introduction: The hepatitis E virus (HEV) represents an important cause of viral hepatitis and could cause chronic infections in immunocompromised patients. However, data about immunocompromised patients other than solid organ transplant recipients are limited. Methods: We identified patients from a laboratory database and retrospectively compiled and analyzed clinical as well as laboratory data in detail. Results: Overall, 22 severely immunosuppressed patients, excluding solid organ transplant recipients, were identified. Four patients did not experience viral clearance (one without and three despite ribavirin therapy). Three patients acquired the infection after allogeneic hematopoietic stem cell transplantation (alloHSCT) and recovered spontaneously, whereas another patient, infected prior to alloHSCT, developed a chronic infection. Four patients failed to clear HEV, resulting in fatal liver failure in 2 patients. The CD4+ cell counts increased in all but 1 patient attaining a sustained virological response (SVR), as compared to patients with clinical failure. Severe immunoglobulin deficiency did not appear to obviate the control of HEV. Six of ten (60%) patients with and nine of 12 (75%) patients without ribavirin therapy achieved an SVR. Conclusions: Upfront ribavirin therapy does not appear mandatory in patients without CD4+ lymphopenia, but a prolonged HEV replication carries the risk of liver failure. Our data suggest that chronic HEV infections could cause T-cell exhaustion, which might be overruled with ribavirin therapy.

Timely course of SARS-CoV-2 infections and vaccinations in patients with hemato-oncological diseases: analysis of a real-life cohort

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has particularly impacted patients with hemato-oncological malignancies, as they showed not only a higher propensity for severe courses but also weaker immune responses after vaccination. Still, data on the influence of pandemic waves and vaccinations on outcomes are rare. This study aimed to analyze the timely course of infections and vaccinations in a real-life cohort of patients with hemato-oncological diseases. In this cohort study, 1817 patients with hemato-oncological diseases from 1 February 2020 to 15 December 2022 at the 'Franz Tappeiner' Hospital in Merano/Meran, Italy, were followed for SARS-CoV-2 infections and vaccinations. Of 1817 patients with hemato-oncological malignancies, 735 (40.5%) were infected at least once with SARS-CoV-2, and 1614 (88.8%) received one or more doses of the approved vaccinations. Patients receiving antineoplastic treatment had a lower SARS-CoV-2 infection rate [35.1% versus 41.0%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95], but higher risk of hospitalization (13.4% versus 6.9%; OR 2.11, 95% CI 1.25-3.69) compared with untreated patients. Overall, the case fatality rate (CFR) was 3.4%. Unvaccinated patients were more prone to severe coronavirus disease 2019 (COVID-19) courses requiring hospitalization (OR 2.34, 95% CI 1.25-4.36) and had a higher CFR (7.3% versus 1.6%; OR 4.98, 95% CI 2.16-12.98) than their vaccinated counterparts. In the Delta wave, patients with two vaccinations had a lower infection risk (OR 0.18, 95% CI 0.10-0.35) and tendentially lower hospitalization rates (OR 0.25, 95% CI 0.05-1.29) than unvaccinated patients. In the Omicron wave, 345/1198 (28.8%) patients with three or more vaccinations had breakthrough infections, resulting in a similar risk for infection (OR 0.88, 95% CI 0.60-1.30) but numerically lower risk for hospitalization (24/345, 7.0%) than unvaccinated individuals (4/40, 10.0%). Scheduled visits were postponed in 128/335 (38.2%) patients due to COVID-19, and deferrals correlated with pandemic wave (P= 0.002) and vaccination status (P < 0.001). SARS-CoV-2 infections and outcomes differ between distinct phases of the pandemic. Vaccination with variant-specific vaccines should be prioritized as general protective measures are increasingly lifted.

Modern T cell technologies for immunotherapy of solid tumors

According to the common concept of immune editing, the interaction of malignant tumor cells and immune system is a complex multifactorial process, which may result in both antitumor effector activity and development of suppressor mechanisms that promote tumor growth. Accumulation of scientific knowledge in the field of studying the antitumor immune response and tolerance has led to emergence of many research and therapeutic approaches that use different components of the immune system to combat neoplastic processes. Along with currently available approaches, there are strategies that use the potential of antigen-specific T lymphocytes, the main effectors of adaptive immunity, in order to fight malignant neoplasms which appeared more than a century ago and have built the scientific basis of cancer immunotherapy. One line of evidence of the significant antitumor potential of T cells in immunotherapeutic schemes for the cancer treatment was presented by successful therapy of hemato-oncological diseases, achieved at the end of the past decade. At the same time, however, the therapy of solid malignant neoplasms still faces significant difficulties that limit the efficiency of treatment. In this regard, the main objective of the review is to accumulate up-to-date information on the successes and limitations of T cell immunotherapy in the patients with solid tumors. To date, the phenotype and functionality of T cells is being investigated and modulated both towards enhancing antitumor cytotoxicity, increasing viability and proliferative activity of T cells, and in overcoming the immunosuppressive effect of the tumor and its tolerogenic microenvironment upon T cells, as well as ensuring targeted migration of the effector T cells to the malignant tissues. This review discusses immunotherapeutic approaches exploiting the potential of effector T lymphocytes, e.g., current clinical trials or applied therapeutic regimens for the treatment of solid malignant neoplasms. Antigen-independent approaches aimed at nonspecific enhancement of the T cell responses, i.e., therapy with recombinant cytokines and inhibition of immune checkpoint molecules. Antigendependent, or antigen-specific approaches such as adoptive T cell therapy with endogenous T lymphocytes are also discussed as well as trials on T cells with modified antigen-recognition receptor (CAR-Tcells, TCR-Tcells), like as usage of bispecific antibodies as T cell engagers. The review describes the benefits and disadvantages of these approaches in monotherapy, as well as current results and prospects for their mutual combinations.

Upraising Stenotrophomonas maltophilia in Critically Ill Patients: A New Enemy?

Stenotrophomonas maltophilia (S. maltophilia), an important pathogen in immuno-compromised patients, has recently gained attention in patients admitted in intensive care units (ICU). We sought to investigate clinical features of infections caused by S. maltophilia in ICU patients and identify risk factors for mortality. We conducted a retrospective study in two multivalent non-COVID-19 ICUs of tertiary-teaching hospitals in Greece and Spain, including patients with isolated S. maltophilia from at least one clinical specimen along with clinical signs of infection. A total of 103 patients (66% male) were analyzed. Median age was 65.5 (54-73.3) years and mean APACHE II and SOFA scores upon ICU admission were 18.36 (±7.22) and 18.17 (±6.95), respectively. Pneumonia was the predominant clinical syndrome (72.8%), while 22% of cases were among hemato/oncology patients. Crude 28-day mortality rate was 54.8%, even though, 14-day clinical and microbiological response was 96%. Age, APACHE II on ICU admission, hemato-oncologic disease, and multi-organ failure were initially identified as potential predictors of mortality. In the multivariable analysis, only increasing age and hemato-oncologic disease were shown to be independent risk factors for 28-day mortality. High all-cause mortality was observed in critically ill patients with predominantly respiratory infections by S. maltophilia, despite initial clinical and laboratory response after targeted treatment. The study elucidates a potentially worrisome emerging pathogen in the ICU.

Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines

Small molecule Bruton’s tyrosine kinase (BTK) inhibitors have been developed for the treatment of various haemato-oncological diseases, and ibrutinib was approved as the first BTK inhibitor for anticancer therapy in 2013. Previous reports proved the receptor kinase human epidermal growth factor receptor 2 (HER2) to be a valid off-target kinase of ibrutinib and potentially other irreversible BTK inhibitors, as it possesses a druggable cysteine residue in the active site of the enzyme. These findings suggest ibrutinib as a candidate drug for repositioning in HER2-positive breast cancer (BCa). This subtype of breast cancer belongs to one of the most common classes of breast tumours, and its prognosis is characterized by a high rate of recurrence and tumour invasiveness. Based on their similar kinase selectivity profiles, we investigated the anticancer effect of zanubrutinib, evobrutinib, tirabrutinib and acalabrutinib in different BCa cell lines and sought to determine whether it is linked with targeting the epidermal growth factor receptor family (ERBB) pathway. We found that zanubrutinib is a potential inhibitor of the HER2 signalling pathway, displaying an antiproliferative effect in HER2-positive BCa cell lines. Zanubrutinib effectively inhibits the phosphorylation of proteins in the ERBB signalling cascade, including the downstream kinases Akt and ERK, which mediate key signals ensuring the survival and proliferation of cancer cells. We thus propose zanubrutinib as another suitable candidate for repurposing in HER2-amplified solid tumours.

Adult-onset Still’s disease

Adult-onset Still's disease (AOSD) is arare autoinflammatory disease characterized by intermittent fever and acombination of symptoms, such as an evanescent rash synchronous with fever, arthralgia/arthritis, lymphadenopathy and hepatosplenomegaly. The diagnosis is based on acharacteristic constellation of symptoms and the exclusion of infections, hemato-oncological diseases, infectious diseases and alternative rheumatological causes. The systemic inflammatory reaction is reflected by high levels of ferritin and C‑reactive protein (CRP). The pharmacological treatment concept includes glucocorticoids often in combination with methotrexate (MTX) and ciclosporine (CSA) for reduction of steroids. The interleukin 1 (IL-1) receptor antagonist anakinra, the IL-1beta antibody canakinumab or an IL‑6 receptor blockage with tocilizumab (off label for AOSD) are used where there is no response to MTX or CSA. Anakinra or canakinumab can be used as aprimary option in AOSD in cases of moderate and severe disease activity.

Higher Age (≥60 Years) Increases the Risk for Adverse Events during Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard of care for patients with hemato-oncologic diseases. This procedure is highly regulated, and a quality assurance system needs to be in place. Deviations from defined processes and outcomes are reported as adverse events (AEs: any untoward medical occurrence temporally associated with an intervention that may or may not have a causal relationship), including adverse reactions (ARs: a response to a medicinal product which is noxious and unintended). Only a few reports on AEs cover the procedure of autoHSCT from collection until infusion. Our aim was to investigate the occurrence and severity of AEs in a large data set of patients who were treated by autoHSCT. In this retrospective, observational, single-center study on 449 adult patients during the years 2016-2019, AEs occurred in 19.6% of the patients. However, only 6.0% of patients had ARs, which is a low rate compared to the percentages (13.5-56.9%) found in other studies; 25.8% of the AEs were serious and 57.5% were potentially serious. Larger leukapheresis volumes, lower numbers of collected CD34+ cells and larger transplant volumes significantly correlated with the occurrence and number of AEs. Importantly, we found more AEs in patients >60 years (see graphical abstract). By preventing potentially serious AEs of quality and procedural issues, AEs could be reduced by 36.7%. Our results provide a broad view on AEs and point out steps and parameters for the potential optimization of the autoHSCT procedure, especially in elderly patients.

Pseudomonas Bacteremia in Children: Clinical and Microbiologic Features and Risk Factors of Mortality: A Retrospective Cohort Study.

Pseudomonas bacteremia is most commonly acquired in hospital. The aim of this study was to investigate the clinical features and antibiotic susceptibility, mortality rate and risk factors of mortality in children with Pseudomonas bacteremia. A retrospective cohort study that included children 18 years of age or younger admitted to a tertiary hospital with Pseudomonas bacteremia between 2005 and 2020. A total of 196 patients with Pseudomonas bacteremia were identified. The proportional rate of Pseudomonas bacteremia was 33.9/100,000 hospital days. Underlying disease was documented in 81.1% of patients, 61% had hemato-oncological disease. Pseudomonas bacteremia was healthcare related in 180 (91.8%) episodes. Multidrug-resistant (MDR) Pseudomonas accounted for 16 (8.2%) and difficult-to-treat organism to 3 (1.5%) of all isolates. Thirty-day mortality was reported in 27 (13.8%) patients, all had Pseudomonas aeruginosa . In multivariate regression analysis, the first model showed that younger age [ P = 0.038, odds ratio (OR) = 1.095, 95% confidence interval (CI): 1.005-1.192] and inappropriate empiric antibiotic treatment ( P = 0.004, OR = 3.584, 95% CI: 1.490-8.621) were significantly associated with higher mortality. The second model also showed higher morality in younger age ( P = 0.021, OR = 1.114, 95% CI: 1.016-1.221) and MDR isolates ( P = 0.001, OR = 9.725, 95% CI: 2.486-38.039). Significant morbidity and mortality due to Pseudomonas bacteremia, but relatively lower mortality than previously published. Although young age, MDR isolates and inappropriate antibiotic treatment have been associated with increased mortality, these factors, especially with low prevalence of MDR isolates, may reflect the baseline mortality rate in vulnerable hosts with continuous contact with healthcare facilities facing such severe infection, and more efforts should be made to emphasize infection control practices to prevent such severe infection.

Heart failure as a manifestation of acute lymphoblastic leukemia

Clinically significant myocardial infiltration by blast cells is a rare occurrence in acute leukemia. Heart failure rate in children with hemato-oncological diseases is unknown. Here we report a clinical case of an 8-year-old female patient with B-cell acute lymphoblastic leukemia as well as heart failure that resolved during specific therapy for the cancer. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

The Role of TRL7/8 Agonists in Cancer Therapy, with Special Emphasis on Hematologic Malignancies.

Toll-like receptors (TLR) belong to the pattern recognition receptors (PRR). TLR7 and the closely correlated TLR8 affiliate with toll-like receptors family, are located in endosomes. They recognize single-stranded ribonucleic acid (RNA) molecules and synthetic deoxyribonucleic acid (DNA)/RNA analogs-oligoribonucleotides. TLRs are primarily expressed in hematopoietic cells. There is compiling evidence implying that TLRs also direct the formation of blood cellular components and make a contribution to the pathogenesis of certain hematopoietic malignancies. The latest research shows a positive effect of therapy with TRL agonists on the course of hemato-oncological diseases. Ligands impact activation of antigen-presenting cells which results in production of cytokines, transfer of mentioned cells to the lymphoid tissue and co-stimulatory surface molecules expression required for T-cell activation. Toll-like receptor agonists have already been used in oncology especially in the treatment of dermatological neoplastic lesions. The usage of these substances in the treatment of solid tumors is being investigated. The present review discusses the direct and indirect influence that TLR7/8 agonists, such as imiquimod, imidazoquinolines and resiquimod have on neoplastic cells and their promising role as adjuvants in anticancer vaccines.

Challenges of the Treatment with Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia – Case Presentation

We present the case of a 33-year-old male patient diagnosed with chronic phase chronic myeloid leukemia in June 2008. According to treatment protocols enforced at that time, the patient started oral treatment with imatinib 400 mg/day, reaching a major molecular response (MMR) in 18- month time. The molecular response improved over time, with an undetectable BCR-ABL1 transcript level after 36 -48 months of treatment. However, the profound molecular response did not last, requiring a switch to the second line of therapy after 75 months of imatinib. Taking nilotinib 400 mg x2/day, the patient achieved a major molecular response in 12 months, and after 18 months of treatment, the level of BCR-ABL1 became undetectable. However, two vasooclusive events occurred in 2018 – a transient left parietal ischemic stroke and a left femoral artery occlusion – and by ESMO 2017 recommendations, nilotinib treatment was interrupted. The treatment-free remission decision was made with monthly monitoring of the BCR-ABL1 transcript level, but since the 4th month of monitoring, the deep molecular response disappeared. Administration of dasatinib, the third tyrosine kinase inhibitor, resulted in a deep molecular response which currently lasted until now, during the 58 months of treatment. The presented case represents the evolution of the concept of treatment in this haemato-oncological disease during the last decade.

Identifying health research in the era of COVID-19: A scoping review.

Health improvements are considered one of the most important fields of research. Since the coronavirus disease 2019 was declared a pandemic, it might have impacted clinical and public health research in various forms. The goal of this study is to explore health research approaches in the era of coronavirus disease 2019. In this scoping review, we reviewed published medical full-text studies and identified potential areas of interest of health research in the era the coronavirus disease 2019 pandemic during the last 3 years within a higher educational setting. A bibliometric analysis was used to compare among published works. Among the 93 studies that met the inclusion criteria, most focused on mental health (n = 23; 24.7%). Twenty-one publications targeted coronavirus disease 2019 and its consequences on general health. Other studies have described hemato-oncological, cardiovascular, respiratory, and endocrinological diseases. 42 studies were cross-sectional or cohort studies and most of them published in Q1 journals. Almost half of them belonged to the Faculty of Medicine (49.5%) followed by the School of Arts, Sciences, and Psychology (26.9%). Health research has been demonstrated to be important, at all times, especially during crises. Therefore, researchers need to invest more efforts into seeking new medical updates in various health-related fields, regardless of their correlation with coronavirus disease 2019.

Prietoková cytometria v diagnostike vybraných onkologických ochorení

Flow cytometry is a versatile and fast method of cell detection. We focus on its application in oncological diseases diagnostics. We briefly describe the characteristics and functional principle of the flow cytometer and its systems, including fluorescence as an important element of this method. Next, we define the methodology, the immunophenotyping principle, and the material used in the diagnostics of oncological diseases by flow cytometry. However, the main emphasis is on presenting flow cytometry as a diagnostic method for selected hemato-oncological diseases, and its application in solid tumors diagnostics, with a specific focus on identifying the metastatic process presence associated with solid tumors by detecting significant markers of metastatic activity.

Adult-onset Still's disease : Diagnosis and treatment according to the new S2e guidelines of the German Society of Rheumatology (DGRh)

Adult-onset Still's disease (AOSD) is arare autoinflammatory disease characterized by intermittent fever and acombination of symptoms, such as an evanescent rash synchronous with fever, arthralgia/arthritis, lymphadenopathy and hepatosplenomegaly. The diagnosis is based on acharacteristic constellation of symptoms and the exclusion of infections, hemato-oncological diseases, infectious diseases and alternative rheumatological causes. The systemic inflammatory reaction is reflected by high levels of ferritin and C‑reactive protein (CRP). The pharmacological treatment concept includes glucocorticoids often in combination with methotrexate (MTX) and ciclosporine (CSA) for reduction of steroids. The interleukin 1 (IL-1) receptor antagonist anakinra, the IL-1beta antibody canakinumab or an IL‑6 receptor blockage with tocilizumab (off label for AOSD) are used where there is no response to MTX or CSA. Anakinra or canakinumab can be used as aprimary option in AOSD in cases of moderate and severe disease activity.

Rehabilitation of patients after CAR T-cell therapy. Experiences on 5 patients

ObjectiveCAR T-cell therapy is an effective treatment for various relapsed or refractory haemato-oncological diseases. However, this therapy results in significant immunosuppression that lasts for months. Whether these patients are at risk during a rehabilitation stay, e.g., due to infections, has not yet been answered. MethodsWe describe the rehabilitation stay under special hygienic conditions of the five patients rehabilitated in our clinic after CAR T-cell therapy. Complications that occurred during rehabilitation are reported, as well as the positive effects of rehabilitation on physical performance, polyneuropathic complaints, anxiety and depression, and individual limitations. ResultsOne patient reported signs of infection already at the beginning of rehabilitation. This was treated with antibiotics, and rehabilitation could be continued. No complications occurred in any of the other patients. All patients reported having benefited physically and psychologically from the rehabilitation, and two expressed the intention to return to work. ConclusionsAs far as we know, this is the first report on several patients after CAR T-cell therapy. Based on the limited data, there is no reason to withhold a rehabilitation stay from patients after CAR T-cell therapy.

Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas.

Pleomorphic dermal sarcomas (PDS) are rare neoplasms of the skin that occur in UV-exposed sites in the elderly, but represent the most common cutaneous sarcomas. Although the majority of PDS can be surgically removed, local recurrences occur in up to 28%, usually occurring within the first two years after primary excision. Metastases are diagnosed in up to 20% of cases, mainly observed in the skin, lymph nodes and lungs, preferentially affecting patients with underlying hemato-oncologic diseases. Similar to other UV-induced tumors, PDS are inflammatory and immunogenic tumors (with a high number of CD4+/CD8+ tumor-infiltrating lymphocytes (TILs) and checkpoint molecule expression such as PD-L1, LAG-3, TIGIT) with a very high mutational burden. The most common genetic alterations include UV-induced TP53 loss of function mutations, followed by alterations in the CDKN2A/B gene. Rarely, targetable genetic alterations can be detected. Compelling experimental data and clinical reports about PD-1/PD-L1-blocking antibodies in patients with PDS suggest its use as first line treatment in unresectable or metastatic tumor stages. However, individual ("off-line") patient management should be discussed in an interdisciplinary tumor board based on molecular genetic testing, mutational burden, PD-L1 expression, and evidence of tumor-infiltrating lymphocytes in addition to comorbities of the individual patient.