Critical care management of chimeric antigen receptor T-cell therapy recipients.

Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapeutic treatment concept that is changing the treatment approach to hematologic malignancies. The development of CAR T-cell therapy represents a prime example for the successful bench-to-bedside translation of advances in immunology and cellular therapy into clinical practice. The currently available CAR T-cell products have shown high response rates and long-term remissions in patients with relapsed/refractory acute lymphoblastic leukemia and relapsed/refractory lymphoma. However, CAR T-cell therapy can induce severe life-threatening toxicities such as cytokine release syndrome, neurotoxicity, or infection, which require rapid and aggressive medical treatment in the intensive care unit setting. In this review, the authors provide an overview of the state-of-the-art in the clinical management of severe life-threatening events in CAR T-cell recipients. Furthermore, key challenges that have to be overcome to maximize the safety of CAR T cells are discussed.

Marked hyperferritinemia in critically ill cancer patients.

OBJECTIVES: To investigate characteristics and outcomes of critically ill cancer patients with marked hyperferritinemia. METHODS: A single-center retrospective analysis comprising cancer patients with a ferritin level >10.000 µg/L treated in the intensive care unit (ICU) between 2012 and 2022 was conducted. RESULTS: A total of 117 patients were included in the analysis. The median age was 59 years (range: 15-86 years). Females accounted for 48% of cases. 90% of patients had a hematologic malignancy. The median maximum ferritin level was 27.349 µg/L (range: 10.300-426.073 µg/L). The diagnostic criteria of septic shock were fulfilled in 51% of cases; 31% of patients had hemophagocytic lymphohistiocytosis (HLH) according to the HLH-2004 criteria. Mechanical ventilation, renal replacement therapy and the use of vasopressors were necessary in 59%, 35% and 70% of cases, respectively. The ICU, hospital, 90-day and 1-year survival rates were 33.3%, 23.1%, 23.7% and 11.7%. Patients with septic shock had a worse survival than those without septic shock (p = .001); the survival of patients who fulfilled the HLH-2004 criteria did not differ from those who did not (p = .88). CONCLUSION: Critically ill cancer patients with marked hyperferritinemia have poor outcomes. The present data may help to make informed decisions for this patient group.

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

Characteristics and outcomes of patients undergoing high-dose chemotherapy and autologous stem cell transplantation admitted to the intensive care unit: a single-center retrospective analysis.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) can be associated with adverse events necessitating treatment on the intensive care unit (ICU). Data focusing on patients admitted to the ICU during hospitalization for high-dose chemotherapy and ASCT are scarce. We thus conducted a single-center retrospective analysis comprising 79 individuals who had high-dose chemotherapy and ASCT between 2014 and 2020 and were admitted to the ICU between the initiation of conditioning therapy and day 30 after ASCT. The median age was 57 years (range: 20-82 years); 38% of patients were female. B-cell non-Hodgkin lymphoma (34%) and plasma cell disorders (28%) were the most common indications for high-dose chemotherapy and ASCT. Sepsis represented the major cause for ICU admission (68%). Twenty-nine percent of patients required mechanical ventilation (MV), 5% had renal replacement therapy, and 44% needed vasopressors. The ICU, hospital, 90-day, and 1-year survival rates were 77.2%, 77.2%, 72.2%, and 60.3%, respectively. Stable disease or disease progression prior to the initiation of high-dose chemotherapy (p = 0.0028) and MV (p < 0.0001) were associated with an impaired survival. A total of 36 patients died during observation. The most frequent causes of death were the underlying malignancy (44%) and sepsis (39%). Taken together, the present analysis indicates a favorable overall outcome for patients admitted to the ICU during hospitalization for high-dose chemotherapy and ASCT. Thus, this patient group should not be denied admission and treatment on the ICU.

Chlorhexidine gluconate-coated gel pad dressings for prevention of central venous catheter-related bloodstream infections in patients with hematologic diseases or autologous stem cell transplantation: A registry-based matched-pair analysis.

OBJECTIVES: Chlorhexidine gluconate (CHG)-coated gel pad dressings for central venous catheter (CVC) may prevent CVC-related bloodstream infections (CRBSI). However, real-world data showing beneficial effects in patients with hematologic malignancies are scarce. METHODS: In a matched-pair analysis with data from a multicenter CVC registry, non-tunneled jugular and subclavian vein CVC in adults with hematologic malignancies or germ cell tumors (including patients receiving autologous hematopoietic stem cell transplantation [ASCT]) with CHG were compared with non-CHG dressings. The primary endpoint was definite CRBSI rate within 14 days (dCRBSI14) of CVC insertion; secondary endpoints were combined rate of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), and CRBSI incidences of all estimates. RESULTS: In total, 2070 CVCs were assessed. There was no statistically significant difference in dCRBSI14 (2.3% vs. 3.5%) between patients with and without CHG gel dressings. Likewise, with regards to dpCRBSI14 (6.2% vs. 6.3%) and the overall dpCRBSI rate (9.2% vs. 10.5%), no significant difference was detected. Furthermore, dCRBSI14 incidence (2.0 vs. 3.2/1000 CVC days), dpCRBSI14 incidence (5.4 vs. 5.6/1000 CVC days), and overall CRBSI incidence (5.5 vs. 6.0/1000 CVC days) showed no significant differences. CONCLUSIONS: CRBSI rates were not reduced by the use of CHG gel dressings in patients with hematologic malignancies and/or ASCT.

Botulism after intragastric botulinum toxin injections for weight reduction.

Although-considering the risk-benefit ratio-botulinum neurotoxin A (BoNT/A) is unequivocally recommended to treat severe neurological diseases such as dystonia, this has not yet been determined for its endoscopic intragastric injection aimed at weight reduction in obesity. However, severe adverse effects of intragastric BoNT/A had not yet been reported, prompting some European countries to endorse its (off-label) use and treat patients transnationally. We here present three cases of botulism after intragastric BoNT/A injections for obesity treatment in a Turkish hospital. Patients presented with cranial nerve affection, bulbar symptoms, and descending paresis, and benefited from treatment with BoNT antitoxin and pyridostigmine. We assume that iatrogenic botulism was induced by overdosing in combination with toxin spread via the highly vascularized gastric tissue. Of note, within a few weeks, more than 80 cases of iatrogenic botulism were reported across Europe after identical intragastric BoNT/A injections. These cases demonstrate the risks of BoNT/A injections if they are not applied within the limits of evidence-based medicine. There is a need for international guidelines to define the indication and a safe dosing scheme, especially in the context of medical tourism.

Critical care of patients with cancer.

Answer questions and earn CME/CNE The increasing prevalence of patients living with cancer in conjunction with the rapid progress in cancer therapy will lead to a growing number of patients with cancer who will require intensive care treatment. Fortunately, the development of more effective oncologic therapies, advances in critical care, and improvements in patient selection have led to an increased survival of critically ill patients with cancer. As a consequence, critical care has become an important cornerstone in the continuum of modern cancer care. Although, in many aspects, critical care for patients with cancer does not differ from intensive care for other seriously ill patients, there are several challenging issues that are unique to this patient population and require special knowledge and skills. The optimal management of critically ill patients with cancer necessitates expertise in oncology, critical care, and palliative medicine. Cancer specialists therefore have to be familiar with key principles of intensive care for critically ill patients with cancer. This review provides an overview of the state-of-the-art in the individualized management of critically ill patients with cancer. CA Cancer J Clin 2016;66:496-517. © 2016 American Cancer Society.

Impact of the insertion site of central venous catheters on central venous catheter-related bloodstream infections in patients with cancer: results from a large prospective registry.

PURPOSE: Overall, insertion of central venous catheter (CVC) into femoral veins (FV) has been shown to be associated with a higher risk of infection compared with subclavian and internal jugular (IJV/SCV) CVC, but no data are available on the impact of the FV insertion site on the CVC-related bloodstream infections (CRBSI) risk in patients with cancer. The objective of the study is to compare CRBSI rates and incidences of FV with those of internal jugular and subclavian vein (IJV/SCV CVC) as observed in the prospective SECRECY registry. METHODS: SECRECY is an ongoing observational, prospective, clinical CRBSI registry active in six departments of hematology/oncology in Germany. Each case of FV CVC was matched at a ratio of 1:1 to a case with IJV/SCV CVC. The propensity score was estimated using a multivariable logistic regression model adjusting for age, sex, cancer type, and duration of indwelling catheter. RESULTS: Of 4268 CVCs included in this analysis, 52 (1.2%) were inserted into the FV and 4216 (98.8%) into the IJV/SCV. 52 cases of FV CVC were matched with 52 IJV/SCV CVC. There was no significant difference in the CRBSI rate (3.8% vs. 9.6%), the CRBSI incidence (5.7 vs. 14.2/1000 CVC days), and the median CVC time (5.5 vs. 5 days) between the FV and the IJV/SCV group. CONCLUSION: Based on this data, inserting FV CVCs in patients with cancer does, at least in the short-term, not appear to be associated with an increased risk of CRBSI as compared to IJV/SCV CVC.

Reinduction therapy with everolimus in combination with dexamethasone, high-dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD-R3i).

Reinduction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second-line standard of care for transplant-eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high-dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant-eligible patients aged 18-60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase-I-part) was administered on day 0-13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end-point of computed tomography (CT)-based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT-based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end-point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy.

Scheduled removal of central venous catheters (CVC) to prevent CVC-related bloodstream infections in patients with hematological disease or autologous stem cell transplantation: a registry-based randomized simulation-study.

Although not generally recommended, scheduled central venous catheter (CVC) removal is sometimes carried out in order to reduce the CVC-related bloodstream infection (CRBSI) incidence. We conducted a simulation for scheduled CVC removal within the multicenter CRBSI registry (SECRECY). Non-tunneled jugular and subclavian CVC in patients with hematological disease or with germ cell tumors (including patients receiving autologous stem cell transplantation [SCT]) were included. Cases were randomized in a 1:1:1:1 ratio to either a simulated, scheduled CVC removal after 7, 14, and 21 days, or to non-simulated, unscheduled CVC removal (control group). The primary endpoint was definitive CRBSI incidence for a scheduled CVC removal after 14 days (dCRBSI-D14rmv). Among other, secondary endpoints were definite CRBSI incidence for a scheduled removal after 7 days (dCRBSI-D7rmv) and 21 days (dCRBSI-D21rmv). Data on 2984 CVC were included. Patients' median age was 59 (range 16-95) years, 58.8% being male. The vast majority (98.4%) were patients with hematological malignancies. Jugular veins were the main insertion site (93.2%). dCRBSI-D14rmv was 3.10/1000 CVC days as compared to 4.15/1000 CVC days in the control group (p = 0.23). There was a significant difference between dCRBSI-D7rmv (0.86/1000 CVC days) and controls (p < 0.001), but not between dCRBSI-D21rmv (4.10/1000 CVC days) and controls (p = 0.96). Our data suggest that in patients with hematological diseases or autologous SCT recipients scheduled CVC removal after 14 days does not result in a lower CRBSI incidence compared to unscheduled removal.Trial registration: DRKS00006551, 2014/09/29, retrospectively registered.

Allogeneic stem cell transplant recipients admitted to the intensive care unit during the peri-transplant period have unfavorable outcomes-results of a retrospective analysis from a German university hospital.

The prognosis of allogeneic stem cell transplant recipients admitted to the intensive care unit (ICU) has improved over the last decades. However, data focusing on patients treated in the ICU during the peri-transplant period are scarce. We therefore conducted an analysis comprising 70 patients who had allogeneic stem cell transplantation at the University Hospital Cologne between 2014 and 2020 and were admitted to the ICU between the initiation of conditioning therapy and day 30 after transplantation. The median age was 59 years (range: 18 - 72 years). 50% of patients were female. Sepsis was the most common cause for ICU admission (49%). Mechanical ventilation (MV) was required in 56% of patients, 27% had renal replacement therapy (RRT), and 64% needed vasopressors. The ICU, hospital, 90-day, and 1-year survival rates were 48.6%, 38.6%, 35.7%, and 16.2%, respectively. MV and/or RRT during the ICU stay were associated with an impaired survival (p < 0.0001). The same was true for the use of vasopressors (p < 0.0001). In contrast, baseline characteristics did not impact the outcome. Cardiopulmonary resuscitation (CPR) was performed in 17% of patients. None of the patients undergoing CPR was alive at 1 year. Among patients who died after discharge from the ICU (n = 23), sepsis and other infectious complications represented the major causes of death (48%). Taken together, the present analysis indicates unfavorable outcomes for allogeneic stem cell transplant recipients admitted to the ICU during the peri-transplant period. The data may help to make informed decisions with patients and their families.

JAK inhibition with ruxolitinib in relapsed or refractory classical Hodgkin lymphoma: Final results of a phase II, open label, multicentre clinical trial (JeRiCHO).

OBJECTIVES: Patients with classical Hodgkin lymphoma (cHL) relapsing after second-line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre-)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL). METHODS: Patients ≥18 years with histologically confirmed r/r cHL who failed second-line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28-day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT-based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression-free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2-stage phase 2 design (Simon 1989). RESULTS: Among the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1-year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported. CONCLUSION: Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1.

Reactivation of EBV and CMV in Severe COVID-19-Epiphenomena or Trigger of Hyperinflammation in Need of Treatment? A Large Case Series of Critically ill Patients.

BACKGROUND: Reactivation of viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are common in critically ill patients and have been described in patients with severe COVID-19. However, it is unclear whether these reactivations are associated with increased mortality and whether targeted treatments are beneficial. METHODS: In a retrospective single-center cohort study, patients with severe COVID-19 treated on our intensive care unit (ICU) were screened for EBV and CMV reactivation as detected by polymerase chain reaction. If present, patient characteristics, temporal connections to severe acute respiratory syndrome coronavirus 2 diagnosis and corticosteroid use, the use of targeted treatments as well as the course of disease and outcome were analyzed. As control group, non-COVID-19 patients with sepsis, treated within the same time period on our ICU, served as control group to compare incidences of viral reactivation. RESULTS: In 19 (16%) of 117 patients with severe COVID-19 treated on our ICU EBV reactivations were identified, comparable 18 (14%) of 126 in the non-COVID-19 control group (P = .672). Similarly, in 11 (9%) of 117 patients CMV reactivations were identified, comparable to the 16 (13%) of 126 in the non-COVID-19 sepsis patients (P = .296). The majority of EBV (58%) and CMV reactivations (55%) were detected in patients under systemic corticosteroid treatment. 7 (37%) of 19 patients with EBV reactivation survived the ICU stay, 2 (29%) of 7 patients with rituximab treatment and 5 (42%) of 12 patients without treatment (P = .568). Five (50%) of 10 patients with CMV reactivation survived the ICU stay, 5 (83%) of 6 patients with ganciclovir treatment and 0 of 4 patients without treatment (P = .048). Follow-up analysis in these patients showed that the initiation of treatment lead to decrease in viral load. CONCLUSION: Critically ill patients with COVID-19 are at a high risk for EBV and CMV reactivations. Whether these reactivations are a cause of hyperinflammation and require targeted treatment remains uncertain. However, in patients with clinical deterioration or signs of hyperinflammation targeted treatment might be beneficial and warrants further studying.

Non-Hodgkin lymphoma after treatment for classical Hodgkin lymphoma: a report from the German Hodgkin Study Group.

Data on non-Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first-line treatment within the randomized German Hodgkin Study Group (GHSG) HD7-HD15 studies. After a median follow-up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five-year event-free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death.

Central venous catheter-related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter-related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.

Adequate anticoagulation and ECMO therapy in COVID-19 patients with severe pulmonary embolism.

SARS-CoV-2 (COVID-19) infections have been recently shown to be associated with a high rate of thromboembolic events due to pro-coagulative mechanisms that have not yet been fully understood. This paper reports on a 55-year-old female COVID-19 patient with severe ARDS and pulmonary embolism (PE) complicated by cardiogenic shock after 12 days of hospitalization under initial prophylactic anticoagulation with low molecular weight heparin (LMWH). An ultima-ratio va (veno-arterial) ECMO implantation and subsequent rapid upgrade to vvaECMO due to insufficient oxygenation was performed. The patient developed severe coagulopathy with intrapulmonary bleeding. The present report aims to highlight and discuss the pros and cons of various anticoagulation strategies in COVID-19 patients focusing on current scientific debates to address this frequently observed complication in the current situation worldwide.

[Toxicity after chimeric antigen receptor T-cell therapy : Overview and management of early and late onset side effects]. / Toxizitäten nach Chimärer-Antigenrezeptor-T-Zell-Therapie : Übersicht und Management früher und verzögerter Nebenwirkungen.

BACKGROUND: The transfusion of chimeric antigen receptor (CAR) T­cells has become established as a new treatment option in oncology; however, this is regularly associated with immune-mediated side effects, which can also run a severe course and necessitate a specific treatment and intensive medical treatment. MATERIAL AND METHODS: A literature review was carried out on CAR T-cell therapy, toxicities and the management of side effects. RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) regularly occur shortly after CAR T-cell treatment. The symptoms of CRS can range from mild flu-like symptoms to multiorgan failure. In addition to mild symptoms, such as disorientation and aphasia, ICANS can also lead to convulsive seizures and brain edema. The management of CRS and ICANS is based on the severity according to the grading of the American Society for Transplantation and Cellular Therapy (ASTCT). Tocilizumab and corticosteroids are recommended for CRS and corticosteroids are used for ICANS. In the further course persisting hypogammaglobulinemia and cytopenia are frequent even months after the initial treatment and promote infections even months after CAR T­cell therapy. DISCUSSION: Potentially severe complications regularly occur after CAR T-cell therapy. An interdisciplinary cooperation between intensive care physicians, hematologists, neurologists and specialists in other disciplines is of decisive importance for the optimal care of patients after CAR T­cell therapy.

Relapsed and refractory nodular lymphocyte-predominant Hodgkin lymphoma: an analysis from the German Hodgkin Study Group.

The optimal treatment of patients with relapsed or refractory nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is ill defined. To shed more light on treatment options and outcome, we performed an analysis using the database of the German Hodgkin Study Group (GHSG). Ninety-nine patients who had received first-line treatment within 12 prospective GHSG studies conducted between 1993 and 2009, and subsequently developed disease recurrence (n = 91) or had primary disease progression (n = 8), were included. At initial NLPHL diagnosis, the median age was 40 years and 76% of patients were male. First-line treatment consisted of radiotherapy (RT) alone (20%), chemotherapy with or without RT (74%), and the anti-CD20 antibody (Ab) rituximab (6%), respectively. The median follow-up from initial diagnosis was 11.2 years. The median time to disease recurrence was 3.7 years. The applied salvage approaches included single-agent anti-CD20 Ab treatment or RT alone (37%), conventional chemotherapy (CT) with or without anti-CD20 Ab treatment with or without RT (27%) and high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) (31%). No salvage treatment was given in 4% of patients. The 5-year progression-free survival and overall survival estimates after NLPHL recurrence were 75.6% and 89.5% (74.1% and 97.2% after single-agent anti-CD20 Ab treatment or RT alone; 68.0% and 77.8% after CT with or without anti-CD20 Ab treatment with or without RT; 84.6% and 89.8% after HDCT and ASCT). Hence, patients with relapsed or refractory NLPHL had a good overall prognosis. Factors such as time to disease recurrence and previous treatment may guide the choice of the optimal salvage approach for the individual patient.

COVID-19 complicated by parainfluenza co-infection in a patient with chronic lymphocytic leukemia.

The number of people suffering from the new coronavirus SARS-CoV-2 continues to rise. In SARS-CoV-2, superinfection with bacteria or fungi seems to be associated with increased mortality. The role of co-infections with respiratory viral pathogens has not yet been clarified. Here, we report the course of COVID-19 in a CLL patient with secondary immunodeficiency and viral co-infection with parainfluenza.

Clostridioides difficile infections in the intensive care unit: a monocentric cohort study.

INTRODUCTION: Patient-level data from Clostridioides difficile infections (CDI) treated in an intensive care setting is limited, despite the growing medical and financial burden of CDI. METHODS: We retrospectively analyzed data from 100 medical intensive care unit patients at the University Hospital Cologne with respect to demography, diagnostics, severity scores, treatment, and outcome. To analyze factors influencing response to treatment and death, a backward-stepwise multiple logistic regression model was applied. RESULTS: Patients had significant comorbidities including 26% being immunocompromised. The mean Charlson Comorbidity Index was 6.3 (10-year survival rate of 2.25%). At the time of diagnosis, the APACHE II was 17.4±6.3 (predicted mortality rate of 25%), and the ATLAS score was 5.2±1.9 (predicted cure rate of 75%). Overall, 47% of CDI cases were severe, 35% were complicated, and 23% were both. At least one concomitant antibiotic was given to 74% of patients. The cure rate after 10 and 90 days was 56% and 51%, respectively. Each unit increment in APACHE II score was associated with poorer treatment response (OR 0.931; 95% CI 0.872-0.995; p = 0.034). Age above 65 years was associated with death (OR 2.533; 95% CI 1.031-6.221; p = 0.043), and overall mortality at 90 days was 56%. CONCLUSIONS: CDI affects a high-risk population, in whom predictive scoring tools are not accurate, and outcomes are poor despite intensive treatment. Further research in this field is warranted to improve prediction scoring and patient outcomes.