Hematological Patients Research Articles

Microbiological risk factors, ICU survival, and 1-year survival in hematological patients with pneumonia requiring invasive mechanical ventilation

PurposeTo identify pathogenic microorganisms and microbiological risk factors causing high morbidity and mortality in immunocompromised patients requiring invasive mechanical ventilation due to pneumonia.MethodsA retrospective single-center study was performed at the intensive care unit (ICU) of the Department of Internal Medicine at Heidelberg University Hospital (Germany) including 246 consecutive patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia from 08/2004 to 07/2016. Microbiological and radiological data were collected and statistically analyzed for risk factors for ICU and 1-year mortality.ResultsICU and 1-year mortality were 63.0% (155/246) and 81.0% (196/242), respectively. Pneumonia causing pathogens were identified in 143 (58.1%) patients, multimicrobial infections were present in 51 (20.7%) patients. Fungal, bacterial and viral pathogens were detected in 89 (36.2%), 55 (22.4%) and 41 (16.7%) patients, respectively. Human herpesviruses were concomitantly reactivated in 85 (34.6%) patients. As significant microbiological risk factors for ICU mortality probable invasive Aspergillus disease with positive serum-Galactomannan (odds ratio 3.1 (1.2-8.0), p = 0.021,) and pulmonary Cytomegalovirus reactivation at intubation (odds ratio 5.3 (1.1–26.8), p = 0.043,) were identified. 1-year mortality was not significantly associated with type of infection. Of interest, 19 patients had infections with various respiratory viruses and Aspergillus spp. superinfections and experienced high ICU and 1-year mortality of 78.9% (15/19) and 89.5% (17/19), respectively.ConclusionsPatients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia showed high ICU and 1-year mortality. Pulmonary Aspergillosis and pulmonary reactivation of Cytomegalovirus at intubation were significantly associated with negative outcome.

Prevalence of kidney disease in patients with different types of cancer or hematological malignancies: a cross-sectional study.

This study investigated the prevalence and risk factors of acute kidney injury (AKI) and chronic kidney disease (CKD) in cancer patients with the aim of providing guidance for clinical treatment of cancer patients. A retrospective study was conducted on all cancer and hematological malignancy patients admitted to Xuanwu Hospital, Capital Medical University, from January 2018 to July 2023. The study population included patients aged 18-80years with a confirmed cancer or malignancy diagnosis. Chi-square tests, Spearman's correlation, and logistic regression were used to evaluate the relationships between demographic factors, comorbidities, cancer types, antitumor drugs and the prevalence of AKI/CKD. Among the 2438 participants, the prevalence rates of AKI and CKD were 3.69% and 7.88%, respectively. Patients with diabetes had higher prevalence of AKI/CKD than those without diabetes (OR = 1.66, 95% CI 1.01-2.68, p = 0.040; OR = 1.60, 95% CI 1.10-2.31, p = 0.012, respectively). In addition, a higher prevalence of CKD was observed in patients with hypertension (OR = 3.49, 95% CI 2.43-5.06, p < 0.001). Underweight patients were more likely to develop AKI (OR = 2.66, 95% CI 1.03-6.08, p = 0.029). Anthracyclines may contribute to a higher risk of AKI, and antimetabolites and immunomodulators may be associated with the development of CKD. Overall, patients with hematological malignancies had significantly higher rates of AKI/CKD than those with solid tumors. Among solid tumor patients, the prevalence of AKI/CKD was low in patients with lung and breast cancer. AKI and CKD prevalence varies across cancer types, influenced by factors, such as diabetes, hypertension, body weight, and antitumor drugs. Tailored treatment plans are essential for improving cancer patient outcomes.

Childhood autoimmune hemolytic anemia: A scoping review.

Autoimmune hemolytic anemia (AIHA) is a rare but important cause of morbidity in pediatric hematology patients. Given its rarity, there is little high-quality evidence on which to base the investigation and management of pediatric AIHA. This scoping review aims to summarize the current evidence and highlight key gaps to inform future studies. This review searched MEDLINE and the Cochrane CENTRAL Trials Register from 2000 to November 03, 2023. Experimental and observational studies reporting AIHA diagnostic criteria, laboratory workup, or treatment/management in populations with at least 20% of patients ≤18 years were included. Forty-three studies were included, with no randomized controlled trials identified. AIHA diagnostic criteria, diagnostic tests, and treatments were highly variable. First-line treatment approaches include corticosteroids, intravenous immunoglobulin, or both. Approaches to AIHA resistance to first-line therapy were widely variable between studies, but most commonly included rituximab and/or cyclosporine. We identify a heterogenous group of observational studies into this complex, immune-mediated disorder. Standardized definitions and classifications are needed to guide collaborative efforts needed to study this rare disease. The work done by the CEREVANCE group provides an important paradigm for future studies.

Donor’s age influences outcome in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide - a single center experience

Haploidentical stem cell transplantation (haplo-SCT) using post-transplantation cyclophosphamide (post-Cy) is considered a reasonable therapeutic option for patients who lack matched donor or who urgently need transplant procedure due to high risk disease. We analyzed the results of haplo-SCT performed in years 2018–2023. Eighty one patients (46 males) at median age of 52 years underwent haplo-SCT using peripheral blood as a stem cell source in most cases. Indications included hematological malignancies (acute leukemias in 88% of cases). In 25 cases (31%) transplantation was performed in relapsed/refractory disease. Majority of patients (61%) presented with very high and high disease risk index (DRI). Conditioning regimens were as follows: nonmyeloablative − 46 cases (57%), myeloablative – in 18 (22%) and reduced intensity – 17(20%). 90% of patients engrafted. All patients received unified immunosuppressive treatment (post-Cy/TAC/MMF). Median follow-up time was 12 months The cumulative incidence of acute and chronic GVHD was 37.5% and 37.6%, respectively. Estimated 2-year overall survival (OS) was 43.1% and donor’s age was the only factor influencing survival. The 2-year progression-free survival (PFS) was 42.5%, whereas relapse incidence (RI) − 35%. The cumulative incidence of non-relapse mortality (NRM) was 44% and was mostly due to infections. Haplo-SCT is a feasible treatment option for hematological patients. Younger donor improves post-transplant survival. Strategies to reduce infection-related mortality and relapse rate remain a challenge.

Thrombosis and infections associated with PICC in onco-hematological patients, what is their relevance?

Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions. Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events. 549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy. Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.

Optimization of a home hospitalization program for hematopoietic stem cell transplantation with ehealth integration and clinical pharmacist involvement.

Home hospitalization represents an alternative to traditional hospitalization, providing comparable clinical safety for hematological patients. At-home therapies can range from the delivery of intravenous antibiotics to more complex scenarios, such as the care during the early period after hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy. Early discharge from conventional hospitalization is feasible and helps reduce hospital resources and waiting lists. The coordinated efforts of multidisciplinary teams, including hematologists, nurses, and pharmacists, ensure patient safety and continuity of care. The traditional model of home hospitalization relies on home visits and telephone consultations with physicians and nurses. However, the use of eHealth technologies, such as MY-Medula, can enhance communication and monitoring, and thereby improve patient outcomes with no additional costs. The active involvement of a clinical pharmacist in home hospitalization programs is essential, not only for the proper logistical management of the medication but also to ensure its appropriateness, optimize treatment, address queries from the team and patients, and promote adherence. In conclusion, the implementation of hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy home hospitalization programs that use both an eHealth tool and a multidisciplinary care model can optimize patient care and improve quality of life without increasing healthcare costs.

Endemic viral infections in immunocompromised hosts: Dengue, Chikungunya, Zika.

Arbovirus infections are a challenge for immunocompromised hosts who travel to or live in endemic regions or who receive organs or tissues from donors who travel or live in such areas. This review addresses Dengue (DENV), Chikungunya (CHIKV), and Zika (ZIKV) infections in hematological patients, hematopoietic cell or solid organ transplant recipients, and people with HIV (PWH). Transmission is mainly due through Aedes mosquito bite. DENV and ZIKV may also be transmitted through blood, tissues or donor grafts. Clinical manifestations are quite similar and diagnosis requires laboratory confirmation to provide appropriate management. The best diagnostic method is PCR since serology may present false negative results in immunocompromised patients, or cross-reactivity as in the case of DENV and ZIKV. There is no specific treatment for any of these infections. Educational and preventive measures are the best strategy: vector control, knowledge of the vector's habits, protection against mosquito bites, avoiding travel to endemic areas or with a current epidemic, and avoiding nonvector transmission according to local recommendations for donor deferral. Vaccination, currently only available for DENV, has not yet been studied in immunocompromised patients and is not currently recommended.

Risk of SARS-CoV-2 infection and severe COVID-19 in hematological patients who received or not pre-exposure prophylaxis with tixagevimab/cilgavimab: a target trial emulation

We emulated a hypothetical target trial in which hematological subjects cared at the University Hospital of Pisa (Italy) received or not SARS-CoV-2 prophylaxis with tixagevimab/cilgavimab. Subjects who received prophylaxis (cases) were compared to those who did not (controls). The main outcome was SARS-CoV-2 infection in the subsequent 6 months. Inverse probability weighting (IPW) was used to adjust for confounders. A multivariable analysis was performed to identify variables associated with SARS-CoV-2 infection. We recruited 462 patients: 228 received prophylaxis, 234 were controls. COVID-19 was lower in cases compared to controls (16.7% vs 24.8%, p = 0.03, after IPW 14.3% vs 24.6%, p = 0.01). On multivariable analysis, B-cell depleting therapies (HR 2.09, 95%CI 1.05-4.18, p = 0.037) were associated with increased risk of COVID-19, while tixagevimab/cilgavimab prophylaxis (HR 0.45, 95%CI 0.27-0.73, p = 0.001) and previous SARS-CoV-2 infection (HR 0.27, 95%CI 0.14-0.51, p < 0.001) were protective. In conclusion, prophylaxis with monoclonal antibodies may reduce the risk of COVID-19 in hematological patients.

Time to antibiotic administration in patients undergoing HSCT with neutropenic fever.

e19501 Background: Cytotoxic chemotherapy for hematologic malignancies may adversely affect myelopoiesis, resulting in profound neutropenia that predisposes patients to severe infections. Patients undergoing hematopoietic stem cell transplantation (HSCT) are at particularly increased risk. Neutropenia is defined by an absolute neutrophil count (ANC) &lt;500 cells/μL per complete blood count with differential. Neutropenic fever is a critical event with one-time temperature ≥101ºF or ≥100.4ºF sustained over one hour. Current standard-of-care is to initiate broad-spectrum antibacterial therapy within 30-60 minutes of presentation. MetroHealth Medical Center in Cleveland, Ohio launched a new Blood and Marrow Transplant program in 2023 in the state-of-the-art Glick Center. This retrospective study explores time to blood culture draw and initiation of antibiotics in HSCT patients with neutropenic fever. Methods: The MetroHealth HSCT database was used to identify hematologic malignancy patients status-post HSCT treated in the Blood and Marrow Transplant program. Tumor type and staging, chemo history, and infection prophylaxis (PPx) were recorded from chart review. Neutropenic fever episodes were identified by review of vitals history. Time to blood culture draw and antibiotic administration was then calculated from the medication administration record (MAR). Results: N = 11 hematologic malignancy patients status-post HSCT and chemotherapy were identified in the MetroHealth database. 8 presented with multiple myeloma (RISS stage II – IV), 2 with Hodgkin lymphoma, and 1 with mantle cell non-Hodgkin lymphoma. All patients were on Valtrex or acyclovir PPx, 10 on levofloxacin PPx, and 9 on fluconazole PPx. 6 of 11 patients had one documented episode of neutropenic fever each. ANC levels ranged from unidentifiable to 420 cells/μL. Half of the episodes saw blood culture draw within 1 hour and initiation of antibiotics in 60-90 minutes. The other 3 episodes saw culture draw at 2:13, 3:09, and 10:10 hours from fever and antibiotic administration at 12:00, 2:53, and 10:23 hours, respectively. Infectious disease (ID) specialists were consulted in each of the latter 3 cases. Conclusions: No patient at MetroHealth with neutropenic fever has seen appropriate initiation of antimicrobials within 30 to 60 minutes of presentation. Hypotheses for this delay include improper chart documentation, nurse training (delay in physician notification), and provider comfort (antimicrobials deferred to day team, ID consults). The latter is of particular concern given incidents of &gt;10 hour delay to antibiotic initiation. Fortunately, there have not been any severe morbidity or mortality outcomes yet. Next steps are to deploy a quality improvement initiative to increase speed to fever identification, blood culture draw, and empiric antimicrobial delivery.

Roginolisib, an oral, highly selective and allosteric modulator of phosphoinositide 3-kinase inhibitor delta (PI3Kδ) in patients with uveal melanoma and advanced cancers.

9597 Background: The highly selective, oral allosteric modulator of PI3Kδ, roginolisib (IOA-244), blocks the activity of PI3Kδ-dependent signaling, in both tumor cells and Tregs. Methods: Continuous daily dosing of roginolisib at 10, 20, 40 and 80 mg in patients (pts) with pretreated solid tumours and Follicular Lymphoma (FL) were evaluated (Part A). Part B consists of a dose confirmation cohort in uveal melanoma (UM) pts of 2 parts, B.1 and B.2. Primary objective: safety of the anticipated biologically effective dose (BED). Secondary objectives: PK; PD (e.g., inhibition of CD63 expression on basophils, changes in immune cell subsets in peripheral blood); RECIST 1.1 or Lugano-based responses; PFS and OS. Exploratory studies: phenotypic changes in circulating immune cells by mass cytometry (i.e., CyTOF); response assessments by radiomics; analysis of circulating protein signatures via Olink proteomics. Results: Part A Solid Tumour (completed): Sixteen pts were treated in 4 cohorts of 4 pts each. Pts characteristics: uveal melanoma (9/16; 56%), cutaneous melanoma (5/16; 31%) and pleural mesothelioma (2/16; 13%). Only Grade 1 and 2 AEs by CTCAE v.5 were observed, including 2 cases of transient (lasting &lt; 24 hrs) diarrhoea and 2 of AST/ALT elevation. Part A FL Cohort (completed): 8 pts were treated at 20 mg (n=4) and 80 mg (n=4). Grade 3 toxicities were transient and observed in 2/8 (25%) pts. 2/4 pts (50%) at the 80 mg had PR as per Lugano criteria. Treatment-emergent adverse events (TEAEs) did not result in study drug discontinuation, immune-related toxicity, or dose-limiting toxicity in either the solid tumor or hematological patients. UM pts (Part A and Part B)&gt;: 29 pts (Part A: 9 pts; Part B.1: 7 pts, Part B.2: 13 pts), of which 23 were treated at 80 mg QD (RP2D). Mean time on treatment: 10.7 mo (range: 1.5-39.6 mo). ORR (RECIST 1.1): PR: 1/29 (3%); SD: 21/29 (72%). Median OS for Part A: 20.8 mo (5/9 with 4 pts alive); Part B.1 20.1 (4/7 with 3 pts alive); Part B.2 not determined; 1-year OS rate: Part A 66.7%; Part B.1 71%; Part B.2 immature. Exploratory Investigations: At 3.7 mo (Cycle 5), there were 2 groups: one with SD (13/29; 45%) and the other with PD (16/29; 55%). At 6 mo, this split continued with 38% (11/29) showing SD and 62% having PD (18/29). Volumetric changes matched durable SDs while having higher sensitivity in the 15 analyzed patients. Interestingly, tumor burden reduction in mediastinal lymph nodes was indicative of SD and 70% of pts had volumetric spleen size reduction. Volumetric and radiomic changes were matched with peripheral changes in plasma proteins and immune cell changes. Conclusions: Roginolisib is well tolerated at 80 mg, demonstrates efficacy, and induces phenotypic changes in circulating immune cells. At the RP2D, the most robust anti-tumour activity was observed in FL (50% PR) and UM pts (3% PR; 72% SD). Clinical trial information: NCT04328844 .

Targeting exercise and sedentary behavior for the prevention of allogeneic stem cell transplant-related cardiovascular dysfunction: The ALLO-Active trial.

12018 Targeting Exercise and Sedentary Behavior to Prevent Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: The ALLO-Active Trial Background: Allogeneic stem cell transplantation (allo-SCT) is a potentially life-saving therapy for hematological malignancy, however, quality of life and longevity post allo-SCT are hampered by exercise intolerance, cardiac dysfunction, and cardiovascular mortality. This randomized controlled trial evaluated the efficacy of a novel multi-component activity program on cardiorespiratory fitness (peak oxygen uptake [VO2peak]) and cardiac function in adults undergoing allo-SCT. Methods: Sixty-two hematological malignancy patients scheduled for allo-SCT were randomized to a 4-month multi-component Activity program (n = 30) designed to increase aerobic and resistance exercise (3-day.week-1) and reduce sedentary time (≥30-min.day-1), or to usual care ( UC, n = 32). The Activity program was delivered over two distinct phases: ‘Inpatient’, which commenced upon admission for allo-SCT and continued until discharge (~4 weeks), and ‘Outpatient’,which commenced at discharge and continued for 12-weeks. Physiological assessments were conducted pre-admission, and 12-weeks post-discharge (4-months from baseline) and included: (1) cardiopulmonary exercise testing to quantify VO2peak, (2) exercise cardiac magnetic resonance imaging to determine peak cardiac output and stroke volume index (COIpeak and SVIpeak), (3) standard of care resting echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and (4) cardiac biochemistry (troponin, B-type natriuretic peptide). Results: Fifty-two patients (84%) completed follow-up (25 Activity; 27 UC), and median (IQR) intervention adherence was 73% (50-81). Activity preserved VO2peak (-0.9ml.kg-1.min-1 [95%CI -2.5, 0.8]) which showed a marked decline with UC (-3.4ml.kg-1.min-1 [95%CI -4.9, -1.8]; interaction, p= 0.029). Activity also showed significant benefits on exercise cardiac function, as shown by a preservation of COIpeak (0.30L.min-1.m2, [95%CI -0.34, 0.41]) and SVIpeak (0.6ml.m2 [95%CI -1.3, 2.5]), both of which declined with UC (COIpeak: -0.68L.min-1.m2, [95%CI -1.3, -0.32]; interaction, p= 0.008; SVIpeak: -2.7ml.m2 [95%CI -4.6, -0.9], interaction, p =0.014). There were no treatment effects of Activity on cardiac injury biomarkers or global longitudinal strain and no changes in left ventricular ejection fraction in either group. Conclusions: Intervening early in the allo-SCT process with an exercise and sedentary behavior intervention can have significant benefits for the preservation of patient’s cardiovascular reserve capacity. Our results may have important long-term implications for cardiovascular disease incidence and mortality in allo-SCT recipients. Clinical trial information: ANZCTR12619000741189.

Budget impact analysis of participating in sponsored clinical trials in cancer within the Colombian healthcare system: A real-world evidence approach.

e23031 Background: Clinical trials (CTs) are a key element in researching and developing new technologies for cancer. Assessing the economic impact of CTs and the potential savings for healthcare systems in Low- and Middle-Income Countries (LMICs) is vital to guide healthcare decision-making. This research aims to quantify the budget impact for the Colombian Health System of including hematology and oncology patients in sponsored clinical trials. Methods: This study uses real-world data (RWD) from CTIC, a high-complexity cancer center from Bogotá, Colombia. We followed the Budget Impact Analysis methodology defined by the local HTA agency using data for five tumors retrieved from an institutional data lake resource using clinical information and related costs. Tumors were selected based on their prevalence and economic burden. CTIC’s clinical experts validated the cost-generating events for each disease. The eligible population for phase 3 clinical trials was estimated from the literature and CTIC oncology units’ leaders’ opinions. Prevalent and incident population data were obtained from the Colombian High-Cost Account (CAC). Results: There are 7,703 potential patients to be included in CTs, representing a total cost of 217,544,023 for 2023 USD (1 USD = 4,325 COP). If at least 25% of patients with these tumors were included in CTs in 2023, the approximate cost would be 54,386,006 USD. Advanced prostate cancer represented the highest cost, given its prevalence and CT inclusion opportunity. Conclusions: With approximately USD 24 billion spent on healthcare (USD 5 billion in drugs), Colombia could save around 4% of its drug expenditure if all potential candidates were to be included in cancer CTs. Furthermore, assuming similar average costs per patient, inclusion rates, and population growth for 5-years, this could represent savings of around USD 1.1 billion. These savings would ease the reimbursement and access to innovation for Colombian patients, improving health outcomes and enhancing long-term financial sustainability. [Table: see text]

Retrospective analysis of the effects of impacted third molar on hematologic patients undergoing hematopoietic stem cell transplantation

ObjectiveThis study aimed to investigate the incidence, treatment status, and impact position of impacted third molars (ITM) and their effects on patients undergoing hematopoietic stem cell transplantation (HSCT). MethodsA retrospective analysis was conducted on the medical records of 454 patients who underwent HSCT, out of which 188 patients had ITM. The presence of ITM and its association with transplant-related infections and complications were recorded and analyzed. ResultsPatients with ITM were significantly younger. The number of mandibular ITM was notably higher than maxillary ones, and the risk of pericoronitis in mandibular ITM was significantly higher than in maxillary ones. Out of 311 ITM in 188 patients, 25 were extracted before transplantation. The proportion of extraction and treatment for ITM with pericoronitis or caries was significantly higher than that for ITM without such problems. Moreover, patients with a history of pre-transplant pericoronitis had a significantly higher probability of developing tooth-related complications during transplantation, caused by pericoronitis in ITM compared to patients without a history of pericoronitis. ConclusionPre-transplant examination and treatment of ITM are essential, especially in cases with a history of pericoronitis. Oral intervention can significantly reduce the occurrence of tooth-related complications related to ITM during transplantation.

Real world data of safety of immune-checkpoint inhibitors in patient with cancer at tertiary care hospital in Saudi Arabia.

e24104 Background: Immune checkpoint inhibitors (ICIs) become an integral part of many cancer therapies, such as melanoma, esophageal carcinoma, breast cancer and other malignancies. Immune checkpoint inhibitors work by activation the immune system that blocks negative regulators expressed on immune or tumor cells. Accordingly, the mechanism of action of ICI may cause autoimmunity-like symptoms called immune-related adverse events (irAEs) that affect many organs in body like skin, liver, lung, endocrine and gastrointestinal tract. These irAEs may reduce the organ function, quality of life and it may cause death. The present work addressed the knowledge gap in understanding real-world outcomes of irAEs associated with ICIs. Real-world patients are more diverse than clinical trial. Methods: This retrospective cohort study investigated the use of immune checkpoint inhibitor (ICI) therapy in an oncology and hematology patients treated at King Fahad Medical City (KFMC) comprehensive cancer center between February 2021 and February 2023. Adult patients (≥ 18 years old) diagnosed with any malignancy or hematological disorder who received at least one dose of ICI therapy during the study period have been included. Patients younger than 18 years old have been excluded. Demographic, clinical, and treatment data have been extracted from the electronic medical records (EMR). The study protocol has been reviewed and approved by the KFMC Institutional Review Board (IRB). The trial still undergoing not yet finished. Results: A total of 44 patients were included by the time preliminary data analysis was conducted on January 1st, 2024. All Patient included were receiving Pembrolizumab 44 patients. In regards to demographics, 27 (61.4%) of the patients were female. Breast cancer was the most common diagnosis (34.1%), followed by non-small cell lung cancer (22.7%). Among patients undergoing ICI, 34.1% had at least one Emergency Room (ER) visit. Notably, 25% of these patients had 1-2 ER visits. The most common reason for ER visits was patient complaints of GI toxicity related to ICI, including nausea, vomiting, and diarrhea (colitis). 12 (26.8%) patients required hospitalization, and 9 (20.5%) stayed for more than seven days.The time to first adverse event of ICI therapy was most commonly seen after nine weeks in 8 (18.2%) patients. Hypothyroidism was the most common adverse event (11.4%), followed by gastrointestinal toxicity (6.8%). Skin, grade 2 hepatotoxicity, and renal toxicity were also reported in 1 (2.3%) patient respectively. Conclusions: Overall, this initial analysis suggests that while ICI known to offers promising potential, it also carries the risk of various adverse events, including a significant rate of ER visits and hospitalizations. Further investigation with larger patient cohorts is warranted to confirm these findings and optimize IO therapy management.

The study design and methodology of antibiotic duration in hematological patients with pseudomonas aeruginosa bloodstream infection.

The study design and methodology of antibiotic duration in hematological patients with pseudomonas aeruginosa bloodstream infection.

Malnutrition and cachexia are associated with poor CAR T-cell therapy outcomes including survival

Background & AimsChimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for patients with refractory or relapsed B-cell malignancies. However, a significant proportion of patients experience negative outcomes, including severe inflammatory toxicities and relapse. Cachexia and malnutrition are known secondary syndromes in many cancer patients, attributed to the effects of active malignancy, systemic inflammation, and cumulative treatment burden; however, further research is required to accurately characterise these issues in CAR T-cell patients. The aims of this service evaluation were to explore the changes in nutritional status (malnutrition and cachexia) in CAR T-cell therapy patients and the potential impact on patient outcomes including survival. Additionally, we describe the utilisation of dietetic resources in this specific patient population in a London tertiary referral centre. MethodsAdult haematology patients receiving licensed CD19-targeting CAR T-cell therapy at University College London Hospital between 01/04/19 and 01/09/21 were included. Data were collected from the time of treatment consent, and throughout admission to day of discharge: body weight (BW), C-reactive protein, albumin, lactate dehydrogenase, nutrition-risk screening scores (hospital-specific) and dietetic input. Clinical outcomes such as 12-month all-cause mortality, intensive care unit (ICU) admission, high-grade toxicities, and length of hospital stay (LoS) were also recorded. Cachexia and malnutrition were defined using the modified Glasgow Prognostic Score (mGPS) and Global Leadership Initiative on Malnutrition (GLIM) consensus, respectively. Results114 patients (55.6±15.1 years; 57% males) with B-cell non-Hodgkin’s lymphoma (n=109) and B-cell acute lymphoblastic leukaemia (n=5), receiving axicabtagene ciloleucel (n=89) and tisagenlecleucel (n=25) were included. Median LoS for treatment was 34 (27-38) days. Prior to treatment, 31.5% of patients developed malnutrition, with pre-cachexia/refractory cachexia (mGPS) identified in 43.6% of patients. This altered nutritional status pre-treatment was significantly associated with adverse patient outcomes post-infusion; mGPS was independently associated with inferior overall survival (HR=3.158, CI=1.36-7.323, p=0.007), with malnutrition and mGPS associated with increased LoS (p=0.037), sepsis (p=0.022) and ICU admission (p=0.039). During admission, patients experienced significant BW loss (-5.6% (-8.8 to -2.4); p=<0.001), with 68.4% developing malnutrition. Malnutrition screening during admission identified 57% patients at-risk, with 66.6% of patients referred to dietetics; however, there was a lack of malnutrition screening and dietetic referrals prior to treatment. ConclusionPre-treatment malnutrition and cachexia was significantly associated with adverse CAR T patient outcomes, including mGPS cachexia status independently associated with inferior overall survival. Further research in this novel space is essential to confirm the extent and impact of nutritional issues, to assist with implementing dietetic pathways, and to identify potential interventions with a view to optimising outcomes.

Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona, Spain

ObjectivesWe aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months.MethodsProspective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation.ResultsFour cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles.ConclusionWe have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.

Development and Validation of a Prediction Model for 1-Year Mortality in Patients With a Hematologic Malignancy Admitted to the ICU.

To develop and validate a prediction model for 1-year mortality in patients with a hematologic malignancy acutely admitted to the ICU. A retrospective cohort study. Five university hospitals in the Netherlands between 2002 and 2015. A total of 1097 consecutive patients with a hematologic malignancy were acutely admitted to the ICU for at least 24 h. None. We created a 13-variable model from 22 potential predictors. Key predictors included active disease, age, previous hematopoietic stem cell transplantation, mechanical ventilation, lowest platelet count, acute kidney injury, maximum heart rate, and type of malignancy. A bootstrap procedure reduced overfitting and improved the model's generalizability. This involved estimating the optimism in the initial model and shrinking the regression coefficients accordingly in the final model. We assessed performance using internal-external cross-validation by center and compared it with the Acute Physiology and Chronic Health Evaluation II model. Additionally, we evaluated clinical usefulness through decision curve analysis. The overall 1-year mortality rate observed in the study was 62% (95% CI, 59-65). Our 13-variable prediction model demonstrated acceptable calibration and discrimination at internal-external validation across centers (C-statistic 0.70; 95% CI, 0.63-0.77), outperforming the Acute Physiology and Chronic Health Evaluation II model (C-statistic 0.61; 95% CI, 0.57-0.65). Decision curve analysis indicated overall net benefit within a clinically relevant threshold probability range of 60-100% predicted 1-year mortality. Our newly developed 13-variable prediction model predicts 1-year mortality in hematologic malignancy patients admitted to the ICU more accurately than the Acute Physiology and Chronic Health Evaluation II model. This model may aid in shared decision-making regarding the continuation of ICU care and end-of-life considerations.

Performance of the Roche Elecsys® IGRA SARS-CoV-2 test for the detection and quantification of virus-reactive T cells in COVID-19-vaccinated immunosuppressed patients and healthy subjects

PurposeComparing the performance of commercially available SARS-CoV-2 T-cell immunoassay responses may provide useful information for future observational or intervention studies as well as to their potential customers.MethodWhole blood was collected from a total of 183 subjects fully vaccinated against COVID-19: 55 healthy controls (Group 1), 50 hematological patients (Group 2), 50 chronic kidney disease patients (Group 3), and 28 elderly nursing home residents (Group 4). Samples were tested with the Roche Elecsys® IGRA (Interferon-gamma release assay) SARS-CoV-2 test (Roche Diagnostics, Rotkreuz, Switzerland), the Euroimmun SARS-CoV-2 test (Euroimmun, Lubeck, Germany), the SARS-CoV-2 T Cell Analysis Kit (Miltenyi Biotec, Bergisch Gladbach, Germany), and a flow-cytometry for intracellular cytokine (IFN-γ) staining-based immunoassay (FC-ICS).ResultsOverall, the Roche Elecsys® assay returned the highest number of positive results (151/179; 84.3%), followed by the Euroimmun test (127/183; 69%), and the FC-ICS (135/179; 75%). The Kappa coefficient of agreement was best between IGRAs (0.64). Most discordant results across assays involved patients from Group 2. Overall, IFN-γ concentrations measured by both IGRAs correlated strongly (rho = 0.78; 95% CI 0.71–0.84; P < 0.001) irrespective of the study group. The frequencies of SARS-CoV-2-reactive IFN-γ T cells and IFN-γ concentrations measured by the IGRAs correlated moderately for CD4+ T cells, however, weakly for CD8+ T cells. SARS-CoV-2-experienced participants displayed stronger responses than SARS-CoV-2-naïve when IGRAs, rather than FC-ICS, were used.ConclusionThe SARS-CoV-2 immunoassays evaluated in the present study did not return interchangeable qualitative or quantitative results either in seemingly healthy individuals or in immunosuppressed patients.

Antifungal Prophylaxis and Treatment of Breakthrough Invasive Fungal Diseases in High-Risk Hematology Patients: A Prospective Observational Multicenter Study

Antifungal Prophylaxis and Treatment of Breakthrough Invasive Fungal Diseases in High-Risk Hematology Patients: A Prospective Observational Multicenter Study