Hematologic Stem Cell Transplantation Research Articles

The psychological effects of protective isolation on haematological stem cell transplant patients: an integrative, descriptive review.

Protective isolation is used during haematopoietic stem cell transplantation (HSCT) to protect patients at increased risk of infection. However, it is suggested that the intensity of strict isolation conditions combined with intense treatments can impact patients psychologically. This review explored the psychological effect of protective isolation on HSCT patients. CINAHL, MEDLINE, and ASSIA databases were used to search for qualitative research undertaken between 2016 and 2023. Quality was appraised using the CASP tool and thematic analysis was utilised to identify themes using Thomas and Harden as a guiding framework. Five papers were included and demonstrated that being in protective isolation during HSCT hospitalisation and after discharge created a feeling of disconnection from others and society, and that long periods of contemplation and a feeling of loss of control led to negative psychological impacts. All included papers found that patients experienced a range of negative emotional states during their time in protective isolation. Psychological health management is an important part of holistic patient care. Patients who experience HSCT report considerable negative psychological effects from the need for protective isolation. Interventions and strategies to improve this are slow to be developed and have not received the necessary focus in recent years. Critically, to maximise the patient experience and provide the best care possible, interventions are urgently required to minimise the longer-term psychological impact of HSCT in this patient group to contribute to maximising quality of life post-HSCT.

P-1759. Antibiotic De-Escalation in Neutropenic Fever

Abstract Background Cancer patients with neutropenic fever are frequently continued on broad-spectrum empiric antimicrobial therapy (EAT) until neutrophil recovery, but recent randomized trials demonstrate that EAT de-escalation prior to neutrophil recovery is safe in certain subgroups. We evaluated outcomes of EAT de-escalation based on clinical criteria in patients with neutropenic fever at our institution. Methods We retrospectively reviewed charts of 49 patients with acute myeloid leukemia (AML) or hematologic stem cell transplantation (HSCT) and neutropenic fever following revisions to Standard of Practice (SOP) institutional guidelines (hereafter “SOP” group) allowing for antibiotic de-escalation using a clinical approach in comparison to a historic cohort of 60 patients. The revised SOP recommended antibiotic de-escalation to levofloxacin prophylaxis in patients who received ≥ 72 hours of EAT, were afebrile and clinically stable for 48 hours, and did not have a clinically or microbiologically documented infection. The primary endpoint was the EAT duration. Secondary end points included incidence of recurrent fever, infections, vasopressor support and/or intensive care unit (ICU) stay, and in-hospital mortality. Results Baseline characteristics were similar between both groups, with differences including a larger proportion of males in the SOP group compared to the control group (59% vs. 35%) and the primary underlying malignancy of multiple myeloma in the SOP group compared to AML in the control group. The median duration of EAT prior to de-escalation was shorter in the SOP group compared to the historic cohort (5.0 [IQR 4.0, 6.0] vs. 7.0 days [IQR 5.0, 10.2], p< 0001). There was no difference in incidence of recurrent fever (20% vs. 30%, p=0.3) or secondary infection (10% vs. 12%, p=0.8). Incidence of vasopressor support and/or ICU stay(10% vs. 3.3%, p=0.2) and in-hospital mortality (2.0% vs. 3.3 %, p >0.9) were also similar between both groups. Conclusion Our study indicates that our new institutional guidelines successfully lead to reduced broad spectrum antimicrobial exposure without increased infections, ICU stays, or mortality. Thus, de-escalation of EAT based on clinical criteria is safe in this high risk patient population. Disclosures Douglas Tremblay, MD, AbbVie: Advisor/Consultant|Astellas: Grant/Research Support|Cogent Biosciences: Advisor/Consultant|Cogent Biosciences: Grant/Research Support|Gilead: Grant/Research Support|GSK: Advisor/Consultant|Novartis: Advisor/Consultant|Sierra Oncology: Advisor/Consultant|Sobi: Advisor/Consultant|Sobi: Grant/Research Support|Sobi: Patent for use of pacritinib and azacitidine in CMML|Sumitomo: Grant/Research Support Samantha E. Jacobs, MD, MS, Ansun Biopharma: Advisor/Consultant|Eurofins, Viracor, LLC.: Grant/Research Support

P-2277. Impacts of Ongoing Quinolone Prophylaxis Following Quinolone-Resistant Bacteremia in Neutropenic Patients

Abstract Background Guidelines that suggest fluoroquinolone (FQ) prophylaxis for intermediate to high-risk hematologic malignancy patients are based primarily on evidence of reduction in bloodstream infections (BSIs) in historic studies, despite no demonstrated reduction in other outcomes such as mortality, septic shock, or ICU admissions. In the era of widespread FQ use for prophylaxis and increasing antimicrobial resistance, ongoing re-evaluation of the benefit is needed. Patients with BSI due to FQ-resistant gram-negative organisms may have particularly reduced benefit from ongoing FQ prophylaxis, however data on this topic is limited. We evaluated characteristics of neutropenic patients with BSI in an attempt to better inform the risk/benefit balance in this population. Figure 1. Numerical breakdown of bacteremia episodes Methods We extracted episodes of gram-negative BSI during a neutropenic episode lasting at least 7 days in adult inpatients with hematologic malignancy and/or stem cell transplant (study period 11/1/2020-11/1/2023). For each BSI episode we collected data on treatment (agent, duration, line removal), FQ susceptibility, underlying disease, neutropenia, and FQ exposure within 90 days. For episodes with an opportunity to resume prophylaxis following treatment of bacteremia (based on persistent neutropenia or recurrent neutropenia with 90 days), we determined rates of recurrent BSI within 90 days, stratified by FQ resistance and decision to resume FQ prophylaxis. Results There were 82 BSI episodes (69 first episodes, 13 recurrent) among 62 patients. FQ resistance was common in first episodes (34/69, 49%) and median prior FQ exposure within 90 days was 16 days. 43 episodes had an opportunity to resume FQ prophylaxis and 19/43 (44%) had FQ resistance. FQ prophylaxis was resumed in 16/19 (84%) with FQ resistance and 21/24 (88%) without, with rates of recurrent bacteremia within 90 days of 44% and 29% respectively. There were no episodes of recurrent bacteremia when FQ prophylaxis was not resumed (0/6).Table 1.Characteristics of bacteremia episodes with an opportunity to resume fluoroquinolone prophylaxis following treatment Conclusion Among bacteremia episodes with eligibility for FQ prophylaxis following treatment, recurrent bacteremia was common, particularly when FQ resistance was present. FQ prophylaxis may have little or no benefit in this setting, however larger studies and controlled data are needed. Disclosures All Authors: No reported disclosures

P-30. Herpes Zoster Burden among US Adults with Immunocompromising or Comorbid Conditions: A Systematic Literature Review

Abstract Background Prior to and since the availability of herpes zoster (HZ) vaccines, the burden of HZ has been summarized across select US patient populations, including those with comorbidities, autoimmune disorders (AID), or immunocompromising (IC) conditions. However, these studies tended to focus on disease incidence, lacked comparisons across multiple conditions, and generally did not include healthcare utilization and cost outcomes associated with HZ. Consequently, this study sought to summarize HZ burden in terms of epidemiology, health outcomes, health care resource utilization and costs, and humanistic impact among those with AID, IC conditions, or comorbidities in the US.Table.Incremental Health Care Costs for Patients with Herpes Zoster among Adults with AID, IC, or Common Comorbid ConditionsAID = autoimmune disorders; CI = confidence interval;IC = immunocompromising , USD ($) = United States dollar; NR = not reported; PPPM = per patient per month; PPPQ = per patient per quarter (3-month period); PPPY = per patient per year Methods This systematic literature review involved 3 separate searches to identify studies published since 2012 reporting on the epidemiology, economic burden, and humanistic burden of HZ in US adults with AID, IC conditions, or common comorbidities. Methods followed those recommended by the Cochrane Collaboration and involved searches within Embase, MEDLINE, proceedings from relevant conferences (2021 to 2023), and the CDC website. Study selection was carried out by 2 independent reviewers and data were extracted from the included studies by 1 reviewer and validated by a second reviewer.Figure 1.PRISMA Flow Diagram: Epidemiological Study SelectionSLR = systematic literature review Results The final review included 51 epidemiological studies (Figure 1), 18 economic analyses (Figure 2), and no publications on humanistic burden. Extensive evidence on HZ incidence was observed across 26 individual AID, IC, or common conditions, with the highest rates among those with hematological malignancies or stem cell transplant recipients. Limited evidence on HZ-related mortality or the prevalence of other HZ-related complications was observed in AID and IC populations. Economic burden of HZ varied considerably by underlying condition(s) (Table) with the majority of incremental costs and resource utilization observed within the first month following HZ diagnosis, primarily driven by inpatient care.Figure 2.PRISMA Diagram: Economic Study SelectionSLR = systematic literature review Conclusion HZ burden is considerable among adults with AID, IC, and/or common comorbid conditions. The observed risk for and burden of HZ reinforces the need to expand vaccination coverage among adults in these patient populations. FUNDING: GSK (VEO-000677) Disclosures Justin Gatwood, PhD, MPH, AstraZeneca: Grant/Research Support|Genentech: Advisor/Consultant|GSK: Employment|GSK: Stocks/Bonds (Public Company)|Merck & Co.: Advisor/Consultant|Merck & Co.: Grant/Research Support Sophie Dodman, BSc, Evidera (part of Thermo Fisher): Employee Aiswarya Shree, MSc, Evidera (part of Thermo Fisher): Employee Bhanu Inuganti, MSc, Evidera (part of Thermo Fisher): Employee Carol A. Forbes, PhD, Evidera (part of Thermo Fisher): Employee|Evidera (part of Thermo Fisher): Stocks/Bonds (Public Company) Nikita Stempniewicz, MSc, GSK: Employment|GSK: Stocks/Bonds (Public Company)

Educational outcomes school year nine in children treated for acute lymphoblastic leukemia: A nationwide registry-based study from Sweden.

Acute lymphoblastic leukemia (ALL) constitutes approximately 25% of pediatric cancers, and with contemporary protocols, the 5-year survival rate is over 90%. Despite improved survival, neurocognitive impairments from treatment raise concerns. This registry study aimed to explore the impact of ALL treatment on educational outcomes from school year nine in Swedish children. A population-based cohort of 503 children diagnosed with ALL from 1990 to 2010 was identified from the Swedish Childhood Cancer Registry and matched with five controls each. Assessed variables were delayed graduation, high school eligibility, total merit value, school grades in Swedish, English, mathematics, and physical education, and results in national tests. Analyses were performed between cases and controls and by sex, age at diagnosis, and risk group. Our results showed that, compared to controls, cases had higher odds for delayed graduation, poorer results in physical education, and higher rates of absence in national tests in English and mathematics. Children in the standard-risk group (treated with first-line chemotherapy only) exhibited similar results to matched controls whereas children in the high-risk group (treated with cranial irradiation, hematological stem cell transplantation, or/and for ALL relapse and thus likely received also radiotherapy) had lower total merit value compared to controls. We conclude that Swedish children diagnosed with ALL between the years 1990-2010 mainly exhibited comparable educational outcomes to controls, although children in the high-risk group had lower results. These findings highlight the importance of evaluating especially children with high-risk ALL in order to identify those requiring educational support and for designing targeted interventions.

Impact of bone marrow fibrosis on outcomes of allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

Bone marrow fibrosis (BMF) of unknown etiology was common in hematological malignancies, but its prognostic value for acute myeloid leukemia (AML) is unclear. We interrogated data from 532 newly diagnosed subjects with AML receiving allogeneic hematological stem cell transplantation to evaluate the prognostic impact of BMF on transplant outcomes. Using the European consensus on the grading of BMF at diagnosis, 255 (48%) subjects were BMF-0, 209 (39%), BMF-1 and 68 (13%), BMF-2-3. Subjects with BMF-2-3 had poor overall survival (P < 0.001), disease-free survival (P < 0.001) and a higher incidence of relapse (CIR, P < 0.001). Multi-variable analyses in subjects achieving pre-transplant complete remission showed BMF-2-3 was an independent risk factor for CIR (Hazard Ratio [HR] = 2.17, (95% CI, 1.11, 4,24); P = 0.02). Furthermore, BMF-2-3 group showed delayed neutrophil and platelet engraftment and delayed B cell recovery post-transplantation. These findings demonstrate the significance of BMF in transplant outcomes and attract more attention to AML with BMF.

Immunotherapy in first line treatment of adult acute lymphoblastic leukemia.

The use of immunotherapy in recent years has changed the paradigm of treatment in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), improving outcomes in the relapsed/refractory setting. New strategies are incorporating immunotherapy into front-line regimens to reduce the toxicity of chemotherapy, prolong survival and increase the possibility of treating older patients. The aim of this review was to describe the new strategies, which have incorporated these drugs into front-line regimens for BCP-ALL patients. Recent studies have demonstrated that immunotherapy can be included in front-line induction, consolidation and/or maintenance regimens for the treatment of BCP-ALL patients by its addition to chemotherapy, by substituting some chemotherapy cycles or even including immunotherapy in chemotherapy-free strategies. The implications of these relevant findings will allow treating older patients, reducing the toxicity of chemotherapy and increasing patient outcomes. In addition, these findings have raised the possibility of avoiding the need for hematologic stem cell transplant in some selected patients.

Impact of hydroxyurea on follicle density in patients with sickle cell disease

AbstractThe impact of hydroxyurea (HU) on the ovarian reserve of female patients with sickle cell disease (SCD) remains poorly elucidated. Only direct histological analysis of ovarian follicle density can effectively evaluate HU’s effect on ovarian reserve. By analyzing digitized slides of ovarian tissue from girls and young women with SCD who underwent ovarian tissue cryopreservation (OTC) before hematological stem cell transplantation, we meticulously counted follicles and categorized them based on their growth stage. We then calculated the densities of different follicle types and assessed their correlation with patient characteristics, clinical manifestations, and treatments extracted from medical records. Seventy-six patients with SCD participated in the study, with a median age at OTC of 10.2 years (interquartile range [IQR], 7.5-14.6), and 50 (65.8%) were prepubertal. Of these, 35 patients (46.1%) had received HU, with a median daily dosage of 23.0 mg/kg (IQR, 20.0-25.0) and median exposure time of 44 months (IQR, 24.0-54.0). Primordial follicle density was comparable between the HU and non-HU groups (5.8 follicles per mm2 [IQR, 1.0-13.3] vs 4.2 follicles per mm2 [IQR, 1.1-14.4], respectively; P = .95). However, in the HU group, after adjusting for age, the density of growing follicles was marginally lower than that in the non-HU group (P = .09). Notably, other parameters such as vaso-occlusive crisis did not affect follicular density. In conclusion, exposure to HU did not demonstrate a reduction in ovarian reserve in girls or women with SCD. Therefore, fertility preservation measures before initiating HU treatment do not seem necessary.

Filtered handheld far-ultraviolet disinfection device in reducing environmental pathogens from high-touch clinical surfaces

Background: Healthcare-acquired infections (HAIs) continue to be a major challenge. In fact, an increased risk of HAIs has been linked to high-touch surfaces contaminated with multidrug-resistant organisms (MDROs), and enhanced environmental disinfection is linked to reduced HAI rates. Recently, more focus has been placed on emerging disinfection technologies, such as UV light-producing portable device that emits light at a wavelength of 222 nm, which has previously demonstrated germicidal capabilities at short contact times. In this study, we aim i) to evaluate the efficacy of a filtered far-UV-C handheld device (FFUHH) to reduce bacterial loads on high-touch surfaces in clinical workrooms in a cancer center, and ii) to isolate, identify and establish a genetic relationship between these environmental clinically significant pathogens and the ones recovered from patients. Methods: Samples were collected weekly on a rotating schedule over a 24-week period from five high-touch items (dictation device, mouse, armchair, desk, and keyboard) in multiple clinical work rooms on hematologic malignancy and stem cell transplant units. Contact plates for colony count and swabs were collected pre- and post-intervention with the FFUHH on standardized adjacent areas respectively for each surface. The swabs were enriched and cultured on selective media to isolate clinically significant pathogens. Whole genome sequencing (WGS) was then performed on environmental pathogens validated by MALDI-TOF as well as clinical samples collected from patients in the same unit around the time of environmental sample collection. Results: A total of 440 plates, 220 pre- and 220 post-interventions, were collected and analyzed. The highest mean colony count pre-treatment was detected from the armchairs and the lowest for the keyboards. The mean reduction of colony forming units (CFUs) ranged between 53% for the keyboard and 83% for the mouse. The reduction was statistically significant across all surfaces with P values &lt; 0.05, except for the keyboard (Figure 1). We isolated many pathogens of the human microbiota identified by MALDI-TOF such as Micrococcus luteus, S. capitis as well as methicillin-resistant S. epidermidis, S. haemolyticus and S. hominis. We also identified several Candida parapsilosis, Pseudomonas stutzeri, one Listeria grayi and one Acinetobacter baumanni. Finally, WSG allowed us to further characterize an environmental multi-drug resistant S. epidermidis ST5 strain associated with patient bacteremia, and ST16 strains detected on surfaces both pre- and post-FFUHH treatment. Conclusion: The FFUHH effectively reduced the microbial burden on high-touch surfaces in clinical workrooms on hematologic malignancy and stem cell units.

Epidemiology and risk factors of community-acquired pneumonia in patients with different causes of immunosuppression

Immunosuppression constitutes a significant risk for community-acquired pneumonia (CAP). Nevertheless, specific causes of immunosuppression and their relevance for incidence, etiology and prognosis of CAP are insufficiently investigated.We conducted a population-based cohort study within a statutory health insurance in Germany from 2015 to 2018. CAP was retrieved by ICD-10-GM codes. Episodes of immunosuppression were identified by coded conditions (hematologic neoplasms, stem cell or organ transplantation, neutropenia, HIV, primary immunosuppressive syndromes) or treatments (immunosuppressants, antineoplastic drugs, systemic steroids). Endpoints were defined as occurrence of CAP (primary), hospitalization, 30-day mortality and CAP associated with rare pathogens. Our analysis utilized the Andersen-Gill model adjusted for sex, age, level of long-term care, vaccination status, community type and comorbidities.942,008 individuals with 54,781 CAPs were included (hospitalization 55%, 30-day mortality 14.5%). 6% of individuals showed at least one episode of immunosuppression during the study period with systemic steroids (39.8%) and hematologic neoplasms (26.7%) being most common. Immunosuppression was recorded in 7.7% of CAPs. Besides classical risk factors such as age and level of long-term care, immunosuppressed patients were most prone to CAP (HR 2.4[2.3–2.5]) and consecutive death (HR 1.9[1.8–2.1]). Organ and stem cell transplantation (HR 3.2[2.6–4.0] and 2.8[2.1–3.7], respectively), HIV (HR 3.2[1.9–5.4]) and systemic steroids (> 20 mg prednisone daily dose equivalent (HR 2.7[2.4–3.1])) showed the highest risk for contracting CAP. CAP by rare pathogens was strongly associated with immunosuppression (HR 17.1[12.0–24.5]), especially HIV (HR 34.1[7.6–153]) and systemic steroids (HR 8.2[4.6–14.8]).Our study elucidates the relevance of particular immunosuppressive conditions including systemic steroids for occurrence and prognosis of CAP.

Central Line Associated Bloodstream Infections Outside the Intensive Care Unit: A 2-Year Analysis

Objective: There is limited data on the rates of central line-associated bloodstream infections (CLABSI) in non-intensive care units (ICU). Our aim was to determine the rates and features of CLABSI in non-ICU units. Method: CLABSI surveillance is performed according to CDC criteria in Internal Medicine Nephrology, Pediatric/Adult Hematology, Oncology and hematopoietic stem cell transplant (HSCT) units. Hospital infections control committee surveillance data was used. Results: Totally, 70028 patient days(pd) and 22358 catheter days, 101 infections were detected in 94 patients. The CLABSI rate was 1.44/1000 pd, the incidence density was 4.2/1000 catheter days, and the device utilization rate was 0.32. The highest infection rate was observed in the adult HSCT unit (15.18/1000 pd). 56.4% of the patients were male (n=53) and the mean age of the patients was 32±2.5 years. The mean length of hospitalization was 27.7±2.5 days. Half of the patients (n=47) had permanent central lines. Hematologic cancer was found in 54.7% and hemodialysis in 19.2%. 21.8% of infections were polymicrobial. Of the 125 microorganisms isolated, 61.6% were Gram negative, 20.8% were fungi and 17.6% were Gram positive. The most frequent pathogen was E.coli (13.6%) followed by and K.pneumoniae (13.6%), Staphylococcus aureus (8%) and C.parapsilosis (7.2%). Crude mortality was 36.2%. Colistin and amikacin were the most effective antibiotics in E.coli and K.pneumoniae, oxacillin resistance was 60% in S. aureus. In Candida species, fluconazole resistance was 15.8%. Conclusion: CLABSI can also be seen outside intensive care units and surveillance in these units is necessary for infection control.

Jaundice That Has Persisted for 5 Days

Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is a significant cause of morbidity and mortality among patients with current or resolved HBV infection. Since no curative treatment for HBV infection is currently available, a large number of individuals in the general population are at risk for HBV reactivation. Populations vulnerable to HBV reactivation include those currently infected with HBV or those who have had past exposure to the virus. The potential consequences of HBV reactivation are particularly concerning when these populations undergo anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for managing various malignancies, rheumatologic diseases, inflammatory bowel disease, or undergo solid-organ or hematologic stem cell transplantation. This article aims to increase awareness of HBV reactivation and to elucidate the mechanisms and risks associated with HBV reactivation in various clinical settings.

Multicenter Retrospective Study of Invasive Fusariosis in Intensive Care Units, France.

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002----2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death.

CYP3A5 influences oral tacrolimus pharmacokinetics and timing of acute kidney injury following allogeneic hematopoietic stem cell transplantation.

Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described. Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642). Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population. Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT.

A Single-Center Study of the Utility of Bronchoalveolar Lavage in Critically Ill Patients With Haematological Malignancy or Stem Cell Transplants.

The aim of this study was to evaluate the yield of bronchoscopy-guided bronchoalveolar lavage (BAL) and decisions on management of antimicrobials in critically ill patients with hematological malignancy and/or hematological stem cell transplant (HSCT). The safety and tolerance of bronchoscopy were also reported. A retrospective cohort study was conducted by reviewing health charts of all adult patients with a hematological malignancy and/or an HSCT who were admitted to the intensive care unit and underwent bronchoscopy and BAL over four years from April 2016 to April 2020 at King Abdulaziz Medical City, Riyadh. Results: The cohort included 75 critically ill patients. Of these 75 patients, 53 (70.7%) had HSCT (allogenic 66%, autologous 32.1%, haplogenic 3.8%). Computed tomography of the chest was abnormal in all patients. Predominant findings included airspace abnormalities, ground glass opacities, and others. The positive yield was found to be 20% for bacterial, 22% for viral, 21% for fungal, and other organisms were identified in 2%. Although cytology was not performed in 18 patients, malignant cells were identified on BAL in two patients. While the overall mortality of the cohort was high (46.7%), the vast majority (94.7%) tolerated bronchoscopy and BAL without any complications. However, three patients (4%) developed a pneumothorax and one patient bled and developed the acute respiratory distress syndrome post bronchoscopy. BAL can identify and detect microorganisms directly influencing the clinical care of patients who have received non-invasive diagnostic tests that yielded negative culture results. Bronchoscopy and BAL are generally safe and well tolerated by critically ill patients with hematological malignancy or HSCT.

Hematological Involvement in Childhood Langerhans Cell Histiocytosis: A Cohort Study of 303 Patients

Introduction: Hematological involvement (HI) is a life-threatening involvement of Langerhans cell histiocytosis (LCH). Since 1975, its definition is based on the Lahey criteria: Anemia (Hb &amp;lt;10 g/dL and &amp;lt;9 g/dL in infants) and/or thrombocytopenia (platelet count &amp;lt;100x10 9/l). Methods: Among 2,234 patients &amp;lt; 18 years enrolled in the French histiocytosis registry (cutoff date May 2023), 303 patients presented HI. We differentiated mild HI (MHI) (Hb &amp;gt; 7 g/dl and Platelets &amp;gt; 20x10 9/l) from severe HI (SHI) (Hb ≤ 7 g/dl and Platelets ≤ 20x10 9/l) by using usual cutoffs for transfusion requirements. Results: Median age at diagnosis was one year and sex was male in 49%. The median follow-up in the 258 survivors was 10.9 years, while death occurred after a median of 0.9 years in the 45 patients who died (Figure 1A). Only 3 patients died later than two years of initial diagnosis. The HI was mild in 150 cases and severe in 153 cases. BRAF v600E was found in 88 among the 101 patients for which mutation analysis was documented. Patients with SHI had significantly more lung involvement (35 % vs 19 %), more hepatic involvement (72 % vs 21 %), and more skin involvement (85 % vs 61 %). Morphological bone marrow infiltration by CD1a positive cells could not differentiate between SHI and MHI and bone marrow features were hardly informative. Signs of myelofibrosis were documented in 9 patients mostly later in the disease course. Lastly, 44 macrophage activation syndromes were observed exclusively in SHI. For 11 of those patients panel analyses of hemophagocytic lymphohistiocytosis genes did not show any bi-allelic pathogenic variants. 20 patients did not receive any therapy, including one with SHI and 19 with MHI. An intensive approach with hematologic stem cell transplantation (HSCT) (n=11) and 2-Cda-Cytarabine (2-Cda-AraC) (n=44) was proposed almost only for SHI. MAPK-inhibition was used in 40 patients. Three deaths were observed among the MHI and 42 among the SHI. From 1983 to 1998 mortality was about 50% and 30 of 63 patients died. With the establishment of the second-line treatment by 2-Cda-AraC mortality decreased drastically and from 1998 to 2014 only 13 of 194 patients died. From 2014 on patients received exclusively MAPK-inhibition as second line treatment and 2 of 46 patients died (one without therapy, one at the initiation). The overall survival is depicted in figure 1A. Neurodegenerative (ND) complications were observed in 32 patients (10.5%) with a median delay of 4.8 years after initial LCH diagnosis and incidence of ND was independent of the MHI or SHI group (Figure 1B). Conclusion: In Langerhans cell histiocytosis, the classic definition of hematological involvement by the Lahey criteria should be reconsidered. HI may be limited to severe HI that included almost all medical complications and warrants innovative approaches, while mild HI can be managed by the classic therapeutical approach. Even if progress has been achieved in the treatment of LCH patients with HI with more than 95% achieving short-term control, long term neurodegeneration remains a challenge in this group of patients, which warrants further research. Figure 1: A) Kaplan-Meier curve of cumulative incidence of death for all the 303 patients, regardless of therapy. B) Risk of clinical neurodegenerative symptoms in the same cohort (considering death as a censor).

Virtual Reality-Assisted Exercise Therapy during Inpatient Treatment after Intensive Chemotherapy for Acute Myeloid Leukemia (AML) and after Autologous or Allogeneic Stem Cell Transplantation

Background and Objectives Medical advances in treatment of hematologic malignancies have led to improved survival. However, aggressive treatments come with the potential of significant side effects that can affect quality-adjusted life years. During treatment, physical activities are markedly reduced and immobility and psychologic burden, especially during long isolation processes, result in fatigue and decline of quality of life as well as loss of cognitive function. Physiotherapy and exercise therapy positively impact muscle strength, quality of life, cognitive functioning and fatigue, but sufficient implementation of training in the inpatient setting is often limited by shortage in human resources. The aim of this study was to assess the feasibility of a virtual reality (VR) based exercise program during inpatient stay of patients undergoing intensive treatment for hematologic malignancies, including autologous and allogeneic hematologic stem cell transplantation (HSCT). Method Patients aged 18 or above, admitted to the hematology ward for HSCT or intensive chemotherapy for acute leukemia were included. As this was a feasibility trial, there was no randomization. After consent, patients were asked to use the VR training device on a daily basis for the length of their stay, accompanied by medical personal. The training program consisted of customized VR-applications addressing movement, concentration and alertness as well as relaxation. An individual program was developed for every patient at the beginning of treatment and continuously readjusted according to individual needs and preferences. Patients who did not want to or were not able to use the VR device were asked to participate in the control group and received the standard-of-care treatment consisting of once daily physiotherapy. As objectives, quality of life, fatigue, strength and cognitive function were assessed once weekly until discharge as well as two weeks post discharge in both groups. The time of usage was recorded by the VR device. A structured interview was conducted after discharge to evaluate the patients' perspective on the intervention. Results Over a three-months period, a total of 10 patients were enrolled in the study, seven patients with intervention, three patients in the control group. The usage was feasible and well tolerated. No unpleasant side effects such as dizziness, nausea or fatigue were reported. Mean time of usage varied between patients (132.6±68.6 minutes, min 12.4, max 463.5 minutes) on 31±28.2% of hospitalization days. Patients in the intervention group achieved a higher overall score in EORTC QLQ-C30 after discharge (s). Moreover, the use of VR was associated with a trend towards improved mean symptom burden (60 vs 43.3 pts), cognitive function (83.3 vs. 16.7pts) and physical strength (63.3 vs 26.7pts) post discharge (significance was not calculated due to the small number of cases). VR occupation time was markedly affected by age and general condition during treatment. The patients perception of the intervention was positive. Conclusions The results show that the use of a VR based exercise program during inpatient stay of patients receiving intensive treatment for hematologic malignancies is feasible and safe, and can improve QoL. Because of the small number of subjects and distinctive differences in time of usage we can only recognize a trend towards positive effects so far. In view of these promising results a larger prospective, randomized trial has been designed.

CCL1 As a Biomarker of Engraftment Syndrome of Hematological Stem Cell Transplantation

BACKGROUND Many complications occur in the practice of hematopoietic stem cell transplantation, especially those presenting with fever, which can be caused by infection as well as engraftment syndrome (ES), which is difficult to distinguish. The mechanism of ES is unknown, and no characteristic biomarkers have been identified. METHODS We attempted to identify cytokines specific to the engraftment syndrome by cytokine array analysis of sera from 7 patients who underwent HSCT at our institution from January 2019 to March 2022 and who developed fever between 1 week before and the day of engraftment. Cases in which pathogens were detected in blood culture at the time of fever were diagnosed as infections, and cases in which blood culture was negative or clinically treated as engraftment syndrome or fever associated with engraftment were diagnosed as engraftment syndrome. Cases that did not present with fever from infusion to engraftment were used as negative controls. RESULTS. Three of the seven patients had fever due to infection and four had fever due to engraftment syndrome. Median age was 41 (21-62) years, 5 males and 2 females. Four patients had acute leukemia, one had chronic myelomonocytic leukemia, and two had nonhematologic tumors. The donors were blood related in 3 cases, unrelated in 3 cases, and cord blood in 2 cases. Pretreatment was myeloablative (MAC) in 2 patients and reduced intensity pretreatment (RIC) in 5 patients. Cytokine arrays identified five cytokines that were elevated in the ES group. Of these, cytokine The cytokine CCL1 (I-309) tended to be elevated in the ES group (p=0.06). The validity of CCL1 with respect to the diagnosis of fever of engraftment was examined using sera from another 16 hematopoietic stem cell transplant cases performed at the same period, and the results showed that CCL1 was only mildly elevated in cases diagnosed with infection, regardless of the elevated values of fever and inflammatory response, but tended to be elevated in fever of engraftment (area under ROC curve: 0.74 (95% confidence interval 0.422-1)). CONCLUSIONS. CCL1 was identified as a cytokine specific for ES, indicating that CCL1 may be useful in differentiating ES from infection. CCL1 is mainly secreted by T lymphocytes and its oversecretion during the hematopoietic recovery process may be involved in immune activation and the engraftment syndrome.

Simultaneously measure the concentrations of busulfan and phenytoin in human plasma using an HPLC-MS/MS method: Application to the TDM for children underwent hematological stem cell transplantation

AbstractIn this work, a simple and rapid high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to carry out the simultaneous measurement of busulfan (BU) and phenytoin (PHT) in the plasma of children. In this method, plasma sample could be prepared by one-step protein precipitation using 1 mL of methanol/water (1:1, v/v). After centrifugation (14,500 rpm, 5 min, 4 °C), 10 μL of the supernatant was injected into a Hypersil Gold C18 column (150 × 2.1 mm, 5 μm, Thermo Fisher Scientific) for separation by gradient elution. Quantification was carried out using multiple reactions monitoring (MRM) under positive scan mode. In the method verification, the calibration curves of BU and PHT showed satisfactory linearity (r &gt; 0.99) at the concentration ranging from 0.02 to 20 μg mL−1. The accuracy and precision were tested at four concentration levels (including the LLOQ level) with the relative error (RE) ranging from −0.80% to 11.45% and coefficient of variation (CV) between 0.93% and 7.74%. There was no pronounced matrix effect to interfere with the quantitative analysis. Compared to determine BU and PHT using two individual methods, less pre-treatment process, labor and blood sample volume are required in this proposed method. Finally, this method was successfully applied to the therapeutic drug monitoring of BU and PHT for children underwent hematological stem cell transplantation.

Seizures in children undergoing stem cell transplantation.

Neurological complications (NCs) are of major concern following hematological stem cell transplantation (HSCT), most of which present with seizures. We performed a retrospective study (2002-2018) of patients undergoing HSCT in order to analyze the incidence and aetiologies related to seizures. Of 155 children undergoing HSCT, 27 (17.4%) developed seizures at some point in 2 years of follow-up. The most frequent etiologies were central nervous system (CNS) infection (n = 10), drug toxicity (n = 8), and vascular disease (n = 5). A statistically significant association was found between seizure and the HSCT type (lower risk for a related identical donor, p = .010), prophylactic or therapeutic mycophenolate use (p = .043 and .046, respectively), steroid use (p = .023), selective CD45RA+ depletion (p = .002), pre-engraftment syndrome (p = .007), and chronic graft-versus-host disease (GVHD) severity (p = .030). Seizures predicted evolution to life-threatening complications and admission to intensive care (p < .001) and higher mortality (p = .023). A statistically significant association was also found between seizures and sequelae in survivors (p = .029). Children who developed seizures had a higher risk of CNS infection and vascular disease (odds ratio 37.25 [95% CI: 7.45-186.05] and 12.95 [95% CI 2.24-74.80], respectively). Neurological complications highly impact survival and outcomes and need to be addressed when facing an HSCT procedure.