Compound staphylococcal lysostaphin for oral mucositis prophylaxis in hematopoietic stem cell transplantation recipients: a non-inferiority randomized trial.

The acute respiratory distress syndrome is a frequent condition following allogeneic hematopoietic stem cell transplantation. Extracorporeal membrane oxygenation may serve as rescue therapy in refractory acute respiratory distress syndrome but has not been assessed in allogeneic hematopoietic stem cell transplantation recipients. Multicenter, retrospective, observational study. ICUs in 12 European tertiary care centers (Austria, Germany, France, and Belgium). All allogeneic hematopoietic stem cell transplantation recipients treated with venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome between 2010 and 2015. None. Thirty-seven patients, nine of whom underwent noninvasive ventilation at the time of extracorporeal membrane oxygenation initiation, were analyzed. ICU admission occurred at a median of 146 (interquartile range, 27-321) days after allogeneic hematopoietic stem cell transplantation. The main reason for acute respiratory distress syndrome was pneumonia in 81% of patients. All but one patient undergoing noninvasive ventilation at extracorporeal membrane oxygenation initiation had to be intubated thereafter. Overall, seven patients (19%) survived to hospital discharge and were alive and in remission of their hematologic disease after a follow-up of 18 (range, 5-30) months. Only one of 24 patients (4%) initiated on extracorporeal membrane oxygenation within 240 days after allogeneic hematopoietic stem cell transplantation survived compared to six of 13 (46%) of those treated thereafter (p < 0.01). Fourteen patients (38%) experienced bleeding events, of which six (16%) were associated with fatal outcomes. Discouraging survival rates in patients treated early after allogeneic hematopoietic stem cell transplantation do not support the use of extracorporeal membrane oxygenation for acute respiratory distress syndrome in this group. On the contrary, long-term allogeneic hematopoietic stem cell transplantation recipients otherwise eligible for full-code ICU management may be potential candidates for extracorporeal membrane oxygenation therapy in case of severe acute respiratory distress syndrome failing conventional measures.

A Simple Prognostic Score to Predict Short and Long-Term Survival Following ICU Admission in Critically Ill Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients: Improved Survival Following Reduced Intensity Conditioning

Background:Cell-free DNA, which may be considered as “liquid” biopsy, may serve as a diagnostic and prognostic marker not only in hematological malignancies but in solid tumors as well.Aims:To investigate the prognostic role of pre-transplant cell-free DNA levels in allogeneic hematopoietic stem cell transplant recipients.Study Design:Retrospective cohort study.Methods:A total of 177 allogeneic hematopoietic stem cell transplant recipients [median age: 36 (16-66) years; male/female: 111/66] with an initial diagnosis of acute leukemia were included in the study. Cell-free DNA was extracted from pre-transplant serum samples by using the MagNA Pure Compact Nucleic Acid Isolation Kit I with the MagNA Pure Compact instrument (Roche Diagnostics, Penzberg, Germany).Results:A positive correlation was demonstrated between cell-free DNA and age (p=0.018; r=0.177). Pre-transplant cell-free DNA levels were lower in bcr-abl (+) patients (p=0.001), while an adverse correlation was indicated between cell-free DNA and bcr-abl levels (p=0.001; r=−0.531). Acute lymphoblastic leukemia patients with bcr-abl positivity (p=0.001) or abnormal cytogenetics (p=0.038) represented significantly lower pre-transplant cell-free DNA levels. Cell-free DNA levels were lower in patients who developed sinusoidal obstruction syndrome (p=0.035). In terms of long-term complications, acute myeloid leukemia patients who experienced post-transplant relapse had significantly lower pre-transplant cell-free DNA levels (p=0.024). Overall survival was not statistically different between high- and low- cell-free DNA groups (45.2% vs 22.5; p=0.821).Conclusion:In general, low serum levels of pre-transplant cell-free DNA seem to be associated with transplant-related morbidities and may be considered an adverse prognostic factor for allogeneic hematopoietic stem cell transplant recipients.

To explore the allogeneic haematopoietic stem cell transplantation recipients' experiences of outdoor physical activity while admitted to the hospital. The study is a descriptive, qualitative study. Fourteen first-time allogeneic stem cell transplantation recipients were included. After going through a tailored outdoor physical activity programme, the participants took part in individual in-depth interviews to describe their experiences of the physical activity programme. The interviews were analysed in accordance with the manifest level of content analysis by Graneheim and Lundman. The participants had different starting points, but the majority experienced taking part in physical activity as positive. The data analysis resulted in five categories: (1) Physical activity is positive; (2) Health condition might challenge activity; (3) Tailored activity; (4) Social aspects and (5) Feeling well. The interest in adherence to the programme seemed to be related to the participants' physical activity prior to admission to the hospital. Furthermore, somatic symptoms were the major challenges to participation. Our findings suggest that participants viewed the physical outdoor programme as a positive reprieve from the hospital setting. The results demonstrate that an outdoor physical activity programme tailored to patients' health conditions is feasible and can have physical and social benefits.

This study was aimed to investigate whether any association could be found between the presence of an inflamed and infected periodontium (e.g., gingivitis and periodontitis) and the development of bacteremia during neutropenia following allogeneic hematopoietic stem cell transplantation (HSCT). Eighteen patients underwent a periodontal examination before HSCT. Patients were classified as periodontally healthy [all periodontal pocket depths (PPD) ≤ 4 mm and bleeding on probing (BOP) ≤ 10%) or as having gingivitis/periodontitis (PPD ≥ 4 mm and BOP > 10%]. Oral mucositis (OM) was scored using the daily mucositis score. Blood cultures were taken at least twice weekly. Five patients were periodontally healthy, while 13 patients had gingivitis or periodontitis. Twelve patients (67%) developed bacteremia during neutropenia, of which 11 patients (61%) had one or more episodes of bacteremia due to coagulase-negative staphylococci (CONS, most often Staphylococcus epidermidis) or to oral viridans streptococci (OVS), or both. Patients with gingivitis/periodontitis more often had bacteremia than those with a healthy periodontium (p = 0.047), and BOP was associated with bacteremia (p = 0.049). All patients developed ulcerative OM, but its severity and duration were not associated with bacteremia. OM duration and the length of stay in the hospital were strongly correlated (R = 0.835, p ≤ 0.001). This study indicates that periodontal infections may contribute to the risk of developing OVS and CONS bacteremia during neutropenia following HSCT. While our results point to the importance of periodontal evaluation and management before HSCT, further studies on periodontal contribution to systemic infectious complications are warranted.

Oral mucositis (OM) is an important side effect related to allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it has been associated with a significative reduction of quality of life. A negative impact of OM in paediatric patients could result in increased use of parenteral feeding and opioids, longer periods of hospitalization, and a higher risk of systemic infection. To investigate the clinical features and clinical outcomes associated with OM development and severity in hematological cancer paediatric patients undergoing allo-HSCT who underwent professional dental care (PDC) and photobiomodulation (PBM) as prophylactic treatment. Medical data and OM presentation were retrieved retrospectively from all patients younger than 18years who received allo-HSCT between 2013 and 2016. The incidence of OM was assessed and graded by two oral medicine specialists following the WHO guidelines, and it was correlated with clinical parameters. Forty-nine consecutive paediatric patients were included. OM was diagnosed in 73.5% of patients, and in 36.1% of patients, OM was classified as severe. Acute lymphoblastic leukemia as a primary diagnosis and the use of a myeloablative regimen were associated with OM development. The primary diagnosis and use of total body irradiation (TBI) were associated with aggressive OM. Neither the incidence nor the severity of OM affected the overall survival, whereas only the use of a myeloablative regimen and a high body mass index (BMI) were determinants of lower OM-free survival rates. A myeloablative conditioning and a high BMI were observed to be independent prognostic determinants of a lower OMFS rate. The cluster analysis allowed us to outline patient profiles with greater susceptibility to the development and severity of oral mucositis, which seems to be a useful tool to determine the risk of OM in paediatric patients.

ABSTRACTThe aim of this study was to evaluate whether digestive tract mucositis is a predictive factor for body weight (BW) alterations during hematopoietic stem cell transplantation (HSCT). Data about characteristics of transplantation, initial nutritional conditions and gastrointestinal mucositis were collected from adult patients (n = 105) who underwent autologous and allogeneic HSCT. Oral mucositis (OM) was not a predictive factor for BW loss, but it was an independent factor for BW gain in autologous HSCT (β = 0.329, P = 0.021). Busulfan-fludarabine conditioning regimen (β = 1.531, P = 0.011) and gender (β = 1.109, P = 0.038) were significant independent risk factors for BW loss in allogeneic HSCT. Overall survival (OS) was significantly affected by the duration of OM in autologous HSCT (HR = 1.243, P = 0.008). In allogeneic HSCT, BW loss (HR = 1.308, P = 0.049) and diarrhea (HR = 1.139, P = 0.012) interfered significantly with OS. In conclusion, OM was not a risk factor for BW loss, but it influenced BW gain and had a negative impact on OS in autologous HSCT patients. Intestinal mucositis explained partially the BW loss and had a negative impact on OS in allogeneic HSCT.

Reactivation of human herpesvirus 6 (HHV-6) occurs in 30%-50% of patients (pts) who receive allogeneic (allo) hematopoietic stem cell transplant (HCT). However, the recommendation for post-transplant HHV-6 monitoring and treatment in pediatric pts is not well established. HHV-6 incidence rates and the clinical outcomes were reported for 139 pediatric pts (≤18years) undergoing first allo-HCT at City of Hope from July 2011 to July 2017, for whom HHV-6 was monitored weekly throughout HCT hospitalization. For 57 pediatric pts, who underwent first HCT from January 2009 to July 2011, HHV-6 was tested as clinically indicated and only rates of HHV-6 viremia were collected. From July 2011 to July 2017, HHV-6 was detected in 88/139 pts (63%). The frequency of HHV-6 viremia was associated with malignant diagnoses, myeloablative conditioning, and cord blood HCT. Treatment with antiviral agents was offered to symptomatic pts with a higher viral load (VL), for whom the time to VL clearance was longer and the frequency of subsequent recurrences was higher. Pts with a lower VL cleared HHV-6 without treatment. HHV-6 viremia was associated with a higher frequency of grade II-IV acute graft-versus-host disease (GVHD) (P=.022), but did not affect overall survival (OS), disease-free survival (DFS), non-relapsed mortality (NRM), myeloid, or platelet (Plt) engraftment. HHV-6 weekly screening is not necessary for all HCT pts but may be considered for high-risk pts with malignant diagnoses undergoing cord blood HCT; otherwise, HHV-6 should be tested as clinically indicated. Only symptomatic pts (especially with a high VL>25000) could benefit from treatment. HHV-6 viremia at the time of initiation and administration of the conditioning regimen cleared promptly without the need to augment the transplant process.

Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)

PurposeOral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens.MethodsMedical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis.ResultsBinary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085–13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41–23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (β = 0.515; 95% CI, 9.712–21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use.ConclusionCryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

This study aimed to clarify the clinical utility of oral management to prevent bloodstream infections by oral bacteria microbiologically in patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT). Ten consecutive patients with hematological malignancies undergoing ASCT were enrolled in this study. We implemented dental treatments before transplantation, if required, and carried out oral hygiene instructions and oral management every other day after transplantation. Molecular analysis of bacterial DNA for seven oral species using a polymerase chain reaction (PCR) assay was performed for oral samples and peripheral blood once a week for 3weeks after transplantation. Periodontitis was found in all 10 patients (mild grade in 3 and middle grade in 7) for whom basic periodontal therapy was conducted. Necessary dental procedures, including tooth extraction were performed in 5 patients. After transplantation, oral mucositis occurred in 10 patients (grade 1 in 3, grade 2 in 2, and grade 3 in 5) for whom oral hygiene instruction and oral care were continued every other day. PCR-identified three to six bacterial species in oral samples from nine patients, but none in peripheral blood from any patient during the observation period. Our study suggests that oral management could prevent bloodstream infections by oral bacteria in ASCT recipients despite the existence of periodontitis or oral mucositis. Its utility was confirmed by microbiological evidence based on molecular data.

Oral Mucositis Is Associated with Distinctive Patterns of Oral Microbiota Injury in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Calcineurin inhibitors impair neutrophil activity against Aspergillus fumigatus in allogeneic hematopoietic stem cell transplant recipients

Objective To identify the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) gargle in patients who had oral mucositis after allogeneic hematopoietic stem cell transplantation. Methods A total of 134 patients were enrolled in this study from 2014 to 2015. They were randomly divided into two groups: the experimental group (n=65) and the control group (n=69). Both groups received preventive measures for oral mucositis. But once oral mucositis occurred, the control group continued with the routine nursing measure, while the experimental group added GM-CSF gargle based on previous routine nursing measure. The effective rate and healing time were compared between two groups. Results The effective rate of the experimental group (81.54%, 53/65) was significantly higher than that of the control group (24.64%,17/69)(χ2=43.434, P=0.000). The median healing time in the experimental group was 4.5 days, shorter than 9.0 days in the control group (Z=-5.379, P< 0.01). Conclusions GM-CSF gargle can control the oral mucositis after allogeneic hematopoietic stem cell transplantation. Key words: Granulocyte-macrophage colony-stimulating factor; Oral mucositis; Allogeneic hematopoietic stem cell transplantation

Clostridioides difficile Infection and Risk of Acute Graft-versus-Host Disease among Allogeneic Hematopoietic Stem Cell Transplantation Recipients