Dissociations of oral foci of infections with infectious complications and survival after haematopoietic stem cell transplantation

Introduction Haematopoietic stem cell transplantation (HSCT) recipients are at increased risk for severe infections. This study examined the associations of common oral infections with survival and infectious complications in HSCT recipients. Materials and methods All autologous and allogeneic HSCT recipients transplanted in the University Hospital of Basel, Switzerland, between 2008 and 2016 and referred to oral infection control pre-HSCT were included in this retrospective case-control study. All patients had a clinical and a panoramic radiological dental examination taken immediately prior to HSCT. Presence of acute or chronic oral foci of infections, decayed, missing or filled tooth index (DMFT) and radiological attachment loss (RAL) were examined. Survival and infections of the subjects were followed up for 6 months post-HSCT. Results Altogether 341 allogeneic and 125 autologous HSCT recipients were included in the study. Within 6 months post-HSCT, 47 (14%) of the allogeneic and 4 (3%) of the autologous recipients died. Oral foci of infections (acute or chronic), DMFT or periodontitis pre-HSCT were not associated with survival 6 months post-HSCT. Oral foci of infections were also not associated with hospital treated infectious diseases or blood culture positive bacteremia during the 6 month follow-up period. Untreated oral foci of infections were not associated with survival or severe infectious complications within 6 months post-HSCT. Conclusion The results of this study suggest that radical dental interventions to chronic oral infections could be postponed until post-HSCT.Peer reviewe

Characterization of engraftment dynamics in myelofibrosis after allogeneic hematopoietic cell transplantation including novel conditioning schemes.

INTRODUCTION Myelofibrosis (MF) is a rare hematopoietic stem cell disorder progressing to bone marrow (BM) failure or blast phase. Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative therapy for a limited subset of patients with advanced MF, who are eligible, but engraftment in MF vs. AML is delayed which promotes complications. As determinants of engraftment in MF are incompletely characterized, we studied engraftment dynamics at our center. METHODS A longitudinal cohort of 71 allogeneic HCT performed 2000-2019 with >50% after 2015 was evaluated. RESULTS Median time to neutrophil engraftment ≥0.5x109/l was +20 days post-transplant and associated with BM fibrosis, splenomegaly and infused CD34+ cell number. Engraftment dynamics were similar in primary vs. secondary MF and were independent of MF driver mutations in JAK2, CALR and MPL. Neutrophil engraftment occurred later upon haploidentical HCT with thiotepa-busulfan-fludarabine conditioning, post-transplant cyclophosphamide and G-CSF (TBF-PTCy/G-CSF) administered to 9.9% and 15.6% of patients in 2000-2019 and after 2015, respectively. Engraftment of platelets was similarly delayed, while reconstitution of reticulocytes was not affected. CONCLUSIONS Since MF is a rare hematologic malignancy, this data from a large number of HCT for MF is essential to substantiate that later neutrophil and platelet engraftment in MF relates both to host and treatment-related factors. Observations from this longitudinal cohort support that novel conditioning schemes administered also to rare entities such as MF, require detailed evaluation in larger, multi-center cohorts to assess also indicators of long-term graft function and overall outcome in patients with this infrequent hematopoietic neoplasm undergoing allogeneic transplantation

Respiratory Syncytial Virus Infection in Patients with Hematological Diseases: Single-Center Study and Review of the Literature

Background.Respiratory syncytial virus (RSV) causes significant mortality in patients with hematological diseases, but diagnosis and treatment are uncertain. Methods.We retrospectively identified RSV-infected patients with upper or lower respiratory tract infection (RTI) by culture, antigen testing, and polymerase chain reaction from November 2002 through April 2007. Patients with severe immunodeficiency (SID; defined as transplantation in the previous 6 months, T or B cell depletion in the previous 3 months, graft-versus-host disease [grade, ⩾2], leukopenia, lymphopenia, or hypogammaglobulinemia) preferentially received oral ribavirin, intravenous immunoglobulin, and palivizumab. The remaining patients with moderate immunodeficiency (MID) preferentially received ribavirin and intravenous im munoglobulin. Results.We identified 34 patients, 22 of whom had upper RTI (10 patients with MID and 12 with SID) and 12 of whom had lower RTI (2 with MID and 10 with SID). Thirty-one patients were tested by polymerase chain reaction (100% of these patients had positive results; median RSV load, 5.46 log10 copies/mL), 30 were tested by culture (57% had positive results), and 25 were tested by antigen testing (40% had positive results). RSV-attributed mortality was 18% (6 patients died) and was associated with having ⩾2 SID factors (P=.04), lower RTI (P=.01), and preengraftment (P=.012). Among 12 patients with MID (7 of whom received treatment), no progression or death occurred. Nine patients with SID and upper RTI received treatment (7 patients received ribavirin, intravenous immunoglobulin, and palivizumab); infection progressed to the lower respiratory tract in 2 patients, and 1 patient died. Ten patients with SID and lower RTI were treated, 5 of whom died, including 4 of 6 patients who received ribavirin, intravenous immunoglobulin, and palivizumab. The duration of RSV shedding correlated with the duration of symptoms in patients with SID but exceeded symptom duration in patients with MID (P<.05). Conclusions.Lower RTI, ⩾2 SID criteria, and preengraftment are risk factors for RSV-attributed mortality. Polymerase chain reaction may optimize diagnosis and monitoring. Oral ribavirin therapy seems safe, but trials are needed to demonstrate its efficac

Case report: mRNA-1273 COVID-19 vaccine-associated myopericarditis: Successful treatment and re-exposure with colchicine

IntroductionVaccine-induced myocarditis is a rare complication of messenger RNA (mRNA) COVID-19 vaccines.Case presentationWe report a case of acute myopericarditis in a recipient of allogeneic hematopoietic cells following the first dose of the mRNA-1273 vaccine and the successful administration of a second and third dose while on prophylactic treatment with colchicine to successfully complete the vaccination.ConclusionTreatment and prevention of mRNA-vaccine-induced myopericarditis represent a clinical challenge. The use of colchicine is feasible and safe to potentially reduce the risk of this rare but severe complication and allows re-exposure to an mRNA vaccine

External Validation of the Revised Pretransplant Assessment of Mortality Score in Allogeneic Hematopoietic Cell Transplantation: A Cohort Study

Pretransplant risk scores such as the revised Pretransplant Assessment of Mortality (rPAM) score help to predict outcome of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). Since the rPAM has not been validated externally in a heterogeneous patient population with different diseases, we aimed to validate the rPAM score in a real-world cohort of allo-HCT patients. A total of 429 patients were included receiving their first allo-HCT from 2008 to 2015. The predictive capacity of the rPAM score for 4-year overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of relapse (CIR) after allo-HCT was evaluated. Moreover, we evaluated the impact of the rPAM score for OS and used uni- and multivariable analyses to identify patient- and transplant-related predictors for OS. In rPAM score categories of 30, the OS probability at 4 years differed significantly with 61%, 36%, 26%, and 10%, respectively (P < 0.0001). In contrast to CIR, the NRM increased significantly in patients with higher rPAM scores (P < 0.001). Regarding the OS, the rPAM score had an area under the receiver operating characteristics curve of 0.676 (95% confidence interval [CI], 0.625-0.727) at 4 years. In the multivariable analysis, the rPAM score was associated with OS-independently of conditioning regimens (adjusted hazard ratio per 1-unit increase, 1.10; 95% CI, 1.06-1.10; P < 0.001). Additionally, forced expiratory volume in 1 second and the disease risk index were the components of the rPAM significantly associated with outcome. In our large real-world cohort with extended follow-up, the rPAM score was validated as an independent predictor of OS in patients with hematologic disorders undergoing allo-HCT

Feasibility of electronic patient-reported outcome monitoring and self-management program in aplastic anemia and paroxysmal nocturnal hemoglobinuria-a pilot study (ePRO-AA-PNH).

INTRODUCTION Electronic patient-reported outcomes (ePRO) are increasingly recognized in health care, as they have been demonstrated to improve patient outcomes in cancer, but have been less studied in rare hematological diseases. The aim of this study was to develop and test the feasibility of an ePRO system specifically customized for aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). METHODS After performing a user-centered design evaluation an ePRO system for AA and PNH patients could be customized and the application was tested by patients and their medical teams for 6 months. Symptom-reporting triggered self-management advice for patients and prompts them to contact clinicians in case of severe symptoms, while the medical team received alerts of severe symptoms for patient care. RESULTS All nine included patients showed a high adherence rate to the weekly symptom-reporting (72%) and reported high satisfaction. The system was rated high for usage, comprehensibility, and integration into daily life. Most patients (78%) would continue and all would recommend the application to other AA/PNH patients. Technical performance was rarely a barrier and healthcare providers saw ePRO-AA-PNH as a useful supplement, but the lacking integration into the hospital information system was identified as a major barrier to usage. CONCLUSION An ePRO system customized for AA and PNH was feasible in terms of adherence, satisfaction, and performance, showing a high potential for these rare conditions in terms of data collection and patient guidance. However, the integration into clinical workflows is crucial for further routine use. TRIAL REGISTRATION ClinicalTrials.gov NCT04128943

Aplastic anemia and concomitant autoimmune diseases

The association of aplastic anemia (AA) with other autoimmune diseases (AID) has been described but so far not systematically evaluated. We assessed the incidence and the outcome of concomitant AID in a retrospective, single-center study of 243 patients with severe AA treated between 1974 and 2006 with either immunosuppression (186) or hematopoietic stem cell transplantation (57) and a median follow-up time of 9.3years (0-33). Clinically manifest AID were observed in 24 out of 243 (10 ± 3.7%) patients. Age at diagnosis of AA was significantly younger in patients without AID compared to patients with AID (median, 20 versus 52years; P < 0.001). In 12 patients where the diagnosis of AID was done before AA therapy, response to antithymocyte globulin was good for AA (ten out of 12) but not for AID (2 out of 12). In 13 patients in which AID occurred after first-line therapy, the median time to the AID was 7years (range 3months-27.5years

Haematopoietic cell transplantation in Switzerland, changes and results over 20 years: a report from the Swiss Blood Stem Cell Transplantation Working Group for Blood and Marrow Transplantation registry 1997-2016.

In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899 patients who had received an HCT (2781 allogeneic [35%] and 5118 autologous [65%]). As some patients had more than one transplant the total number of transplants was 3067 allogeneic and 6448 autologous. We compared patient characteristics and outcome of the first decade (1997-2006) and second decade (2007-2016) of the registry. There were numerous changes over time. For allogeneic HCT, transplant rates, and therefore use of HCT technology, increased from 14 to 21.8 HCTs per 1 million inhabitants per year from the first to the second decade. Likewise autologous HCTs increased from 24.8 to 37.2 annually corrected for population growth. Allogeneic transplant recipients were older (38.4 vs 48.3 years) and more frequently had unrelated donors in the second decade. Similarly, age increased for recipients of autologous HCT (50.8 vs 56.4 years). Analysis of outcome showed that the probabilities of overall and progression-free survival were stable over time, in spite of the treatment of older and higher risk patients. In multivariate analysis, nonrelapse mortality decreased in recipients of allogeneic HCT (relative risk 0.68, 95% confidence interval 0.52-0.87) over the two decades. Improvement in adjusted nonrelapse mortality compensated for the fact that higher risk patients were treated in more recent years, resulting in similar overall survival. Five-year survival probabilities were 56% (53-59%) in the first and 54% (51-57%) in the second decade for allogeneic HCT, and 59% (57-61%) in the first and 61% (59-63%) in the second decade for autologous HCT. Detailed analyses of changes over time are presented. This study included all HCTs performed in Switzerland during the period of observation and the data are useful for quality assurance programmes, healthcare cost estimation and healthcare planning. Between 50 and 60% of patients were long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care and observation