Antithrombotic therapy with rivaroxaban in five patients with paroxysmal nocturnal haemoglobinuria and thrombotic events

Five patients with paroxysmal nocturnal haemoglobinuria and thrombotic complications under oral antithrombotic treatment with vitamin K antagonist were switched to receive the direct oral anticoagulant rivaroxaban an factor Xa inhibitor. In all five patients haematological and biochemical parameters and adverse events were evaluated for a period of twelve months. Therapy with rivaroxaban was well tolerated in all cases and one patient showed a significant reduction of bleeding and transfusion requirement. All patients obtained a significant reduction in days of hospitalization with a consequent improvement in their quality of life after rivaroxaban treatment

Multi‑parametric MRI in the diagnosis and scoring of gastrointestinal acute graft‑versus‑host disease

Objectives Acute gastrointestinal graft-versus-host disease (GI-aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). Diagnosis relies on clinical, endoscopic, and pathological investigations. Our purpose is to assess the value of magnetic resonance imaging (MRI) in the diagnosis, staging, and prediction of GI-aGVHD-related mortality. Methods Twenty-one hematological patients who underwent MRI for clinical suspicion of acute GI-GVHD were retrospectively selected. Three independent radiologists, blinded to the clinical findings, reanalyzed MRI images. The GI tract was evaluated from stomach to rectum by analyzing fifteen MRI signs suggestive of intestinal and peritoneal inflammation. All selected patients underwent colonoscopy with biopsies. Disease severity was determined on the basis of clinical criteria, identifying 4 stages of increasing severity. Disease-related mortality was also assessed. Results The diagnosis of GI-aGVHD was histologically confirmed with biopsy in 13 patients (61.9%). Using 6 major signs (diagnostic score), MRI showed 84.6% sensitivity and 100% specificity in identifying GI-aGVHD (AUC = 0.962; 95% confidence interval 0.891–1). The proximal, middle, and distal ileum were the segments most frequently affected by the disease (84.6%). Using all 15 signs of inflammation (severity score), MRI showed 100% sensitivity and 90% specificity for 1-month related mortality. No correlation with the clinical score was found. Conclusion MRI has proved to be an effective tool for diagnosing and scoring GI-aGVHD, with a high prognostic value. If larger studies will confirm these results, MRI could partly replace endoscopy, thus becoming the primary diagnostic tool for GI-aGVHD, being more complete, less invasive, and more easily repeatable. Key Points • We have developed a new promising MRI diagnostic score for GI-aGVHD with a sensitivity of 84.6% and specificity of 100%; results are to be confirmed by larger multicentric studies. • This MRI diagnostic score is based on the six MRI signs most frequently associated with GI-aGVHD: small-bowel inflammatory involvement, bowel wall stratification on T2-w images, wall stratification on post-contrast T1-w images, ascites, and edema of retroperitoneal fat and declivous soft tissues. • A broader MRI severity score based on 15 MRI signs showed no correlation with clinical staging but high prognostic value (100% sensitivity, 90% specificity for 1-month related mortality); these results also need to be confirmed by larger studies

Photo-biomodulation as a prevention modality of oral mucositis in patients undergoing allogeneic hematopoietic stem cell transplantation

The aim of the study was to observe the eectiveness of a photo-biomodulation (PBM) protocol for the prevention of oral mucositis (OM) in patients undergoing allogeneic hematopoietic stem cell transplantation (aHSCT). A case-control study was conducted on 40 patients undergoing aHSCT. The patients were divided into two groups; the preventive group (PG) included 20 patients (7 females and 13 males) who were subjected to intra-oral PBM for five sessions a week, starting one day before the conditioning regimen and continuing until the 10th day after transplantation (D+10). In each session, ten points on the at-risk mucosal surfaces were irradiated using a double diode laser that emits two wavelengths simultaneously at 650 nm and at 904–910 nm with the following parameters at each point: energy of 4 J, and power of 88.9 mW. The control group (CG) included 20 patients (10 females and 10 males) who were not subjected to laser therapy and were selected retrospectively to compare the obtained results. For all patients, OM was assessed by the World Health Organization (WHO) grading scale. Eight patients in the PG did not experience OM during their hospitalization period (with grade 0). Severe OM was observed in 40% of the patients in the PG, while in the CG, severe OM was shown in 85% of the patients. The mean duration of OM in the PG was significantly lower than that of CG (4.7 days in the PG and 15 days in the CG) (p < 0.001). The study demonstrated that the preventive PBM protocol reduced the severity and duration of OM in patients undergoing aHSCT

Anti-HLA donor-specific antibodies in allogeneic stem cell transplantation: management and desensitization protocol

The role of antibodies directed against the human leukocyte antigen (HLA) system has been well analyzed in rejection of solid organ transplantations [1, 2] and in transfusion medicine [3]. In the setting of allogeneic hematopoietic stem cells transplantation (HSCT), only in the recent years their importance has been better defined, even though anti-HLA antibodies are frequently detectable in hematologic patients, due to sensitization from multiple transfusions, usually before the introduction of online universal leukoreduction, previous transplantations, and pregnancies in female patients

Combined antiviral therapy as effective and feasible option in allogenic hematopoietic stem cell transplantation during SARS-COV-2 infection: a case report

Here we describe the case of a 51 years old Italian woman with acute lymphoblastic leukemia who underwent to hematopoietic stem cell transplantation (HSCT) during SARS-COV-2 infection. She presented a prolonged COVID-19 successfully treated with dual anti SARS-COV-2 antiviral plus monoclonal antibody therapy

Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia after Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Background Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P =.01). Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840

Low Body Mass Index Is Associated with Increased Risk of Acute GVHD after Umbilical Cord Blood Transplantation in Children and Young Adults with Acute Leukemia: A Study on Behalf of Eurocord and the EBMT Pediatric Disease Working Party

Abstract Body mass index (BMI) may influence outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of BMI on survival in children undergoing HSCT is not well defined, with conflicting results being reported on this issue. We analyzed 855 patients age 2 to 20 years with diagnosis of acute leukemia who underwent umbilical cord blood transplantation (UCBT) from 1990 to 2015. Patients were classified according to BMI as normal (fifth to 85th percentile), underweight (less than fifth percentile), overweight (85th to 95th percentile), and obese (>95th percentile) using growth charts for age and sex. All patients received single-unit UCBT after a myeloablative conditioning regimen. Diagnosis was acute lymphoblastic leukemia in 68% of the patients. Sixty-one percent of patients (n = 523) were in the normal BMI category, 11% (n = 96) were underweight, 16% (n = 137) overweight, and 12% (n = 99) obese. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was 35% (32% to 38%). According to pretransplantation BMI, aGVHD was 46% (33% to 59%) for underweight, 34% (31% to 42%) for normal, 36% (18% to 38%) for overweight, and 27% (15% to 37%) for obese ( P  = .04). In multivariate analysis, a BMI less than the fifth percentile was associated with higher incidence of acute grade II to IV GVHD compared with normal-BMI patients (hazard ratio,  1.61; 95% confidence interval, 1.15 to 2.26; P  = .006). Our results show that being underweight at the time of transplantation is associated with an increased risk of aGVHD, highlighting the importance of nutritional status before UCBT

Final Evaluation of a Clinical Phase III Trial Comparing Treosulfan to Busulfan-Based Conditioning Therapy Prior to Allogeneic Hematopoietic Stem Cell Transplantation of Adult Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients Ineligible to Standard Myeloablative Regimens

Background Allogeneic hematopoietic stem cell transplantation (HCT) remains a challenge in elderly and comorbid AML and MDS patients. This patient population is at increased risk for non-relapse mortality (NRM) when treated with standard myeloablative conditioning and was selected to compare a newly developed treosulfan-based with a well-established reduced intensity busulfan-based preparative regimen in a prospective randomized clinical phase III trial. Methods Adult patients with AML in remission or MDS scheduled for HCT from matched related or unrelated donors, aged ≥50 years or with a comorbidity index (HCT-CI) of >2 were enrolled by a central stratified randomization procedure. Treatment arms consisted of intravenous (IV) treosulfan (10 g/m²/day [d-4 to d-2]) or IV busulfan (3.2 mg/kg/day [d-4 to d-3]), both combined with IV fludarabine (30 mg/m²/day [d-6 to d-2]). The primary objective was to compare event-free survival (EFS) at two years with relapse/progression of disease, graft failure, or death reported as events. Secondary endpoints were safety evaluation (according to CTCAE v4.03), engraftment, chimerism, overall survival (OS), relapse/progression incidence (RI), NRM and acute or chronic GvHD. After a previously conducted confirmatory interim analysis (based on 476 patients), which resulted in early termination of patient accrual due to significant non-inferiority of treosulfan treatment with improved EFS, NRM and OS (Beelen et al., ASH 2017), results of the final analysis of all 570 randomized patients including post surveillance data are provided here. Results Median age of the 551 patients (352 AML; 199 MDS) included in the full analysis set (268 treosulfan; 283 busulfan) was 60 years (range: 31, 70). Frequencies of early adverse events (d-6 to d+28) and incidences of acute and chronic GvHD were largely comparable between the two regimens, while extensive chronic GvHD was numerically in favor of treosulfan (19.7% vs. 26.7%; p=0.0750). Primary neutrophil recovery at day +28 was comparable, while the rate of complete donor-type chimerism (day +28) was higher after treosulfan (93.2% vs. 83.3%; p Conclusions Final evaluation of this phase III trial substantiates the previous confirmatory analysis resulting in significantly improved survival after treosulfan-based conditioning. Due to the reduction of NRM a major clinical benefit of the new treosulfan conditioning regimen was demonstrated in the selected AML/MDS patient population