The Role of Complement Activating Collectins and Associated Serine Proteases in Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT)

We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3 months post transplantation. The results were compared with data from 267 healthy controls and analyzed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however not associated with hospital infections or post-HSCT recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up. Paradoxically, high MBL serum levels were a risk factor for prolonged fever and some infections. The first possible association of MBL2 gene 3′-untranslated region polymorphism with cancer (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G mutation was relatively frequent in lymphoma patients who experienced bacteremia during hospital stay. The median concentration of CL-LK was higher in myeloma patients compared with healthy subjects. Chemotherapy induced marked increases in serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively slighter decline in CL-LK level within 1 week. Conflicting findings on the influence of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination with phagocytic cells after their recovery

Ruxolitinib in the treatment of severe graft versus host disease

Choroba przeszczep przeciwko gospodarzowi (GvHD) jest jednym z głownych czynnikow przyczyniających się do śmiertelności po allogenicznej transplantacji komorek krwiotworczych. Standardem postępowania w przypadku przewlekłej postaci GvHD (cGvHD) jest steroidoterapia. W przypadku oporności brakuje ścisłych zaleceń dotyczących wyboru optymalnego leczenia. Wprowadzenie do terapii ruksolitynibu może przyczynić się do zmian w standardach leczenia cGvHD. W pracy przedstawiono opis przypadku pacjentki leczonej ruksolitynibem z powodu steroidoopornej cGvHD.Graft-versus-host disease (GvHD) is one of the major factors contributing to mortality after allogeneic hematopoietic cell transplantation. The standard of care for chronic GvHD (cGvHD) is steroid therapy. In the case of steroid resistance, there are no strict recommendations regarding the choice of optimal treatment. The introduction of ruxolitinib to treatment may contribute to changes in the standards of cGvHD treatment. The paper presents a patient treated with ruxolitinib for steroid refractory-GvHD

Tolerance and efficacy of total body irradiation and cladribine prior to allogeneic hematopoietic cells transplantation in patients with acute myeloid leukemia and myelodysplastic syndromes — synopsis of clinical study

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is a standard of care for patients with acute myeloid leukemia (AML) and patients with intermediate and high-risk myelodysplastic syndrome (MDS). Despite many years of experience. there is still no standard for conditioning regimen. The aim of this study is to analyse the efficacy and safety of a conditioning treatment with cladribine in combination with total body irradiation (TBI). Material and methods: A group of 40 adult patients referred for allo-HCT due to AML and MDS are to be enrolled in the study. The inclusion criteria are: informed consent, chemo-sensitivity for cladribine treatment regimens (when used in induction therapy), age 18–60, and performance status 0–2 according to World Health Organization. The conditioning regimen consists of cladribine and TBI at a total dose of 12 Gy in three fractions given over three consecutive days. The goal of the study is to assess the tolerability and efficacy of the regimen. Results: Our results may stimulate further investigation in this field i.e. phase III trials to compare this regimen to others. Conslusion: A myeloablative conditioning regimen consisting of total body irradiation in combination with cladribine may contribute to improved outcomes after allo-HCT for AML and MDS patients

The effect of an online acceptance and commitment intervention on the meaning-making process in cancer patients following hematopoietic cell transplantation: study protocol for a randomized controlled trial enhanced with single-case experimental design

Abstract Background Hematopoietic cell transplantation (HCT) is a highly invasive and life-threatening treatment for hematological neoplasms and some types of cancer that can challenge the patient’s meaning structures. Restoring meaning (i.e., building more flexible and significant explanations of the disease and treatment burden) can be aided by strengthening psychological flexibility by means of an Acceptance and Commitment Therapy (ACT) intervention. Thus, this trial aims to examine the effect of the ACT intervention on the meaning-making process and the underlying mechanisms of change in patients following HCT compared to a minimally enhanced usual care (mEUC) control group. The trial will be enhanced with a single-case experimental design (SCED), where ACT interventions will be compared between individuals with various pre-intervention intervals. Methods In total, 192 patients who qualify for the first autologous or allogeneic HCT will be recruited for a two-armed parallel randomized controlled trial comparing an online self-help 14-day ACT training to education sessions (recommendations following HCT). In both conditions, participants will receive once a day a short survey and intervention proposal (about 5–10 min a day) in the outpatient period. Double-blinded assessment will be conducted at baseline, during the intervention, immediately, 1 month, and 3 months after the intervention. In addition, 6–9 participants will be invited to SCED and randomly assigned to pre-intervention measurement length (1–3 weeks) before completing ACT intervention, followed by 7-day observations at the 2nd and 3rd post-intervention measure. The primary outcome is meaning-related distress. Secondary outcomes include psychological flexibility, meaning-making coping, meanings made, and well-being as well as global and situational meaning. Discussion This trial represents the first study that integrates the ACT and meaning-making frameworks to reduce meaning-related distress, stimulate the meaning-making process, and enhance the well-being of HCT recipients. Testing of an intervention to address existential concerns unique to patients undergoing HCT will be reinforced by a statistically rigorous idiographic approach to see what works for whom and when. Since access to interventions in the HCT population is limited, the web-based ACT self-help program could potentially fill this gap. Trial registration ClinicalTrials.gov ID: NCT06266182. Registered on February 20, 2024

Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group

Abstract Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment

Antimicrobial prophylaxis in adults and children undergoing hematopoietic cell transplantation: 2021 Polish recommendations

Infections are still a major reason of morbidity and one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper is presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation of Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing ECIL (European Conference on Infections in Leukemia) and EBMT (European Society of Blood and Marrow Transplantation) guidelines, as well as results of survey performed among all Polish transplant centers, were the background material for working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented