Search

We have identified and characterized a novel β-thalassemic mutation in an Afghanistani family. The molecular pathology consists of a single base substitution (T G G→T A G) at codon 37 of the β-globin gene, giving rise to a stop codon (TAG). Premature stop of translation results in a truncated protein and usually the phenotype of β-thalassemia (thal) major in homozygous individuals. However, this was not the case in our proband, who was homozygous for the codon 37 mutation. He presented with the phenotype of thalassemia intermedia with a hemoglobin (Hb) level of 8.1 g/dL and no previous history of blood transfusions. High performance liquid chromatography (HPLC) analysis showed exclusively Hb F except for a Hb A 2 level within normal limits. Subsequent analysis demonstrated homozygosity for the Xmn I G γ polymorphism and heterozygosity for a deletional α-thal (αα/ - α - 3.7 ). These findings might, at least partly, explain the β-thal intermedia phenotype observed in the proband. [ABSTRACT FROM AUTHOR]

Non-pharmacological interventions have the potential to enhance health-related quality of life (HRQoL) through symptom management. This systematic review aims to identify, collate, and assess randomized controlled trials investigating the effect of non-pharmacological interventions on symptoms and HRQoL within hematology. MEDLINE/PUBMED, EMBASE, CINAHL, PSYCINFO and COCHRANE were searched up to April 2021. Outcomes were changes in symptoms and HRQoL. Sixty-five studies were categorized into five intervention types: Mind/body (n=9), Web-based (n=9), Music/art (n=6), Consultation-based (n=4), and Physical activity (n=37). We found significantly reduced fatigue (n=12 studies), anxiety (n=8) and depression (n=7), with 11 studies showing significant improvements in HRQoL. The evidence for non-pharmacological interventions shows substantial variation in efficacy and methodological quality. While specific symptoms and HRQoL outcomes significantly favored the intervention, no particular intervention can be emphasized as more favorable, given the inability to conduct a meta-analysis. [Display omitted] • Non-pharmacological interventions may be beneficial in hematological malignancies. • Fatigue was the most investigated symptom with significant findings in 12 studies. • Quality of life was measured in 35 studies with 11 significant findings. • Results from diverse non-pharmacological interventions show varying efficacy. • Randomized trials with adequate power are needed in supportive care in hematology. [ABSTRACT FROM AUTHOR]

Allogenic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning traditionally requires 30 days of hospitalization after stem cell infusion. However, advancements in supportive and prophylactic care have allowed for a trend toward outpatient management of allo-HCT, potentially leading to improved patient quality of life and increased cost-effectiveness of the procedure. In 2014, fludarabine and treosulfan (FluTreo) conditioning was introduced as a myeloablative regimen with reduced toxicity at Copenhagen University Hospital, Rigshospitalet (CUH). After gaining experience with the regimen, an outpatient program was established. Here we share the outcomes of outpatient conditioning with FluTreo allo-HCT at CUH. This study was conducted to investigate the safety and feasibility of outpatient FluTreo allo-HCT, as well as to investigate the potentially improved cost-effectiveness of outpatient allo-HCT primarily through a reduction in hospital length of stay compared to the 30 days of hospitalization associated with standard myeloablative conditioning. This retrospective study included all patients undergoing FluTreo allo-HCT due to malignant diseases (n = 124) at CUH between 2018 and 2022. Patients received outpatient treatment (n = 91) unless certain circumstances necessitated planned hospitalization (n = 33). As conditioning, patients received i.v. fludarabine 90 mg/m 2 and treosulfan either 30 or 42 g/m 2 . Statistical analyses included descriptive statistics and Kaplan-Meier survival analysis. The median duration of hospitalization in the outpatient group was 4 days (interquartile range [IQR], 0 to 12.5 days) from day -6 to day +28 compared to a median of 28 days (IQR, 26 to 34 days) in the inpatient group. Thirty-two patients (35%) in the outpatient group did not require hospitalization before day +28 post-transplantation. The remaining 59 patients (65%) were hospitalized after a median of 12 days (IQR, 7 to 16 days) from the start of conditioning, with a median stay of 10 days (IQR, 5 to 18 days). The outpatient group required significantly less i.v. antibiotics, i.v. opioids, and parenteral nutrition compared to the inpatient group, despite no differences in treatment toxicity, acute graft-versus-host disease, or relapse between the groups. The outpatient group experienced no early deaths during the first 3 months after transplantation, and 1-year nonrelapse mortality was 6%. Outpatient allo-HCT with FluTreo conditioning is feasible and safe in a selected group of patients, significantly reducing hospitalization days without compromising patient outcomes. Outpatient FluTreo allo-HCT potentially provides a more cost-effective and patient-friendly alternative compared to traditional in-patient management., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: To explore study participants' experiences with chronic hematologic malignancies and their perspectives on symptom management based on patient-reported outcomes during follow-up care., Methods: This qualitative descriptive study used semi-structured telephone interviews conducted from May 2022 to February 2023. A purposeful sample was recruited, with participants invited consecutively. Participants were adults ≥18 years diagnosed with a chronic hematological malignancy and participating in a symptom management intervention. Reflexive thematic analysis, as described by Braun and Clarke, was used to perform an inductive analysis of the interview data., Results: A total of 19 telephone interviews were conducted with 17 participants. Participants had nuanced perspectives on managing life with a chronic and uncommon hematological malignancy reflected in the following themes: not allowing the disease to dominate, struggling to understand and manage the disease, navigating everyday life with the disease, and evaluating impact and tailoring of patient reported outcome-based symptom management., Conclusion: This study emphasizes the ambiguity of living with a chronic hematological malignancy. Participants strive to prevent the disease from dominating their lives, despite their struggles to understand and manage the disease. The use of patient-reported outcomes in dialogue and targeted symptom management helped participants navigate daily life challenges. These findings underscore important considerations for enhancing follow-up care for patients with chronic hematological malignancies., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Cancer treatment with high-dose chemotherapy damages the mucosal barrier of the gastrointestinal (GI) tract and is associated with severe toxicity involving mucositis, severe inflammation and organ dysfunction. Currently, there is no effective prophylaxis against this. Glucagon-like peptide 1 (GLP-1), a well-known regulator of blood glucose, has been suggested in mouse studies to possess trophic effects on gut epithelial cells as well as anti-inflammatory properties. In line with this, endogenous GLP-1 levels have been shown to be inversely correlated with toxicities after haematopoietic stem cell transplantation (HSCT) and treatment with a GLP-1 receptor agonist (GLP-1RA) was shown to limit chemotherapy-induced mucositis in rodents. This present study investigates the effects of the GLP-1RA semaglutide on GI mucositis severity score in patients with lymphoma undergoing high-dose chemotherapy followed by autologous (auto) HSCT., Methods and Analysis: This is a randomised, double-blind, placebo-controlled, two-centre investigator-initiated clinical study. Forty adult patients with malignant lymphoma referred for auto-HSCT will be randomised in a 1:1 manner to receive either semaglutide or placebo once-weekly for 8 weeks. This includes a run-in period of 3-4 weeks with semaglutide 0.25 mg prior to high-dose chemotherapy treatment followed by a period of 4-5 weeks with semaglutide 0.5 mg including the 1 week of high-dose chemotherapy treatment. Clinical assessment of endpoint measurements and safety will be performed weekly during treatment and in a follow-up period of 10 weeks. The primary endpoint is GI mucositis severity (mean severity grade (0-II) during week 1-4 after auto-HSCT). Secondary endpoints include C-reactive protein increment, quality of life and safety. Fever, bacteraemia, antibiotic use, weight loss, morphine consumption, duration of hospitalisation, use of parenteral nutrition, change in muscle mass and clinical and laboratory evidence of organ toxicities will also be assessed., Ethics and Dissemination: The study complies with Danish and European Union legislation and is approved by the Danish Medicines Agency, the Danish National Medical Research Ethics Committee (EU CT #2022-502139-20-00) and the Danish Data Protection Agency. The study is monitored by the Capital Region of Denmark's good clinical practice unit. All results, positive, negative and inconclusive, will be disseminated at national and international scientific meetings and in peer-reviewed scientific journals., Trial Registration Number: NCT06449625., Competing Interests: Competing interests: MES, AOG, DMT, SG, HK, BK and KM declare no competing interest. FKK is currently employed by Novo Nordisk A/S., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ruxolitinib has become the new standard of care for steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Our aim was to collect comparative data between ruxolitinib and extracorporeal photophoresis (ECP). We asked EBMT centers if they were willing to provide detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. 31 centers responded positively and we included all patients between 1/2017-7/2019 treated with ECP or ruxolitinib for moderate or severe SR-cGVHD. We identified 84 and 57 patients with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-cGVHD (steroid dependent vs. refractory vs. intolerant to steroids). At day+180 after initiation of treatment for SR-cGVHD the odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.35 (95% CI = [0.64; 2.91], p = 0.43). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-cGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-cGVHD., (© 2024. The Author(s).)

Soluble ST2 is established as a prognostic biomarker of nonrelapse mortality (NRM) when measured early after allogeneic hematopoietic cell transplantation (HCT). However, less is known about the prognostic value of ST2 measured before transplantation. We hypothesized that pretransplantation plasma ST2 level was associated with 1-year NRM and could add to our current prognostic assessment. Moreover, we aimed to investigate the associations between pretransplantation plasma ST2 levels and patient characteristics and other plasma biomarkers and to reproduce previous associations between post-transplantation plasma ST2 levels and outcomes of HCT. We conducted this cohort study of 374 adults who underwent allogeneic HCT at our center between July 2015 and December 2019 (median age, 59 years; 55% with a nonmyeloablative conditioning regimen). ST2 levels were measured by enzyme-linked immunosorbent assay in stored plasma samples obtained at a median of 23 days before HCT and also in samples obtained on days +7 and +14 post-HCT. A logistic regression model of 1-year NRM was fitted using an a priori defined set of covariates consisting of age, Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), and conditioning intensity (myeloablative versus nonmyeloablative), to which the pretransplantation ST2 level was added as a variable to assess its incremental prognostic value. Models also were fitted of 1-year all-cause mortality, relapse, and grade II-IV acute graft-versus-host disease (GVHD) for pretransplantation and post-transplantation ST2 levels. The median pretransplantation plasma ST2 level was 20.4 ng/mL (interquartile range, 15.2 to 27.2 ng/mL). Pretransplantation ST2 levels were higher in males compared with females (median, 22.2 ng/mL versus 18.1 ng/mL; P < .001) and were correlated with HCT-CI (Spearman ρ = .18; P < .001), body mass index (ρ = .10; P = .05), and plasma levels of C-reactive protein (ρ = .34; P < .001), creatinine (ρ = .17; P = .001), and albumin (ρ = -.17; P < .001). Pretransplantation ST2 levels added prognostic information about 1-year NRM to age, HCT-CI, and conditioning intensity (adjusted odds ratio [OR] of 1-year NRM per 10 ng/mL increase in ST2, 1.32; 95% confidence interval [CI], 1.05 to 1.65; P = .02). Although adding pretransplantation ST2 levels did not notably improve model discrimination (.674 to .675, ΔAUC = .001), it increased the diversity of the predicted risks (P = .02, likelihood ratio test). Pretransplantation ST2 levels also were prognostic of 1-year all-cause mortality (adjusted OR per 10-ng/mL increase, 1.23; 95% CI, 1.02 to 1.48; P = .03), but not of relapse (P = .47) or acute GvHD (P = .81). Plasma ST2 levels at day +7 were prognostic of 1-year NRM, all-cause mortality, relapse, and acute GVHD, whereas levels at day +14 were prognostic of 1-year NRM and all-cause mortality. Our results show that pretransplantation plasma ST2 levels added prognostic information about 1-year NRM to age, HCT-CI, and conditioning intensity, and suggest that ST2 has potential as a biomarker of pretransplantation vulnerability and should be considered in future developments of prediction models of NRM after allogeneic HCT., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Infusion of ex vivo transduced haematopoietic stem cells (HSC) has emerged as a promising new treatment of certain monogenetic disorders. Since early clinical studies on patients with severe combined immune deficiency were halted due to de novo leukaemia, the technology has matured. Thus, treatment of transfusion-dependent thalassaemia and adenosine deaminase deficient severe combined immunodeficiency by using lentiviral vectors for gene correction of autologous HSC can induce expression of the deficient protein and thus potentially cure the patients. The review summarises recent advances allowing for clinical implementation of the treatment in Denmark.

The study is a randomized phase II trial investigating graft-versus-host disease prophylaxis after non-myeloablative (90 mg/m(2) fludarabine and 2 Gy total body irradiation) human leukocyte antigen matched unrelated donor transplantation. Patients were randomized as follows: arm 1 - tacrolimus 180 days and mycophenolate mofetil 95 days (n=69); arm 2 - tacrolimus 150 days and mycophenolate mofetil 180 days (n=71); arm 3 - tacrolimus 150 days, mycophenolate mofetil 180 days and sirolimus 80 days (n=68). All patients had sustained engraftment. Grade II-IV acute graft-versus-host disease rates in the 3 arms were 64%, 48% and 47% at Day 150, respectively (arm 3 vs. arm 1 (hazard ratio 0.62; P=0.04). Owing to the decreased incidence of acute graft-versus-host disease, systemic steroid use was lower at Day 150 in arm 3 (32% vs. 55% in arm 1 and 49% in arm 2; overall P=0.009 by hazard ratio analysis). The Day 150 incidence of cytomegalovirus reactivation was lower in arm 3 (arm 1, 54%; arm 2, 47%; arm 3, 22%; overall P=0.002 by hazard ratio analysis). Non-relapse mortality was comparable in the three arms at two years (arm 1, 26%; arm 2, 23%; arm 3, 18%). Toxicity rates and other outcome measures were similar between the three arms. The addition of sirolimus to tacrolimus and mycophenolate mofetil is safe and associated with lower incidence of acute graft-versus-host disease and cytomegalovirus reactivation. (clinicaltrials.gov identifier: 00105001)., (Copyright© Ferrata Storti Foundation.)

We have identified and characterized a novel beta-thalassemic mutation in an Afghanistanifamily. The molecular pathology consists of a single base substitution (TGG-->TAG) at codon 37 of the beta-globin gene, giving rise to a stop codon (TAG). Premature stop of translation results in a truncated protein and usually the phenotype of beta-thalassemia (thal) major in homozygous individuals. However, this was not the case in our proband, who was homozygous for the codon 37 mutation. He presented with the phenotype of thalassemia intermedia with a hemoglobin (Hb) level of 8.1 g/dL and no previous history of blood transfusions. High performance liquid chromatography (HPLC) analysis showed exclusively Hb F except for a Hb A2 level within normal limits. Subsequent analysis demonstrated homozygosity for the XmnI Ggamma polymorphism and heterozygosity for a deletional alpha-thal (alphaalpha/-alpha(-3.7)). These findings might, at least partly, explain the beta-thal intermedia phenotype observed in the proband.