BACKGROUND:Chronic graft-versus-host disease (cGVHD) represents a major complication after allogeneic stem cell transplantation (alloHSCT). In 2009 and 2018 a survey among German, Austrian, and Swiss transplant centers showed a homogeneous 1st-line treatment practice, while 2nd-line treatment as well as management of progressive onset type and bronchiolitis obliterans syndrome (BOS) displayed significant heterogeneity. Since the last survey, ruxolitinib (rux) has been approved and other new agents are explored in treatment of cGVHD. OBJECTIVE:We conducted a follow-up survey in 2024 to document the impact of recent approvals and new agents on treatment pattern focusing on management of 2nd-line treatment, progressive onset type, BOS, and sclerotic manifestations. STUDY DESIGN:A paper-and-pencil-based questionnaire was sent electronically to 60 German speaking centers performing alloHSCT. 20 centers responded, representing 45% of the patients receiving an alloHSCT in 2023 in Germany, Austria, and Switzerland. RESULTS:In 1st-line treatment of classic standard risk cGVHD, single agent prednisone represents standard of care (14/20 centers) which may be combined with calcineurin inhibitor (CNI) (4/20), while rux is used in selected cases only. In 2nd-line treatment rux is now used by the majority of centers (19/20). In the presence of cytopenia, rux remains the preferred agent (12/20) while use of extracorporeal photopheresis (ECP) is considered by 8 of 20 centers. In case of active infections, ECP is preferred by 15 of 20 centers and both agents are regarded as steroid-sparing agents in 2nd-line treatment of steroid-dependent cGVHD. Rux would be applied in the presence of active infections by 5/20 centers only. Moreover, rux (15/20) and ECP (6/20) are also preferred treatment modalities in treatment of progressive onset cGVHD. For BOS, systemic and inhalative corticosteroids, montelukast and azithromycin (FAM, 13/20), rux (15/20), ECP (17/20) and CNI (10/20) are frequently applied agents, while abatacept (8/20), belumosudil (7/20), imatinib (5/20), mycophenolate mofetil (MMF) (5/20), everolimus (4/20) and ibrutinib (3/20) are used as salvage options in selected patients only. In case of new sclerotic manifestations after failure of 2nd-line treatment including steroids, CNI and rux, most centers would use ECP (14/20), whereas subsequent or alternative salvage treatment of sclerotic manifestations remains heterogenous comprising belumosudil (13/20), ibrutinib (5/20), imatinib (5/20), rituximab (4/20), cyclosporine (3/20), tacrolimus (3/20), everolimus (3/20), sirolimus (3/20), methotrexate (3/20) and MMF (3/20). The preferred taper sequence of immunosuppressive agents in case of response applied in 12/20 centers is initial taper of steroids, followed by taper of CNI and final termination of rux. CONCLUSION:The survey documents the effect of evidence and approval on clinical care with single agent prednisone representing the standard of care in 1st-line treatment while rux combined with steroids defines the new standard for 2nd-line treatment of cGVHD. ECP is used in case of contraindication for rux and both agents are also used in progressive onset cGVHD. In contrast, treatment of BOS and sclerotic cGVHD beyond 2nd-line treatment remains heterogeneous with new agents being integrated in the treatment landscape.

eHealth-supported integrated care models (eICMs) enable early complication management and foster self-management. The SMILe-ICM, an Advanced Practice Nurse (APN)-led eICM for patients after hematopoietic cell transplantation, was previously tested in Germany and adapted for Switzerland.This study evaluated the Swiss SMILe-ICM in a hybrid effectiveness–implementation randomized controlled trial. Implementation outcomes (acceptability, feasibility, appropriateness) were assessed via 5-point Likert scales (higher = better). The primary effectiveness outcome was time to first rehospitalization; secondary outcomes included rehospitalization rates, durations, and causes, as well as survival, dropout, recruitment time, and adverse events.From April 2021 to July 2022, 80 patients were randomized (1:1) to intervention (IG) or usual care (UCG). Dropout was 35%; recruitment ended nine months early. APNs and patients rated implementation outcomes very high (mean = 4.9, SD = 0.3). Median time to first unplanned rehospitalization was longer in IG (86.5 vs. 56.0 days). Group differences were non-significant (HR = 0.84; p = 0.57) but causes differed (relapse (IG) vs. infection (UCG)). One-year survival was comparable (81% vs. 83%, HR = 1.17; p = 0.74). No adverse events occurred.Despite being underpowered, findings confirm high implementation success and suggest effectiveness going in hypothesized trends. Larger multicenter cluster-RCTs are warranted.

Therapeutic drug monitoring of busulfan (Bu) used as conditioning for allogeneic stem cell transplantation (allo-HSCT) is recommended as pharmacokinetics (PK) display variability. Since 2019, we give Bu 1x/d (Bu-Q24) instead of 4x/d (Bu-Q6) for practical convenience, despite limited studies evaluating the best way of application. Our aim was to analyze the correlation between Bu administration (Bu-Q6 versus Bu-Q24), Bu-PK and clinical outcome in adult patients receiving Bu as conditioning regimen for allo-HSCT. This was a retrospective study of 256 adult patients receiving a myeloablative chemotherapeutic regimen containing Bu to treat hematological malignancies. The population was separated into 2 groups according to Bu administration, namely Bu-Q6 and Bu-Q24. A total of 133 patients received Bu-Q6 and 123 Bu-Q24. Bu-Q6 patients were more commonly treated with cyclophosphamide and Bu-Q24 with fludarabine. Bu-Q6 showed lower cumulative area-under-the-curve (AUC) values than Bu-Q24 (63.78 mg*h/L in Bu-Q6 and 70.12 mg*h/L in Bu-Q24, P = .06). Only 44% of the patients fell within the 1st AUC FDA target range in Bu-Q6 versus 62% in Bu-Q24 (P < .01). Overall, Bu-Q24 appeared to be superior to Bu-Q6 for most outcomes, showing lower incidence of toxicity grade ≥ II (78% versus 90%, P = .02), with less uro-renal (14% in Bu-Q24 versus 26% in Bu-Q6; P = .02), pulmonary (2% versus 8%, P = .05) and gastro-intestinal toxicities (10% versus 17%, P < .01). Patient receiving Bu-Q24 had fewer infections (51% versus 65%; P = .04), particularly bacterial (33% versus 47%, P = .03) and fungal infections (10% versus 20%; P = .03). At 2 yr, Bu-Q24 tended to have lower treatment-related mortality (TRM) (5% versus 10%, P = .13), relapse rate (37% versus 42%, P = .55) and incidence of acute and chronic graft-versus-host-disease (24% versus 28%; 32% versus 36%, respectively). The overall survival (OS) was 81% (95% CI 74% to 89%) in Bu-Q24 and 69% (95% CI 62% to 77%, P = .03) in Bu-Q6. The only benefit of Bu-Q6 was mucositis grade ≥ III, with an incidence of 36% versus 60% in Bu-Q24 (P < .01). Patients with a cumulative AUC < 59.11 mg*h/L had the lowest TRM, without impact on the OS. Bu clearance was largely influenced by BMI and age > 60 yr. Bu administered once a day shows benefit both in the short and long term compared to Bu administered 4 times a day, but data are heterogeneus, Bu-Q24 being more commonly associated with use of fludarabine, Bu-Q6 with use of cyclophosphamide in this study.

Allogeneic stem cell transplantation (alloSCT) is one of the most complex medical interventions. It requires long-term adherence to medication and follow up care, necessitating effective patient-centered communication. However, physician-patient-communication frequently fails on multiple layers. To gain insights into the perceived communication needs of patients with chronic Graft-versus-Host Disease (cGvHD), we performed a community advisory board (CAB) with 12 European patients, which revealed major communication gaps. The CAB included 12 patient advocates, 9 of whom had personally undergone alloSCT and developed cGvHD. The results of the CAB were complemented by three studies where we interviewed 72 German patients in total. Twenty patients were interviewed prior to alloSCT and 52 at a median of 2.7 years (range: 1.2-5) after alloSCT. The results were subsequently discussed within an international symposium involving 35 healthcare providers and researchers from various disciplines, including physicians, psychologists, communication scientists, physiotherapists and nurses, as well as patient advocates. The symposium aimed to align the findings with joint guidance on short- and long-term goals to improve patient communication related to alloSCT. Several areas of need were identified. Patients perceive informed consent processes as overwhelming, leading to a lack of recall, which increases over time and impairs the ability to participate in shared decision making. Intercultural mismatches (e. g., related to language barriers or misconceptions regarding roles and responsibilities in communication) commonly contribute to the feeling of being overwhelmed and remain challenging for physicians, patients and their support persons. Patients frequently report a lack of knowledge of the early symptoms of cGvHD and other late effects often leading to delayed diagnosis. The need for dynamic patient information throughout the transplant course was repeatedly emphasized, including a lack of information on tapering hygiene restrictions and occupational rehabilitation. Psychosocial symptom load (e. g., psychological distress, cognitive impairment, challenges with adherence) is frequently neither recognized nor addressed by the healthcare team. This is in part due to the discordance between patients and physicians in terms of who is considered responsible for bringing-up symptoms and concerns. There is confusion as to what falls into the physicians' responsibility vs. the patients' responsibility. Physicians are often unsure how best to identify patients' needs, and many patients are reluctant to raise issues unrelated to physical symptoms or issues often considered as taboos, such as sexual health. At the organizational level, patients report a lack of intersectional communication between healthcare providers and an urgent need for reliable low-barrier access to transplant centers. The availability of an accessible healthcare provider (e. g., nurse) as a central point of contact and a back-up source to address physician-patient communication gaps was emphasized. Moreover, the context of outpatient counselling, involving limited time to focus on individual patients' needs, rotating staff and a lack of feedback systems (e.g., patient satisfaction surveys), contributes to perceived communication gaps. An additional area of information needs arises from the lack of expertise of non-transplantation healthcare providers in transplant-specific complications, which commonly leads to conflicting diagnoses and increases in patient distress. To address the identified communication gaps, which interfere with effective medical management, impair quality of life and delay patient recovery, a NIH taskforce was created. The taskforce aims to discuss and further develop short- and long-term interventions designed to help deliver optimal care prior and post alloSCT. Strategies include improved patient information, supporting shared decision making and self-management of symptoms. A more active discussion of frequently ignored topic areas could be achieved by implementing patient question prompt lists, as well as physician checklists for patient needs and understanding. In addition, further training on optimal patient-centered care could help improve communication with patients and support persons, as well as within the multidisciplinary team.

Pruritus is a common symptom of cutaneous graft-versus-host disease (GVHD) following haematopoietic stem cell transplantation (HSCT). However, little is known about its prevalence, pathophysiology, perceptual characteristics, impact on quality of life and response to antipruritic therapies. The aim of this review was to determine the current knowledge on pruritus in cutaneous GVHD. The review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Of the 338 studies screened, 13 were included. The prevalence of pruritus in cutaneous GVHD was reported in three studies, ranging from 37.0% to 63.8%. Only four trials used pruritus assessment tools. There was little or no information on the intensity of pruritus, its qualitative perception, the location of pruritus and the impact of pruritus on quality of life. Antipruritic treatments for GVHD-associated pruritus were mentioned in five studies (38.5%), including topical ointments (steroids, tacrolimus and calcipotriene), broadband UVB, systemic antihistamines and oral ursodeoxycholic acid. In conclusion, pruritus in cutaneous GVHD appears to be common, but very little is known about the pathophysiology, impact on quality of life and effective treatment options. Basic research and controlled clinical trials are warranted to improve knowledge and management of this important issue.

Introduction: Long-term survival after allogeneic hematopoietic cell transplantation (alloHCT) is limited by chronic pulmonary graft-versus-host disease (cGvHD) which comprise classical bronchiolitis obliterans (BO), but also various forms of restrictive disease. Histological confirmation of BO by transbronchial forceps biopsy has a low sensitivity and surgical lung biopsy is gold standard. The clinical diagnosis of BO syndrome (BOS) is based on lung function and radiological data. However, sensitivity of BOS-criteria for biopsy-proven BO is unsatisfactory. Aim: Retrospective study to investigate the diagnostic value of transbronchial cryobiopsy in alloHCT-patients with suspicion of pulmonary cGvHD not fulfilling BOS-criteria. Histology was integrated into the multidisciplinary discussion (MDD) and diagnostic consensus was sought. Results: 20 patients underwent cryobiopsy. In 13/20 patients (65%) cryobiopsies revealed findings leading to a specific diagnosis: obliterative/lymphocytic bronchiolitis in four (20%), distinct parenchymal abnormalities leading to the diagnosis of interstitial lung disease (ILD) or cGvHD-associated ILD in 9/20 patients (45%). In 7/20 patients (35%), cryobiopsies showed normal lung parenchyma. In 4/7, a consensus diagnosis of BOS was reached after MDD. Complications of cryobiopsy included pneumothorax (25%) and locally controlled bleeding (20%). Conclusion: In alloHCT-patients with suspicion of pulmonary cGvHD not fulfilling BOS-criteria, transbronchial cryobiopsy led to a histology-based diagnosis in two-thirds of patients, and – embedded in an MDD - to a final diagnosis in 90% of patients.

Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.

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.

We read with great interest the manuscript by Iglói et al. on an investigation of a human parainfluenza virus-3 (HPIV-3) outbreak in a haematology ward. This outbreak was controlled by implementing several measures, including systematic screening of all newly admitted patients for HPIV-3, the use of surgical masks by personnel and visitors, and the use of masks by patients when visiting the outpatient department or when moving through the hospital [1].

The contribution of related donors to the globally rising number of allogeneic haematopoietic stem cell transplantations (HSCT) remains increasingly important, particularly because of the growing use of haploidentical HSCT. Compared with the strict recommendations on the suitability for unrelated donors, criteria for related donors allow for more discretion and vary between centres. In 2015, the donor outcome committee of the Worldwide Network for Blood and Marrow Transplantation (WBMT) proposed consensus recommendations of suitability criteria for paediatric and adult related donors. This Review provides updates and additions to these recommendations from a panel of experts with global representation, including the WBMT, the European Society for Blood and Marrow Transplantation donor outcome committee, the Center for International Blood and Marrow Transplant Research donor health and safety committee, the US National Marrow Donor Program, and the World Marrow Donor Association, after review of the current literature and guidelines. Sections on the suitability of related donors who would not qualify as unrelated donors have been updated. Sections on communicable diseases, clonal haematopoiesis of indeterminate potential, paediatric aspects including psychological issues, and reporting on serious adverse events have been added. The intention of this Review is to support decision making, with the goal of minimising the medical risk to the donor and protecting the recipient from transmissible diseases.