Harmonized Immune Recovery Monitoring after HCT: Evidence & Practical Guidance from the Westhafen Intercontinental Group.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative option for patients with high-risk malignancies and non-malignant disorders. Long-term survival depends on robust immune reconstitution (IR), which governs overall immune homeostasis and risks of infection, graft-versus-host disease, and relapse. However, despite its centrality to post-transplant outcomes, IR is not consistently monitored across transplant centers, limiting ability to generate meaningful, comparable, and translatable data.

Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM Trial.

In the randomized cohort of the international phase-III FORUM trial, which showed the superiority of total-body irradiation (TBI) over chemotherapy-based conditioning prior to hematopoietic stem cell transplantation (HSCT) for pediatric acute lymphoblastic leukemia (ALL), type of conditioning and remission phase, but not pre-HSCT minimal residual disease (MRD), were associated with outcome. We report the impact of MRD within the extended FORUM cohort. Patients (n=1014), 4-21 years old, transplanted from a matched donor who had ≥1 MRD measurement prior to and/or 100 days and/or 1 year after HSCT were eligible.

Exercise-induced symptoms in young childhood cancer survivors.

Purpose: Exercise-induced symptoms (EIS) are common in children and understudied in childhood cancer survivors (CCS). We assessed the prevalence of EIS in CCS and identified associated risk factors.

Methods: We included CCS aged 6-21 years who were diagnosed with cancer ≥ 1 year before study entry, were treated with systemic anticancer treatment, chest surgery, radiotherapy, or hematopoietic stem cell transplantation, completed cancer treatment, and received pediatric oncology follow-up care.

Identifying Targeted Therapies for CBFA2T3::GLIS2 Acute Myeloid Leukemia.

fusion positive pediatric acute myeloid leukemia (AML) remains one of the worst prognostic AML subgroups. To uncover innovative targeted therapeutic approaches in this disease subtype we performed genome-scale CRISPR-Cas9 screening that highlighted a strong, selective dependency on compared to other types of cancer. Using a doxycycline-inducible knockout (KO) system, we validated dependency in cell lines, observing impaired proliferation in vitro and in vivo and induced apoptosis with KO.

A Health Service Research Study on a Low-Threshold Hearing Screening Program for Childhood Cancer Survivors in Switzerland: Protocol for the HEAR Study.

Background: Hearing loss is a common late effect in childhood cancer survivors, caused by ototoxic cancer treatments, such as platinum chemotherapy, cranial radiation with doses of ≥30 Gray, and surgery involving the auditory system. Early recognition of hearing loss as part of follow-up care allows for therapeutic support to mitigate consequences. However, hearing tests are usually only repeated in childhood cancer survivors with abnormal hearing during or right after treatment ends, leaving hearing loss undetected in childhood cancer survivors with late onset or when missed during cancer treatment.

Meeting the Challenges of Post-Transplant Lymphoproliferative Disorders After Liver Transplantation in Children: A Proposed Diagnostic and Management Algorithm.

Background: Post-transplant lymphoproliferative disorders (PTLD) may significantly impair outcomes in children after solid organ transplantation (SOT). Diagnosis and treatment may be challenging. We analyze a representative pediatric liver transplant (LT) cohort in light of these challenges.

Assessing Pulmonary Function in Children and Adolescents After Cancer Treatment: Protocol for a Multicenter Cohort Study (Swiss Childhood Cancer Survivor Study FollowUp-Pulmo).

Background: Childhood cancer survivors (CCS) are at risk of pulmonary dysfunction due to cancer treatments, but evidence on prevalence and risk factors remains limited. Most previous studies had small sample sizes or retrospective study designs, little information about treatments, or a lack of standardization of pulmonary function tests (PFTs) or limited their investigation to certain PFTs. Since spirometry mainly assesses the large airways but cancer therapy also affects peripheral airways, additional functional tests are needed.

Awareness about the risk of hearing loss after ototoxic treatments in Swiss childhood cancer survivors.

Objectives: The International Guideline Harmonization Group recommends childhood cancer survivors (CCS) exposed to ototoxic treatments be aware of the risk of hearing loss. We assessed awareness among adult CCS.

Methods: We identified adults diagnosed with cancer < 20 years who received ototoxic treatments through the Swiss Childhood Cancer Registry (ChCR) and invited them to the HEAR-study.

Financial Support and Income Satisfaction Among Grandparents of Childhood Cancer Patients: A Brief Report.

Childhood cancer imposes a financial burden on families. We explored the financial support grandparents provide to parents of childhood cancer patients and their income satisfaction over the two years post-diagnosis. Twenty-nine families shared contact information for 85 grandparents, of whom 41 (48%) participated in a longitudinal questionnaire study, and seven were interviewed about financial support.

Neuroblastoma response to RAS-MAPK inhibitors and APR-246 (eprenetapopt) co-treatment is dependent on SLC7A11.

Background: We previously demonstrated that APR-246 (eprenetapopt) could be an efficient treatment option against neuroblastoma (NB), the most common pediatric extracranial solid tumor. APR-246's mechanism of action is not completely understood and can differ between cell types. Here we investigate the involvement of well-known oncogenic pathways in NB's response to APR-246.

Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study).

Introduction: Sickle cell disease (SCD) is one of the most common genetic diseases in the world, annually affecting approximately 310 000 births and causing >100 000 deaths. Vaso-occlusive crisis (VOC) is the most frequent complication of SCD, leading to bone pain, thoracic pain (acute chest syndrome) and/or abdominal spasms. It is the main cause of mortality in patients with SCD, reducing life expectancy.

In vitro screening of UGT2B10 in silico prioritized putative ligands from drugs used in the pediatric hematopoietic stem cell transplantation setting.

UGT2B10 is a phase II drug metabolizing enzyme with limited information on its role in the metabolism of drugs, especially in the pediatric hematopoietic stem cell transplantation setting. Previously, we investigated UGT2B10's role through in silico analyses and prioritized acetaminophen (APAP), lorazepam (LOR), mycophenolic acid (MPA), and voriconazole N-oxide (VCZ N-oxide) for in vitro investigations. In this report, we present in vitro screening of these candidates and of voriconazole (VCZ) to assess their potential to be substrates and/or inhibitors of UGT2B10.

Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM.

The superiority of total body irradiation (TBI)-based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing 417 patients aged 4-18 years in complete remission (CR), who received allo-HSCT from HLA-matched sibling or unrelated donors. Because of the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the prespecified comparison of outcomes of patients receiving busulfan (BU)- or treosulfan (TREO)-based regimens from 2013 to 2018. Overall, 180 and 128 patients received BU/thiotepa (THIO)/fludarabine (FLU) or TREO/THIO/FLU, respectively.

Single-cell transcriptome analysis reveals atypical monocytes circulating ahead of acute graft-versus-host disease clinical onset.

Acute graft-versus-host disease (aGVHD) represents the rejection of the recipient's skin, gut, and liver tissues of an allogeneic hematopoietic stem cell transplantation (HSCT) by the donor T cells. The onset of aGVHD is often rapid and its evolution is unpredictable. We undertook the single-cell RNA sequencing of peripheral blood mononuclear cells collected before aGVHD clinical onset in 3 patients and from 1 patient afterward.

Microcavity-assisted cloning (MAC) of hard-to-clone HepG2 cell lines: cloning made easy.

Cloning is a key molecular biology procedure for obtaining a genetically homogenous population of organisms or cell lines. It requires the expansion of new cell populations starting from single genetically modified cells. Despite the technical progress, cloning of many cell lines remains difficult.

A practical guide to therapeutic drug monitoring in busulfan: recommendations from the Pharmacist Committee of the European Society for Blood and Marrow Transplantation (EBMT).

Busulfan (Bu) is an important component of many conditioning regimens for allogeneic hematopoietic cell transplantation. The therapeutic window of Bu is well characterized, with strong associations between Bu exposure and the clinical outcome in adults (strongest evidence in myelo-ablative setting) and children (all settings). We provide an overview of the literature on Bu as well as a step-by-step guide to the implementation of Bu therapeutic drug monitoring (TDM).

Haplotype Inference Using Long-Read Nanopore Sequencing: Application to GSTA1 Promoter.

Recovering true haplotypes can have important clinical consequences. The laboratory process is difficult and is, therefore, most often done through inference. In this paper, we show that when using the Oxford nanopore sequencing technology, we could recover the true haplotypes of the GSTA1 promoter region.