Generating ESC-Derived RGCs for Cell Replacement Therapy.

In several ocular diseases, degeneration of retinal neurons can lead to permanent blindness. Transplantation of stem cell (SC)-derived RGCs has been proposed as a potential therapy for RGC loss. Although there are reports of successful cases of SC-derived RGC transplantation, achieving long-distance regeneration and functional connectivity remains a challenge. To address these hurdles, retinal organoids are being used to study the regulatory mechanism of stem cell transplantation. Here we present a modified protocol for differentiating human embryonic stem cells (ESCs) into retinal organoids and transplanting organoid-derived RGCs into the murine eyes.

[Caregiving Experience With a Young Father With Multiple Myeloma Undergoing Renal Dialysis and Autologous Stem Cell Transplantation].

This case report addresses the author's experience providing nursing care to a 37-year-old patient diagnosed with multiple myeloma requiring regular renal dialysis due to disease progression who received autologous stem cell transplantation. The patient was diagnosed with cancer in young adulthood and, as a father figure, faced various psychological issues associated with the unexpected challenges encountered during their treatment phase. Psychosocial health, which is closely associated with quality of life in patients with cancer, has gained increasing attention in recent years. The limited research published on the subject of fathers diagnosed with cancer encouraged the author to detail her experience with this case. The care period was from August 5th to August 19th, 2022. During the care period, the Gordons's 11 functional health assessment was applied, with potentially severe infections, coping disorders, anxiety, potential risk of injury existing or potential nutritional deficiencies, oral mucosal changes, and diarrhea identified as the primary health problems of concern. Nursing interventions applied included providing protective isolation measures to prevent post-transplant infection, helping the patient learn effective ways to cope with emotional distress, and providing comprehensive follow-up care information and health education to alleviate the anxiety associated with hospital discharge and life after discharge. The challenges of providing nursing care to adolescent and young adult patients differ significantly from those faced in the care of either elderly or pediatric patients. Furthermore, although extensive research has been conducted on mothers diagnosed with cancer, little research has addressed the impact on the paternal role when fathers are diagnosed with cancer, with limited information available regarding their psychological concerns and issues or the impact on family dynamics. The author hopes this case care experience offers an insightful reference and guide for nursing practice that contributes to a better understanding of the psychological aspects of young adult fathers diagnosed with cancer and facilitates more appropriate care in clinical settings.

[Survey of Preventing Exposure Regarding Sweat in Patients Receiving Antineoplastic Agents at Base Hospitals for Promoting Hematopoietic Stem Cell].

This survey aimed to reveal the actual preventing exposure for handling of clothing and sweat of patients treated with anticancer drugs, following the publication of "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition" (Guideline 2019). A survey was conducted among nurses working at 95 hematopoietic stem cell transplantation promotion base hospitals from September 1, 2023 to October 31, 2023. The response rate was 84.2% (80 facilities). Of the respondents, 45% wore gloves when touching patients' skin to administer anticancer drugs. Almost the nurses identified "urine" and "feces" as fluids on contaminated linen, while 14.1% also identified "sweat." For new staff, the results for preventing exposure education on "if touching the patients' skin" and "if handling clothing and linen" were 23.8% and 34.9%, respectively. This survey shows that nurses may not be following the Guideline 2019 for use of personal protective equipment and handling of clothes. Medical institutions handling anticancer drugs need to educate their staff for preventing occupational exposure.

[Update on treatment strategies for mantle cell lymphoma].

Mantle cell lymphoma (MCL) is a type of lymphoid malignancy that is rare in Japan. MCL is refractory to conventional chemotherapy and has dismal outcomes. Nonetheless, the prognosis of MCL has gradually improved with the advent of autologous stem cell transplantation and BTK inhibitors. First-line therapies incorporating BTK inhibitors are currently under development, and are expected to further improve the prognosis. Nevertheless, subsets with poor prognosis have been identified, including p53 abnormalities (TP53 mutations or deletions), blastoid variant, high MIPI-c, and POD24, and these show resistance to conventional treatments including BTK inhibitors. To overcome these challenges, novel therapies such as CAR-T therapy and combination therapy with BTK and BCL2 inhibitors are being developed, and should soon become clinically available in Japan. The therapeutic landscape for MCL is evolving dynamically, and this article will discuss the future of MCL treatment strategies in Japan.

[Pathogenesis and novel therapies for chronic GVHD].

Treatment for chronic graft-versus-host disease, the most important long-term complication of allogeneic hematopoietic cell transplantation, has changed significantly over the past decade. Development of novel targeted therapies has advanced as objective criteria for the diagnosis and evaluation of chronic GVHD have been established and understanding of the biological pathways to pathogenesis has increased. This paradigm shift is driving chronic GVHD practice significantly toward individualized therapy while minimizing exposure to steroids. Treatment using a variety of novel agents, tailored to each individual patient's condition, is expected to improve quality of life and overall survival by preventing chronic GVHD, controlling disease progression, and maintaining motor and occupational functions. This article reviews the pathogenesis of chronic GVHD and discusses prospects for the treatment of chronic GVHD, along with recently approved drugs and promising drugs in development.

[Induction and regulation of intestinal graft-versus-host disease by the intestinal microbiota].

The intestinal microbiota is an important prognostic factor for allogeneic hematopoietic stem cell transplantation (allo-HCT), and decreased diversity of the intestinal microbiota is linked to shorter overall survival, high transplant-related mortality, and acute graft-versus-host disease (GVHD). Major factors that alter the intestinal microbiota during allo-HCT are broad-spectrum antibiotics and intestinal GVHD. Broad-spectrum antibiotics dysregulate the immune system and impair intestinal epithelial regeneration by reducing beneficial commensal bacteria and activating mucus-degrading bacteria, which disrupts the colonic barrier function. Intestinal GVHD leads to decreased secretion of antimicrobial peptides into the intestinal lumen, as well as mitochondrial dysfunction in the intestinal epithelium, altering the intestinal microbiota. Various therapeutic approaches targeting the intestinal microbiota have been investigated in clinical trials. Protecting the intestinal microbiota may further enhance the safety and efficacy of allo-HCT by regulating intestinal immune responses, promoting intestinal epithelial regeneration, and facilitating the production of beneficial metabolites derived from commensal bacteria.

[Allogeneic transplantation as a therapeutic option for atypical chronic myeloid leukemia].

Atypical chronic myeloid leukemia (aCML) is a rare disease classified as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Recent advances in gene mutational profiling have clarified the characteristics of aCML as a disease entity relative to other MDS/MPNs. Although some studies suggest the efficacy of DNA demethylating agents and tyrosine kinase inhibitors, data about these agents are limited due to the small number of patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is only therapeutic option that can provide durable remission for aCML and other MDS/MPNs. Retrospective studies from Europe and Japan revealed the clinical results of allo-HSCT for aCML. This review summarizes the pathogenesis of aCML and the development of allo-HSCT and other therapeutic options.

Long-Term Survival and Immune Reconstitution of Donor-Derived Chimeric Antigen Receptor T-Cell Therapy for Childhood Molecular Relapse of B-Cell Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (n = 3) showed a trend of higher 3-year leukemia-free survival and 3-year overall survival than those who did not (n = 8; 100% vs. 75.0%; 95% CI, 45.0-104.9%; p = 0.370). No treatment-related mortalities were observed. Among patients who did not bridge to second-HSCT and remained in complete remission until the last follow-up (n = 6), five of them had not recovered normal immunoglobulin concentrations with a median follow-up of 43 months. CAR-T therapy may be a safe and effective treatment strategy to improve survival after allo-HSCT; however, the problem of prolonged hypogammaglobulinemia in patients who do not bridge to second-HSCT is worth noting.

Measurable residual disease assessment prior to allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndromes: a 20-year monocentric study.

Patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who undergo allogeneic hematopoietic stem-cell transplantation (alloHSCT) can have divergent survival outcomes while all in morphological complete remission (CR). Techniques of measurable residual disease (MRD) have allowed us to refine their prognosis in two categories: MRD-positive and MRD-negative patients. We conducted a monocentric retrospective study (01/2000-12/2020) to assess the prognosis of pretransplant MRD status measured by multiparametric flow cytometry (MFC) and molecular biology assessed by PCR. 192 patients were included. The median follow-up period was 77 months. Among patients undergoing alloHSCT in CR, overall survival (median-OS: 130.6 vs. 16.0 months, P < 0.001), disease-free survival (median-DFS: 109.6 vs. 7.1 months, P < 0.001) and cumulative incidence of relapse (12-month CIR: 7.3% vs. 33.7%, P < 0.0001) were significantly different between MRD-negative and MRD-positive patients. Patients with discordant intermethod results had intermediate DFS. MRD-negative patients according to molecular PCR-based techniques, WT1 overexpression and MFC had longer median-DFS, compared to MRD-positive patients (P = 0.001, P < 0.001, P < 0.001, respectively). Looking into subgroups, MRD-positive patients among the ELN2017 adverse-category (P < 0.0001), myeloablative and reduced-intensity conditioning regimens (P < 0.0001, P = 0.005), < 60-year patients (P < 0.001) and AML patients (P < 0.001) were associated with lower DFS. This difference was not found in ≥ 60-year patients (P = 0.27) and MDS patients (P = 0.70). MRD-positive patients within the favorable/intermediate ELN2017 category trended toward lower DFS (P = 0.05). We confirmed that MRD status prior to alloHSCT is a strong prognostic factor for OS, DFS and CIR. Combining MFC and molecular-PCR techniques to assess MRD seems primordial as inter-method discordance can be consequential.

Insights into cytomegalovirus-associated T cell receptors in recipients following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) reactivation is a serious problem in recipients of allogeneic hematopoietic stem cell transplantation. Long-term latency depends on specific T cell immune reconstitution, which identifies various pathogens by T cell receptors (TCRs). However, the mechanisms underlying the selection of CMV-specific TCRs in recipients after transplantation remain unclear. METHODS: Using high-throughput sequencing and bioinformatics analysis, the T cell immune repertoire of seven CMV reactivated recipients (CRRs) were analyzed and compared to those of seven CMV non-activated recipients (CNRs) at an early stage after transplant. RESULTS: The counts of unique complementarity-determining region 3 (CDR3) were significantly higher in CNRs than in CRRs. The CDR3 clones in the CNRs exhibit higher homogeneity compared to the CRRs. With regard to T cell receptor ß-chain variable region (TRBV) and joint region (TRBJ) genotypes, significant differences were observed in the frequencies of TRBV6, BV23, and BV7-8 between the two groups. In addition to TRBV29-1/BJ1-2, TRBV2/BJ2-2, and TRBV12-4/BJ1-5, 11 V-J combinations had significantly different expression levels between CRRs and CNRs. CONCLUSIONS: The differences in TCR diversity, TRBV segments, and TRBV-BJ combinations observed between CNRs and CRRs might be associated with post-transplant CMV reactivation and could serve as a foundation for further research.

Stem cell transplantation in cerebrovascular accidents: A global bibliometric analysis (2000-2023).

BACKGROUND: Cerebrovascular accident (CVA) is a major global contributor to death and disability. As part of its medical management, researchers have recognized the importance of promising neuroprotective strategies, where stem cell transplantation (SCT) is thought to confer advantages via trophic and neuroprotective effects. AIM: To evaluate the current state of research on SCT in patients with CVA, assess key trends and highlight literature gaps. METHODS: PubMed was screened for SCT in CVA-related articles in October 2023, for each country during the period between 2000 and 2023. Using the World Bank data, total population and gross domestic product were collected for comparison. VOSviewer_1.6.19 was used to create the VOS figure using the results of the same query. Graphs and tables were obtained using Microsoft Office Excel. RESULTS: A total of 6923 studies were identified on SCT in CVA, making 0.03% of all published studies worldwide. Approximately, 68% were conducted in high-income countries, with a significant focus on mesenchymal stem cells. The journal "Stroke" featured the largest share of these articles, with mesenchymal SCT having the highest rate of inclusion, followed by hematopoietic SCT. Over time, there has been a noticeable shift from in vitro studies, which assess stem cell proliferation and neurogenesis, to in vivo studies aimed at evaluating efficacy and safety. Additionally, the number of reviews increased along this approach. CONCLUSION: This bibliometric analysis provides a comprehensive guide for physicians and researchers in the field through an objective overview of research activity, and highlights both current trends and gaps. Having a potential therapeutic role in CVA, more research is needed in the future to focus on different aspects of SCT, aiming to reach a better treatment strategy and improve life quality in patients.

Case report: Successful combination of CLL1 CAR-T therapy and hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory acute myeloid leukemia.

The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.

The diagnosis and management of mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive inherited lysosomal storage disease. With pathogenic variants of the IDS gene, the activity of iduronate-2-sulfatase (IDS) is reduced or lost, causing the inability to degrade glycosaminoglycans (GAGs) in cells and influencing cell function, eventually resulting in multisystemic manifestations, such as a coarse face, dysostosis multiplex, recurrent respiratory tract infections, and hernias. Diagnosing MPS II requires a combination of clinical manifestations, imaging examinations, urinary GAGs screening, enzyme activity, and genetic testing. Currently, symptomatic treatment is the main therapeutic approach. Owing to economic and drug availability issues, only a minority of patients opt for enzyme replacement therapy or hematopoietic stem cell transplantation. The limited awareness of the disease, the lack of widespread detection technology, and uneven economic development contribute to the high rates of misdiagnosis and missed diagnosis in China.

Healthcare resource utilization and associated costs in patients with chronic graft-versus-host disease post allogeneic hematopoietic stem cell transplantation in England: HCRU and associated costs in patients with cGvHD in England.

BACKGROUND: Limited evidence suggests chronic graft-versus-host disease (cGvHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases healthcare resource utilization (HCRU) and costs. However, this burden has not been well characterized in England. OBJECTIVE: This study assesses secondary care HCRU and costs for patients following allo HSCT in England with cGvHD and patients who did not develop graft versus-host disease (GvHD). Further stratification was performed among patients who did or did not subsequently receive high-cost therapies for the treatment of cGvHD. STUDY DESIGN: This descriptive, retrospective cohort study used Hospital Episode Statistics (HES) data from April 2017-March 2022. HES data captures information on reimbursed diagnoses and procedures from all National Health Service (NHS) secondary care admissions and attendances in England. High-cost drugs as defined by NHS England are recorded in HES, these drugs and other procedures including plasma exchange, were used to identify patients with cGvHD who were in receipt of high-cost therapies. HCRU and costs were described for patients with cGvHD following allo-HSCT (n=721) and were matched with patients with no evidence of GvHD following allo-HSCT (n=718). HCRU and costs were also described for the subset of patients with cGvHD (n=198) following receipt of high-cost therapies and patients with cGvHD prior to or without such therapies (n=523). RESULTS: A higher proportion of patients with cGvHD had at least one inpatient or intensive care unit (ICU) admission or emergency care attendance than patients without GvHD (inpatient: 74.6% vs 66.6%; emergency care: 39.3% vs 30.5%; ICU: 7.4% vs 4.7%; respectively); whilst the proportion of patients with an outpatient attendance were similar for both groups (outpatient: 80.3% vs 84.1%; respectively). The cost across all secondary care settings was higher for patients with cGvHD than patients without GvHD, with a mean cost of inpatient admissions of £17,339 ppy for those with cGvHD vs £8,548 ppy in patients without GvHD. A higher proportion of patients who received high-cost therapies for the treatment of cGvHD had at least one secondary care admission or attendance, than patients who did not (inpatient: 85.4% vs 66.4%; ICU: 7.1% vs 5.4%; outpatient: 87.9% vs 76.7%; emergency care: 44.4% vs 36.5%; respectively). Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean number (14.6 vs 8.2 ppy, respectively) for all-cause inpatient admissions after treatment, than patients who did not. In all secondary care settings, the total cost ppy was higher for patients who received high-cost therapies for the treatment of cGvHD, than for those who did not. Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean cost (£21,137 vs £15,956 ppy, respectively) for all-cause inpatient admissions than patients who did not. CONCLUSIONS: This study demonstrates that cGvHD and the use of associated high-cost therapies impacts healthcare activity and costs across various secondary care settings in England more than patients without GvHD and patients with cGvHD who received no high-cost therapies.

Efficacy of nebulized GM-CSF inhalation in preventing oral mucositis in patients undergoing hematopoietic stem cell transplantation: A retrospective study.

Objective: To study the efficacy of oxygen atomization inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) for preventing oral mucositis in patients following hematopoietic stem cell transplantation. Methods: Data from patients who received hematopoietic stem cell transplantation and were treated with GM-CSF for the prevention/treatment of oral mucositis in our hospital from June 2021 to June 2023 were collected. The enrolled patients were divided into an observation group and a control group according to the use of GM-CSF. The WHO Mucositis Scale Assessment Criteria were utilized to evaluate the characteristics of patients with oral mucositis (OM) from the beginning of the pretreatment period until they were discharged from the hospital. The general data, preconditioning protocol, transplantation method, overall grade and duration of oral mucositis, pain score, nutritional score and number of days of parenteral nutrition use, oral mucosal infection status and antibiotic use intensity, the granulocyte and megakaryocyte reconstruction time, and adverse reaction reports of the patients were collected and summarized through the medical records system. Results: A total of 143 patients were included in this study, including 75 patients in the observation group. In the observation group, there were 36 males and 39 females aged 22-67 years. There were 45 patients who received autologous transplantation and 30 patients who received allogeneic transplantation. In terms of the disease distribution, there were 33 cases of leukemia, 24 cases of lymphoma, 11 cases of multiple myeloma, and 8 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 2 cases of myelofibrosis, 1 case of POEMS syndrome). There were 68 patients in the control group, including 33 males and 35 females; the control group patients were aged 25-74years. Forty-one patients received autologous transplantation, and 27 patients received allogeneic transplantation. The disease distribution included 29 cases of leukemia, 17 cases of lymphoma, 12 cases of multiple myeloma, and 7 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 1 case of myelofibrosis, 1 case of POEMS syndrome). There were no significant differences between the two groups concerning age, sex, disease distribution or the transplantation method (P > 0.05). In the observation group, 13 cases did not develop oral mucositis, and 32 cases developed oral mucositis (16 cases of Grade I, 14 cases of Grade II, 2 cases of Grade III, and 0 cases of Grade IV). In the control group, there were 5 cases without mucositis and 36 cases with oral mucositis (6 cases of Grade Ⅰ, 16 cases of Grade Ⅱ, 8 cases of Grade Ⅲ, and 6 cases of Grade Ⅳ), the difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). In the observation group, 8 patients did not develop oral mucositis, and 22 patients developed oral mucositis (13 cases of Grade I, 7 cases of Grade II, 1 case of Grade III, and 1 case of Grade IV). In the control group, 1 case did not develop mucositis, and 26 cases developed oral mucositis (3 cases of Grade Ⅰ, 10 cases of Grade Ⅱ, 9 cases of Grade Ⅲ, and 4 cases of Grade Ⅳ). The difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral mucosal infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). No adverse reactions were reported in either group. Conclusion: In both autologous transplantation and allogeneic transplantation patients, GM-CSF atomized inhalation can improve the prevention and treatment of oral mucositis in stem cell transplantation patients, reduce the incidence of oral infection, reduce the intensity of antibiotic use and the number of days of parenteral nutrition use, and thus promote the process of hematopoietic reconstruction.

Efficacy of Ruxolitinib with corticosteroids in idiopathic pneumonia syndrome post-allogeneic hematopoietic stem cell transplantation: A single-center experience and systematic review.

BACKGROUND: Idiopathic Pneumonia Syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-threatening complication with high morbidity and mortality. IPS is thought to arise from damage caused by various inflammatory mediators. This study assesses the effectiveness of Ruxolitinib, a Janus Kinase (JAK) 1 and 2 inhibitor that blocks cytokine production, in combination with corticosteroids (CS) for managing IPS after allo-HSCT, compared to the conventional use of CS alone in a case series and a systematic review of previously published literature. METHODS: The study includes a retrospective case series of three patients treated for IPS with Ruxolitinib and CS from the University of Kansas Medical Center and a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement 2020 guidelines. The systematic review encompassed seven studies involving 346 cases including three cases from the case series. Statistical analyses were conducted using SPSS v.25. RESULTS: The case series included three patients with IPS after allo-HSCT who received ruxolitinib and CS with favorable results. All patients showed substantial improvement with no IPS-associated mortality. Two of the three patients in the case series were discharged on a 2 L nasal cannula, which was later discontinued during follow-up visits, while the third was discharged on room air. There was marked improvement observed on the computed tomography (CT) following the use of ruxolitinib. Of the total 346 cases included in the systematic review, the median age was 46.6 years (Range 5-72), and 62 % were males. The primary disorders were acute leukemia (52 %), chronic myeloid leukemia (12 %), myelodysplastic syndrome (11 %), Lymphoma (10 %), and others (21 %). Stem cell sources were peripheral blood (45 %), bone marrow (49 %), and cord blood (6 %). Donor types involved match unrelated (55 %), match related (36 %), and mismatched related (4.5 %). Most patients received myeloablative conditioning (81 %). Acute GVHD was observed in 47 %, and chronic GVHD in 38 %. The primary treatment was CS (96 %), with limited use of ruxolitinib (1 %) and etanercept (9.5 %). The mortality rate was 63.3 %, whereas in our case series with the use of ruxolitinib, it was zero. CONCLUSION: The combination of Ruxolitinib and CS for treating IPS post-allo-HSCT suggested promising results in the case series, with favorable response and improved survival by blocking the cytokine production contributing to IPS. The significant mortality difference in the systematic review supports the need for innovative treatment approaches, highlighting the potential role of Ruxolitinib in CS-refractory cases. Despite the positive outcomes in the case series, the absence of randomized controlled trials emphasizes the necessity for further research.

Toxoplasma qPCR kinetics to guide pre-emptive treatment of toxoplasmosis after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Recent ECIL-guidelines recommend a quantitative PCR (qPCR) guided pre-emptive treatment approach to toxoplasmosis in seropositive recipients of allogeneic hematopoietic cell transplantation (allo-HCT). While qPCR might serve as a sensitive tool for early Toxoplasma detection, its role in treatment follow-up remains unknown. METHODS: We analyzed the qPCR kinetics of allo-HCT recipients experiencing either Toxoplasma infection (TI, n=71) or disease (TD, n=14) in relation to different parameters. We included 85 patients with available qPCR values expressed as quantitative cycle (Cq) from four large hematological centers from 2009 to 2023, and kinetic analysis was performed in a selection of 74 patients screened at least weekly with blood qPCR. Day 0 (D0) was the day of anti-Toxoplasma treatment start or (when untreated) day of diagnosis. RESULTS: Time to qPCR negativity was inversely proportional to the Cq value at D0 (p=0.0063). Not reaching negativity at D10 was associated with a significantly higher mortality at D30 (p=0.023). Patients with a high D0-parasitic load and patients with TD showed slower clearance (p<0.001, p=0.032). Time to negativity was not significantly different for patients started on prophylactic vs curative doses as first-line treatment regimen (p=0.16). CONCLUSIONS: This study underscores the predictive value of qPCR kinetics monitoring in allo-HCT patients with toxoplasmosis. With the aforementioned risk factors, clinicians can identify patients at high-risk for worse outcome. Our results support to consider a therapeutic change or reinforcement if the parasitic load does not decrease after 10 days, supplementing existing clinical guidelines.

Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Graft-versus-host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug-drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics. This study aimed to assess the impact of inflammation, as indicated by C-reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no-to-mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation. The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.

Sorafenib maintenance after allogeneic stem cell transplantation in patients with FLT3+ AML receiving midostaurin during induction and consolidation: a retrospective analysis.

Introduction: Acute myeloid leukemia (AML) relapse is the main cause of death after allogeneic stem cell transplant (allo-SCT). In AML FLT3+, it was shown that Sorafenib used as maintenance therapy after allo-SCT, significantly reduces the risk of relapse and death. Methods: We analyzed 29 adult patients with FLT3m AML and underwent allogeneic stem cell transplant from 2019 to 2023. All patients received midostaurin plus conventional CT during induction and consolidation. After transplantation, Sorafenib maintenance was administered in all patients independently from MRD status at transplantation. Results: Sorafenib maintenance was applied in 18 patients out 29 patients (62%). Median time to start sorafenib was 100 days (range 37-225) and median duration of treatment was 775 days (range 140-1064). For the whole population (n=29), 2-year OS, LFS, and CIR was 76%, 68% and 28%, respectively. The median time to relapse was 137 days (range 49-246). For patients treated with sorafenib (n=18), the 2-year OS, LFS, and CIR were 94%, 84% and 11%, respectively. For the whole population, the 100-day NRM was 0% and 1-year NRM was 3%. Death was caused by transplant-associated thrombotic microangiopathy in 1 patient. For patients who were administered with Sorafenib, the 1-y NRM was 5%. Death was caused by transplant associated transplant-associated thrombotic microangiopathy. Discussion: This retrospective study suggests that sorafenib maintenance seem to be effective even in patients pre-treated with midostaurin.

Allogeneic transplantation for adult T-cell leukemia/lymphoma in adolescent and young adults and young patients: A nationwide retrospective study by the ATL working group of the Japan society for transplantation and cellular therapy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides durable remission for patients with adult T-cell leukemia/lymphoma (ATL); however, few studies have focused on post-transplant outcomes in ATL patients ≤49 years. To clarify prognostic factors in ATL among patients <40 years (adolescents and young adult [AYA]; n = 73) and 40-49 years (Young; n = 330), we conducted a nationwide retrospective study. Estimated 3-year overall survival (OS) rates were 61.8% and 43.1% in AYA and Young patients, respectively (p = 0.005). In the multivariate analysis, Young patients showed worse OS (Hazard ratio (HR) [95% confidential interval] 1.62 [1.10-2.39], p = 0.015), chronic graft-versus-host disease (GVHD)-free and relapse-free survival (CRFS) (HR 1.54 [1.10-2.14], p = 0.011), and GVHD-free and relapse-free survival (GRFS) (HR 1.40 [1.04-1.88], p = 0.026) than AYA patients. No significant differences were observed in OS, CRFS, or GRFS between the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens; however, non-relapse mortality was significantly lower in patients with the RIC regimen than those with the MAC regimen (HR 0.46 [0.24-0.86], p = 0.015). In summary, OS was worse in Young patients than in AYA patients in the allo-HSCT setting for ATL. Furthermore, the RIC regimen has potential as an alternative treatment option for ATL patients ≤49 years.