Prolonged thrombocytopenia (PT) is a serious complication after haematopoietic stem cell transplantation (HSCT). PT has been suggested to be associated with an increased platelet transfusion requirement and poor outcomes after transplantation. Due to the complex mechanism of PT development, it is difficult to diagnose in the early post-transplant period. Our study aimed to identify an early predictive marker for PT after HSCT. Previous studies showed that the clinical utility of immature platelet fraction (IPF) predicts platelet recovery after chemotherapy and successful engraftment. However, the relationship between IPF and PT after HSCT remains unclear. Fifty-two patients with malignant haematological diseases who underwent HSCT were included in the study. We observed the kinetics of recovery of haematological parameters after transplantation and performed receiver operating characteristics (ROC) curve analysis using data from the 52 HSCT patients. The days to rise and peak of IPF, absolute IPF count (A-IPF) and highly fluorescent IPF (H-IPF) were almost synchronised in all patients, at day 10 and day 15, respectively. The begin to rise levels of IPF, H-IPF and A-IPF were all significantly lower in the PT group than in the good engraftment (GE) group (p=0.0016, p=0.0094, p=0.0086, respectively). The peak levels of IPF were significantly lower in the PT group than the GE group (p=0.0036). However, the peaks of H-IPF and A-IPF were not statistically significant between the two groups (p=0.3383, p=0.0887, respectively). The area under the ROC curve (AUC) of IPF rise was 0.739 (95% CI 0.583-0.896; p<0.05) and the cut-off value was 3.5%, while the AUC of IPF peak was 0.800 (95% CI 0.637-0.962; p<0.01) and the cut-off value was 8.0%. In conclusion, early low levels of IPF predict the development of PT after HSCT. These findings may help improve the management and treatment strategies for PT after HSCT.

In this study, we used the whole-exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty-five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse-free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis.

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T-cell mediated immunity. This literature review focuses on acyclovir-refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir-refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug-resistant HSV strains. Our systematic review reports a median incidence of acyclovir-resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft-versus-host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir-refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase-primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir-refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk.

OBJECTIVE: There is limited real-world data on cyclosporin A (CsA)-induced liver injury (CILI). This study aims to investigate the incidence, clinical classification and risk factors of CILI, thereby providing evidence to inform the treatment of CILI.
METHODS: Inpatients receiving haematopoietic stem cell transplantation (HSCT) and treated with CsA were included. Patient information was collected to assess suspicious CILI by the Roussel Uclaf causality assessment method (RUCAM) scale. We evaluated the pattern and severity of CILI. The independent risk factors of CILI were identified by multivariable logistic regression.
RESULTS: A total of 216 allogeneic HSCT (allo-HSCT) recipients were included in this study. The incidence of CILI was 15.3% (95% confidence interval [CI]: 10.4%-20.1%). Among these cases, 84.8% displayed a hepatocellular pattern, and 90.9% of CILI was of mild severity. Baseline alanine aminotransferase (ALT) level (OR = 1.030, 95% CI: 1.008-1.053, P = .008) and trough concentration level of CsA (OR = 1.007, 95% CI: 1.002-1.012, P = .009) were identified as independent risk factors for CILI.
CONCLUSIONS: The incidence of CILI in allo-HSCT recipients is notably high. Recipients with elevated baseline ALT levels and higher exposure to CsA are more susceptible to developing CILI.

Allogeneic transplantation of haematopoietic stem cells is still the only curative treatment for certain haematological malignancies. This treatment can be responsible for a number of side-effects, leading to multiple and interdependent physical and psychological deficiencies that affect patients\' quality of life and social participation, and can be experienced as a handicap, sometimes for several years after the transplant. For several years now, the integration of post-transplant rehabilitation pathways has been becoming more widespread, and initiatives to provide multidisciplinary care at an increasingly early stage are being studied. The aim of this early management is to improve the patient\'s overall functional state before, during and after the transplant, in order to limit the impact of the treatment and ensure the quickest possible return to a life that is as satisfying as possible. The international literature and the experiments carried out throughout the French-speaking world describe heterogeneous practices. Based on this literature and experience, the aim of this study is to issue homogenous recommendations for good clinical practice and to identify areas for further research into pre-transplant, per-transplant and post-transplant rehabilitation of haematopoietic stem cells.

This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small-dose infusions of granulocyte-colony-stimulating factor (G-CSF)-mobilized haploidentical lymphocytes as post-ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease-free survival (DFS) compared to those without maintenance therapy, with 4-year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate-risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate-risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long-term prognosis in this patient population.

To analyse the effect of HLA-DPA1 and HLA-DPB1 allelic mismatches on the outcomes of unrelated donor haematopoietic stem cell transplantation (URD-HSCT), we collected 258 recipients with haematological disease who underwent HLA-10/10 matched URD-HSCT. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5, -DQA1, -DPA1 and -DPB1 typing was performed for the donors and recipients using next-generation sequencing (NGS) technology. After excluding 8 cases with DQA1 or DRB3/4/5 mismatches, we included 250 cases with HLA-14/14 matching for further analysis. Our results showed that the proportion of matched DPA1 and DPB1 alleles was only 10.4% (26/250). The remaining 89.6% of donors and recipients demonstrated DPA1 or DPB1 mismatch. In the DPA1 matched and DPB1 mismatched group, accounting for 18.8% (47/250) of the cohort, DPB1*02:01/DPB1*03:01 allelic mismatches were associated with decreased 2-year OS and increased NRM. DPB1*02:02/DPB1*05:01 and DPB1*02:01/DPB1*05:01 mismatches showed no impact on outcomes. Moreover, the specific allelic mismatches observed were consistent with the DPB1 T-cell epitope (TCE) classification as permissive and non-permissive. We innovatively established an analysis method for DPA1 ~ DPB1 linkage mismatch for cases with both DPA1 and DPB1 mismatched, accounting for 70% (175/250) of the total. DPA1*02:02 ~ DPB1*05:01/DPA1*02:01 ~ DPB1*17:01 linkage mismatches were associated with lower 2-year OS, especially among AML/MDS recipients. DPA1*02:02 ~ DPB1*05:01/DPA1*01:03 ~ DPB1*02:01 linkage mismatches showed no impact on outcomes. In conclusion, applying the DPA1 ~ DPB1 linkage mismatch analysis approach can identify different types of mismatches affecting transplant outcomes and provide valuable insight for selecting optimal donors for AML/MDS and ALL recipients.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a substantial therapeutic procedure for the treatment of a wide spectrum of severe diseases. Despite advancements in treatment and supportive care, alloHSCT still carries a considerable mortality risk, primarily caused by graft-versus-host disease (GvHD). Our retrospective analysis aimed to identify the factors influencing overall survival and GvHD development in HLA-identical sibling alloHSCT. We have analyzed patients\' and donors\' age, AB0 compatibility, recipient-donor gender match, stem cell source, time from the diagnosis to alloHSCT, conditioning regimen type, GvHD prophylaxis, and relapse.
METHODS: Our study included 96 patients (54 male, 42 female) who underwent HLA-identical sibling alloHSCT. The median follow-up was 64.5 months (range 1-218 months), and the median age of both recipients and donors was 34 years. Malignant hematological diseases were the most common indications for alloHSCT.
RESULTS: GvHD and its complications accounted for the highest number of deaths (N = 24; 46.2%), followed by relapse (N = 18; 34.6%). Acute GvHD developed in 30 patients (31.3%), while chronic GvHD occurred in 25 patients (26.0%), resulting in a total of 45 patients (46.9%) experiencing GvHD. Male recipients with female donors had significantly worse overall survival compared to other patients (P = 0.01; HR = 2.33). Overall survival was better in patients transplanted within 1 year from the diagnosis compared to those transplanted after 1 year (P = 0.03; HR = 1.93). No factor reached statistical significance regarding the impact on acute GvHD, chronic GvHD, or overall GvHD.
CONCLUSIONS: We confirmed that sex mismatch, specifically in the case of a female donor and a male recipient, significantly negatively affects overall survival after alloHSCT. Additionally, overall survival is significantly shorter when the interval between the diagnosis and alloHSCT exceeds one year.

OBJECTIVE: Financial toxicity (FT) refers to the subjective perception of financial distress resulting from objective economic strain due to illness, exerting a detrimental influence on health outcomes. This study aimed to describe FT among allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients within a public health framework, employing a social determinants of health approach.
METHODS: A multi-centre cross-sectional study involving adult allo-HSCT patients was conducted across three public hospitals in Madrid. FT was assessed using a validated COST scale (range 0-44; lower scores indicating higher FT). Patient-administered paper/online questionnaires were utilized to collect data on sociodemographic, socioeconomic, clinical, and healthcare access variables. Descriptive, non-parametric univariate statistical analysis and multiple linear regression models were performed.
RESULTS: Sixty-six patients, with a mean age: 52.5 years (SD: 11.5), 50% women, 28.7% displaced to Madrid for HSCT, and 71.4% lacking financial support were included. The median FT score was 20 points (IQR 12-27.25). Independent factors associated with higher FT included being females (Coef = -3.26; p = 0.079), perceived income loss after HSCT (Coef = -6.81; p < 0.001) and a monthly household income of ≤1000 € compared to 1001-2500€ (Coef = 8.29; p = 0.005) or >2500 € (Coef = 15.75; p < 0.001).
CONCLUSIONS: Despite the limited sample size, our findings underscore the presence of financial toxicity among allo-HSCT patients, shaped by social determinants of health. Recognizing and addressing FT within the HSCT process is essential to mitigate social inequalities in health.