Outcome Of Hematopoietic Stem Cell Transplantation Research Articles

PROJECT OF A DASHBOARD FOR BRAZILIAN CENTERS AFFILIATED WITH CENTER FOR INTERNATIONAL BLOOD AND MARROW RESEARCH

Since the first hematopoietic stem cell transplantation (HSCT) was performed at the Federal University Hospital (Curitiba, PR) in 1979, the number of centers offering this modality of treatment has increased. However, accessing comprehensive HSCT outcomes has become a challenge due to lack of an official Brazilian registry. The partnership between the Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) and the Center for International Blood and Marrow Research (CIBMTR) was an important milestone in the establishment of the HSCT Brazilian registry (HSCTBR). By using CIBMTR’s Data Back to Center (DBtC) tool, we have gained insights into HSCT outcomes through the Brazilian Summary Slides. While understanding the country's transplant scenario is crucial, it is equally important for each center to assess their own outcomes. In order to help the Brazilian centers with the CIBMTR, the data manager of SBTMO working group has developed a business tool solution to facilitate this important task.

Treatment Patterns and Clinical Outcomes of Patients with Moderate to Severe Acute Graft-Versus-Host Disease: A Multicenter Chart Review Study.

Acute graft-versus-host disease (aGVHD) remains a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT) outcomes. Contemporary comprehensive analyses of real-world clinical outcomes among patients who develop aGVHD post-HSCT are needed to better understand the unmet needs of this patient population. This multicenter, retrospective chart review describes treatment patterns and clinical outcomes among patients (≥18 years old) from Finland, Sweden, and France who developed grades II-IV aGVHD after their first HSCT (January 2016-June 2017). From 13 participating centers, 151 patients were included. The median (Q1, Q3) age at HSCT was 56 (45, 62) years old. One line of aGVHD treatment was received by 47.7%, and the most common first-line treatment was methylprednisolone (alone or in a combination regimen, 74.2%; monotherapy, 25.8%). Among patients treated with methylprednisolone, 79.5% achieved a complete or partial response. The median (Q1, Q3) number of treatment lines was 2.0 (1.0, 3.0). The median (Q1, Q3) time to obtain an aGVHD diagnosis from transplant was 29.5 (21.0, 44.0) days, and 14.5 (7.0, 34.0) days to achieve the best response for 110 evaluable patients. At 6 and 12 months, 53.6% and 49.0%, respectively, achieved a complete response. Chronic GVHD occurred in 37.7% of patients, and aGVHD reoccurred in 26.5%. Following aGVHD diagnosis, mortality rates were 30.0% at 6 months and 37.3% at 12 months. Findings from this study demonstrate a continuing unmet need for new therapies that control aGVHD and improve mortality.

Nutritional and Body Composition Changes in Paediatric β-Thalassemia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Study Using Bioelectrical Impedance Analysis.

This retrospective study evaluated nutritional status and body composition changes in paediatric β-thalassemia (β-TM) patients before and after hematopoietic stem cell transplantation (HSCT), using bioelectrical impedance analysis (BIA), and explored their relationship with HSCT outcomes. A cohort of 40 paediatric β-TM patients undergoing allogeneic HSCT was assessed for their nutritional status, anthropometric parameters, including body mass index (BMI), weight, and height, and body composition parameters pre-and post-HSCT, focusing on BIA measurements, including intracellular water (ICW), extracellular water (ECW), fat mass (FAT), fat-free mass (FFM), Skeletal Muscle Mass (SMM), soft Lean Mass (SLM), percent body fat (PBF), Body Cell Mass (BCM), Phase angle (PA) and muscle balance pre- and post-HSCT. Post-HSCT clinical outcomes, including acute graft-vs-host disease (aGVHD), engraftment time, oral mucositis (OM), sinusoidal obstruction syndrome (SOS), and diarrhoea in relation to nutrition status after HSCT were analysed. After HSCT, 28.21% experienced diminished nutritional status, with 71.43% of those who were wasting before HSCT showing diminished nutritional status, significantly higher than the normal group (18.75%, P = 0.012). Anthropometric changes included significant weight reduction (87.5%, 22.15 ± 7.46 vs 20.74 ± 6.57, P < 0.001) and BMI decrease (90%, 15.19 ± 1.70 vs 14.05 ± 1.48, P < 0.001). Body composition parameters, which are FFM, SMM, SLM, ICW, ECW, BCM, and PA (18.26 ± 5.71 vs 17.27 ± 5.19, 8.68 ± 3.30 vs 7.93 ± 3.02, 17.11 ± 5.28 vs 16.06 ± 4.84, 8.19 ± 2.54 vs 7.62 ± 2.31, 5.15 ± 1.58 vs 4.94 ± 1.47, 11.74 ± 3.63 vs 10.92 ± 3.32, 4.42 ± 0.50 vs 3.90 ± 0.57, respectively, P < 0.001) analysis revealed significant decreases. No significant differences in clinical outcomes were observed based on nutritional status. Paediatric β-TM patients undergoing HSCT exhibit significant changes in nutrition status and body composition, emphasizing the need for focused attention on malnourished children who are more prone to diminished nutritional status. Comprehensive BIA aids in understanding the impact, urging consideration for extended follow-up and larger cohorts in future research.

Impact of prior COVID-19 infection on allogeneic hematopoietic stem cell transplantation outcomes.

There are limited data on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recipients with prior COVID-19 infection. This single-center retrospective study included 54 adult patients who received allo-HSCT from July 2020 to September 2021 after previous COVID-19 infection and 122 control group patients without a history of COVID-19 who underwent HSCT during the same period, with a median follow-up of 17 months. Median time from COVID-19 to allo-HSCT was 211 days. The incidence of main complications in the post-transplant period was not significantly different between the two groups: deep vein thrombosis (p =.85), TMA (p=.8), VOD (p=.25), bloodstream infections (p=.21), pneumonia of any etiology (p=.41), viral infections (p=.85), invasive fungal disease (p=.08). The 2-year non-relapse mortality, relapse incidence, overall survival, and progression-free survival also were comparable in the study and the control groups: 22% (95% CI 10.5-36.2) versus 26.3% (95% CI 18.7-34.6) p =.4; 15.6% (95% CI 7.3-26.9) versus 23.6% (95% CI 16.0-32.3) p =.39; 67.9% (95% CI 50.4-80.3) versus 59.8% (95% CI 50.2-68.1) p =.24 and 62.3% (95% CI 45.5-75.3) versus 49.9% (95% CI 40.0-59.1) p =.18, respectively. The history of previous COVID-19 infection did not affect the results of allo-HSCT.

Retrospective study to compare the outcomes of matched related donor vs matched unrelated donor in patient with acute myeloid leukaemia

BackgroundIndia's need for bone marrow donation and transplantation is increasing in the context of the rising incidence of haematological neoplasms like acute myeloid leukaemia (AML). The use of matched related donors (MRD) for hematopoietic stem cell transplantation (HSCT) is a feasible option, but the lack of HLA-matched donors in India remains a significant obstacle to successful treatment. MethodologyThis retrospective study was conducted at the Department of Hemato-Oncology & Bone Marrow Transplant, Rajiv Gandhi Cancer Institute in New Delhi, India over a period of 6 months. The study enrolled 77 AML MRD and 19 AML MUD patients based on the inclusion and exclusion criteria. ResultThe one-year survival rate was higher in MRD than in MUD, but there was no significant difference in mortality in multivariate analysis. The study also found that chronic graft-versus-host disease (GVHD) and relapse were associated with worse survival outcomes in both MRD and MUD HSCT. ConclusionThis study supports the use of matched unrelated donor (MUD) transplant for HSCT in AML patients when a matched sibling donor is not available.

Donor matters: Donor selection impact on hematopoietic stem cell transplantation outcomes in Hispanic patients with B-cell acute lymphocytic leukemia: Insights from a myeloablative HSCT study

BackgroundHematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients. MethodologyThis single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023. ResultsCompared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036). ConclusionOur data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients.

Lentivirus-Mediated BCL-XL Overexpression Inhibits Stem Cell Apoptosis during Ex Vivo Expansion and Provides Competitive Advantage Following Xenotransplantation.

Hematopoietic reconstitution after hematopoietic stem cell transplantation (HSCT) is influenced by the number of transplanted cells. However, under certain conditions donor cell counts are limited and impair clinical outcome. Hematopoietic stem and progenitor cell (HSPC) expansion prior to HSCT is a widely used method to achieve higher donor cell counts and minimize transplantation-related risks such as graft failure or delayed engraftment. Still, expansion in a non-physiological environment can trigger cell death mechanisms and hence counteract the desired effect. We have shown earlier that during HSCT a relevant amount of HSPCs were lost due to apoptosis and that cell death inhibition in donor HSPCs improved engraftment in xenotransplantation experiments. Here, we assessed the effect of combined ex vivo expansion and cell death inhibition on HSPC yield and their reconstitution potential in vivo. During expansion with cytokines and the small molecule inhibitor StemRegenin 1, concomitant lentiviral overexpression of antiapoptotic BCL-XL resulted in an increased yield of transduced HSPCs. Importantly, BCL-XL overexpression enhanced the reconstitution potential of HSPCs in xenotransplantation experiments in vivo. In contrast, treatment with caspase and necroptosis inhibitors had no favorable effects on HSPC yields nor on cell viability. We postulate that overexpression of antiapoptotic BCL-XL, both during ex vivo expansion and transplantation, is a promising approach to improve the outcome of HSCT in situations with limited donor cell numbers. However, such apoptosis inhibition needs to be transient to avoid long-term sequelae like leukemia.

Allogeneic hematopoietic cell transplantation for older patients with AML with active disease. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Older adults with acute myeloid leukemia (AML) refractory to initial or reinduction chemotherapy have a dismal prognosis if they do not undergo hematopoietic stem-cell transplantation (HCT). However, data assessing HCT outcomes from different donors are scarce. We evaluated results from a retrospective analysis on patients aged ≥70 years, with AML not in remission who received an allogeneic HCT from HLA-matched sibling donor (MSD), HLA-10/10 matched unrelated donor (MUD), or T-cell replete haploidentical (Haplo) donor, from 2010 to 2021, reported to the ALWP-EBMT database. A total of 360 patients (median age 72 years, range 70-79) were included in the analysis. Median follow-up for the entire population was 35.5 months. Donors were MSD (n = 58), 10/10 HLA-MUD (n = 228), and Haplo (n = 74). A total of 213 (59.2%) patients were primary induction failures, while 147 (40.8%) were in first or subsequent relapse. Graft source was peripheral blood in 92% of the patients. Patients transplanted from Haplo donors more frequently received marrow grafts (p < 0.01) and presented the combination female donor to male recipient (p < 0.01). The overall 2-year rates of overall survival (OS) and leukemia-free survival (LFS) were: 62.4% (95% CI 47.2-74.3) and 47.6% (95% CI 33.1-60.8) for MSD, 43% (95% CI 35.8-49.9), and 37.5% (95% CI 30.7-44.4) for MUD, and 25.9% (95% CI 15.8-37.2), and 26.5% (95% CI 16.3-37.8) for recipients of Haplo transplants. The 2-year cumulative incidence of relapse (RI) was slightly lower for Haplo recipients at 29.6% (95% CI 19-40.9), for MUD it was 30.2% (95% CI 23.9-36.7), and for MSD 34.9% (95% CI 22-48.2); counterbalanced by a higher incidence of non-relapse mortality (NRM) of 43.9% (95% CI 31.6-55.6) for Haplo recipients, 32.2% (95% CI 26-33.1) for MUD and 17.5% (95% CI 8.4-29.3) for MSD. Graft-versus-host disease (GVHD-free, relapse-free survival (GRFS) was 35.3% (95% CI 22.3-48.5) for MSD, 29.6% (95% CI 23.2-36.2) for MUD, and 19.2% (95% CI 10.7-29.6) for Haplo patients. In the multivariate model, compared to the referent group of MSD recipients, the risk of NRM was higher among patients transplanted from Haplo donors ([hazard ratio] HR 5.1, 95% CI 2.23-11.61, p < 0.001) and MUD (HR 3.21, 95% CI 1.48-0.6.94, p = 0.003). Furthermore, both Haplo and MUD were associated with inferior OS, (HR 3.6, 95% CI 1.98-0.6.56, p < 0.001, and HR 2.3, 95% CI 1.37-0.3.88, p = 0.002, respectively), and LFS (HR 2.24, 95% CI 1.31-0.3.84, p = 0.003, and HR 1.64, 95% CI 1.04-0.2.60, p = 0.034, respectively). Patients transplanted from Haplo donors were also associated with worse GFRS (HR 1.72, 95% CI 1.07-2.77, p:0.025) compared with MSD patients. Older adult AML patients with active disease transplanted from MSD experienced prolonged OS and LFS compared to 10/10 MUD and Haplo due to lower NRM. Prospective clinical trials are warranted.

Using Targeted Transcriptome and Machine Learning of Pre- and Post-Transplant Bone Marrow Samples to Predict Acute Graft-versus-Host Disease and Overall Survival after Allogeneic Stem Cell Transplantation.

Acute graft-versus-host disease (aGvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We performed RNA analysis of 1408 candidate genes in bone marrow samples obtained from 167 patients undergoing HSCT. RNA expression data were used in a machine learning algorithm to predict the presence or absence of aGvHD using either random forest or extreme gradient boosting algorithms. Patients were randomly divided into training (2/3 of patients) and validation (1/3 of patients) sets. Using post-HSCT RNA data, the machine learning algorithm selected 92 genes for predicting aGvHD that appear to play a role in PI3/AKT, MAPK, and FOXO signaling, as well as microRNA. The algorithm selected 20 genes for predicting survival included genes involved in MAPK and chemokine signaling. Using pre-HSCT RNA data, the machine learning algorithm selected 400 genes and 700 genes predicting aGvHD and overall survival, but candidate signaling pathways could not be specified in this analysis. These data show that NGS analyses of RNA expression using machine learning algorithms may be useful biomarkers of aGvHD and overall survival for patients undergoing HSCT, allowing for the identification of major signaling pathways associated with HSCT outcomes and helping to dissect the complex steps involved in the development of aGvHD. The analysis of pre-HSCT bone marrow samples may lead to pre-HSCT interventions including choice of remission induction regimens and modifications in patient health before HSCT.

Stem cell transplantation therapy for acute myeloid leukemia

Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy, presenting a significant challenge in the field of medicine. In this context, Hematopoietic Stem Cell Transplantation (HSCT) has garnered widespread attention as a potential therapeutic approach. This paper reviews the current research progress in the field of AML treatment, with a specific focus on the application of HSCT. Through a comprehensive analysis of recent literature and clinical trials, it systematically summarizes the therapeutic effects of HSCT in different patient populations. Despite demonstrating certain efficacy in AML treatment, there remain research gaps in the application of HSCT, particularly in specific patient groups and contexts. This paper extensively discusses the principles, types, and application scenarios of HSCT in AML patients. By reviewing recent research findings, this article analyzes the treatment outcomes of HSCT in both young and elderly patients and compares relevant survival data. This paper presents future prospects for research, including in-depth investigations into novel HSCT treatment strategies, the impact of age differences on treatment outcomes, and more. These prospects aim to provide more precise directions for improving the therapies for AML patients.

Hypomagnesemia May Predict Better Survival and Reduced Nonrelapse Mortality in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Magnesium (Mg) is an essential element that is required as a cofactor for many cellular reactions, including immunologic pathways. The aim of this study was to investigate the potential impact of serum Mg levels on allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes. Medical records of 340 alloHSCT recipients (median age: 45 [18-71] years; M/F: 210/130) were reviewed for this retrospective study. Serum Mg levels on days -28, -7, 0, +7, +14, +21, +30, +60, and +90 were included in the analysis. Serum Mg+14 levels predicted nonrelapse mortality (NRM) (P = .025) and had a significant impact on the development of mucositis (P = .027), fungal infection (P = .006), engraftment syndrome (P < .001), sinusoidal obstruction syndrome (SOS) (P = .001), cytomegalovirus (CMV) reactivation (P = .039), and acute graft vs host disease (GvHD) (P < .001). Based on the optimal threshold of serum Mg+14 level (1.33 mg/dL; area under the curve: 0.581 [0.515-0.648]; P = .018), the study group was divided into 2 subgroups as low- and high-Mg+14. The incidence of acute GvHD (P = .002), SOS (P = .013), engraftment syndrome (P = .013), CMV reactivation (P = .001), and Epstein Barr virus reactivation (P = .005) was significantly lower in low-Mg+14 group. The probability of overall survival (OS) was significantly better (P = .002), whereas NRM was lower in the low-Mg+14 group (P = .001). Hypomagnesemia seems to provide a considerable advantage for the post-transplant outcome, which may confirm its potential role in the immunologic microenvironment and adaptive immunity.

Autologous hematopoietic stem cell transplantation for multiple sclerosis: Long-term follow-up data from Norway

Background: Autologous hematopoietic stem cell transplantation (HSCT) is a potent treatment option for patients with aggressive relapsing-remitting multiple sclerosis (RRMS). Objective: To evaluate long-term outcomes of HSCT in MS. Methods: National retrospective single-center observational study of patients with aggressive RRMS that underwent HSCT in Norway from January 2015 to January 2018. Criteria for receiving HSCT included at least two clinical relapses the last year while on disease modifying treatment (DMT). Results: In total, 29 patients, with a mean follow-up time of 70 months (standard deviation:14.3), were evaluated. Twenty patients (69%) had sustained no evidence of disease activity (NEDA-3) status, 24 (83%) were relapse-free, 23 (79%) free of magnetic resonance imaging (MRI) activity, and 26 (90%) free of progression. Number of patients working full-time increased from 1 (3%), before HSCT, to 10 (33%) after 2 years and 15 (52%) after 5 years. Conclusion: HSCT offers long-term disease-free survival with successively increasing work participation in patients with aggressive MS resistant to DMTs.

A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes.

Data on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce. We performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host disease (sGvHD), fitting proportional hazard and subdistributional models to data of n=1,392 recipients of European ancestry from three centres. The single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene (SEMA3C), was genome-wide significantly associated with event-free survival (p=7.0x10-8) and sGvHD (p=7.5x10-8). Further associations were detected for SNPs in the Paxillin gene (PXN) with death without prior relapse or sGvHD, as well as for SNPs of the Plasmacytoma Variant Translocation 1 gene (PVT1, a long non-coding RNA gene), the Melanocortin 5 Receptor (MC5R) gene and the WW Domain Containing Oxidoreductase gene (WWOX), all associated with the occurrence of sGvHD. Functional considerations support the observed associations. Thus, new genes were identified, potentially influencing the outcome of HSCT.

Change in Conditioning Regimen Improves Hematopoietic Stem Cell Transplant Outcomes in Children with Lysosomal Storage Disorders

Change in Conditioning Regimen Improves Hematopoietic Stem Cell Transplant Outcomes in Children with Lysosomal Storage Disorders

Allogenic hematopoietic stem cell transplantation outcomes of patients aged ≥ 55 years with acute myeloid leukemia or myelodysplastic syndromes in China: a retrospective study

BackgroundElderly patients with acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) have historically had poor prognoses. However, there has been a recent increase in the use of allogenic hematopoietic stem cell transplantation (allo-HSCT) are in this patient population. Nevertheless, the optimal choice of donor type for the patients remains an unmet need. Limited data exist on the use of allo-HSCT in elderly patients with AML/MDS from China. To better understand and optimize the selection of donor type for the elderly patients, particularly for those with refractory or relapsed disease, in comparison with the previous studies in the US and Europe.MethodsOur retrospective study enrolled 259 patients aged over 55 years who underwent their first allo-HSCT between April 2015 and August 2022. These patients were divided into three groups based on donor type: haploidentical related donor group (haploidentical related donor transplantation [HID], n = 184), matched sibling donor group (matched sibling donor transplantation [MSD], n = 39), and matched unrelated donor group (matched unrelated donor transplantation [MUD], n = 36). Statistics were performed with the chi-square test, the log-rank and Fine-Gray tests.ResultsThe median age of the cohort was 57 years (range: 55–75) and 26.25% of patients were over 60 years old. Younger patients had a higher incidence of acute graft-versus-host disease (HR = 1.942, P = 0.035), faster neutrophil recovery (HR = 1.387, P = 0.012), and better overall survival (HR = 0.567, P = 0.043) than patients aged ≥ 60 years across the entire cohort. Patients with refractory or relapsed (R/R) diseases had delayed neutrophil engraftment (P = 0.010, HR = 0.752) and platelet engraftment (P < 0.001, HR = 0.596), higher incidence of relapses (HR = 2.300, P = 0.013), and inferior relapse-free survival (RFS) (HR = 1.740, HR = 0.016) regardless of donor type. When it came to graft-versus-host-disease-free, relapse-free survival (GRFS), MUDs turned out to be superior to HIDs (HR = 0.472, P = 0.026) according to the multivariable analysis. In contrast, we found MSDs had an inferior GRFS to HIDs in parallel (HR = 1.621, P = 0.043).ConclusionThe choice of donor type did not significantly affect the outcomes of allo-HSCT. However, when considering the quality of post-transplant life, MUDs or HIDs from younger donors may be the optimal choice for elderly patients.

Comparing between HLA-matched sibling donor allogenic HSCT and non-sibling matched related donor allogenic HSCT outcome in pediatric patients; single center retrospective study.

Extended family donor search other than siblings may yield an HLA matched donor in communities with high rate of consanguinity. The outcome of patients who are transplanted from non-sibling matched related donors (NS-MRD) including engraftment and graft versus host disease (GVHD) are scarce in comparison with matched sibling donor (MSD). We retrospectively reviewed the outcome of all our pediatric hematopoietic stem cell transplantation (HSCT) patients who had non-sibling matched related donor and controlled them with matched sibling donor HSCT (based on age, indication of HSCT, conditioning regimen, GVHD prophylaxis, serotherapy, stem cell source and cytomegalovirus status). A total of 76 patients were reviewed during study period. Thirty patients (39.5%) in NS-MRD arm and 46 patients in MSD (60.5%) were identified after matching in age, disease, and conditioning regimens. All patients had similar approach including stem cell source and GVHD prophylaxis (CNI + 2nd agent). Out of the NS-MRD group, 18 patients (59%) had one of their parents as a donor and the rest as second degree relatives. Both groups were equally distributed and were homogeneous. Both groups had no statistically significant difference in outcome including engraftment, GVHD and Chimerism tests results. GVHD was seen in (13%) NS-MRD patients compared to (11%) in MSD patients. All patients remain alive with median follow up of 1249 days (431-3525). This study showed no significant difference in allogenic HSCT outcomes between matched sibling donors and non-sibling matched related donors and support using the same management approach in terms of conditioning therapy, GVHD prophylaxis, and serotherapy only if indicated.

Music intervention in patients undergoing hematopoietic stem cell transplantation: A systematic review and meta-analysis.

To explore whether music intervention improves the quality of life (QOL) of patients undergoing hematopoietic stem cell transplantation (HSCT) and to evaluate its impact on patients' symptoms of depression/anxiety and fatigue. This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Cochrane CENTRAL, and EMBASE were searched from inception to September 30, 2022. The search strategy used a combination of the keywords "music" and "hematopoietic stem cell transplantation" or "HSCT." The outcomes assessed were QOL, depression and anxiety, and fatigue. Pooled standardized mean differences with 95% confidence intervals were calculated to compare the outcomes between the music intervention and control groups. Heterogeneity across the studies was assessed using a chi-square-based test, and the I2 and Q statistics. Meta-analysis of the included study population showed that music intervention for patients undergoing HSCT was associated with patients' improved QOL, and resulted in reduced depression/anxiety and fatigue compared to patients without music intervention. Music intervention benefits HSCT outcomes, including better QOL, less depression/anxiety, and less fatigue postoperatively. Future trials with larger samples are still warranted to strengthen the evidence supporting the benefits of music intervention in this patient population.

Hematopoietic Stem Cell Transplantation in Sickle Cell Disease: A Multidimentional Review.

While exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) have been approved by the US Food and Drug Administration (FDA) as the first cell-based gene therapies for the treatment of patients 12 years of age and older with sickle cell disease (SCD), this treatment is not universally accessible. Allogeneic hematopoietic stem cell transplant (HSCT) has the potential to eradicate the symptoms of patients with SCD, but a significant obstacle in HSCT for SCD is the availability of suitable donors, particularly human leukocyte antigen (HLA)-matched related donors. Furthermore, individuals with SCD face an elevated risk of complications during stem cell transplantation due to SCD-related tissue damage, endothelial activation, and inflammation. Therefore, it is imperative to consider optimal conditioning regimens and investigate HSCT from alternative donors. This review encompasses information on the use of HSCT in patients with SCD, including the indications for HSCT, conditioning regimens, alternative donors, and posttransplant outcomes.

Altered Serum Alpha1-Antitrypsin Protease Inhibition before and after Clinical Hematopoietic Stem Cell Transplantation: Association with Risk for Non-Relapse Mortality.

α1-Antitrypsin (AAT), an acute-phase reactant not unsimilar to C-reactive protein (CRP), is a serine protease inhibitor that harbors tissue-protective and immunomodulatory attributes. Its concentrations appropriately increase during conditions of extensive tissue injury, and it induces immune tolerance, in part, by inhibiting the enzymatic activity of the inflammatory serine protease, proteinase 3 (PR3). Typically administered to patients with genetic AAT deficiency, AAT treatment was recently shown to improve outcomes in patients with steroid-refractory graft-versus-host disease (GVHD). GVHD represents a grave outcome of allogeneic hematopoietic stem cell transplantation (HSCT), a potentially curative intervention for hematological diseases. The procedure requires radio/chemotherapy conditioning of the prospective marrow recipient, a cytotoxic process that causes vast tissue injury and, in some formats, interferes with liver production of AAT. To date, changes in the functional profile of AAT during allogeneic HSCT, and during the cytotoxic intervention that precedes HSCT, are unknown. The present study followed 53 patients scheduled for allogeneic HSCT (trial registration NCT03188601). Serum samples were tested before and after HSCT for AAT and CRP levels and for intrinsic anti-proteolytic activity. The ex vivo response to clinical-grade AAT was tested on circulating patient leukocytes and on a human epithelial cell line treated with patient sera in a gap closure assay. According to the ex vivo experiments, circulating leukocytes responded to AAT with a favorable immune-regulated profile, and epithelial gap closure was enhanced by AAT in sera from GVHD-free patients but not in sera from patients who developed GVHD. According to serum collected prior to HSCT, non-relapse mortality was reliably predicted by combining three components: AAT and CRP levels and serum anti-proteolytic activity. Taken together, HSCT outcomes are significantly affected by the anti-proteolytic function of circulating AAT, supporting early AAT augmentation therapy for allogeneic HSCT patients.

Effect of serum panel reactive antibodies on allogeneic hematopoietic stem cell transplantation in pediatric thalassemia patients: A single-center experience.

The aim of this study was to assess the impact of serum panel reactive antibodies (PRA) on the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric thalassemia patients. A total of 73 pediatric patients with thalassemia were included in this single-center study. Pre-transplant PRA levels were evaluated, and the patients were divided into two groups: PRA-negative (group 1; n = 44) and PRA-positive (group 2; n = 29). Patient characteristics, including age, gender, donor type, stem cell source, and HLA compatibility, were analyzed. Transplant outcomes, including engraftment, transfusion requirements, and transplant-related complications, were compared between the two groups. Further subgroup analysis was performed based on MFI values. At the time of transplantation, patients in group 1 were younger than those in group 2 (p = .008). The number of fully matched donors within the family (MSD and MFD) was significantly higher in group 1 (p = .049). Additionally, Rh blood group incompatibility was higher in group 2 (p = .03). There was no statistically significant difference in the engraftment days of neutrophils, platelets, and erythrocytes between the two groups. The frequency of poor graft function and graft failure was higher in the group 2, but there was no statistically significant difference. Post-transplant transfusion requirements for platelets and red blood cells were significantly higher in the group 2 (p < .001). Transplant-related complications such as VOD, PRES, and aGvHD were more common in the group 2, but no statistical significance was detected. Serum PRA in pediatric thalassemia patients may impact the outcomes of HSCT. PRA-positive patients had higher rates of blood product transfusion requirements. Although poor graft function, graft failure, and post-transplant complications were more common in the group 2, statistical significance was not observed. Identifying patients with high PRA levels can assist in optimizing transplant strategies and post-transplant care, leading to improved outcomes for the patients.