Hematopoietic Stem Cell Transplantation Patients Research Articles

Abstract 16432: Screening for Cardiovascular Complications in Pediatric Hematopoietic Stem Cell Transplant Patients

Introduction: Hematopoietic stem cell transplantation (HSCT) carries a risk of cardiovascular morbidity, with reported incidences of pericardial effusion, pulmonary hypertension (PH), and reduced left ventricular ejection fraction (LVEF). Screening for cardiovascular complications in children undergoing HSCT may be essential, but its utility remains unexplored. Hypothesis: Screening HSCT children using echocardiography and brain natriuretic peptide (BNP) can detect cardiovascular complications associated with adverse outcomes in this population. Methods: This prospective single-center cohort study analyzed children undergoing HSCT over a 2-year period. Baseline, 7-day, and 30-day echocardiograms and BNP levels were obtained. Multilevel linear regression assessed changes in echocardiograms and BNP. Logistic regression determined associations between cardiac complications and outcomes. Results: The study included 43 patients, with a median age of 8.6 years (IQR 3.7, 14.6). Echocardiograms were obtained at baseline (n=43), day+7 (n=34), and day+30 (n=25). BNP levels were obtained at baseline (n=41), day+7 (n=34), and day+30 (n=12). Adverse outcomes included TMA (n=7), endothelial dysfunction (n=36), mechanical ventilation (n=8), and death (n=8). Pericardial effusion was the most common finding (n=2(6%) at day+7, n=4(16%) at day+30). Pericardial effusion at either day+7 or day+30 predicted death (OR 15.7, 95% CI 1.8-137, p=0.013) and TMA (OR 13.1, 95% CI 1.7-103, p=0.014). A 10% decrease in LVEF was observed in 6 (17%) of patients at day+7 and 2 (8%) at day+30, and was associated with reduced mortality (OR 0.1, 95% CI 0-0.6, p=0.009). The change in BNP level at day+7 was 7pg/mL (IQR 6, 66) and 5pg/mL (IQR 3, 20) at day+30. A 10 point increase in BNP carried an increased risk of endothelial dysfunction (OR 4.1, 95% CI 1.3-263, p<0.001). No patients developed PH. Conclusions: Cardiovascular complications are common after HSCT in children and carry diagnostic and prognostic significance. Further refinement of the screening protocol is necessary to determine the optimal timing of testing and assess its clinical utility.

A novel flow-cytometric based method to assess post-HSCT donorchimerism exploiting RNA hybridization.

Analysis of donor-recipient chimerism after hematopoietic stem cell transplantation (HSCT) is of pivotal importance for patient's clinical management, especially in the context of mixed chimerism. Patients are routinely monitored for chimerism in sorted subsets of peripheral blood cells. However, measurement of chimerism in sorted immune cell subsets is technically challenging and time consuming. We here propose a novel, flow cytometry-based approach to detect donor cell chimerism in sex-mismatched HSCT. We exploit RNA PrimeFlow™ system, based on RNA hybridization, to detect mRNA from a lysine demethylase encoded by Y chromosome, KDM5D. This approach allows to distinguish male and female derived cells with around 1% sensitivity. The procedure can be coupled with multiparametric immunophenotyping to assess chimerism in specific immune cell subsets without the need for prior FACS-sorting. We apply this method to a cohort of HSCT patients (n = 10) and we show that it is consistent with standard PCR-based method. We also show that different T lymphocyte subsets display variable degrees of donor chimerism, especially in CD8+ T cell compartment where we observe an enrichment for recipient chimerism in central memory T cells. This method can be exploited to advance current knowledge on immune reconstitution focusing on specific subsets avoiding prior FACS-sorting.

Persistent Hypogammaglobulinemia after Receiving Rituximab Post-HSCT Is Not Caused by an Intrinsic B Cell Defect.

In the setting of hematopoietic stem cell transplantation (HSCT), Rituximab (RTX) is used for the treatment and prevention of EBV-associated post-transplantation lymphoproliferative disease or autoimmune phenomena such as autoimmune hemolytic anemia (AIHA). Persistent hypogammaglobulinemia and immunoglobulin substitution dependence has been observed in several patients after RTX treatment despite the normalization of total B cell numbers. We aimed to study whether this is a B cell intrinsic phenomenon. We analyzed four patients with different primary diseases who were treated with myeloablative conditioning and matched unrelated donor HSCT who developed persistent hypogammaglobulinemia after receiving RTX treatment. They all received RTX early after HSCT to treat EBV infection or AIHA post-HSCT. All patients showed normalized total B cell numbers but absent to very low IgG positive memory B cells, and three lacked IgA positive memory B cells. All of the patients had full donor chimerism, and none had encountered graft-versus-host disease. Sorted peripheral blood naïve B cells from these patients, when stimulated with CD40L, IL21, IL10 and anti-IgM, demonstrated intact B cell differentiation including the formation of class-switched memory B cells and IgA and IgG production. Peripheral blood T cell numbers including CD4 follicular T-helper (Tfh) cells were all within the normal reference range. In conclusion, in these four HSCT patients, the persistent hypogammaglobulinemia observed after RTX cannot be attributed to an acquired intrinsic B cell problem nor to a reduction in Tfh cell numbers.

Development of a Combined Risk Assessment Model for Venous Thromboembolism and Bleeding in Hematopoietic Stem Cell Transplantation Patients

Background: Venous thromboembolism (VTE) and bleeding are common complications amongst allogeneic and autologous hematopoietic stem cell transplant (HSCT) patients. Balancing risk of bleeding and thrombosis in this population is particularly challenging as HSCT patients are concurrently pancytopenic and coagulopathic. However, risk factors for bleeding and thrombosis in HSCT patients are understudied. We aimed to derive a combined bleeding and VTE risk assessment tool to be used in the immediate post-transplant period (90 days). Methods: We conducted a retrospective cohort study of adult patients who underwent allogeneic or autologous HSCT between January 1, 2011 and December 31, 2021 at a tertiary care centre in Canada. The risk models patients were followed from transplant until occurrence of the event of interest with last follow up at Day 90 post-transplant, or death. Primary outcome for VTE was the occurrence of a confirmed thrombosis including proximal upper and lower extremity deep vein thrombosis, pulmonary embolism, or thrombosis of unusual sites, including cerebral and splanchnic. Primary outcome for bleeding was the occurrence of a major or clinically significant non-major bleeding event, not related to anticoagulation, as per the definition of the International Society of Thrombosis and Hemostasis. Group characteristics were compared using chi-square, Fisher's exact, or Student's T-tests as appropriate. Potential predictors for VTE and bleed amongst our patients were evaluated using single variable logistic regression and confirmed with multiple variable logistic regression with forward selection. For continuous variables, optimal cut-off points were estimated using ROC curves. Final VTE and bleed risk scores were derived based on weighted variables and compared using Cox regression with non-parametric bootstrapping used for internal validation. Results: A total of 476 patients (317 autologous, 159 allogeneic) were included. 47 patients (9.8%) suffered from VTE, and 32 patients (6.7%) suffered from bleed unrelated to anticoagulation within 90 days post-HSCT. A VTE risk assessment tool was derived, and internally validated, and it included: second central venous catheter insertion (due to complications from first central line) (2 points), and previous cancer treatment with steroids (1 point). The overall cumulative incidence of VTE was 31.8% in the high-risk group (>2 points) versus 7.6% in the low-risk group (0-1 points). The high-risk group was associated with higher mortality at 90 days (15.9% versus 3.2%, p <0.001; Figure 1). A bleeding risk assessment tool was also derived, and internally validated, and it included: baseline (day 0 of transplant) platelet count of <90 (1 point), and baseline hemoglobin of <96 (1 point). The overall cumulative incidence of bleed was 17.2% in the high-risk group (2 points), versus 4.3% in the low-risk group (0-1 points). The high-risk group was associated with higher mortality at 90 days (12.6% versus 2.6%, p<0.001). Amongst the low-risk bleed group, overall cumulative incidence of VTE was 10.03%, with 31.03% in the high-risk VTE group versus 8.33% in the low-risk VTE group (p<0.001). The positive VTE group was associated with higher mortality at 90 days (10.26% versus 1.72%, p=0.001; Figure 2). Amongst the high-risk bleed group, overall cumulative incidence of VTE was 9.19%, with 33.33% in the high-risk VTE group, versus 4.17% in the low-risk VTE group (p<0.001). The positive VTE group was associated with higher mortality at 90 days (37.5% versus 10.13%, p=0.026). Conclusion: We derived a predictive score, VTE and Bleeding in Marrow Transplant (VBMT) - risk score, for both VTE and bleeding in the immediate post-transplant period (90 days), to be used in conjunction with other criteria for bleeding and thrombosis. Amongst the low-risk bleed patients, we recommend strong consideration of chemical VTE prophylaxis, especially amongst the high-risk VTE group. These risk assessment models will help stratify patients based on bleed and thrombosis risk, and ultimately help guide VTE prophylaxis and surveillance strategies amongst HSCT patients.

Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic Syndromes (MDS)

Purpose. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for patients with myelodysplastic syndromes (MDS). Several issues must be considered when evaluating the benefits and risks of HSCT for patients with MDS, with the timing of transplantation during the disease course being a crucial question. Recently the integration of genomic screening (by Molecular International Prognostic Scoring System, IPSS-M) into patient's assessment has resulted into a significant improvement in predicting clinical outcomes with respect to the conventional prognostic score (Revised IPSS, IPSS-R), including better stratification of post-HSCT outcome. Here, we aimed to develop and validate a Decision Support System to define the optimal timing of HSCT in MDS patients based on clinical and genomic information as provided by IPSS-M vs conventional IPSS-R. Patients and methods. We studied a retrospective, international cohort of 8,326 patients with MDS for whom complete set of clinical and molecular information was available. Patients were stratified into a learning and validation cohorts (65%, n= 5411 vs. 35%, n=2915). The decision-strategy analysis was divided into two parts. First, we developed a multi-state model to estimate transition hazards between different disease strata. Age and IPSS-R/IPSS-M were used as explanatory variables. The time elapsed between the diagnosis of MDS and HSCT was also considered as covariate in the models, which were further adjusted for disease-modifying therapy (if any). Next, we developed a Semi-Markov multi-state decision model based on microsimulation to compare various transplantation strategies according to the timing of the procedure, conditionally on covariates of interest. The microsimulation strategy simulates a hypothetical randomized clinical trial where subjects are randomized to receive HSCT at different time points. Results were used to estimate the average survival time over an 8-year time horizon (Restricted Mean Survival Time, RMST) for each combination of covariates, and then determine the optimal transplantation policy by compared the different strategies. Results. When considering patient life expectancy for patients who received a HSCT (Restricted Mean Survival Time, RMST) in the learning cohort, in both scenarios of IPSS-R and IPSS-M based transplantation policies, early disease stage was associated with a better clinical outcome. Indeed, life expectancy after transplantation was higher for younger vs elderly patients ( Figure 1 and 2). Under an IPSS-R based policy, patients with low-risk disease clearly benefit from a delayed transplantation policy across all age groups, while in patients belonging to intermediate, high/very high risk categories immediate transplantation was associated with a prolonged life expectancy, regardless of age. ( Figure 1) Considering an IPSS-M based policy, patients with either low and moderate-low risk benefit from a delayed transplantation policy (across all age groups), while in those belonging to moderate-high, high and very high risk categories immediate transplantation was associated with a prolonged life expectancy (across all age groups, Figure 2). Importantly, all these results were confirmed in the validation cohort, thus providing evidence for their reliability and generalizability. Modelling decision analysis on IPSS-M vs. original IPSS-R changed transplantation policy in a significant proportion of patients, resulting in a gain-in-life expectancy under an IPSS-M based policy across all age groups (P<0.001). Specifically, 19% of candidates to be immediately transplanted under an IPSS-R based policy would benefit from a delayed strategy under an IPSS-M based policy, while 21% of candidates to delayed transplantation under an IPSS-R based policy, would benefit from immediate HSCT under an IPSS-M based policy. We have created a prototype web application for the MDS Transplantation Decision Support System, that allows clinicians to define the best timing for HSCT starting from individual patient demographics, IPSS-R, and IPSS-M information. Conclusion. We provided evidence for the clinical relevance of including genomic features into the transplantation decision making process, specifically regarding the optimal timing of HSCT, allowing personalizing of the hazards and effectiveness of HSCT in patients with MDS.

An Assessment of Marrow-Infiltrating T Cells in Early Relapsed Hematologic Cancer Patients Post Allogeneic Hematopoietic Stem Cell Transplantation

Background: Relapse is the major treatment failure of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. Especially, early relapse had seriously bad prognosis. And tumor-infiltrating T cells play an important role in disease progression and recurrence. However, there is lack of data about the marrow-infiltrating T cell of early relapsed patients compared to those with complete remission (CR) at an early timepoint after HSCT. Therefore, we analyzed the differentiation stage and expression of inhibitory receptors of the marrow-infiltrating T cell in the early stages of allogeneic HSCT. Method: A total of 40 samples from patients treated at Chungnam National University Hospital were collected between April 2021 and October 2022. We used flow cytometry to classify T cells into five subtypes using CD45RA, CD95, and CCR7: naïve, stem cell memory (SCM), central memory (CM), effector memory (EM) and effector memory with positive CD45RA (EMRA). Otherwise, we analyzed regulatory T cell (Treg) by defining as CD25 highCD127 low and divided them into three categories using CD25 and CD45RA: naïve, active and non-suppressive Treg. We defined early relapse (ER) as relapse within 6 months of allogeneic HSCT. High-throughput single-cell RNAseq assays from BM lymphocytes isolated by density gradients were performed to determine the expression and cell composition of previously irradiated markers. Results: With this approach, marrow-infiltrating T cells were analyzed in 40 patients (10 patients with early relapse) with a median age of 57 years (ranged from 30 to 71). AML is the most common disease at 60%, followed by MDS (20%), ALL (15%) and PMF (2.5%). Stem cell sources were 32.5% from matched sibling donor, 37.5% from haplo-identical donor and 27.5% from matched unrelated donor. All patients received mobilized peripheral blood stem cell transplantation. Marrow-infiltrating CD3+T cell counts were lower in patients with allogeneic HSCT compared to normal subjects (CD3+T cells: 13.89% in HSCT patient and 9.116% in ER patients vs. 34.19% in normal subjects, p< 0.0001). In addition, CD3+CD8+T cells were higher in CR than ER patients (CD3+CD8+T cells: 50.39% in CR vs. 30.41% in ER patients, p< 0.0033). In HSCT patients, naïve was higher, and EM and EMRA were lower than those in normal subjects among CD4+T cells (naïve; 8.629% in ER patients and 5.119% in CR patient's vs 45.76% in normal subjects, p< 0.0001/EM; 54.04% in ER patients and 55.93% in CR patients vs 18.61 in normal subject, p= 0.0003 and p< 0.0001 respectively). Of CD3+T cells, the proportion and expression level of TIM-3 was higher ER patients than in CR patients (56.33% in ER patients vs 39.20% in CR patients, p= 0.0185/MFI; 1873 in ER patients vs. 826.7 in CR patients, p= 0.0331). Of CD4+T cells, the percentage of TIM-3 was lower in normal subjects than in allogeneic HSCT patients (7.794% in normal vs 30.11% in CR patients and 26.04% in ER patients, p= 0.0002 and p= 0.0102 respectively). In patients with ER, naïve and EM was higher than those in CR patients among CD8+T cells (naïve; 8.680% in ER patients vs 4.066% in CR patients, p= 0.4001 /EM; 54.44% in ER patients vs 44.33% in CR patients, p= 0.3039). Of CD8+ EMRA T cell, the expression of TIM-3 was higher in ER patients than in CR patients (MFI; 1441 in HSCT patients vs 421.7 in normal, p=0.1038). Otherwise, of CD3+CD4-CD8-, The percentage of TIM3 was higher in ER patients than CR patients (80.33 % in ER patients vs 62.49% in CR patients, p= 0.0333). Treg levels were no significant difference between CR and ER. We have obtained single-cell sequencing data from two CR (complete response) patients and two ER (early relapse) patients, representing each group. Since the classified groups exhibited ambiguous phenotypes, they were reclassified based on specific markers of cell groups. The reclassified groups showed a higher proportion of HCS (Hematopoietic Stem Cell)-like cells in relapsed patients (+10.14%, P=0.368) and a lower proportion of CD8+ T cells (-13.40%, p=0.068). The HSC-like cells in relapsed patients exhibited higher expression of TIM3 ligand than in CR patients Conclusion: Among the IRs, TIM3 had the highest expression of all cell groups (CD4 T cells, CD8 T cells and Treg) compared with other IRs at the early stage of allogeneic HSCT. So, TIM3 might be a potential target for preventing relapse in hematologic cancer patients after allogeneic HSCT in the future.

High Incidence of Vitamin D Deficiency Among Patients Undergoing Hematopoietic Stem Cell Transplant and a Single Ultra-High Dose Vitamin D Replacement

Introduction: Vitamin D involves in several important human physiologic pathways from bone metabolism to inflammation and immune regulation. Patients who undergo hematopoietic stem cell transplant (HSCT) are at risk of developing vitamin D deficiency from various mechanisms and replacement of vitamin D in these patients can be challenging according to several reasons. In addition, vitamin D may potentially affect outcomes, overall health and quality of life after HSCT. An ultra-high dose vitamin D replacement was previously explored in pediatric HSCT patients but has never been investigated in adult patient population. In this study, we explored the incidence of vitamin D deficiency, the safety and efficacy of a single ultra-high dose vitamin D replacement including its effect on bone health among adult patients with hematologic malignancy undergoing HSCT. Patients and Methods: First, we looked at the retrospective cohort of patients who underwent HSCT between January 2017 and August 2022 to explore the incidence of vitamin D deficiency (25-hydroxy vitamin D level <20 ng/mL) in Thailand. Subsequently, we prospectively included adult patients with hematologic malignancy undergoing both autologous (ASCT) and allogeneic HSCT (alloHSCT) from September 2022 to June 2023. All patients received a single ultra-high dose vitamin D on the day of admission prior to the initiation of conditioning regimens. We reported the safety and efficacy of a single ultra-high dose vitamin D (Ergocalciferol; Vitamin D2) replacement as calculated by weight and pre-transplantation vitamin D level among these patients using the Stoss protocol previously described. The effect of an ultra-high dose vitamin D on bone turnover was also monitored. Results: In the retrospective cohort, 229 patients underwent HSCT (146 ASCT and 83 alloHSCT). Vitamin D deficiency was observed in 147 patients (64.6%) including 91 (62.3%) ASCT and 56 (67.5%) alloHSCT. The median 25-hydroxy (25-OH) vitamin D level was 17.6 (4.0-86.3) ng/mL comparable between autologous and allogeneic patients. In the prospective cohort, 45 patients underwent HSCT (27 ASCT and 18 alloHSCT). The median age of patients at the time of HSCT was 49 (23-67) years with 18 patients (40%) being male. The median pre-transplant 25-OH vitamin D level was 20.2 ng/mL with 22 patients (48.9%) (13 ASCT, 9 alloHSCT) meeting the criteria of vitamin D deficiency. The median dose of vitamin D2 used was 500,000 (300,000-600,000) IU. At day +28 post-HSCT, 40% of patients were able to attain 25-OH vitamin D level above 30 ng/mL comparable between ASCT and alloHSCT but significantly higher compared to the retrospective cohort. The time to neutrophil and platelet engraftment were 13 (9-26) days and 14 (9-33) days, comparable between the controlled retrospective cohort and high dose replacement prospective cohort. The median levels of parathyroid hormone (PTH) and bone turnover markers including osteocalcin, β-CrossLaps (β-CTx), and procollagen type I N-propeptide (PINP) at day+28 was 45.4 (19.4-152.2) pg/mL, 11.3 (6.0-16.8) ng/mL, 0.79 (0.1-13.0) ng/ml and 43.7 (19.7-133.7) mcg/L, respectively. Among patients who underwent alloHSCT, the incidence of cytomegalovirus reactivation and acute graft versus host disease was 72.2% and 11.1% (no grade 3-4), respectively. Figure 1 shows the kinetic of serum 25-OH vitamin D, Calcium, β-CTx and PINP of patients in the prospective cohort from baseline to day +28 post-HSCT. At all timepoints (day 0, +7, +14, +21, +28), the median level of vitamin D level was significantly higher whereas the median serum PINP level was significantly lower compared to the baseline level. There was no occurrence of hypercalcemia or bony events during the time of the study. Conclusion: Our study highlights a high incidence of vitamin D deficiency in HSCT patients. Utilizing a single ultra-high dose vitamin D is an effective and safe approach to replace vitamin D in adult patients undergoing HSCT. A high percentage of patients could maintain adequate vitamin D level during post-transplant period. PINP level was sustainably decreased after vitamin D replacement indicating a lower bone resorption. Whether this approach will translate into improved immune function, long-term bone health and outcomes compared to the conventional replacement strategy warrants further exploration in prospective randomized clinical trials.

Analysis of Laboratory Parameters before the Occurrence of Hepatic Sinusoidal Obstruction Syndrome in Pediatric Patients after Hematopoietic Stem Cell Transplantation

Introduction: Hepatic sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease of the liver, is a serious complication following hematopoietic stem cell transplantation (HSCT). Early diagnosis and treatment with defibrotide can improve patient outcome. The pathogenesis is not fully understood, but it is obvious that some laboratory parameters are already changed before the onset of SOS. The aim of our retrospective study was to detect laboratory parameters following HSCT that can predict the occurrence of SOS. Methods: We analyzed 182 children with a median age of 7.2 years who underwent allogeneic or autologous HSCT for the first time and without defibrotide prophylaxis. Our study population consisted of 126 patients who received allogeneic HSCT (69.2%) and 56 patients who underwent autologous HSCT (30.8%). The stem cell sources were peripheral blood stem cells (50.5%) or bone marrow (49.5%) and the most frequent underlying diseases were solid tumors (34.1%), genetic diseases (19.2%), acute lymphoblastic leukemia (18.1%), and acute myeloid leukemia (13.7%). The diagnosis of SOS was based on the pediatric criteria of European Society for Blood and Marrow Transplantation. We investigated the following 15 laboratory parameters after HSCT before the onset of SOS: international normalized ratio (INR), activated partial thromboplastin time (aPTT), reptilase time, factor VIII, factor XIII, von Willebrand factor (vWF), von Willebrand factor activity (vWF activity), fibrinogen, antithrombin III, protein C, protein S, D-dimer, alanine aminotransferase (ALT), bilirubin, and ferritin. The last laboratory values within one week before the onset of SOS were analyzed in the SOS patient group. In the non-SOS patient group, we investigated the parameters for four weeks after transplantation and calculated the median. We selected cut-off values for the continuous parameters based on receiver operating characteristic curves analyses and existing reference values. We performed Mann-Whitney U test, univariate and multivariate analyses to find significant ( P < .05) associations between the values of laboratory parameters and the occurrence of SOS. The probability of developing SOS was calculated using the significant independent variables. Results: The overall incidence of SOS was 14.8% at a median time of 13 days after HSCT. SOS developed in 24 of 126 allogeneic (19.1%) and in 3 of 56 autologous (5.4%) HSCT patients. Only 3 out of 27 patients (11.1%) who suffered from very severe SOS died within 100 days after HSCT. In the univariate analysis, we found significant associations between the onset of SOS and the following parameters: INR ≥ 1.3, aPTT ≥ 40 sec, reptilase time ≥ 18.3 sec, factor VIII ≤ 80%, antithrombin III ≤ 75%, protein C ≤ 48%, D-dimer ≥ 315 µg/L, bilirubin ≥ 9 µmol/L, and ferritin ≥ 3100 µg/L. In multivariate analysis, we confirmed INR ≥ 1.3 [odds ratio (OR) = 8.104, P = .006], aPTT ≥ 40 sec (OR = 10.174, P = .001), protein C ≤ 48% (OR = 5.215, P = .014), and ferritin ≥ 3100 µg/L (OR = 7.472, P = .004) as independent risk factors after HSCT before SOS. If three of the four significant cut-off values were present, the probability of developing SOS was more than 70%. The probability of SOS was 96%, if all four laboratory parameters were changed according to the cut-off values. The values of factor XIII, vWF, vWF activity, protein S, fibrinogen, and ALT were not relevant for the occurrence of SOS. Conclusions: In summary, the laboratory parameters INR, aPTT, protein C, and ferritin were very useful to predict the occurrence of SOS. These four parameters can enable earlier diagnosis and treatment leading to an improved outcome. In addition, this is the first report on a significant association between SOS and high values of INR and aPTT after HSCT before SOS.

Addition of Myeloablative Doses of Total Marrow Irradiation (TMI) to Myeloablative Fludarabine/Busulfan Conditioning for Allogeneic HSCT in Patients with High-Risk AML, CML, or Myelodysplastic Syndrome: A Phase II Clinical Trial

In allogeneic hematopoietic stem cell transplantation (HSCT) for high-risk myeloid disorders, the intensity of the conditioning regimen correlates with the risk of relapse, but its benefit may be offset by its risk of toxicity. The addition of increasing doses of TMI to myeloablative conditioning was previously shown to have acceptable toxicity in a phase I trial by our group (PMID 25234438), but the efficacy of this strategy remains uncertain. From 2017 to 2023, 31 patients with high-risk acute myeloid leukemia (AML, n=20) or myelodysplastic syndrome (MDS, n=5), or chronic myeloid leukemia (CML, n=3) in accelerated phase or blast crisis, were enrolled into a prospective phase II clinical trial of allogeneic HSCT using myeloablative TMI at 9Gy in combination with standard myeloablative fludarabine (160 mg/m2) and targeted IV busulfan (daily exposure of AUC 4800 μM*min over 3 hours) (FluBu4) chemotherapy. TMI was delivered by using volumetric modulated arc therapy (VMAT) at 1.5Gy twice per day for 3 days for a total of 9Gy. The primary objective of the trial was to achieve >50% Disease-Free Survival (DFS) at 1 year. Here, we report the results on 28 patients who received the TMI-based transplant, whereas among the remaining 3, 1 had not started the conditioning yet and 2 became ineligible due to progression of disease and deterioration of performance status, respectively. The study included patients with matched related donors (MRD, n=9) receiving TMI/FluBu4 as a preparative regimen and patients with matched unrelated (MUD, n=13) or 1-antigen mismatched unrelated (MMUD, n=6) donors receiving conditioning with TMI/FluBu4 + rabbit anti-thymocyte globulin (rATG). Graft-versus-host disease (GVHD) prophylaxis was with methotrexate and tacrolimus, and palifermin was used to prevent severe mucositis. Patients' gender ratio was 16 female/12 male; race was Caucasian in 17 patients, African American in 4, Latino in 7; and median age was 53 years (range: 20-68). The median HCT-Comorbidity Index (HCT-CI) was 3 (range: 0-7). All 20 AML patients were at high risk of relapse because of adverse cytogenetic or molecular profile at diagnosis (n=13), or in second complete remission (CR2) (n=2), or with active disease at the time of transplant (n=5). All patients received peripheral blood stem cells (PBSC) (median CD34+ cell dose: 8.5 x 10 6/kg, range: 2.4-19.9) and fully engrafted. The median time to absolute neutrophil count (ANC) and platelet engraftment was 14 (range: day 9-22) and 15 (range: day 9-43) days, respectively. Grade 3-4 extramedullary toxicities were: mucositis in 57% (n=16), nausea/vomiting in 11% (n=3) and diarrhea in 7% (n=2) of the patients. Acute GVHD grade III-IV was seen in 3 patients (10%). Moderate/severe chronic GVHD was observed in 10 patients (36%). With a median follow-up of 1315 days (range: 158-1925 days) for patients alive, the overall 1 year and current overall survival were 73% and 64%, respectively. GVHD-Free Relapse-Free Survival (GRFS) at 1-year was 54%. Of 5 AML patients transplanted with active disease, 3 were alive and in remission at 1 year and at current date, while 2 died of relapsed disease. Of 28 patients in the study, 6 relapsed/progressed (21%) and 5 of them died of the disease (18%); whereas 5 patients (18%) died of transplant-related mortality (TRM) (2 deaths from septic shock, 1 from disseminated toxoplasmosis, 1 from idiopathic pneumonia and 1 from unknown causes). Kaplan Meyer curves for Overall Survival (OS) and DFS are shown in Figure 1 and 2, respectively. Addition of myeloablative TMI at 9Gy to standard myeloablative targeted FluBu4 was well tolerated and achieved very encouraging results in a group of patients with myeloid malignancies at high risk of relapse (clinicaltrials.gov Identifier: NCT03121014).

Exploring Autologous Hematopoietic Stem Cell Transplantation (HSCT) Utilization and HSCT Refusal Trends in Multiple Myeloma Patients: A Comprehensive Examination of NCDB Data from 2004 to 2020

Background: Autologous hematopoietic stem cell transplantation (HSCT) remains standard of care in multiple myeloma (MM) in eligible patients and is proven to improve survival. However, a significant number of patients can decline HSCT as part of their treatment. Understanding the patterns and factors behind HSCT refusal is crucial for optimizing patient care and tailoring effective interventions. Methods: A total of 43,653 patients MM patients recommended for HSCT from 2004 to 2020 were identified via the NCDB, after excluding cases with incomplete values. KM curves compared overall survival (OS) between HSCT and non-HSCT patients, with both groups receiving induction chemotherapy. Factors influencing HSCT refusal were determined using multivariate logistic regression with backward elimination. SAS version 9.4 was used to analyze the data. Results: Among 43,653 patients recommended for HSCT only 1.95% (850 individuals) refused HSCT and 98.05% received HSCT. The patient characteristics are presented in Table 1. As noted in Figure 1, the median OS of MM patients who opted for induction chemotherapy followed by HSCT, had a much higher OS of 124 months, compared to the MM patients who declined HSCT and had chemotherapy alone with a median OS of 95 months. On multivariate logistic regression analysis patients aged 60-69 and those aged 70 and above demonstrated higher odds of refusing HSCT compared to those below 50 years, with OR of 1.50 (p = 0.0120) and 3.26 (p < 0.0001), respectively. Male patients exhibited decreased odds of HSCT refusal compared to females, with an OR of 0.84 (p = 0.0329). Black patients showed a higher likelihood of HSCT refusal than White patients (OR = 1.38, p = 0.0022). Hispanic patients were less likely to refuse HSCT compared to non-Hispanic patients (OR = 0.65, p = 0.0296). Patients without insurance, those covered by Medicaid/other government insurance and Medicare, exhibited increased odds of HSCT refusal compared to private insurance with ORs of 2.23 (p = 0.0066), 1.38 (p = 0.0366) and 1.34 (p = 0.0048), respectively. Moreover, patients with a Charlson-Deyo score of 2 or 3 had a higher likelihood of HSCT refusal compared to those with a score of 0 (OR = 1.48, p = 0.0024). Patients treated at non-academic facilities were more likely to refuse HSCT than those treated at academic facilities (OR = 2.67, p < 0.0001). Furthermore, patients with a median household income less than $38,000 had increased odds of HSCT refusal compared to those earning $63,000 or more (OR = 1.62, p = 0.0002). Patients with incomes in the ranges of $38,000-$47,999 and $48,000-$62,999 also demonstrated higher odds of refusal with ORs of 1.39 (p = 0.0043) and 1.34 (p = 0.0050), respectively. The year of diagnosis exhibited a significant association with the likelihood of HSCT refusal: patients diagnosed in 2004-2007, 2008-2011 and 2012-2015 had lower odds of refusing HSCT compared to those diagnosed in the reference period (2016-2020), with ORs of 0.16 (p < 0.0001), 0.56 (p < 0.0001) and 0.75 (p = 0.0024), respectively. Geographic location significantly influenced HSCT refusal, with the South Atlantic region (SA) as the reference category. Lower odds of refusal were observed in West South Central (OR 0.29, p < 0.0001), Mountain (OR 0.53, p = 0.001), East South Central (OR 0.63, p = 0.025), and East North Central (OR 0.72, p = 0.01) regions. Conclusion: Our analysis of large real-world database shows that the HSCT significantly improves survival in MM and should be recommended for eligible patients. Furthermore, the study shows that the HSCT refusal rate in real-world is low at ~2% but still represents a missed opportunity to provide standard of care with room for improvement. Older patients (age >60), females, Blacks, non-Hispanics, patients with non-private health insurance, higher comorbidities, non-academic facilities, and lower income (<$63,000/yr), were found to be associated with increased odds of declining HSCT. There was also geographic variation across the USA with higher HSCT refusal in the South Atlantic region compared to other regions. In addition, the increasing trend in HSCT refusal from 2004 to 2020 is likely due to advances in MM therapeutics due to the availability of novel agents and anti-CD38-immunotherapy. Our study suggests significant racial, economic, and geographic variation regarding the utilization of HSCT across the US which should be further studied in prospective studies.

Patient Characteristics and Outcomes of Sinusoidal Obstruction Syndrome with and without Hematopoietic Stem Cell Transplant

Introduction Sinusoidal obstruction syndrome (SOS), also called hepatic veno-occlusive disease (VOD) is a condition causing damage of hepatic vascular endothelial cells, it can progress to multi-organ failure and is associated with high mortality ( >80%). It is known to occur mainly after high dose chemotherapy use in hematopoietic stem cell transplant (HSCT) but with recent advances in chemotherapy, there is an increase in its incidence in non-hematopoietic stem cell transplant patients (non-HSCT). Currently, there is limited literature comparing the patient characteristics and survival of SOS in HSCT vs non-HSCT patients. Therefore we conducted this retrospective analysis. Methods We performed a retrospective analysis using the 2016-2020 National inpatient sample (NIS) database, generated by the Health care cost and utilization project (HCUP). We gathered data on all patients who had SOS/VOD during this time period. They were divided into two cohorts, those who received hematopoietic stem cell transplant (HSCT group) vs those who did not receive hematopoietic stem cell transplant (non-HSCT group). Among the two cohorts we compared the patients characteristics, underlying malignancies, comorbidities and mortality. Results From the NIS database during the study period 1740 cases had documented SOS/VOD. Of those, 520(30%) had a history of HSCT and 1220(70%) did not have HSCT. Of the 520 cases with HSCT, 135 (26%) had Acute lymphoblastic leukemia (ALL), 105 (20.2%) had Acute myeloid leukemia (AML), 55 (10.6%) had Non-Hodgkin lymphoma (NHL), 20 (3.8%) had Chronic myeloid leukemia (CML), 15 (2.9%) had Hodgkin lymphoma (HL), the rest were other malignancies which were not included in the search. Of the 1220 cases without HSCT, 320 (26.2%) had ALL, 150 (12.3%) had AML, 90 (7.4%) had Solid tumors, 55 (4.5%) had NHL, 15 (1.2%) had CML, 15 (1.2%) had HL, the rest were likely malignancies not included in the search. ALL was the predominant cancer in both HSCT and non-HSCT groups (26% and 26.2% respectively), followed by AML, with more AMLs noted in the HSCT group (20%) versus the non-HSCT group (12.3%). The study population predominantly consisted of Whites followed by Hispanics and then African-Americans in both groups. The population also consisted predominantly of males across both cohorts. (Table 1). The solid tumors which were associated with SOS in the non-HSCT group included colorectal cancer, liver cancer, pancreatic cancer and Breast cancer in that order (Table 2). Preexisting liver disease was present in 215 (17.6%) of patients in non-HSCT cohort vs 60 (11.5%) patients in SCT cohort. Pre-existing lung disease was insignificant in both groups. Mortality was compared between the two groups after adjusting for primary cancer, age, sex, race and we found that SCT group had higher odds of mortality compared to non-SCT (14.4% vs 7.4%, aOR 1.866, 95% CI 1.29-2.68, p<0.01). Further multivariate analysis could not be carried out due to low sample size. Discussion Although traditionally, SOS/VOD has been thought to be a complication related to SCT, our study goes on to show that there is actually a higher incidence of SOS in the non-SCT patient population. ALL was the most common hematological malignancy encountered and had similar prevalence in both groups indicating that treatment regimens used in this cancer carry a high risk of SOS. Drugs like inotuzumab ozogamicin are the possible culprits although this information could not be obtained from our database. AML patients also exhibited high rates of SOS, more so in the SCT setting. Patients with preexisting liver disease and hematological malignancies could also benefit from close monitoring for symptoms of SOS with a high index of suspicion based on our results. Despite rising incidence in non-SCT patients, SCT patients with SOS continue to have a higher mortality possibly indicating the higher toxicity of chemotherapy regimens used in this setting. Thus, our study brings forth some important differences between HSCT and non-HSCT SOS and enables clinicians to identify the associated risk factors.

Impact of a Trampoline-Based Exercise Program on Strength and Endurance in Pediatric Stem Cell Transplant Patients

P Glogowski and L Thérond contributed equally to this work. Background Pediatric patients receive physiotherapy support during hematopoietic stem cell transplantation (HSCT) to prevent the deterioration of condition and musculature and to promote rehabilitation. Despite the good arguments in favor of physiotherapy, children often do not enjoy the exercises, or even refuse to participate. In our prospective study we show that our unique training program on the trampoline is convincing and superior to the standard physical therapy during HSCT. Patients and Methods In this monocentric, randomized, prospective study of the University Children's Hospital Tübingen, 52 HSCT patients between 5 and 22 years of age were followed during the in-patient stay in the context of HSCT, as well as in the post-transplant period until day +200 after HSCT. The therapy group (TG; n=26; TG) received a specially created exercise program five days a week with elements of strength and endurance training using a trampoline and an exercise ball. The TG was compared with a control group (CG; n=26) that received standard physical therapy. After in-patient discharge, TG patients were given an exercise plan and an exercise diary to complete independently at home. On six predefined approximate observation days (baseline: day of in-patient admission before HSCT, between day +3 to +8 after leukocyte/granulocyte “take”, after HSCT, day +60, day +100, day +150, and day +200 after HSCT), patients in both groups were assessed for muscle strength (full-ball bump, triple hop), stamina and endurance (timed-up-and-go, 6-minute walking), muscle development (muscle circumferences of M. triceps surae and M. quadriceps), emotional state and quality of life (questionnaires: SAM, KINDL-Onco-module). Data from the training tests, as well as from the questionnaires was used to fit linear mixed models. The equation used to fit the models can be described by DV ijk = β 0j + β 1j * day k + ϑ 0i + ϑ 1i + ε ijk. In this model equation DV ijk denotes the dependent variable of patient i = 1, ..., 52, in group j = 1 (CG) or 2 (TG), at day k = -53, ..., 367 after HSCT. β 0j and β 1j denote the fixed effects where β 0j is the intercept estimate (i.e. the dependent variable at day 0 after HSCT) and β 1j is the slope estimate (i.e. how much the dependent variable decreases or increases each day) for the respective group j. ϑ 0i and ϑ 1i describe the individual specific random intercept and slopes, while ε ijk is the error term. Results A total of 52 patients with a median age of 9.8 years (range 5.2 to 20.3 years), 29 of whom were females (55.8%), were included in this study. Of the patients, 45 (86.5%) and 7 (13.5%) underwent allogeneic or autologous HSCT, respectively. The underlying diseases were malignant in 63.5% of the cases (e.g., acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma) and non-malignant in 36.5% of the cases (e.g., beta-thalassemia, sickle cell disease). The granulocyte and leukocyte take were each reached at a median of day +17 (range day +8 to day +30). The estimated fixed effects of the slopes of the analyzed data for the training tests and questionnaires can be found in the table. In the TG, there was a significant increase in the results of the walking test, the triple hop, the full ball bump, and triceps and quadriceps circumferences. No significant improvement over time was found in the CG. Looking at the difference between groups, the improvement in the TG was significantly greater for the walking test, the triple hop, and the quadriceps circumferences. For the questionnaire data, it was shown that both the CG and the TG had a significant decrease in debilitating physical, as well as debilitating psychological symptoms over time (KINDL body and KINDL mind). There was no significant difference between groups in these scales. For self-reported anxiety (SAM) and illness-related worries (KINDL disease) there was a significant decrease, while the scales KINDL friends and KINDL school increased significantly in the TG but not in the CG. For anxiety and the KINDL school scale this improvement was significantly greater in the TG than in the CG. Conclusions Our unique and new trampoline-based exercise program was able to counter standard physical therapy with significant improvements in muscle strength, endurance, as well as a reduction in anxiety and worry and an improved quality of life for the patients. And most importantly, our patients had an incredible amount of fun doing it.

Impact of self-directed exercise intervention in a minority rich, hematopoietic stem cell transplant (HSCT) inpatient population at high risk for sarcopenia and falls.

390 Background: Extended hospitalizations in the adult HSCT population increase patients’ risk for deconditioning and sarcopenia. Sarcopenia negatively impacts overall survival in adult HSCT patients (Armenian et al, 2019) and is strongly associated with falls among older adults (Yeung et al, 2019; Marques A & Queirós C., 2018; Wheatley et al, 2021). Methods: In a safety net, minority rich, academic medical center in suburban NYC, stationary pedals were placed inside patient rooms in a 31-bedded inpatient HSCT unit starting Q4 2020. Intentional, inpatient room placement prevented additional risk of infectious exposures to COVID-19 in late 2020-2021, allowed for safe access to pedals from a seated position in chairs inside patient rooms, and provided insight into self-directed exercise participation. Attending MDs, PAs and RNs encourage HSCT patients to utilize stationary pedals up to 3 times daily, while usage remains self-directed. Direct observation of patient pedal usage and patient-verbalized interest in participation reflects positive acceptance and consistent usage since implementation. Results: 2019-2023 Midas Event Reporting data was reviewed by the author. Total numbers of Weak/Impaired Gait patient falls decreased in the post-implementation period: 19 falls at baseline versus 13 falls in 2021, 11 falls in 2022, and 3 falls in Q1 2023. Pre-intervention 2019 data indicates 63.3% of falls are among Weak/Impaired Gait patients. (2020 falls data is not included due to unit closures during the COVID-19 pandemic). Post-intervention 2021-2023 data reveals a mean of 51.2% of falls are in Weak/Impaired Gait patients, indicating a 12.1% decline in falls in the post-intervention period of 2.25 years. Conclusions: Sarcopenia and inpatient falls impact patient outcomes (i.e., injuries, extended hospitalizations, and survival) and are financially burdensome. Each inpatient fall, whether injurious or not, costs hospitals approximately 35,000 (Dykes et al, 2023). Reductions in numbers of inpatient falls at this institution are potentially associated with the following hospital cost savings: 210K in 2021, 280K in 2022 and a projected 245K in 2023. Reduction in sarcopenia during extended hospitalizations, when reviewed alongside the financial impact of inpatient falls, supports the ongoing implementation of self-directed exercises in this population. Next steps include self-directed use of resistance bands, chair-based and bed-based stretches, and utilizing self-tracking devices to record exercise duration. (Full references available upon request).

QuantiFERON-CMV and monitor predict cytomegalovirus, mortality, and graft-versus-host disease in transplant recipients.

Cytomegalovirus (CMV) is the most prevalent infection in recipients of hematopoietic stem cell transplant (HSCT). QuantiFERON-CMV (QF-CMV) and QuantiFERON-Monitor (QFM) assays were used to test whether immune-competent adult allogeneic HSCT recipients with CMV-specific T cells can control CMV infection or reactivation. Our data demonstrated a significant correlation between CMV infection measured by CMV-antigenemia test and QF-CMV results, graft versus host disease (GvHD), and mortality rates. The QF-CMV test revealed that CMV-specific T cells with higher interferon-γ (IFN-γ) release were correlated with lower CMV infection rates. There was a significant negative association between QF-CMV results, GvHD, and mortality rates. Data showed that a one-unit rise in IFN-γ was linked with a 12.7% reduction in GvHD and a 20.7% reduction in the mortality odds ratio. In addition, a negative correlation was found between QF-M results and CMV infection, with the QFM test predicting protection against CMV infection by 1.9%. This is one of the few studies establishing the QF-CMV test's predictive value for GvHD and mortality, its use to monitor HSCT patients for pre-emptive therapy, and the use of the QFM test to predict CMV infection and mortality in HSCT patients. Thus, these assays could be utilized to optimize preventive and pre-emptive therapy procedures to reduce transplant recipient adverse effects and posttransplant therapy costs.

Autologous hematopoietic stem cell transplantation is superior to alemtuzumab in patients with highly active relapsing multiple sclerosis and severe disability

ObjectiveTo assess the differences of treatment outcomes regarding disease activity in patients with highly active relapsing multiple sclerosis (RMS), treated with autologous hematopoietic stem cell transplantation (HSCT) or alemtuzumab (ATZ). MethodsOpen-label prospective single-center observational cohort study, enrolling patients with highly active RMS for treatment with ATZ or HSCT between 2014 and 2021. ResultsA total of 50 patients (31/50 (62 %) in HSCT vs 19/50 (38 %) in ATZ group) were included. There were no significant differences in relapse rate, MRI activity or disability worsening between the two study groups during the first two years after treatment onset. However, at 3 to 5 years follow-up, HSCT was superior to ATZ in all the aforementioned aspects. Kaplan-Meier analysis at 5 years post treatment revealed superiority of HSCT in relapse rate (69.6 % vs 95.7 %, p = 0.027), MRI activity (54.5 % vs 75.1 %, p = 0.038) and disability worsening (57.1 % vs 90.9 %, p = 0.031). ConclusionsATZ may halt disability progression early in the course of highly active RMS, but the disability starts accumulating later, while in HSCT patients disability improvement is consistent both 3 and 5 years after treatment onset.

Loading dose vitamin D3 improves vitamin D insufficiency in adults undergoing hematopoietic stem cell transplantation: A randomized controlled trial.

Allogeneic hematopoietic stem cell transplant (aHSCT) patients are well known to be at high risk of vitamin D (vit D) deficiency. This study assessed whether a loading dose (100,000 IU) of vitamin D3 pre-aHSCT could effectively achieve and maintain sufficient post-transplant vit D levels (serum total 25 hydroxy vitamin D (25(OH)D) ≥ 75nmol/L). Dual-energy X-ray absorptiometry (DXA) was also conducted for bone health evaluation. 74 patients were enrolled and randomly assigned, in a 1:1 ratio, either to the high vit D group (single loading dose (100,000 IU) plus 2,000 IU vit D3 daily) or the control group (2,000 IU vit D3 daily). Vit D levels were measured at three time points (baseline, day 30 and day 100 post-aHSCT). At baseline, fewer than 50% patients had a sufficient 25(OH)D (control: 42.9%; high vit D: 43.6%). The proportion of patients with sufficient 25(OH)D (nmol/L) was increased at day 30 and day 100, with a trend of higher proportion in the high vit D group at day 30 (high vit D vs. control: 89.7% vs. 74.3%, p = 0.08). The increased 25(OH)D was significantly higher in the high vit D group at day 30 (high vit D vs. control: 29±25.2 vs. 14 ±21.9, p = 0.01). Insufficient vit D level before transplant (baseline) was an independent risk factor for vit D insufficiency (serum 25(OH)D < 75nmol/L) post-aHSCT (OR = 4.16, p = 0.03). DXA suggested significant bone loss for total hip in both groups, and in the femoral neck for the control group only. In conclusion, single loading dose vitamin D3 significantly increased total 25(OH)D levels at day 30 post-transplant, and the intervention was especially beneficial for patients with baseline vit D insufficiency. We acknowledge that the primary outcome at day 100 post-aHSCT indicating superiority of loading dose versus daily dose supplementation was not met.

The impact of malnutrition on mortality and complications of hematopoietic stem cell transplantation in patients with acute leukemia

Malnutrition is common in hematopoietic stem cell transplantation (HSCT) patients. However, there are few studies on the association between malnutrition and post-transplant outcomes, with inconsistent results. No standard screening tool has been established for malnutrition in these patients. Previous research suggests the Global Leadership Initiative on Malnutrition (GLIM) criteria is effective in predicting outcomes in other cancers. This study investigates the link between malnutrition based on the GLIM criteria with mortality and complications following allogeneic HSCT. This single-center, observational, longitudinal, and prospective study of 98 adult leukemia patients at the Hematology Center of Shariati Hospital in Tehran, Iran, monitored patients before transplantation until 100 days after the procedure, focusing on overall survival and mortality as a primary outcome, and secondary endpoints including oral mucositis, acute GVHD, infection during hospitalization, and readmission rates. This study involved 98 allogeneic HSCT patients with a median age of 38 years old, 64.3% with acute myeloid leukemia (AML), and 35.7% with acute lymphoblastic leukemia (ALL). Among them, 26.5% were categorized as malnourished based on GLIM criteria. During 100 days of follow-up, 13 patients died, but there was no significant difference in overall survival and mortality between malnourished and well-nourished patients. Malnourished patients demonstrated a noticeable upward trend in the incidence of oral mucositis, hospital readmission, and infection during their hospitalization. It is important to highlight that although this observed trend is discernible, it did not attain statistical significance in statistical analyses (P>0.05). The current study determined that, when assessed using the GLIM criteria, malnutrition did not exert a statistically significant influence on survival, mortality, or complications within the specified age range of 18-55 years, underscoring its limited impact on this cohort of younger patients.

Parasitic infections in hematopoietic stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is a vital treatment for various hematological disorders. However, HSCT recipients face increased risks of infectious complications due to immunosuppression. Parasitic infections are a significant concern in this vulnerable population and can lead to substantial morbidity and mortality. This review examines parasitic infections in HSCT recipients, focusing on major infections affecting different organ systems, including intestinal parasites (Giardia spp., Entamoeba histolytica, and Cryptosporidium spp.), hematologic parasites (Plasmodium spp. and Babesia spp.), and tissue/visceral parasites (Toxoplasma gondii, Leishmania spp., and Trypanosoma cruzi). A systematic search of relevant literature was conducted and included studies up to August 2023. Databases included PubMed, Google Scholar, were queried using specific keywords related to parasitic infections in HSCT patients. The epidemiology, risk factors, clinical presentation, diagnostic methods, and treatment approaches for each infection were evaluated. Knowing the epidemiology, risk factors, and clinical presentationsare crucial for timely intervention and successful management. By emphasizing early detection, effective therapies, and the unique challenges posed by each of these infections, this review highlights the importance of tailored strategies for HSCT recipients. Future research can further refine management protocols to enhance care and outcomes for these patients.

The efficacy of a specifically designed printed material on satisfaction from information provision and Quality of Life of hematopoietic stem cell transplantation patients: A randomized controlled trial

Background: Patients with hematological malignancies who undergo hematopoietic stem cell transplantation (HSCT) face complex challenges and need appropriate information to help them cope with the physical and psychological demands of their treatment and experience greater health related quality of life (HRQoL). This study investigated the impact of a specially designed booklet about HSCT, on patients’ satisfaction from information, overall emotional distress and HRQoL. Method and Material: A total of 127 HSCT patients were randomly assigned to receive standard verbal information (control group, n=63) or the additional printed information (intervention group, n=64). Patients’ satisfaction was assessed at two time-points; at admission to the transplant unit and at discharge. Emotional distress and HRQoL were also evaluated at 3 and 6 months post-HSCT. Intention-to-treat analysis was performed. Results: Patients’ characteristics were similar in the two arms. The experimental group reported highest levels of satisfaction when compared with patients attending standard verbal approach (p&lt;0.004). No significant differences between groups were noted, regarding patients’ desired attitude about the amount of perceived information. Overall, 65% of patients wanted all the available information. Most participants considered that the booklet was easy to read and helpful in recalling medical instructions. High levels of satisfaction were strongly correlated with reduction in anxiety levels and improvement in overall HRQoL, at discharge from the transplant unit. Conclusion: Our results demonstrate printed materials can be a beneficial and practical method for patients to gain comprehensible information for HSCT. However, further well-designed, longitudinal multicenter randomized trials are needed to confirm our findings.

COVID-19 in hematopoietic stem-cell transplant recipients: A systematic review and meta-analysis of clinical characteristics and outcomes.

Patients who undergo hematopoietic stem-cell transplantation (HSCT) are more susceptible to developing severe forms of COVID-19 with an increased risk of mortality. The aim of this study was to analyze, by performing a systematic review and meta-analysis, all studies that evaluated COVID-19 in HSCT adult recipients and present clinical characteristics and outcomes. Studies were eligible for inclusion if they: (I) described the clinical characteristics of COVID-19 in adult (aged 18years old or above) HSCT recipients; (II) described outcomes of COVID-19 in this population, mainly lethality; (III) were full-text articles. We searched MedLine, Embase, SCOPUS, LILACS and Web of Science for full-text studies that evaluated COVID-19 in adult HSCT patients until 26 Apr 2023. Two independent reviewers screened the articles and extracted the data. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data was used to assess quality of the included studies. Meta-analysis was performed and the pooled prevalence of severe/critical disease and of death with a 95% CI was calculated with the random-effects model. Sixteen studies were included; seven (43.7%) were multicenter. Most of the studies were from Europe (37.5%). All of them had a low risk of bias using the JBI Checklist. A total of 1186 patients were included. Allogeneic HSCT patients were the majority in most studies, with a total of 861 patients (72.5%). The symptomatic rate was 79.4%. The pooled prevalence of severe/critical COVID-19 was 24.0% (95% CI 0.13-0.36; I2 =94%; n=334/990). The pooled prevalence of death for the entire population was 17% (95% CI 0.13-0.22; I2 =76%; n=221/1117), 17% (95% CI 0.12-0.23; I2 =67%; n=152/822) for allogeneic-HSCT and 14% (95% CI 0.08-0.22; I4 =65%; n=48/293) for autologous-HSCT. In conclusion, frequently the infection of SARS-CoV-2 in HSCT was symptomatic and lethality is higher than in general population. Thus, it is essential to focus on the implementation of measures to mitigate the risk of SARS-CoV-2 infection in this population, as well as to carefully assess HSCT recipients who develop COVID-19.