Hematopoietic Stem Cell Transplantation Patients Research Articles

Successful allogeneic hematopoietic stem cell transplantation in a patient with type I CD36 deficiency: a case study and literature review.

CD36-deficient individuals may produce anti-CD36 antibodies through antigenic exposure to CD36, in situations including blood transfusions. Therefore, allogeneic hematopoietic stem cell transplantation (HSCT) from CD36-positive donors to CD36-negative patients remains a challenge. A 64-year-old man with acute myeloid leukemia became refractory to platelet transfusions during chemotherapy. Anti-CD36 antibodies without anti-HLA antibodies were detected in serum, and the absence of CD36 expression on platelets and monocytes confirmed type I CD36 deficiency. The patient achieved complete remission, and received maintenance therapy with CD36-negative platelet transfusions. However, he relapsed soon afterward, and thus underwent peripheral blood stem cell transplantation (PBSCT) from a CD36-positive unrelated donor. The anti-CD36 antibody titer had decreased before the transplant, and the PBSCT-course was uneventful. The patient has been well without any complications associated with CD36 status mismatch. The few reports of allogeneic HSCT in patients with CD36 deficiency have suggested that anti-CD36 antibodies could be involved in several post-transplant complications, such as delayed platelet recovery, transfusion refractoriness, and transfusion-related acute lung injury. Our present case confirmed that stem cell transplantation from CD36-positive donors to negative patients is feasible, when it includes careful prior assessment of anti-CD36 antibody titers and interventions to attenuate them.

Predictors and significance of kidney dysfunction in patients with chronic graft-versus-host disease.

Kidney complications have been studied in allogeneic hematopoietic stem cell transplant patients but not specifically among chronic graft-versus-host disease (cGVHD) patients. Participants (n = 365) enrolled in the cross-sectional cGVHD natural history study (NCT00092235) were assessed for kidney dysfunction and overall survival. Kidney dysfunction was analyzed for associations in univariate and multivariable analyses. Kidney dysfunction (eGFR < 60) was found in 64 patients, and 29 patients had moderate-severe kidney dysfunction (eGFR < 45). Patients with kidney dysfunction were more likely treated with cyclosporine at evaluation or to have received it for GVHD prophylaxis, or prior treatment of GVHD. Patients with kidney dysfunction were less severely affected by cGVHD of skin, mouth, and joints/fascia. In multivariable modeling, history of cyclosporine use (OR = 2.19, 95% CI 1.13-4.25), angiotensin receptor blocker use (OR = 5.57, 95% CI 1.49-20.84), proteinuria (OR = 2.39, 95% CI 1.19-4.79), lower CRP (OR = 0.95, 95% CI 0.91-0.99), lower C3 (OR = 0.98, 95% CI 0.97-0.99), and lower hemoglobin (OR = 0.70, 95% CI 0.58-0.84) were jointly associated with kidney dysfunction. Overall survival was lower in those with moderate-severe kidney dysfunction (p = 0.015), demonstrating the importance of addressing kidney dysfunction in this population. The association of kidney dysfunction with less severe cGVHD suggests an etiology unrelated to cGVHD but potentially a consequence of drug-related toxicities.

Limited Sampling Strategy Using End of Infusion and Six-Hour Concentrations Overestimates Intravenous Busulfan Clearance Compared With Standard Six-Point Sampling in Hematopoietic Stem Cell Transplant Patients.

Therapeutic drug monitoring for busulfan (Bu) is important to improve outcomes of hematopoietic stem cell transplantation. However, standard therapeutic drug monitoring requires multiple samples and is inconvenient, labor-intensive, and costly. Accordingly, a limited sampling strategy (LSS) was evaluated, using 2-point sampling at end of infusion and at 6 hours, and the area-under-the-curve and Bu clearances (CLs) were compared with the results obtained from the standard sampling strategy (SSS) using 5-6 samples. The analysis was based on retrospective clinical data from 202 patients receiving intravenous Bu before hematopoietic stem cell transplantation for malignant or nonmalignant conditions. Bu plasma concentrations were measured via liquid chromatography tandem-mass spectrometry, and pharmacokinetic parameters were calculated using the PKCNA package in R program. A total of 502 doses were analyzed by applying SSS and LSS. Using the modified Bland-Altman plot, the mean percentage difference in CL between the SSS and LSS estimates of Bu 6-hourly regimen was -41% (Limits: -53% and -30%). In the once daily regimen, the mean difference in CL between the 2 strategies on the modified Bland-Altman plot was -22% (Limits: -66% and +22%). The Bu CL values estimated based on the BU concentration at end of infusion and at 6 hours postinfusion were significantly higher than the values obtained via the SSS.

Characteristics of Molecular Genetic Mutations and Their Correlation with Prognosis in Adolescent and Adult Patients with Acute Lymphoblastic Leukemia

Introduction: The prognosis of acute lymphoblastic leukemia (ALL) in adolescents and adults is poor, and recurrence is an important cause of their death. Changes of genetic information play a vital role in the pathogenesis and recurrence of ALL; however, the impact of molecular genetic mutations on disease diagnosis and prognosis remains unexplored. This study aimed to explore the frequency spectrum of gene mutations and their prognostic significance, along with the minimal residual disease (MRD) level and hematopoietic stem cell transplantation (HSCT), in adolescent and adult patients aged ≥15 years with ALL. Methods: The basic characteristics, cytogenetics, molecular genetics, MRD level, treatment regimen, and survival outcome of patients with untreated ALL (≥15 years) were collected, and the correlation and survival analysis were performed using the SPSS 25.0 and R software. Results: This study included 404 patients, of which 147 were selected for next-generation sequencing (NGS). NGS results revealed that 91.2% of the patients had at least one mutation, and 67.35% had multiple (≥2) mutations. NOTCH1, PHF6, RUNX1, PTEN, JAK3, TET2, and JAK1 were the most common mutations in T-ALL, whereas FAT1, TET2, NARS, KMT2D, FLT3, and RELN were the most common mutations in B-ALL. Correlation analysis revealed the mutation patterns, which were significantly different between T-ALL and B-ALL. In the prognostic analysis of 107 patients with B-ALL, multivariate analysis showed that the number of mutations ≥5 was an independent risk factor for overall survival and the RELN mutation was an independent poor prognostic factor for event-free survival. Discussion: The distribution of gene mutations and the co-occurrence and repulsion of mutant genes in patients with ALL were closely related to the immunophenotype of the patients. The number of mutations ≥5 and the RELN mutation were significantly associated with poor prognosis in adolescent and adult patients with ALL.

Robust spike-specific CD4+ and CD8+ T cell responses in SARS-CoV-2 vaccinated hematopoietic cell transplantation recipients: a prospective, cohort study.

Poor overall survival of hematopoietic stem cell transplantation (HSCT) recipients who developed COVID-19 underlies the importance of SARS-CoV-2 vaccination. Previous studies of vaccine efficacy have reported weak humoral responses but conflicting results on T cell immunity. Here, we have examined the relationship between humoral and T cell response in 48 HSCT recipients who received two doses of Moderna's mRNA-1273 or Pfizer/BioNTech's BNT162b2 vaccines. Nearly all HSCT patients had robust T cell immunity regardless of protective humoral responses, with 18/48 (37%, IQR 8.679-5601 BAU/mL) displaying protective IgG anti-receptor binding domain (RBD) levels (>2000 BAU/mL). Flow cytometry analysis of activation induced markers (AIMs) revealed that 90% and 74% of HSCT patients showed reactivity towards immunodominant spike peptides in CD8+ and CD4+ T cells, respectively. The response rate increased to 90% for CD4+ T cells as well when we challenged the cells with a complete set of overlapping peptides spanning the entire spike protein. T cell response was detectable as early as 3 months after transplant, but only CD4+ T cell reactivity correlated with IgG anti-RBD level and time after transplantation. Boosting increased seroconversion rate, while only one patient developed COVID-19 requiring hospitalization. Our data suggest that HSCT recipients with poor serological responses were protected from severe COVID-19 by vaccine-induced T cell responses.

Oral and Gut Microbiota Dysbiosis is Associated with Mucositis Severity in Autologous Hematopoietic Stem Cell Transplantation: Evidence from an Asian Population

Mucositis is a debilitating complication of hematopoietic stem cell transplant (HSCT). It is unclear how changes in the composition of microbiota, which are modulated by geographical location and ethnicity, may influence immune regulation leading to the development of mucositis, and the study of both oral and gut microbiota in a single population of autologous HSCT in the Asian region is lacking. The study aimed to characterize the oral and gut microbiota changes, and the impact on both oral and lower gastrointestinal (GI) mucositis, with its associated temporal changes in a population of adult autologous HSCT. Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood, saliva and fecal samples were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month post-transplant. Longitudinal differences in alpha and beta diversities were determined using Wilcoxon signed-rank test and Permutational Multivariate Analysis of Variance, respectively. Changes in relative abundances of bacteria across timepoint were assessed using the Microbiome Multivariate Analysis by Linear Models function. The combined longitudinal effects of clinical, inflammatory and microbiota variables on mucositis severity were measured using the generalized estimating equation. From the 96 patients analyzed, oral mucositis and diarrhea (representing lower GI mucositis) were reported at 58.3% and 95.8%, respectively. Alpha and beta diversities were significantly different between sample types (p<0.001) and across timepoints, with alpha diversity reaching statistical significance at Day 0 in fecal (p<0.001) and Day+7 in saliva samples (p<0.001). Diversities normalized to baseline by 6-month. Significant microbiota, clinical and immunological factors were associated with increasing mucositis grades. Increasing relative abundances of saliva Paludibacter, Leuconostoc and Proteus, were associated with higher oral mucositis grades, whilst increasing relative abundances of fecal Rothia and Parabacteroides were associated with higher GI mucositis grades. Meanwhile, increasing relative abundances of saliva Lactococcus and Acidaminococcus, and fecal Bifidobacterium were associated with protective effects against worsening oral and GI mucositis grades, respectively. This study provides real-world evidence and insights into the dysbiosis of the microbiota in patients exposed to conditioning regimen during HSCT. Independent of clinical and immunological factors, we demonstrated significant associations between relative bacteria abundances with the increasing severities of oral and lower GI mucositis. The findings presented in our study offer a potential rationale to consider the inclusion of preventive and restorative measures targeting oral and lower GI dysbiosis as interventional strategies to ameliorate mucositis outcome in HSCT patients.

Standardization of Pediatric Hematopoietic Stem Cell Transplant Patient Discharge to Reduce Readmission Rates.

Background: The time period after a pediatric hematopoietic stem cell transplant (P-HSCT) is tenuous as the patient is severely immunocompromised and awaiting immune reconstitution. Managing activities of daily living and medication administration after discharge from the hospital requires 24-hour care placing a heavy burden on caregivers and patients. Patients who do not adhere to the posttransplant regimen are at a higher risk for hospital readmission within the first 30 days of initial discharge with serious potential for life-threatening complications. The objective of this project was to improve 30-day readmission rates and caregiver readiness for discharge through the implementation of an evidence-based discharge protocol for P-HSCT patients and caregivers. Methods: This quality improvement project included development and implementation of comprehensive Pediatric Blood & Marrow Transplant Guidelines and discharge protocol for patients who received an inpatient autologous or allogeneic HSCT and were scheduled for discharge from a 16-bed inpatient pediatric hematology-oncology unit of a children's hospital in the southeastern United States. Readmission rates were captured through the hospital-monitored system. Results: The comprehensive discharge protocol was implemented for six patients, and 30-day readmission rates decreased from 27.29% to 3.57% following the intervention. Discussion: Results suggest the combination of an evidence-based discharge protocol with a focus on caregiver readiness for discharge and a 24-hour Rooming-In period can influence caregiver confidence and reduce 30-day readmission rates after initial discharge from a P-HSCT.

Patient Blood Management after Hematopoietic Stem Cell Transplantation in a Pediatric Setting: Starting Low and Going Lower.

Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) and platelet (PLT) transfusion practices during the first 100 days after HSCT at the pediatric hematology/oncology unit of our hospital between 2016 and 2019, due to a more restrictive approach adopted after 2016. We also evaluated the impact on patient outcomes. A total of 146 consecutive HSCT patients were analyzed. In patients without hemorrhagic complications, the Hb threshold for RBC transfusions decreased significantly from 2016 to 2017 (from 7.8 g/dL to 7.3 g/dL; p = 0.010), whereas it remained the same in 2017, 2018, and 2019 (7.3, 7.2, and 7.2 g/dL, respectively). Similarly, the PLT threshold decreased significantly from 2016 to 2017 (from 18,000 to 16,000/μL; p = 0.026) and further decreased in 2019 (15,000/μL). In patients without severe hemorrhagic complications, the number of RBC and PLT transfusions remained very low over time. No increase in 100-day and 180-day non-relapse mortality or adverse events was observed during the study period. No patient died due to hemorrhagic complications. Our preliminary observations support robust studies enrolling HSCT patients in patient blood management programs.

Monitoring of cytomegalovirus, Epstein-Barr virus and adenovirus infections in hematopoietic stem cell transplant recipients

Purpose: Haematopoietic stem cell transplant (HSCT) recipients with iatrogenic immunosuppression are high-risk patients for viral infections. The aim of this study was to investigate the incidence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) infections in HSCT recipients. &#x0D; Materials and Methods: We prospectively monitored 35 patients aged 0-17 years who had allogeneic (n=30) and autologous (n=5) HSCT by quantitative real-time polymerase chain reaction tests for CMV, EBV, and ADV. The monitoring was performed one week before HSCT and weekly for the first 100 days, once a month up to one year after HSCT. In addition, seropositivity for viruses was analysed by Enzyme-Linked Immuno Sorbent Assay a week before transplantation.&#x0D; Results: Before transplantation, all 35 (100%) patients who underwent HSCT were CMV IgG positive, 30 (85.7% - 95% CI: 74.1%-97.3%) HSCT recipients were found to be EBV IgG positive. CMV infection was found in 24 (80% - 95% CI: 65.7%-94.3%), ADV infection in 11 (36.7% - 95% CI: 19.4%-53.9%) and EBV infection in 8 (26.7% - 95% CI: 10.8%-42.5%) allogeneic HSCT patients. In this group, CMV DNA viral load in 8 (26.7%) patients, of which one (3.3%) coinfected with EBV DNA and one (3.3%) with ADV DNA, was higher than 1000 copies/mL which was required for pre-emptive treatment. Among 5 autologous HSCT recipients, CMV DNA was detected in 2 patients, EBV DNA in 5 and ADV DNA in 2. Pre-emptive treatment was given to 11 (%31.4 - 95% CI: 16%-46.8%; 6 CMV, 2 EBV, 1 ADV, 1 CMV-EBV and 1 CMV-ADV infection) of 35 patients. Thus, the development of viral disease was prevented in 7 (63.6% - 95% CI: 35.2%-92.1%). Of the total 35 patients, only 2 (5.7% - 95% CI: 0.0%-13.4%) died due to viral infection. &#x0D; Conclusion: Early diagnosis of viral infections by prospective monitoring of viral loads in HSCT patients would be effective in preventing morbidity and mortality by ensuring timely initiation of pre-emptive therapy.

Coronavirus Disease 2019 and Bone Marrow Transplantation: A Mini-review

Abstract Since the first incidence of coronavirus disease 2019 (COVID-19) was identified in 2019, the illness has rapidly spread, increasing the number of cases, hospital admissions, and fatalities associated with COVID-19. The epidemic is putting an unprecedented amount of stress on the health-care system, including programs that perform both allogeneic and autologous hematopoietic stem cell transplantation (HSCT) and cellular treatment employing T cells. The risk of a severe COVID-19 infection in HSCT patients is widely acknowledged, and the COVID-19 vaccine is strongly advised. This mini-review provides a succinct overview of recent advances in COVID-19 and bone marrow transplantation.

Mir-155 expression is downregulated in hematopoietic stem cell transplantation patients with Epstein-Barr virus infection.

MicroRNAs (miRNAs) are a class of short length double strand genome encoded RNAs that are produced to repress post-transcriptionally the expression of cellular mRNAs. 2578 unique mature miRNAs are currently annotated in the human genome and participate in the regulation of multiple events, such as cellular proliferation or apoptosis. The over-expression of miR-155 of cellular origin might play a key role in the life cycle of EBV. In this study 24 pediatric patients undergoing HSCT seropositive and seronegative to EBV were enrolled. Thirty-one peripheral blood samples were collected from these patients. The mir-155 expression profile has been evaluated by a stem-loop Real Time PCR in all these conditions. Of 24 patients, 4 were seronegative to EBV and EBV negative to PCR (Group I), 10 were seropositive to EBV and EBV negative to PCR (Group II) and 10 were seropositive to EBV and EBV positive to PCR (Group III). Based on relative quantification, the mir-155 expression was compared among the groups. The comparison between HSCT patients without EBV infection seronegative to EBV (Group I) showed higher levels of mir-155 expression than patients seropositive to EBV (P=0.1419). The mir-155 expression levels in seronegative to EBV were not significantly different compared with the patients seropositive to EBV (P=0.6504). The mir-155 expression levels in seropositive to EBV without and with EBV infection (positive viral load), were not significantly (P=0.7667). Also, when we evaluated the mir-155 expression levels comparing all EBV negative patients with an active EBV infection, we did not observe a statistically significant difference (P=0.9782). Our results are controversial, showing a higher production of mir-155 levels during EBV infection.

Adenovirus F41 infection and liver cytolysis in adult hematopoietic stem cell transplant recipients.

Human adenoviruses (HAdVs) of the F species are commonly responsible for acute gastroenteritis. A few cases of systemic infections have been described in adults or children who have received a hematopoietic stem cell transplant (HSCT), but with no report of liver cytolysis. Since January 2022, several countries have reported an increase in cases of acute hepatitis of unknown cause in children. Adenovirus species F type 41 (HAdV-F41)infection was predominantly identified. The objective of this study is to describe HAdV-F41 infections diagnosed since January 2022 in adult HSCT recipients in two French hospitals. All four patients had diarrhea and liver cytolysis at the time of diagnosis of infection. HAdV viremia was observed in three patients (#1, #3, and #4), but no disseminated disease was reported. HAdV whole genome sequencing and metagenomics characterization were performed on stool and blood samples. The complete HAdV-F41 genome sequence was obtained for three patients and phylogenetic analysis showed that the strains consisted of similar lineage (2b). We did not identify any new HAdV-F41 strains. Metagenomics analysis found adeno-associated virus 2 and torque-teno virus infection in patient #1 and Epstein-Barr virus in patient #4. This is the first case series reporting liver cytolysis during HAdV-F41 infection in adult HSCT patients.

Clinical data analysis of 86 patients with invasive infections caused by Malassezia furfur from a tertiary medical center and 37 studies.

Malassezia furfur (M. furfur) is a lipophilic, conditionally pathogenic yeast that mainly causes skin infections, but the reports of related invasive infections are increasing. The aim of this study is to provide clinical data to assist physicians in the management of patients with invasive infections caused by M. furfur. A case of pulmonary infection caused by M. furfur in a hematopoietic stem cell transplant patient for aplastic anemia was reported. In addition, the literature on invasive infection by M. furfur published in PubMed and Web of Science in English until 31 July 2022 was reviewed. Clinical data analysis of 86 patients (from 37 studies and our case) revealed that most of them were preterm (44.2%), followed by adults (31.4%). M. furfur fungemia occurred in 79.1% of the 86 patients, and 45 of them were clearly obtained from catheter blood. Other patients developed catheter-related infections, pneumonia, peripheral thromboembolism, endocarditis, meningitis, peritonitis and disseminated infections. Thirty-eight preterm infants had underlying diseases such as very low birth weight and/or multiple organ hypoplasia. The remaining patients had compromised immunity or severe gastrointestinal diseases. 97.7% of patients underwent invasive procedures and 80.2% received total parenteral nutrition (TPN). Fever, thrombocytopenia and leukocytosis accounted for 55.8%, 38.4% and 24.4% of patients with M. furfur invasive infections, respectively. 69.8% of the patients received antifungal therapy, mainly amphotericin B (AmB) or azoles. Of 84 patients with indwelling catheters, 58.3% underwent the removal of catheters. TPN were discontinued in 30 of 69 patients. The all-cause mortality of 86 patients was 27.9%. M. furfur can cause a variety of invasive infections. These patients mostly occur in premature infants, low immunity and severe gastrointestinal diseases. Indwelling catheters and TPN infusion are major risk factors. AmB, l-AmB and azoles are the most commonly used agents, and simultaneous removal of the catheter and termination of TPN infusion are important for the treatment of M. furfur invasive infections.

Prognostic Factors and Treatment Outcome of Relapsing and Refractory Pediatric Mature B-cell Non-Hodgkin Lymphoma, Children's Cancer Hospital Egypt Experience.

Relapsed non-Hodgkin lymphoma treated by chemotherapy and hematopoietic stem cell transplantation (HSCT) has a dismal prognosis. It is a retrospective study, including pediatric patients diagnosed as mature B-cell non-Hodgkin lymphoma who were primarily refractory or relapsed over 8 years at CCHE. The aim of the study was to analyze the prognostic factors and outcomes of this group of patients. Our result is, 53 of 750 (7%) patients were included. Thirty-four (64.2%) patients had Burkitt lymphoma. Forty-eight (90.6%) patients received LMB 96 protocol initially. The median delay of duration between chemotherapy cycles in first-line treatment was 37 days. Thirty-five (66%) patients relapsed, 23 (65.7%) of them relapsed early, whereas 18 (34%) had tumor progression. Thirty-one (58.5%) patients presented with stage IV at the time of relapse. rituximab, ifosfamide, carboplatin, etoposide was the second line of treatment in 42 (79.24%) patients, and complete second remission was achieved only in 13 (24.3%) patients. Allogeneic HSCT was done for 4 (7.5%) patients, and auto HSCT was done for 3 (5.7%) patients. Three years of overall survival for relapsed and progressed patients were 35.3% and 11.1%, respectively, with a P-value of 0.009. Three years overall survival for patients who underwent HSCT was 85.7% compared with 18.1% for no HSCT with a P-value of 0.007. The relapse rate is higher than literatures because of the delay of duration between chemotherapy cycles in first-line treatment and more advanced stage at time of relapse. Progression of the disease had a worse outcome than relapse. HSCT in patients with the second remission markedly improved the outcome.

Hematopoietic Stem Cell Transplantation Patients Are Skilled at Adapting to “Out of the Ordinary” Situations: A Qualitative Study

ObjectiveBlood cancers can potentially be cured by hematopoietic stem cell transplantation (HCT), but HCT recipients can remain immunocompromised for extended periods of time and require caregiver support. Though the COVID-19 pandemic has globally affected the livelihood and well-being of all individuals, it has affected certain populations in unique ways, HCT recipients being one of them. This study intends to understand the lived experience of HCT recipients and HCT-eligible patients during the COVID-19 pandemic. Data SourcesThis qualitative study enrolled participants (N=25) from a parent study that recruited transplant patients (HCT eligible or HCT recipients) between May and October 2020. Participants were invited to participate on a one-on-one interview via an electronic platform. A phenomenologic qualitative approach was used to identify emerging themes and subthemes. ConclusionThree themes were developed: a) the pandemic experience was influenced by the transplant journey; b) participants found ways to thrive despite the odds and access support in unique ways; and c) participants described challenges during the pandemic regarding non-transplant care, vaccine considerations, and distrust in media. Implications for Nursing PracticeResults from this study highlighted that HCT recipients were uniquely prepared for “out of the ordinary” situations during the pandemic and underscored challenges faced by them during this time, identifying areas for improvement in the health care system. Nurses in their unique role can initiate and lead process changes to address barriers such as lack of access to reliable information, poor communication, and inadequate resources for accessing non-transplant care especially during uncertain times.

Azacitidine and lenalidomide combination: a novel relapse prophylaxis regimen after allogeneic hematopoietic stem-cell transplantation in patients with acute myeloid leukemia.

While allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be a curative regimen for acute myeloid leukemia (AML), relapse of AML remains a serious risk post-transplantation. Once relapsed, salvage options are limited and management of AML is difficult. Here we designed a prospective study to examine the efficacy and tolerability of maintenance therapy with azacytidine (AZA) plus low-dose lenalidomide (LEN) to prevent relapse after allo-HSCT for AML patients (ChiCTR2200061803). AML patients post-allo-HSCT were treated with AZA (75 mg/m2 for 7 days), followed by LEN (5 mg/m2, day 10-28), and a 4-week resting interval, which was defined as one treatment cycle. A total of 8 cycles was recommended. 37 patients were enrolled, 25 patients received at least 5 cycles, and 16 patients finished all 8 cycles. With a median follow-up time of 608 (43-1440) days, the estimated 1-year disease free survival (DFS) was 82%, cumulative incidence of relapse (CIR) was 18%, and overall survival (OS) was 100%. Three patients (8%) had grade 1-2 neutropenia without fever; one patient developed grade 3-4 thrombocytopenia and minor subdural hematoma; 4/37 patients (11%) developed chronic GVHD with a score of 1-2, without requiring systemic treatment; No patient developed acute GVHD. After AZA/LEN prophylaxis, increasing numbers of CD56+NK and CD8+ T, and decreasing of CD19+ B cells were observed. Azacitidine combined with low-dose lenalidomide was observed to be an effective relapse prophylaxis option after allo-HSCT in AML patients, and can be administered safely without significantly increasing the risk of GVHD, infection and other AEs. www.chictr.org, identifier ChiCTR2200061803.

Investigating racial disparities in quality-of-life years after pediatric hematopoietic stem cell transplant.

While racial disparities in the clinical outcomes of hematopoietic stem cell transplant (HSCT) patients have been explored, racial disparities in quality of life (QoL) during the re-adjustment phase after transplant are yet to be investigated in pediatric patients. The objective of this study was to examine the role of patient race in QoL at least 2years after pediatric HSCT. We conducted a retrospective chart review of patients under 21years of age at diagnosis who received an allogeneic transplant at our institution between January 2007 and December 2017. Patient QoL was assessed using the Pediatric Quality-of-Life Inventory Generic Score Scales (PedsQL TM 4.0) at least 2years post transplant. Patient demographic, treatment, and transplant outcome data were obtained for subsequent analysis, where patient race was categorized as either Black, White, Hispanic, or Native American. Data were collected on 86 pediatric patients who underwent HSCT. Forty patients (46.5%) were non-Hispanic White, 29 (33.7%) Hispanic, 10 (11.6%) Black, and seven (8.1%) Native American. Where preliminary analyses indicated a difference in QoL by patient race, there were no significant differences in physical, emotional, social, and school functioning by patient race after adjusting for transplant characteristics (age at transplant, sex, diagnosis, donor type, and conditioning regimen) and determinants of socioeconomic status (insurance type, estimated household income). Pediatric patients had comparable QoL, regardless of race, at a median of 3years after HSCT in our study cohort.

#3585 FAT1 ANTIGEN IN PATIENTS WITH MEMBRANOUS NEPHROPATHY AFTER HEMATOPOIETIC STEM CELL ALLOTRANSPLANTATION: A CASE SERIES

Abstract Background and Aims Nephrotic syndrome (NS) is a rare complication of haematopoietic stem cell transplantation (HSCT). When it occurs, it usually develops after cessation of immunosuppressive therapy, which is why it is commonly denominated as a renal form of chronic graft-versus-host disease. Membranous nephropathy (MN) is the most common pathological finding. The protocadherin FAT1 antigen is a novel antigen identified only in patients with MN who have undergone allogeneic HSCT. PLA2R and NELL1 antigens can also be found, even though they are rare and not specific to HSCT-associated MN. The aim of this study was to present a case series of allogeneic HSCT-associated MN, the treatment, outcomes and presence of a novel antigen specifically detected in this population. Method All patients with full blown NS due to MN after HSCT in UHC Zagreb were enrolled. Kidney biopsy was performed and examined by light, immunofluorescence and electron microscopy. Biopsy samples were sent to Renal Pathology Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic for detection of FAT1 antigen in biopsy tissue samples Results In last 30 years there had been 1302 HSCT in UHC Zagreb and three of them developed MN. The first two patients were treated with allogeneic HSCT for acute myeloid leukaemia (AML). Both developed NS after cessation of GVHD prophylaxis, after 1 and 8 months respectively. The first patient's kidney function was preserved, while the second patient's was reduced. Kidney biopsy showed MN. Thorough examination found no secondary cause of the disease. In the first patient, complete remission (CR) was achieved after 5 months of steroids, 2 boluses of cyclophosphamide (CP) and cyclosporine treatment. The second patient reached partial remission (PR) after 6 months of steroid treatment and oral CP. Immunosuppression was terminated due to infectious complications. CR was achieved after an additional 8 months while the patient was not taking immunosuppressants. Both patients remained in CR during the follow-up period. The third patient with acute lymphoblastic leukaemia (ALL) underwent a related peripheral blood HSCT. Sixteen years later, he developed NS with preserved renal function and was diagnosed with MN. Apart from thyroid disease, no secondary cause was detected and he was treated with rituximab. Partial remission (PR) was achieved after 24 months of therapy. Anti-PLA2R antibodies were negative in all three cases. Tissue samples from patients 1 and 2 were positive for FAT1 antigen using laser microdissection and tandem mass spectrometry (MS/MS) of glomeruli. The third patient was negative for FAT1. Clinical and biopsy findings in our cohort of HSCT-associated MN are summarised in Tables 1 and 2. Conclusion MN can occur at different points in time, sometimes even years, after HSCT. It can be successfully treated with steroids and immunosuppressants, achieving long-term remission. Most patients with HSCT-associated MN are FAT1-positive, although it is not the only antigen associated with MN in HSCT patients. In the future, serum testing for anti-FAT1 antibodies in patients with HSCT could be of similar significance in diagnosing FAT1-associated MN as PLA2R antibodies are for PLA2R-associated MN.

CD3+TCRαβ/CD19+-Depleted Mismatched Family or Unrelated Donor Salvage Stem Cell Transplantation for Graft Dysfunction in Inborn Errors of Immunity

A minority of children experience significant graft dysfunction after an allogeneic hematopoietic stem cell transplant (HSCT) for inborn errors of immunity (IEI). The optimal approach to salvage HSCT is unclear with respect to conditioning regimen and stem cell source. This single-centre retrospective case series reports the outcomes of salvage CD3+TCRαβ/CD19 depleted mismatched family or unrelated donor stem cell transplantation (TCRαβ-SCT) between 2013 - 2022 for graft dysfunction in 12 children with IEI. Outcomes of interest were overall survival (OS), event free survival (EFS), graft-versus-host disease (GvHD)-free and event-free survival (GEFS), toxicities, GvHD, viremia and long-term graft function. A retrospective audit of patients who underwent second CD3+TCRαβ/CD19 depleted mismatched donor graft using Treosulfan-based reduced toxicity myeloablative conditioning. Median age at first HSCT was 8.76 months (range, 2.5 months - 6 years) and at second TCRαβ-SCT was 3.6 years (1.2 - 11 years). Median interval between first and second HSCT was 1.7 years (3 months - 9 years). The primary diagnoses were: severe combined immunodeficiency (SCID) (n=5) and non-SCID IEI (n=7). The indications for second HSCT were: primary aplasia (n=1), secondary autologous reconstitution (n=6), refractory aGVHD (n=3) and secondary leukemia (n=1). Donors were either haploidentical parental donors (n=10) or mismatched unrelated donors (n=2). All received TCRαβ/CD19-depleted-PBSC with a median CD34+ cell dose of 9.3 × 106/kg (2.8-32.3 × 106/kg) and a median TCRαβ+ cell dose of 4 × 104/kg (1.3-19.2 × 104/kg). All engrafted with median days to neutrophil and platelet recovery of 15 (12-24) and 12 (9-19). One developed secondary aplasia and one had secondary autologous reconstitution, but both underwent a successful third HSCT. Four (33%) had grade II aGvHD and none had grade III-IV aGvHD. None had cGvHD but one developed extensive cutaneous cGVHD after third HSCT using PBSC and ATG. Nine (75%) were noted to have at least one episode of blood viremia with HHV6 (n=6, 50%), adenovirus (n=6, 50%), EBV (n=3, 25%) or CMV (n=3; 25%). Median duration of follow-up was 2.3 years (range: 0.5 - 10 years) and the 2-year OS, EFS and GEFS were 100% (95% confidence interval, 0-100%), 73% (37-90%) and 73% (37%-90%) respectively. TCRαβ-SCT from mismatched family or unrelated donors, using a chemotherapy only regimen, is a safe alternative donor salvage transplant strategy for second HSCT in patients without a suitably matched donor.

Abstract 42: Hematopoietic Stem Cell Transplants and Treatment of Severe Blood Disorders: Role of Providers in Medical Tourism

Abstract Purpose: Medical tourism provides international patients with medical services, but little data is present on the role of medical tourism in regard to hematopoietic stem cell transplant (HSCT) services. Over the last 10 years, the University of Illinois at Chicago Blood &amp; Marrow Transplant program has established an international network (GlobalBMT) of LMIC centers, that includes hospitals in Nepal, India, Nigeria, Tanzania, Bolivia, Cuba, Argentina, Ukraine. This project involves each hospital of the GlobalBMT network to: 1. qualitatively assess the current role of medical providers in international care of HSCT patients and 2. quantitatively and qualitatively assess the current policies of medical institutions for sending and accepting international transplant candidates. Methods: This is a mixed-methods cross-sectional study with a quantitative component (questionnaire) and a qualitative component (interview). A questionnaire was disseminated to 12 medical providers in 8 countries, who either refer or accept international HSCT patients, to assess the demographics, volume, and frequency of international referrals. We also conducted semi-structured virtual interviews with willing healthcare providers to qualitatively assess the current infrastructure in medical tourism for international HSCT candidates, as well as elicit ways in which this structure can be improved. Results: Here we will report on the results of the mixed-methods cross-sectional study that was conducted within the GlobalBMT network. In the setting of this research project, we suggest a need for a formalized provider-to-provider framework in the sphere of medical tourism for HSCT patients to be sent outside of their home countries to receive a HSCT, diminishing the impact of third party brokers and misinformation. Our data have uncovered themes in the existing structure of third-party agents searching for a profit, difficulty connecting with home physicians to coordinate care, and limited information for patients on the procedure. Conclusion: The data collected in this project provide an example of existing structures in medical tourism for HSCT in some LMICs. Gaps in center-to-center patient information, role of middle-men directly contacting patient families, or lack of advanced medical care in LMIC, are some of the relevant findings that based on this initial study could be exploited in a large multicenter international registry study. Citation Format: Deepika Khanna, Damiano Rondelli. Hematopoietic Stem Cell Transplants and Treatment of Severe Blood Disorders: Role of Providers in Medical Tourism [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 42.