Hematopoietic Stem Cell Transplantation Research Articles

Human papillomavirus vaccine uptake among adolescent survivors of hematopoietic stem cell transplant

Human papillomavirus vaccine uptake among adolescent survivors of hematopoietic stem cell transplant

Allowable total error in CD34 cell analysis by flow cytometry based on state of the art using Spanish EQAS data.

CD34+ hematopoietic stem cell (HSC) enumeration, crucial for HSC transplantation, is performed by flowcytometry to guide clinical decisions. Variability in enumeration arises from biological factors, assay components, and technology. External quality assurance schemes (EQAS) train participants to minimize inter-laboratory variations. The goal is to estimate total error (TE) values for CD34 cell enumeration using state-of-the-art (SOTA) methods with EQA data and to define quality specifications by comparing TE using different cutoffs. A total of 3,994 results from 40 laboratories were collected over 11 years (2011-2022) as part of the IC-2 Stem Cells Scheme of the GECLID Program that includes absolute numbers of CD34 cells. The data were analyzed in two periods: 2011-2016 and 2017-2022. The TE value achieved by at least 60 %, 70 %, 80 %, and 90 % of laboratories was calculated across the two different periods and at various levels of CD34 cell counts: above 25, 25 to 15, and under 15 cells/μL. A decrease in the SOTA-based TE for CD34 cell enumeration was observed in the most recent period in 2017-2021 compared with 2012-2016. A significant increase of P75 TE values in the low CD34 range (<15 cells/μL) levels was found (p<0.001). Technical advancements contribute to the decrease TE over time. The TE of CD34 cell FC counts is measure-dependent, making it responsive to precision enhancement strategies. The TE measured by EQAS in this study may serve as a quality specification for implementing ISO 15189 standards in clinical laboratories for CD34 cell enumeration.

Prognostic significance of early nk cell recovery in pediatric t-cell replete allogeneic hematopoietic stem cell transplantation.

Early immune reconstitution, particularly of natural killer (NK) cells with strong graft-versus-leukemia effects, is crucial for the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study examined 122 pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who underwent T-cell replete allo-HSCT at the Children's Hospital of Soochow University from 2019 to 2021. Peripheral blood lymphocyte counts on days 30 and 60 post-transplant were analyzed, focusing on NK cell recovery and its impact on overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), relapse, graft-versus-host disease, and CMV reactivation. Patients were categorized into high and low NK cell groups by the median NK cell counts at day 30 (NK30) and day 60 (NK60) after HSCT. Patients with high NK30 and NK60 levels had significantly better 3-year OS rates compared to their respective low NK count groups (86.8% ± 4.7% versus 67.6% ± 7.0%, P = 0.046; 95.7% ± 3.0% versus 63.7% ± 8.7%, P < 0.001, respectively). NK60 was found to be an independent predictor for 3-year OS and RFS in multivariate analysis. Early NK reconstitution was also related to lower NRM rates. However, this correlation disappeared in patients with ALL and those undergoing haploidentical transplantation. In addition, A positive association between early T cell and NK cell reconstitution was found in our study. Higher NK cell counts on days 60 can predict superior OS, RFS and lower NRM in pediatric AML allo-HSCT patients.

A prophylactic tyrosine kinase inhibitor strategy based on measurable residual disease pre-transplantation for Ph+ acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation: A prospective multicenter cohort study.

Relapse is the major cause of treatment failure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of a prophylactic tyrosine kinase inhibitor (TKI) strategy on relapse in this population. Patients were assigned to prophylactic or control groups based on measurable residual disease (MRD) pre-transplantation. The primary endpoint was the cumulative incidence of relapse. A total of 110 patients with Ph+ ALL undergoing allo-HSCT were enrolled in this prospective study. Thirty-eight patients with positive MRD pre-transplantation were included in the prophylactic group, and 72 with negative MRD pre-transplantation were included in the control group. The 4-year cumulative incidence of relapse was 25.3% (95% CI: 12.1%-41.0%) and 20.3% (11.6%-30.7%; HR = 1.272, 95% CI: 0.551-2.940, p = .549), and non-relapse mortality was 10.5% (3.3%-22.7%) and 9.7% (4.2%-17.9%; HR = 1.094, 95% CI: 0.320-3.738, p = .928) in the prophylactic and control groups. The 4-year overall survival was 71.8% (53.2%-84.1%) and 84.1% (72.9%-90.9%; HR = 1.746, 95% CI: 0.741-4.112, p = .196), and leukemia-free survival was 64.1% (45.8%-77.7%) and 70.0% (57.6%-79.4%; HR = 1.212, 95% CI: 0.607-2.421, p = .585) in the prophylactic and control groups. Our results suggest that prophylactic TKI post-HSCT in patients with positive MRD pre-transplantation can produce outcomes comparable to negative MRD pre-transplantation without TKI post-HSCT.

A New Tool Supporting the Selection of the Best Hematopoietic Stem Cell Donor by Modelling Local Own Real-World Data

Background: The selection of the best donor for each specific patient is crucial for the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, there is debate on the choice of the best donor when multiple suitable donors exist. Methods: By using own data from two transplant centers, we have developed a calculator able to provide the patients’ 2-year overall survival (OS) associated with each of the potential donor options during the selection process, in order to support the transplant physician during the choice. Data on 737 HSCTs with HLA-identical siblings, and unrelated or related haploidentical donors from January 2010 to July 2022 have been retrospectively obtained. Results: Patients’ age, disease, comorbidity index, and donor type were found to be significant variables able to predict the outcome with robustness (concordance index: 0.677). Estimates are provided within an example in the text showing outcomes with four donor options for a specific patient. Conclusions: We present the prototype of a tool supporting the selection of the best donor, guiding transplant physicians during the delicate process of donor selection before HSCT. This approach relies on real data from the centers, reflecting their local clinical experience. Improvements are underway with a larger, ongoing multicenter study.

Application of artificial intelligence and machine learning for risk stratification acute kidney injury among hematopoietic stem cell transplantation patients: PCRRTICONIC AI Initiative Group Meeting Proceedings.

Acute kidney injury (AKI) is a frequent, severe complication of hematopoietic stem cell transplantation (HSCT) and is associated with an increased risk of morbidity and mortality. Recent advances in artificial intelligence (AI) and machine learning (ML) have showcased their proficiency in predicting AKI, projecting disease progression, and accurately identifying underlying etiologies. This review examines the central aspects of AKI post-HSCT, veno-occlusive disease (VOD) in HSCT recipients, discusses present-day applications of artificial intelligence in AKI, and introduces a proposed ML framework for the early detection of AKI risk.

Case report: CD7-targeted autologous CAR-T therapy for the treatment of T-cell acute lymphoblastic leukemia undergoing allogeneic peripheral blood stem cell transplantation in the long-term follow-up

IntroductionChimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising approach for treating relapsed/refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL). However, it is mostly used as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, secondary allo-HSCT is costly and associated with significantly high treatment-related mortality rate than the primary transplants. In this report, we present the case of an adult T-ALL patient who underwent CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT.Case presentationThe adult T-ALL patient relapsed for a third time after undergoing allogeneic peripheral blood stem cell transplantation (PBSCI) and achieving the first complete remission (CR1). Therefore, the patient was administered CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT. Towards this, the endogenous CD7-deleted CAR (CD7-CAR7) T cells were generated using CRISPR/Cas9 gene-editing technology. However, after the first infusion, the CD7 CAR-T cells did not show significant proliferation when analyzed at two weeks and the patient became positive for peripheral measurable residual disease (MRD). Therefore, after a two-week period, an augmented dose of CAR-T cells was administered. MRD was monitored in the peripheral blood and bone marrow samples. The patient achieved complete remission and did not require targeted treatment after the completion of CD7 CAR-T-cell therapy. The current follow-up data has shown that the patient is negative for MRD and has been disease-free for more than 42 months.ConclusionThe results of this case study provide evidence for the long-term efficacy of CD7-targeted autologous CAR-T-cell therapy without requiring secondary allo-HSCT in patients with r/r T-ALL that have relapsed after previous allogeneic PBSCT.

Venetoclax plus low intensity chemotherapy for adults with acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL), the BCL2 inhibitor venetoclax may enhance the efficacy of chemotherapy allowing dose reductions that reduce toxicity. We designed a phase 1b study of venetoclax plus attenuated chemotherapy to determine the recommended phase 2 dose (RP2D) of venetoclax. The study enrolled 19 patients with ALL either newly diagnosed (≥60 years, n=11 [B-cell, n=8; T-cell, n=3]) or R/R (≥18 years, n=8 [B-cell, n=3; T-cell, n=5]). Venetoclax was given for 21 days with each cycle of mini-hyper-CVD (cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). There were no dose limiting toxicities at dose level (DL) 1 (n=3, 400 mg/day) or DL2 (n=6, 600 mg/day); DL2 was the RP2D and explored further (n=10). The most common non-hematologic adverse events were grade 3+ infections. There were no deaths within 60 days and no patients discontinued therapy for toxicity. There was no tumor lysis syndrome, hepatotoxicity, or prolonged cytopenias. Among patients with newly diagnosed ALL, 10/11 (90.9%) achieved a measurable residual disease-negative (<0.01% sensitivity) complete remission (CR) including 6 patients with hypodiploid TP53 mutated ALL. All patients in CR bridged to hematopoietic stem cell transplant (n=9) or completed protocol (n=1). With a median follow-up of 60.0 months, median disease-free survival (DFS) for patients with newly diagnosed ALL was 54.6 months (95% CI: 35.5 months - NA) with a 2-year DFS rate of 90% (95% CI, 71% - 100%). Among patients with R/R ALL, 3/8 (37.5%) achieved CR. In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well-tolerated with promising efficacy. NCT03319901.

Association between early anti-cytomegalovirus therapy and the incidence of chronic graft-versus-host disease.

Ganciclovir and foscarnet are two representative anti-cytomegalovirus (CMV) agents. A previous regional study revealed a lower risk of chronic graft-versus-host disease (GVHD) in patients who received pre-emptive foscarnet. We conducted a retrospective nationwide study to confirm the results. A total of 8890 patients aged 16 or older with hematological malignancies who received foscarnet (n = 1555) or ganciclovir (n = 7335) during their first hematopoietic stem cell transplantation (HSCT) were included. The risks of chronic GVHD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.13-1.40; P < 0.001) and extensive chronic GVHD (HR, 1.16; 95% CI, 1.01-1.33; P = 0.033) were higher with ganciclovir. Among male patients with a female donor, the incidence of extensive chronic GVHD 3years after HSCT was clearly lower with foscarnet (13%; 95% CI, 9-16%) than with ganciclovir (27%; 95% CI, 25-29%; P < 0.001). In male patients who received HSCT from female donors, foscarnet recipients showed significantly lower incidence of extensive chronic GVHD than ganciclovir recipients, regardless of donor source or previous acute GVHD. While caution is necessary, these results indicate that foscarnet affects alloimmunization and might reduce the incidence of chronic GVHD.

Dissecting the genomic traits and clinical course of secondary myelodysplastic syndrome following aplastic anaemia: A milestone.

Dissecting the genomic traits and clinical course of secondary myelodysplastic syndromefollowing aplastic anaemia is a milestone. The report by Li and colleagues investigates determinants of evolution to myelodysplastic syndrome and acute myeloid leukaemia in patients with aplastic anaemia and paroxysmal nocturnal haemoglobinuria with a specific focus on post-transplant outcomes. Commentary on: Li etal. Clinical and genetic profiles and outcomes of allogeneic haematopoietic stem cell transplantation in secondary myelodysplastic syndrome following aplastic anaemia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19855.

Pharmacokinetic Positron Emission Tomography Imaging of an Optimized CD38-Targeted 68Ga-Labeled Peptide in Multiple Myeloma: A Pilot Study.

Multiple myeloma (MM) is an incurable disease characterized by its clinical and prognostic heterogeneity. Despite conventional chemotherapy and autologous hematopoietic stem cell transplantation, the management of relapsed and refractory MM disease poses significant challenges, both medically and socioeconomically. CD38, highly expressed on the surface of MM cells, serves as a distinct tumor biological target in MM. Peptides offer advantages over antibodies, enabling precise tumor imaging and facilitating early tumor diagnosis and dynamic immunotherapy monitoring. In this study, we developed PF381, a CD38-targeted peptide, and investigated its role in diagnosis, biodistribution, and dosimetry through 68Ga-labeling for preclinical evaluation in tumor-bearing models. We screened a microchip-based combinatorial chemistry peptide library to obtain the amino acid sequence of PF381. Affinity for human CD38 was evaluated by SPRi. PF381 was conjugated with DOTA for radiolabeling with 68Ga, and the complex was characterized by HPLC. PET imaging was performed in murine tumor models after the administration of [68Ga]Ga-DOTA-PF381. Biodistribution analysis compared CD38-positive H929 and CD38-negative U266 tumors, and human radiation dosimetry was estimated. Tumor sections were stained for CD38 expression. SPRi showed that PF381 had a high affinity for CD38 with a KD of 2.49 × 10-8 M. HPLC measured a radiolabeling efficiency of 78.45 ± 7.91% for [68Ga]Ga-DOTA-PF381, with >98% radiochemical purity. PET imaging revealed rapid and persistent accumulation of radioactivity in CD38-positive H929 tumors, contrasting with negligible uptake in CD38-negative U266 tumors. Biodistribution confirmed higher uptake in H929 tumors (0.75 ± 0.03%ID/g) vs U266 (0.26 ± 0.08%ID/g, P < 0.001). The kidney received the highest radiation dose (3.57 × 10-02 mSv/MBq), with an effective dose of 1.41 × 10-02 mSv/MBq. Immunofluorescence imaging supported PET and biodistribution findings. We developed a novel peptide targeting CD38 and proved that 68Ga-labeled PF381 had rapid targeting and good tumor penetration capabilities. Therefore, 68Ga-labeled PF381 could achieve high sensitivity in vivo imaging for CD38-positive hematological malignancies.

Germ Cell Dysfunction is Universal in Male Patients with β-Thalassemia Following Hematopoietic Stem Cell Transplantation During Childhood and Adolescence.

To assess gonadal function in adolescent male patients with β-thalassemia who underwent successful hematopoietic stem cell transplantation (HSCT) during childhood or adolescence. Fifty-two male patients with β-thalassemia, aged ≥10 years, who had undergone HSCT ≥2 years were included. Clinical data, such as age, genital Tanner (GT) stage at HSCT and enrollment, serum ferritin levels, and cumulative doses of alkylating agents, were collected. Gonadal function was evaluated through measurements of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B levels, and semen analysis. Age at enrollment and HSCT were 17 (10-31) and 9 (1-19) years, respectively. The duration from HSCT to enrollment was 7.5 (2-20) years. Of 52 patients, 46 (88%) exhibited Sertoli cell dysfunction. Thirty-one patients had relatively small testes for their GT stage, 34 of 44 with GT V had elevated FSH of ≥5 IU/L, and 20 of 49 with GT stages II-V had low serum inhibin B levels. None of the patients with GT stage V showed Leydig cell dysfunction or gonadotropin deficiency. Serum FSH ≥8 IU/L showed the best diagnostic accuracy for detecting oligo- and azoospermia. All 39 patients who underwent semen analysis had >1 abnormal parameters. Having relatively small testes for GT stage and serum FSH ≥8 IU/L were associated with oligo- and azoospermia (p <0.01). Male patients with β-thalassemia after HSCT experienced universal spermatogenesis impairment and frequent Sertoli cell dysfunction but their Leydig cell function appears to be preserved. The high likelihood of future subfertility should be informed before HSCT.

Prolonged catamnesis of a child with type I mucopolysaccharidosis, Gurler syndrome, receiving enzyme replacement therapy

Hereditary pathology makes up a significant part of the structure of childhood morbidity, disability and mortality. Mucopolysaccharidosis type I is a hereditary lysosomal accumulation disease, with an autosomal recessive type of inheritance. At birth, children with Gurler syndrome look normal, but in the future, they develop symptoms characteristic of mucopolysaccharidosis, and the first clinical manifestations of the disease are often hernias and hepatosplenomegaly. The presented clinical case demonstrates the difficulties of early diagnosis of mucopolysaccharidosis type I, which lead to a later prescription of enzyme replacement therapy and the inability to use a more effective method of therapy – hematopoietic stem cell transplantation, due to the development of serious manifestations of the cardiovascular system. While the positive effects of enzyme replacement therapy in the early stages of treatment may seem promising, it does not guarantee a favorable prognosis for the future.Conclusion. Currently, early diagnosis of mucopolysaccharidosis type I is difficult due to the lack of early manifestations. Often, the progression of clinical manifestations leads to disability, and in severe cases, to death. Therefore, it is important to have early diagnosis and appropriate treatment.

Case report: A novel JAK3 homozygous variant in a patient with severe combined immunodeficiency and persistent COVID-19

Inborn errors of immunity (IEI) encompass a broad range of disorders with heterogeneous clinical presentations, often leading to challenges in early diagnosis. This study presents a case of a Brazilian patient with a T-B+NK- severe combined immunodeficiency (SCID) diagnosed at the age of 6 months when was admitted to the hospital due to multiple infectious diseases. Despite undergoing hematopoietic stem cell transplantation (HSCT), the patient had recurrent infections, requiring constant hospital care, including IgG infusions and several antibiotic treatments for the following months. One year after HSCT, presenting mixed chimerism, the patient tested positive for SARS-CoV-2 in nasopharyngeal, duodenum, and intestine samples, with persistent positive tests over a six-month period. Whole exome sequencing identified a private homozygous missense variant (c.1202T&amp;gt;C; p.Leu401Pro) in the Janus Kinase 3 (JAK3) gene. This substitution is located in a highly conserved position, and different bioinformatic variant effect predictors classified the variant as damaging. In silico structural analysis suggested that the variant led to increased structural instability, disrupting the hydrophobic interactions within the SH2 domain, thereby influencing the neighboring residues and potentially altering the interaction between JAK3 and gamma chain (γc) intracellular receptors. This study provides evidence for the novel pathogenicity classification of the variant and highlights the importance of the JAK3 and SH2 domain modulating protein function and their contribution to the SCID pathogenesis.

MTOR inhibitors potentially preserve fertility in female patients with haematopoietic malignancies: a narrative review.

Haematologic malignancies are considered among the more common adolescent and young adult (AYA) cancers. Many female AYA patients with haematopoietic malignancies face impaired fertility. Haematologic malignancies patients tend to be treated with more aggressive systemic chemotherapy than that of solid tumours. In adult women, treatment-related contraception causes age-related fertility loss. Graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation is associated with decreased fertility. Ovarian cryopreservation is often indicated for haematopoietic malignancies; however, follicle loss associated with ovarian cryopreservation and ovarian minimal residual disease, which result in the withdrawal of the transplantation, are important issues. These problems may not be fully addressed by conventional methods of fertility preservation, such as oocyte, embryo, and ovarian cryopreservation, leaving room for research into new treatment approaches, such as fertility preservation drugs. In recent years, preclinical studies have shown that mTOR inhibitors may preserve chemotherapy-induced follicular loss, may have follicle-preserving effects on follicle loss associated with cryopreservation and transplantation of ovarian tissue, may have fertility-preserving effects on aging-related infertility. Clinical studies have shown that mTOR inhibitors may have the potential for indirect fertility preservation by controlling GVHD, have a limited anti-tumor effect against haematopoietic malignancies. The purpose of this article is to outline the various issues faced by female survivors of haematopoietic malignancies and discuss the potential of mTOR inhibitors as a safe treatment option. Based on current research, mTOR inhibitors seem promising and innovative fertility preservation agents regarding preclinical conditions, and further study, including clinical trials, should be expected.

Evaluation of Subclinical Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Hematopoietic Stem Cell Transplantation: An Echocardiography Study

Background: Hematopoietic stem cell transplantation (HSCT) is a potentially curative procedure that is used in various hematological malignancies. However, among an increasing number of HSCT, the amount of cancer therapy-related cardiac dysfunction (CTRCD) is increasing as well. This study aimed to determine the prevalence of subclinical CTRCD in HSCT patients 12 months after HSCT and to assess the impact of clinical factors on the development of CTRCD. Material and Methods: We included 55 patients who underwent autologous or allogeneic HSCT. The patients were assessed using an echocardiography method before and 12 months after a HSCT procedure. Results: Our study revealed that during the 12-month follow-up period, asymptomatic CTRCD was observed in 15 patients (27.3%), 6 experienced moderate CTRCD, and 9 experienced mild CTRCD. Patients with previous use of anthracyclines tended to have CTRCD more often: nine patients (60%) in the CTRCD group and nine patients (22.5%) in non-CTRCD group. Patients who received the BEAM regimen for conditioning also experienced CTRCD more often: five patients (33.3%) in CTRCD group vs. two patients (5%) in the non-CTRCD group. Conclusions: Our study showed that asymptomatic CTRCD was found in 27.3% of the patients 12 months after HSCT. The BEAM chemotherapy conditioning protocol following prior anthracycline use were identified as factors contributing to the development of CTRCD.

Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation

Background: Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (&lt;440ms), Grade 1 (440-480ms), and Grade ≥2 (&gt;480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score. Results: Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc. Conclusions: In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation

Abstract 4125252: Pre-Hematopoietic Stem Cell Transplantation Echocardiographic Indices and Post-Transplant Cardiovascular Outcomes

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with adverse cardiovascular (CV) events including the development of heart failure (HF) and arrythmias. While transthoracic echocardiogram (TTE) is routinely obtained prior to HSCT, its role in predicting the incidence of HSCT related CV events is poorly understood. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center from 2008-2019. In this analysis, we included patients from UMHS with a baseline TTE. Data on pre-HSCT TTE parameters and post-HSCT CV outcomes were collected through manual chart review. Left ventricular (LV) function and dimensions were categorized into normal, mildly abnormal, and moderately/severely abnormal based on American Society of Echocardiography guidelines. The primary outcomes were new-onset HF and atrial fibrillation/flutter post-HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT CV risk score. Results: Of the 2071 patients (mean age at HSCT 55.5 + 12.9 years; 59.5% male) with a pre-HSCT TTE (median 25 days pre-HSCT), 116 (5.6%) and 128 (6.2%) patients experienced HF and atrial fibrillation/flutter, respectively, over a median period of 2.2 years. Greater abnormalities in left ventricular internal diameter at end-diastole (LVIDd) and end-systole (LVIDs) were linearly associated with a higher risk of HF (P-trend 0.018 and 0.004, respectively) (Table). Similarly, moderately/severely abnormal LVIDd was associated with a 2.41-fold (95% CI: 1.07, 5.43) increase in risk of atrial fibrillation/flutter (Table). Pre-HSCT ejection fraction (EF) was not associated with either endpoint. Conclusion: LV dilation, even when mild, was notably associated with increased risk of developing new HF or atrial arrythmias post-HSCT, regardless of EF. Whether evidence of LV dilation should prompt the initiation of guideline directed medical therapy to minimize the risk of incident HF warrants further study.

Cytomegalovirus Infections in Hematopoietic Stem Cell Transplant: Moving Beyond Molecular Diagnostics to Immunodiagnostics

Human CMV, regularly reactivated by simple triggers, results in asymptomatic viral shedding, powerful cellular immune responses, and memory inflation. Immunocompetent individuals benefit from a robust immune response, which aids in viral management without causing clinically significant illness; however, immunodeficient individuals are always at a higher risk of CMV reactivation and disease. Hematopoietic stem cell transplant (HSCT) recipients are consistently at higher risk of CMV reactivation and clinically significant CMV illness due to primary disease, immunosuppression, and graft vs. host disease. Early recovery of CMV-CMI responses may mitigate effects of viral reactivation in HSCT recipients. Immune reconstitution following transplantation occurs spontaneously and is mediated initially by donor-derived T cells, followed by clonal growth of T cells produced from graft progenitors. CMV-specific immune reconstitution post-transplant is related to spontaneous clearance of CMV reactivation and may eliminate the need for prophylactic or pre-emptive medication, making it a potential predictive marker for monitoring CMV reactivation. This review highlights current thoughts and therapeutic options for CMV reactivation in HSCT, with focus on CMV immune reconstitution and post-HSCT monitoring. Immune monitoring aids in risk stratification of transplant recipients who may progress from CMV reactivation to clinically significant CMV infection. Implementing this approach in clinical practice reduces the need for periodic viral surveillance and antiviral therapy in recipients who have a high CMV-CMI and thus may experience self-limited reactivation. Therefore, in the age of precision medicine, it is critical to incorporate CMV-specific cellular immune surveillance into conventional procedures and algorithms for the management of transplant recipients.

Evaluation of the Incidence and Stage of Oral Mucositis in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Study.

This study aims to retrospectively evaluate the incidence and stage of oral mucositis in patients undergoing hematopoietic stem cell transplantation. A total of 102 patient records of patients hospitalized between 2014 and 2019 in the adult hematopoietic stem cell transplantation clinic of a tertiary university hospital in Turkey were evaluated. Data were collected through a retrospective evaluation of patient records. Records made according to the WHO Oral Toxicity Scale included in the patient records during hospitalization in the adult hematopoietic stem cell transplantation clinic were evaluated. Oral mucositis data from recordings were analyzed at baseline, and on days 5, 10, 15, and 30). 96.1% (n=98) of 102 patients developed oral mucositis; only 10.7% had Grade 3, and 2.7% had Grade 4. Oral mucositis development time was 8.28 ± 0.32 days, and recovery time was 14.25 ± 0.78 days. It was determined that smoking, diagnosis, transplantation type, and preparatory regimen affected the oral mucositis healing process. While the incidence of oral mucositis in patients undergoing hematopoietic stem cell transplantation in our study was similar to be similar with the reported findings in the literature, the proportions of Grade 3 and 4 oral mucositis were lower in our study.