Hematopoietic Stem Cell Transplantation Research Articles

Use of T2Bacteria Panel in Pediatric Hematopoietic Stem Cell Transplant Patients: A Single Center Experience

Abstract Background Bloodstream infection is a common complication following hematopoietic cell transplant (HCT), occurring in 10-40% of patients (1,2). Rapid identification of causative bacteria is imperative to provide proper empiric therapy and ensure optimal patient outcomes. The T2Bacteria Panel detects five bacterial pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli) using T2 magnetic resonance (T2MR, T2Biosystems, Lexington MA, USA) directly from blood specimens. Previous studies have reported per-patient sensitivity, specificity, and negative predictive value (NPV) of 84-90%, 85.9-90%, and 99.7%, respectively, as well as 100% positive agreement and 98.4% negative agreement when compared to blood culture (3-5). To date, there have been no studies on the use of this test in pediatric HCT recipients. Methods We reviewed all pediatric HCT patients at St. Jude Children’s Research Hospital who had a T2Bacteria Panel performed for fever and suspected infection between January 2019 and September 2022. A total of 706 T2Bacteria Panel results and concurrent blood culture results from 251 unique patients were analyzed to determine assay performance for detection of the 5 targeted pathogens. Results T2Bacteria PCR and blood culture showed concordant results in 97% of cases. Overall, our study revealed 65% positive percent agreement with blood culture and 95% negative percent agreement for bacteremia caused by any of the target pathogens. PPV, NPV, sensitivity and specificity for each organism detected by the panel, and the panel overall, are presented in Table 1. Positive predictive value ranged from 28-73%. Negative predictive value was high for all organisms (98-100%). Sensitivity was highest for Pseudomonas aeruginosa (88%), and lowest for Escherichia coli (44%). Specificity was high for all organisms (97-99%). Conclusion In pediatric HSCT patients, the T2Bacteria Panel was most useful for rapidly ruling out the presence of target pathogens, with high negative percent agreement, NPV, and specificity. Positive percent agreement was lower than noted in previous studies. Positive predictive value and sensitivity varied per pathogen.

Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy

BackgroundGene therapy with elivaldogene autotemcel (eli-cel) consisting of autologous CD34+ cells transduced with lentiviral vector containing ABCD1 complementary DNA (Lenti-D) has shown efficacy in clinical studies for the treatment of cerebral adrenoleukodystrophy. However, the risk of oncogenesis with eli-cel is unclear.MethodsWe performed integration-site analysis, genetic studies, flow cytometry, and morphologic studies in peripheral-blood and bone marrow samples from patients who received eli-cel therapy in two completed phase 2–3 studies (ALD-102 and ALD-104) and an ongoing follow-up study (LTF-304) involving the patients in both ALD-102 and ALD-104.ResultsHematologic cancer developed in 7 of 67 patients after the receipt of eli-cel (1 of 32 patients in the ALD-102 study and 6 of 35 patients in the ALD-104 study): myelodysplastic syndrome (MDS) with unilineage dysplasia in 2 patients at 14 and 26 months; MDS with excess blasts in 3 patients at 28, 42, and 92 months; MDS in 1 patient at 36 months; and acute myeloid leukemia (AML) in 1 patient at 57 months. In the 6 patients with available data, predominant clones contained lentiviral vector insertions at multiple loci, including at either MECOM–EVI1 (MDS and EVI1 complex protein EVI1 [ecotropic virus integration site 1], in 5 patients) or PRDM16 (positive regulatory domain zinc finger protein 16, in 1 patient). Several patients had cytopenias, and most had vector insertions in multiple genes within the same clone; 6 of the 7 patients also had somatic mutations (KRAS, NRAS, WT1, CDKN2A or CDKN2B, or RUNX1), and 1 of the 7 patients had monosomy 7. Of the 5 patients with MDS with excess blasts or MDS with unilineage dysplasia who underwent allogeneic hematopoietic stem-cell transplantation (HSCT), 4 patients remain free of MDS without recurrence of symptoms of cerebral adrenoleukodystrophy, and 1 patient died from presumed graft-versus-host disease 20 months after HSCT (49 months after receiving eli-cel). The patient with AML is alive and had full donor chimerism after HSCT; the patient with the most recent case of MDS is alive and awaiting HSCT.ConclusionsHematologic cancer developed in a subgroup of patients who were treated with eli-cel; the cases are associated with clonal vector insertions within oncogenes and clonal evolution with acquisition of somatic genetic defects. (Funded by Bluebird Bio; ALD-102, ALD-104, and LTF-304 ClinicalTrials.gov numbers, NCT01896102, NCT03852498, and NCT02698579, respectively.)

Maintenance Therapy Post-Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia.

High-risk acute myeloid leukemia has been associated with a poor outcome. Hematopoietic stem cell transplantation (HSCT) represents the only curative option for eligible patients. Relapse after HSCT is a dramatic event with poor chances of survival. With the aim of reducing the rate of post-HSCT relapse, maintenance treatment has been investigated in this setting. Results from clinical trials suggest an advantage in the use of a maintenance strategy; however, standardized guidelines are not yet available due to the lack of prospective clinical trials. In this review, we have reported the most important strategies adopted as post-HSCT maintenance, highlighting their efficacy, but the current research also opens questions.

Asciminib plus dasatinib and prednisone for Philadelphia chromosome–positive acute leukemia

AbstractDasatinib is an effective treatment for Philadelphia chromosome–positive (Ph+) acute leukemia, but some patients develop resistance. Combination treatment with dasatinib and asciminib, an allosteric inhibitor of BCR::ABL1, may deepen responses and prevent the emergence of dasatinib-resistant clones. In this phase 1 study (NCT03595017), 24 adults with Ph+ acute lymphoblastic leukemia (ALL; ALL, n = 22; p190, n = 16; p210, n = 6) and chronic myeloid leukemia in lymphoid blast crisis (n = 2) were treated with escalating daily doses of asciminib in combination with dasatinib 140 mg daily plus prednisone 60 mg/m2 daily to determine the maximum tolerated dose. After a 28-day induction, dasatinib and asciminib were continued indefinitely or until hematopoietic stem cell transplant. The median age was 64.5 years (range, 33-85; 50% aged ≥65 years). The recommended phase 2 dose of asciminib was 80 mg daily in combination with dasatinib and prednisone. The dose limiting toxicity at 160 mg daily was asymptomatic grade 3 pancreatic enzyme elevation without symptomatic pancreatitis. There were no vaso-occlusive events. Among patients with de novo ALL, the complete hematologic remission rates at days 28 and 84 were 84% and 100%, respectively. At day 84, 100% of patients achieved complete cytogenetic remission, 89% achieved measurable residual disease negativity (<0.01%) by multicolor flow cytometry, and 74% and 26% achieved BCR::ABL1 reverse transcription polymerase chain reaction <0.1% and <0.01%, respectively. Dual BCR::ABL1 inhibition with dasatinib and asciminib is safe with encouraging activity in patients with de novo Ph+ ALL. This trial was registered at www.clinicaltrials.gov as #NCT02081378.

Recurrent Hypoglycemia during Sorafenib Maintenance Post-Allogeneic Hematopoietic Stem Cell Transplantation

Recurrent Hypoglycemia during Sorafenib Maintenance Post-Allogeneic Hematopoietic Stem Cell Transplantation

Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy

BackgroundCerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing ABCD1 complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.MethodsIn a phase 2–3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI). The primary efficacy end point was survival without any of six major functional disabilities at month 24. The secondary end points included overall survival at month 24 and the change from baseline to month 24 in the total neurologic function score.ResultsA total of 32 patients received eli-cel; 29 patients (91%) completed the 24-month study and are being monitored in the long-term follow-up study. At month 24, none of these 29 patients had major functional disabilities; overall survival was 94%. At the most recent assessment (median follow-up, 6 years), the neurologic function score was stable as compared with the baseline score in 30 of 32 patients (94%); 26 patients (81%) had no major functional disabilities. Four patients had adverse events that were directly related to eli-cel. Myelodysplastic syndrome (MDS) with excess blasts developed in 1 patient at month 92; the patient underwent allogeneic hematopoietic stem-cell transplantation and did not have MDS at the most recent follow-up.ConclusionsAt a median follow-up of 6 years after lentiviral gene therapy, most patients with early cerebral adrenoleukodystrophy and MRI abnormalities had no major functional disabilities. However, insertional oncogenesis is an ongoing risk associated with the integration of viral vectors. (Funded by Bluebird Bio; ALD-102 and LTF-304 ClinicalTrials.gov numbers NCT01896102 and NCT02698579, respectively.)

Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Graft-versus-host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug-drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics. This study aimed to assess the impact of inflammation, as indicated by C-reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no-to-mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation. The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.

Urinary L-FABP Assay in the Detection of Acute Kidney Injury following Haematopoietic Stem Cell Transplantation.

Background: Acute Kidney Injury (AKI) is a condition that affects a significant proportion of acutely unwell patients and is associated with a high mortality rate. Patients undergoing haemopoietic stem cell transplantation (HSCT) are in an extremely high group for AKI. Identifying a biomarker or panel of markers that can reliably identify at-risk individuals undergoing HSCT can potentially impact management and outcomes. Early identification of AKI can reduce its severity and improve prognosis. We evaluated the urinary Liver type fatty acid binding protein (L-FABP), a tubular stress and injury biomarker both as an ELISA and a point of care (POC) assay for AKI detection in HSCT. Methods: 85 patients that had undergone autologous and allogenic HSCT (35 and 50, respectively) had urinary L-FABP (uL-FABP) measured by means of a quantitative ELISA and a semi-quantitative POC at baseline, day 0 and 7 post-transplantation. Serum creatinine (SCr) was also measured at the same time. Patients were followed up for 30 days for the occurrence of AKI and up to 18 months for mortality. The sensitivity and specificity of uL-FABP as an AKI biomarker were evaluated and compared to the performance of sCr using ROC curve analysis and logistic regression. Results: 39% of participants developed AKI within 1 month of their transplantation. The incidence of AKI was higher in the allogenic group than in the autologous HTSC group (57% vs. 26%, p = 0.008) with the median time to AKI being 25 [range 9-30] days. This group was younger (median age 59 vs. 63, p < 0.001) with a lower percentage of multiple myeloma as the primary diagnosis (6% vs. 88%, p < 0.001). The median time to AKI diagnosis was 25 [range 9-30] days. uL-FABP (mcg/gCr) at baseline, day of transplant and on the 7th day post-transplant were 1.61, 5.39 and 10.27, respectively, for the allogenic group and 0.58, 4.36 and 5.14 for the autologous group. Both SCr and uL-FABP levels rose from baseline to day 7 post-transplantation, while the AUC for predicting AKI for baseline, day 0 and day 7 post-transplant was 0.54, 0.59 and 0.62 for SCr and for 0.49, 0.43 and 0.49 uL-FABP, respectively. Univariate logistic regression showed the risk of AKI to be increased in patients with allogenic HSCT (p = 0.004, 95%CI [0.1; 0.65]) and in those with impaired renal function at baseline (p = 0.01, 95%CI [0.02, 0.54]). The risk of AKI was also significantly associated with SCr levels on day 7 post-transplant (p = 0.03, 95%CI [1; 1.03]). Multivariate logistic regression showed the type of HSCT to be the strongest predictor of AKI at all time points, while SCr levels at days 0 and 7 also correlated with increased risk in the model that included uL-FABP levels at the corresponding time points. The POC device for uL-FABP measurement correlated with ELISA (p < 0.001, Spearman 'correlation' = 0.54) Conclusions: The urinary biomarker uL-FABP did not demonstrate an independent predictive value in the detection of AKI at all stages. The most powerful risk predictor of AKI in this setting appears to be allograft recipients and baseline renal impairment, highlighting the importance of clinical risk stratification. Urinary L-FAPB as a POC biomarker was comparable to ELISA, which provides an opportunity for simple and rapid testing. However, the utility of LFABP in AKI is unclear and needs further exploration. Whether screening through rapid testing of uL-FABP can prevent or reduce AKI severity is unknown and merits further studies.

Risk Factors of Cytomegalovirus Retinitis Occurrence After Allogeneic Hematopoietic Stem Cell Transplantation

ABSTRACT Purpose To explore the potential risk factors for the occurrence of human cytomegalovirus (HCMV) retinitis (CMVR) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. Methods This is a retrospective, nested case-control study conducted in hematological patients with CMVR who underwent allo-HSCT. Patients diagnosed with CMVR after allo-HSCT were included as the case group, and those without CMVR were matched by a ratio of 1:2 and were recruited as controls. We selected 19 pre- and post-transplant indicators for univariate analysis between the cases and controls, and then Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) for exploration of risk factors of the CMVR occurrence. Results A total of 1308 allo-HSCT patients from January 1, 2020 to July 31, 2023 were analyzed, and 27 patients were diagnosed CMVR with a median onset time of 222 days after transplantation. In univariate analysis, donors of stem cells source, HLA-match types (including matched sibling donor, haploidentical donor, and unrelated donor), post-transplant Epstein-Barr virus (EBV) viremia, platelet implantation time, and serostatus of CMV-IgG were more easily to develop CMVR than controls (p < 0.001, p = 0.003, p < 0.001, p = 0.032, p = 0.038, respectively). Multivariate logistic regression analysis showed that stem cells source (OR 7.823, 95% CI 1.759-34.800), HLA-match types (OR 7.452, 95% CI 1.099-50.542), and post-transplant EBV infection (OR 7.510, 95% CI 1.903-29.640) were positively associated with the onset of CMVR. Conclusion Stem cells derived from bone marrow and peripheral blood, HLA-match types, and post-transplant EBV viremia are important risk predictors of CMVR in allo-HSCT patients. These results suggest that clinicians should pay more attention to these indicators when formulating preventive measures pre- and post-transplant.

Incremental eligibility criteria for the BMT CTN 1507 haploidentical trial for children with sickle cell disease

AbstractThe Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507 leadership and the data safety monitoring board (DSMB) established incremental entry criteria for children aged 5 to 14.99 years with sickle cell disease (SCD) enrolling in a phase 2 trial of HLA-haploidentical hematopoietic stem cell transplantation. First, the enrollment was limited to overt stroke in the first 10 participants (stage 4). Subsequently, the DSMB reviewed the interim results and expanded the eligibility to include children with silent cerebral infarcts or abnormal transcranial Doppler velocities with magnetic resonance angiography–defined cerebral vasculopathy (stage 3). A third cohort was enrolled after the DSMB reviewed the clinical outcomes in these cumulative initial enrollments (n = 18). Additions to the entry criteria included nonneurologic morbidities (stage 2). Eligibility criteria included the following: (1) life-threatening acute chest syndrome requiring exchange transfusion; (2) right heart catheterization confirmed pulmonary hypertension; (3) persistent systemic hypertension despite maximum medical therapy; (4) acute pain despite maximum medical therapy in the absence of psychosocial factors and unmanaged asthma after adjudication; or (5) 2 major priapism episodes in 12 months or 3 in 24 months. Children with SCD who did not meet the criteria for stages 4, 3, and 2 were not eligible. To our knowledge, for the first time, we introduce a staged strategy for eligibility in a curative therapy trial for children with SCD concordant with 45 Code of Federal Regulations § 46.405(b). The research governance–mandated eligibility strategy used within the BMT CTN 1507 phase 2 study may apply to future pediatric SCD curative therapy trials. This trial was registered at www.ClinicalTrials.gov as #NCT032635590.

Pre-Transplant Dual-Energy X-ray Absorptiometry (DXA)-Derived Body Composition Measures as Predictors of Treatment Outcomes and Early Post-Transplant Complications in Patients with Multiple Myeloma (MM) Treated with Autologous Hematopoietic Stem Cell Transplantation (AutoHSCT).

Background/Objectives: Changes in muscle mass and bone density are common in multiple myeloma (MM) patients. Dual-energy X-ray absorptiometry (DXA) offers precise, non-invasive insights into a patient's physical condition before autologous stem cell transplantation (autoHSCT). This study examines how pre-transplant body composition impacts treatment outcomes and early complications in MM patients undergoing autoHSCT. Methods: This study is a single-center, retrospective analysis of patients with MM who were treated with first or second autoHSCT and underwent DXA pre-transplant between 11 August 2019 and 12 June 2024. Results: We conducted a study of pre-transplant body composition in 127 patients with MM. Among them, 108 (85%) qualified for first autoHSCT, while 19 (15%) qualified for a second. The median age of the patients was 64 years (range 50-73). In the Cox proportional hazards regression conducted in the group of women, Total Body %Fat was a statistically significant predictor for progression-free survival (PFS) (HR = 0.07, 95% CI = 0.01,0.6, p = 0.0157). In the Mann-Whitney U test conducted on males, Lean Mass/Height2 and Appen. Lean Height2 were statistically significant predictors of early infections after autoHSCT (Z = 1.98, p = 0.0473 and Z = 2.32, p = 0.0204, respectively). In males, Fat Mass/Height2 was a significant predictor of non-infectious toxicity related to treatment (Z = -1.98, p = 0.0476). Conclusions: In women, higher levels of adipose tissue initially appear to exert a protective effect; however, this benefit diminishes over time, with greater fat mass eventually correlating with an increased risk of disease progression. In men, muscle mass has been identified as a significant predictor of early infection risk post-autoHSCT. Furthermore, our findings indicate that an increased amount of adipose tissue in men is statistically associated with a higher risk of non-infectious treatment-related toxicity. These conclusions highlight the critical need for further investigation into the role of body composition.

Early Fever in Allogeneic Stem Cell Transplantation: Are Presepsin and YKL-40 Valuable Diagnostic Tools?

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510-0.802) and Day 3 (AUC 0.698; 95% CI: 0.559-0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572-0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 μg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

Toxoplasma qPCR kinetics to guide pre-emptive treatment of toxoplasmosis after allogeneic hematopoietic stem cell transplantation.

Recent ECIL-guidelines recommend a quantitative PCR (qPCR) guided pre-emptive treatment approach to toxoplasmosis in seropositive recipients of allogeneic hematopoietic cell transplantation (allo-HCT). While qPCR might serve as a sensitive tool for early Toxoplasma detection, its role in treatment follow-up remains unknown. We analyzed the qPCR kinetics of allo-HCT recipients experiencing either Toxoplasma infection (TI, n=71) or disease (TD, n=14) in relation to different parameters. We included 85 patients with available qPCR values expressed as quantitative cycle (Cq) from four large hematological centers from 2009 to 2023, and kinetic analysis was performed in a selection of 74 patients screened at least weekly with blood qPCR. Day 0 (D0) was the day of anti-Toxoplasma treatment start or (when untreated) day of diagnosis. Time to qPCR negativity was inversely proportional to the Cq value at D0 (p=0.0063). Not reaching negativity at D10 was associated with a significantly higher mortality at D30 (p=0.023). Patients with a high D0-parasitic load and patients with TD showed slower clearance (p<0.001, p=0.032). Time to negativity was not significantly different for patients started on prophylactic vs curative doses as first-line treatment regimen (p=0.16). This study underscores the predictive value of qPCR kinetics monitoring in allo-HCT patients with toxoplasmosis. With the aforementioned risk factors, clinicians can identify patients at high-risk for worse outcome. Our results support to consider a therapeutic change or reinforcement if the parasitic load does not decrease after 10 days, supplementing existing clinical guidelines.

The prognosis and related factors impacting renal response in newly diagnosed multiple myeloma patients with renal impairment

Objective: To investigate the prognosis and related factors impacting renal response in newly diagnosed multiple myeloma (NDMM) patients with renal impairment. Methods: A total of 375 NDMM patients diagnosed at the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University from August 2012 to April 2022 were retrospectively recruited. Patients were categorized into non-renal impairment group(n=273) and renal impairment group (n=102) according to renal function at initial diagnosis. All patients received≥2 cycles of bortezomib-based induction chemotherapy after admission. The hematological response included stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) and stable disease (SD). The renal responses were defined as CR, PR, minor response (MR) and non-response (NR). General clinical data of the patients were collected, and patients were followed up by telephone. The follow-up deadline was December 3, 2022, and the median follow-up time [M (Q1, Q3)] was 42 (22, 61) months. Kaplan-Meier analysis was used to plot the survival curve. The log-rank test was utilized for inter-group comparisons. Multivariate logistic regression modeling facilitated the exploration of associated factors impacting renal response. Results: In the renal impairment group, there were 68 males and 34 females with a median age [M (Q1, Q3)] of 64 (58, 69) years. In the non-renal impairment group, there were 149 males and 124 females with a median age of 62 (54, 68) years. Compared with the renal impairment group, the age, lactate dehydrogenase and 24-hour urinary protein quantity were increased, the proportion of patients with light chain M protein and the proportion of patients at the DS-Ⅲ stage, ISS-Ⅲ stage and R-ISS-Ⅲ stage were higher, the hemoglobin level and the proportion of patients receiving autologous hematopoietic stem cell transplantation were lower in the renal impairment group (all P<0.05). In 102 patients with renal impairment, renal responses of CR, PR, MR and NR were obtained in 53 (52.0%), 8 (7.9%), 18 (17.6%), 23 (22.5%) patients, respectively, and the overall response rate was 77.5% (79/102). Kaplan-Meier survival curve revealed that the median progression-free survival (PFS) was 24.0 (95%CI: 18.3-29.7) months in the renal impairment group, which was shorter than 31.0 (95%CI: 24.7-37.3) months in the non-renal impairment group (P=0.003). The median overall survival (OS) was 46.0 (95%CI: 36.5-55.5) months in the renal impairment group, which was shorter than 79.0 (95%CI: 59.9-98.1) months in the non-renal impairment group (P=0.002). Among the renal impairment group, patients with renal response of less than PR exhibited a median PFS of 19.0 (95%CI: 9.7-28.3) months, which was shorter than 28.0 (95%CI: 21.4-34.5) months for those achieving PR or better (P=0.048). The median OS was 31.0 (95%CI: 23.5-38.5) months in renal response with less than PR group, which was also worse than 57.0 (95%CI: 42.8-71.2) months for those who achieved PR or better (P=0.003). The results of multivariate logistic regression showed that hematological response achieving VGPR or better was a factor associated with renal response achieving PR (OR=4.20, 95%CI: 1.20-14.68, P=0.025). Conclusions: The prognosis of NDMM patients with renal impairment is poor. The hematological response with VGPR or better is related to the renal response achieving PR.

High-dimensional Immune Profiles and Machine Learning May Predict Acute Myeloid Leukemia Relapse Early following Transplant.

Identification of early immune signatures associated with acute myeloid leukemia (AML) relapse following hematopoietic stem cell transplant (HSCT) is critical for patient outcomes. We analyzed PBMCs from 58 patients with AML undergoing HSCT, focusing on T cell subsets and functional profiles. High-dimensional flow cytometry coupled with Uniform Manifold Approximation and Projection dimensionality reduction and PhenoGraph clustering revealed distinct changes in CD4+ and CD8+ T cell populations in 16 patients who relapsed within 1 y of HSCT. We observed increased IL-2, IL-10, and IL-17-producing CD4+ T cells, alongside decreased CD8+ T cell function early in relapsing patients. Notably, relapsing patients exhibited increased TCF-1intermediate cells, which lacked granzyme B or IFN-γ production in the CD4+ T cell compartment. We then developed a supervised machine learning algorithm that predicted AML relapse with 90% accuracy within 30 d after HSCT using high-throughput assays. The algorithm leverages condensed immune phenotypic data, alongside the ADASYN algorithm, for data balancing and 100 rounds of XGBoost supervised learning. This approach holds potential for detecting relapse-associated immune signatures months before clinical manifestation. Our findings demonstrate a distinct immunological signature potentially capable of predicting AML relapse as early as 30 d after HSCT.

Central line-associated bloodstream infection outbreak related to Ralstonia pickettii-contaminated saline in a pediatric hematopoietic stem cell transplant center.

Ralstonia pickettii is an aerobic Gram-negative non-fermentative bacillus. It is an opportunistic pathogen that has recently prompted nosocomial outbreaks. Although it has low virulence, it can cause a wide range of invasive diseases in immunosuppressive patients. The characteristics of R. pickettii-related central line-associated bloodstream infection (CLABSI) outbreak in pediatric hematopoietic stem cell transplant (HSCT) recipients are presented in this study. This was a single-center, retrospective analysis conducted at Bahcesehir University Goztepe Medicalpark Hospital . The clinical and laboratory characteristics of twelve children with Ralstonia-related CLABSIs were analyzed. Of the twelve patients with R. pickettii growth, seven were female. The median age was 12.1 (2-17) years. Autologous HSCT was performed in two of the patients and allogeneic HSCT was performed in ten patients for both malignant and non-malignant diseases. In the conditioning regimens, all patients were given myeloablative therapy. Clinical sepsis was the most common presentation. As a result of the investigations, R. pickettii growth was observed in saline solutions. All cases were successfully treated with the appropriate antibiotic regimen and the bacteria was not found in repeat cultures. Catheter removal was required in two patients. Mortality was not observed in any patient as the outcome of the infection episode. The detection and control of the infectious source are critical in pediatric HSCT patients with severe immunosuppression, as medical equipment-related outbreaks can be life-threatening.

Psychiatric disorders among survivors of childhood acute lymphoblastic leukemia in Denmark and Sweden.

The diagnosis and treatment of childhood acute lymphoblastic leukemia (ALL) may impact mental health. We investigated the long-term risk of psychiatric disorders among survivors of ALL in a population-based cohort study. We identified patients diagnosed with ALL in Denmark and Sweden before age 20 during 1982-2008. Survivors of ALL (n=2026), their siblings (n=3027), and population comparison subjects (n=9713) were followed for hospital contacts for psychiatric disorders from 5years after ALL diagnosis (or corresponding index date) until 2017. By age 30, the absolute risk of psychiatric hospital contacts was 19.9% (95% confidence interval [CI]: 17.9-22.1) for ALL survivors, 18.5% (95% CI: 16.9-20.2) for siblings, and 18.3% (95% CI: 17.3-19.2) for population comparison subjects. Overall, survivors were at higher risk of any psychiatric disorders than siblings (hazard ratio [HR]=1.25; 95% CI: 1.04-1.50), and population comparison subjects (HR=1.20; 95% CI: 1.06-1.35). The subgroup of survivors (n=332) who received a hematopoietic stem cell transplantation (HSCT) and/or had a relapse were at highest risk of psychiatric disorders (HR=2.07; 95% CI: 1.26-3.41 compared to siblings; HR=1.67; 95% CI: 1.25-2.23 compared to population comparison subjects). The overall absolute risk of psychiatric hospital contacts among ALL survivors was close to that in siblings and population comparison subjects. The modestly increased relative risk was mainly driven by the subgroup of survivors who received HSCT and/or had a relapse. Our findings are reassuring for the large subgroup of ALL survivors without HSCT or relapse, and provide novel insight on both absolute and relative risk of hospital contacts for psychiatric disorders.

Prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients.

Post-transplant lymphoproliferative disorder (PTLD) is a devastating complication of immunosuppressive treatment in both solid organ transplantations (SOT) and hematopoietic stem cell transplantations (HSCT). Epstein-Barr virus (EBV) infection precedes PTLD in 90% of patients. Rituximab, a monoclonal anti-CD20 antibody, depletes B-lymphocytes, which are the ultimate reservoir for EBV. Although rituximab therapy is commonly used as a preventive measure for PTLD in high-risk HSCT, it is not established in SOT. Pediatric kidney transplant recipients (PKTR) underwent routine EBV-PCR surveillance. Patients with increasing viral loads, despite immunosuppressive dose reduction, were managed with preventive rituximab therapy. Between 2012 and 2023, we identified eight episodes of asymptomatic EBV-PCR-positive blood tests in seven out of 65 PKTR (11%) under our care. EBV DNAemia emerged 120-720days post-transplantation. Five of seven patients with EBV DNAemia (71%) were EBV-seronegative prior to transplantation. All five patients did not respond to MMF dose reduction and were therefore treated with preventive rituximab therapy. Following this treatment, EBV PCR clearance was observed in all patients with only minimal complications. PKTR who are EBV-naïve prior to transplantation are expected to have a higher prevalence of EBV DNAemia. We found that PKTR who were EBV seronegative prior to transplantation were less likely to achieve EBV clearance in response to immunosuppression dose reduction. We suggest that rituximab therapy in PKTR may be safe and effective in EBV clearance and PTLD prevention.

Shrimp allergy leading to severe transfusion reaction: A case report

AbstractBackgroundTransfusion reactions occur at an estimated incidence of 2 per 1.000 transfused products. Anaphylactic transfusion reactions are rarer, and seen in 1 per 10.000 transfusions, and are mostly related to platelet transfusions. Here, we describe a rare cause of a transfusion reaction.Case presentationA 19‐year‐old man underwent an allogeneic haematopoietic stem cell transplantation for sickle cell disease and developed an anaphylactic shock following a platelet transfusion, after excluding all common causes. The patient reported a shrimp allergy, and one of the blood/platelet donors had consumed shrimp the day before donation. Elevated levels of specific immunoglobulin E (IgE) against shrimp and tropomyosin were found in the patient. Subsequent transfusions were performed with apheresis platelets from selected donors who were instructed to avoid shrimp consumption, and these transfusions were uneventfully.ConclusionWhen a severe transfusion reaction occurs in a patient with a known food allergy, an IgE‐mediated (food‐related) transfusion reaction should be considered after excluding other causes.

9175 Pretransplant Clinical Characteristics Related To Change In Bone Mineral Density In Adults 1 Year After Allogeneic Hematopoietic Stem Cell Transplantation At Bucaramanga, Colombia Reference Center

Abstract Disclosure: G.A. Parra-Serrano: None. C.L. Sossa: None. K.J. Moreno Medina: None. M. Ochoa: None. A. Reyes Gonzalez: None. A. Plata: None. P. Mantilla Mantilla: None. Introduction: Hematopoietic stem cell transplantation (HSCT) , refractory to pharmacological management, increases 10-year survival by 80%, Chronic complications include alterations in bone metabolism, that increase appearance of osteoporosis (13.8 - 17%), non traumatic fractures, and loss of Bone mineral density (BMD) at the hip -4.2%, L1L4 -2% and femoral neck-9%. Methods Calculate Change at (BMD) in adults undergoing allogenic (HSCT) after 1y and determine pretransplant factors related to this change. Composite endpoint osteoporosis/lowbonemass (osteoporosis Tscore&amp;lt;-2.5 and/or low bone mass Zscore-2.0) 1 year after transplant, Adult patients Retrospective cohort study, ethical comittee approval, anonymized database, undergoing allogeneic (HSCT) between 2009 and 2022, (BMD) measured at lumbar spine (L1L4) and femoral neck before and one year after transplant; Also paraclinical variables: TSH, vitaminD, kidney function, glucocorticoid, Graft vs host disease, disease relapse, diabetes. Descriptive analisis performed, simple linear regresion analisis for delta L1L4 and femoral neck BMD before and 1 year after transplant, and multivariate regresion analisis for variables p&amp;lt;0.2 on simple lineal regression analysis . Results 123 patients, (48 included, 73 excluded (22 died, 50 densitometry data not suitable)). BMD change At lumbar spine, -4.7% (NS) , and at femoral neck -9.8% (p&amp;lt;0.05), Simple regression analysis no correlation for preclinical variables at lumbar spine. negative correlation between prednisolone dose at femoral neck BMD (p 0.007, coefficient B -0.0086 [IC95% -0.014, 0.0025]). Mutivariate regression analysis performed for BMD diference at femoral neck, after adjusting for variables p&amp;lt;0.2 on simple regression analysis, model that include (prednisone dose, diabetes and relapse before transplant showed Rsquare 0.19 coefficient 0.0092 p 0.003. For every gram of glucocorticoid (prednisolone) bone loss decrease -0.9% of BMD at femoral neck at 1 year follow up. Proportion of patients with composite osteoporosis/lowbonemass at femoral neck pre-transplant (n2) 4.17%, postransplant (n14) 29.17%. * p 0.0005. no difference observed at lumbar spine. Fracture incidence n2 (4%) at lumbar spine and n1 (2%) at femoral neck. Conclusions At femoral neck, People with HSCT present significant decrease in (BMD) and higuer incidence of Osteoporosis or low bone mass, not observed at lumbar spine, after adjusting for multiple variables. for every 1gr of prednisolone equivalent dose, (BMD) decrease -0.9%, at femoral neck p0.003. The model only explain 19% of change of BMD at femoral neck, that suggest immune response caused by allogenic transplantation might be responsible, in part, of BMD change. Presentation: 6/3/2024