allo-HSCT Patients Research Articles

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.

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.

Mutations in human cytymegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) UL97 gene lead to increase in viremia duration and poor antiviral response in recipients of allogeneic hematopoietic stem cells.

Human cytomegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) (HCMV) is one of the most commonly detected viruses in recipients of allogeneic hematopoietic stem cell (allo-HSCT) transplants. However, the emergence of resistance to antiviral drugs such as ganciclovir (GCV) poses a challenge in managing these patients. This study aims to investigate the prevalence and impact of mutations in the HCMV UL97 gene associated with resistance to GCV on the course of infection among allo-HSCT patients. The study examined the association between UL97 mutations and the clinical course of HCMV infection in allo-HSCT patients. Genetic sequencing was performed to identify mutations, and their impact on viral replication and resistance to GCV was assessed. Six mutations were identified (D490A, T502A, C592G, C592F, E596G, C603W). C592G, C592F, E596G, and C603W are associated with resistance to antiviral drugs, while D490A and T502A described for the first time. When comparing patients with wild-type and those carrying the mutant variant, several parameters of peripheral blood were significantly lower in the former group. The median time to peak viral load following allo-HSCT, duration of viremia, and rate of virological response to high-dose therapy also differed significantly between the two groups. It was shown that approximately one third (4 out of 14) of allogeneic stem cell transplant recipients had mutations associated with resistance to GCV. Patients carrying the mutant variant of HCMV had longer viremia and took longer to achieve a negative virological test result after starting high-dose therapy. Performing genotyping may help make more evidence-based therapeutic decisions.

Progress in prevention and treatment of cytomegalovirus infection in patients with allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an effective treatment for hematological malignancies. Cytomegalovirus (CMV) infection is one of the common Infection complications after hematopoietic stem cell transplantation, and also the main cause of death of transplant recipients, which has a significant impact on the prognosis and survival of transplant recipients. It is particularly important to take timely and effective prevention and treatment for CMV infected transplant patients. This article discusses the latest prevention and treatment of CMV infection after transplantation,and reviews the recent progress in the prevention and drug treatment of CMV infection in allo-HSCT patients by searching the relevant literature through Pubmed.

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.

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.

Chemotherapy and allo-HSCT for young patients with aggressive ATL

Adult T-cell leukemia-lymphoma (ATL) is an aggressive malignancy with a poor prognosis, especially for patients with the aggressive subtype. While conventional chemotherapy offers short-term disease control, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most promising curative approach for young, transplant-eligible patients. This review focuses on current treatment strategies for aggressive ATL in this specific population. We discuss the rationale for early upfront allo-HSCT following induction chemotherapy. The advent of allo-HSCT using alternative donors, particularly haploidentical HCT, has broadened the applicability of early upfront allo-HSCT in patients with aggressive ATL worldwide. Finally, we address emerging therapies that may improve outcomes in the context of allo-HSCT, paving the way for further advancements in the treatment of aggressive ATL.

Effect of CYP3A5 Gene Polymorphisms on Tacrolimus Blood Concentrations and Adverse Events in Allogeneic Hematopoietic Stem Cell Transplant Patients

BackgroundTacrolimus is the core basic immunosuppressant after transplantation. Cytochrome P450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The aim of this study was to investigate the effect of CYP3A5 gene polymorphisms on tacrolimus blood concentrations and acute graft versus host disease (GVHD) in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). MethodsThis study included adult patients who received allo-HSCT at the First Affiliated Hospital of Wannan Medical College from January 2021 to June 2022, and received postoperative treatment with tacrolimus. Tacrolimus blood levels were obtained by fully automatic chemiluminescence immunoassay analyzer. Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 allelic variants. ResultsIn a total of 50 transplant patients, 30 patients were detected with CYP3A5*3/*3 genotype, 15 patients with CYP3A5*1/*3 genotype, and 5 patients with CYP3A5*1/*1 genotype. The initial tacrolimus blood concentrations in allo-HSCT patients with CYP3A5*1/*1, *1/*3, and *3/*3 genes were 7.75, 8.61, and 10.19 ng/mL, respectively; The initial blood concentration/dose (C/D) ratios were 4.08, 4.42 and 5.66 ng/(mL·mg), respectively. The C/D ratios of allo-HSCT patients carrying CYP3A5*1/*1, *1/*3, and *3/*3 genes were 4.35 and 4.71 and 5.58, 4.19, 4.56 and 5.71 ng/(mL·mg) in the second and 3rd weeks after operation. These results showed that the blood concentration and C/D ratio of tacrolimus in patients with CYP3A5*3/*3 genotype were significantly higher than those in patients with CYP3A5*1/*3 or CYP3A5*1/*1 genotype. Moreover, the incidence of acute GVHD after allo-HSCT in patients with CYP3A5*1/*1 genotype was significantly higher than that in patients with CYP3A5*1/*3 or CYP3A5*3/*3 genotype. ConclusionsMost patients carry the mutant allele CYP3A5*3. CYP3A5 gene polymorphisms affect tacrolimus blood concentrations and acute GVHD after allo-HSCT.

Human gut microbiota-reactive DP8α Tregs prevent acute graft-versus-host disease in a CD73-dependent manner.

Graft-versus-host disease (GvHD) is a life-threatening complication frequently occurring following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since gut microbiota and regulatory T cells (Tregs) are believed to play roles in GvHD prevention, we investigated whether DP8α Tregs, which we have previously described to harbor a T cell receptor specificity for the gut commensal Faecalibacterium prausnitzii, could protect against GvHD, thereby linking the microbiota and its effect on GvHD. We observed a decrease in CD73+ DP8α Treg frequency in allo-HSCT patients 1 month after transplantation, which was associated with acute GvHD (aGvHD) development at 1 month after transplantation, as compared with aGvHD-free patients, without being correlated to hematological disease relapse. Importantly, CD73 activity was shown to be critical for DP8α Treg suppressive function. Moreover, the frequency of host-reactive DP8α Tregs was also lower in aGvHD patients, as compared with aGvHD-free patients, which could embody a protective mechanism responsible for the maintenance of this cell subset in GvHD-free patients. We also showed that human DP8α Tregs protected mice against xenogeneic GvHD through limiting deleterious inflammation and preserving gut integrity. Altogether, these results demonstrated that human DP8α Tregs mediate aGvHD prevention in a CD73-dependent manner, likely through host reactivity, advocating for the use of these cells for the development of innovative therapeutic strategies to preclude aGvHD-related inflammation.

CD34 Chimerism Directed Donor Lymphocyte Infusion With or Without Azacitidine Results in Reduced Relapse and Superior Overall Survival When Full Donor Chimerism is Achieved in Allogeneic Stem Cell Transplant Recipients With Acute Myeloid Leukaemia/Myelodysplastic Syndrome

BackgroundRegular monitoring of CD34 donor chimerism (DC) is a highly sensitive method of predicting relapse in allogeneic stem cell transplant (alloHSCT) recipients with AML/MDS. A fall of CD34 DC below 80% is an indicator of ensuing relapse. There are limited studies assessing the efficacy of donor lymphocyte infusion (DLI) triggered by mixed CD34 DC (MDC), in addressing falling chimerism. Patients and methodsWe performed a retrospective analysis of consecutive alloHSCT patients between 2012 to 2023 who received DLI (with or without azacitidine) for CD34 MDC without morphologic relapse at the time of infusion. ResultsOf the 21 patients with follow up CD34 DC available, 14 (66.7%) achieved CD34 full donor chimerism (FDC) following DLI with or without azacitidine (dli-FDC), while 7 (33.3%) did not (dli-MDC). The 2-year cumulative incidence of relapse (CIR) was significantly lower in dli-FDC compared to dli-MDC (21.4% vs. 85.7%, P < 0.001), correlating with superior overall survival (OS; median years not reached vs. 0.67 years [95% CI, 0.58-ND], P < .001). Rates of grade II-IV acute GVHD post-DLI were 14.9%, and moderate-severe cGVHD was 42.8% in the dli-FDC group. The 5-year nonrelapse mortality (NRM) of the dli-FDC group was 7.1% following DLI. ConclusionOur study shows the restoration of CD34 FDC post-DLI is associated with reduced relapse and improved overall survival, with low NRM.

Reduced Dose of Post-Transplant Cyclophosphamide with Tacrolimus for the Prevention of Graft-versus-Host Disease in HLA-Matched Donor Peripheral Blood Stem Cell Transplants: A Prospective Pilot Study.

PTCY 50 mg/kg/day on days +3/+4 is an excellent strategy to prevent GVHD. However, its use is associated with adverse outcomes such as delayed engraftment, increased risk of infection, and cardiac complications. This pilot study evaluates the efficacy and toxicity of a reduced dose of PTCY (40 mg/kg/day) combined with tacrolimus in 22 peripheral blood HLA-matched alloHSCT patients. At day +100, the cumulative incidences of grade II-IV and III-IV acute GVHD were 18.2% and 4.5%, respectively. No grade IV acute GVHD or steroid-refractory disease was observed. The cumulative incidences of all-grade and moderate-severe chronic GVHD at 1-year were 11.4% and 6.4%, respectively. No patient died from transplant-related complications. Two-year OS and RFS were 77.1% and 58.3%, respectively. All patients engrafted, with neutrophil and platelet recovery occurring at a median of 15 (IQR 14-16) and 16 days (IQR 12-23), respectively. The cumulative incidences of bloodstream bacterial infections, polyomavirus BK hemorrhagic cystitis, HHV6 reactivation, CMV reactivation, and fungal infections were 13.6%, 9.1%, 9.1%, 4.6%, and 6%, respectively. Only one early cardiac event was observed. These results suggest that PTCY 40 mg/kg/day on a +3/+4 schedule provides adequate immunosuppression to allow for engraftment and prevent clinically significant GVHD with a low toxicity profile.

CD19 chimeric antigen receptor-T cells as bridging therapy to allogeneic hematopoietic cell transplantation improves outcome in patients with refractory/relapsed B-cell acute lymphoblastic leukemia

Chimeric antigen receptor (CAR)-T cell therapy has been confirmed improving remission rates in refractory patients or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). However, the added benefits of undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T therapy remain a subject of debate. In this research we investigated the efficiency and long-term outcomes of CD19 CAR-T bridging with allo-HSCT in R/R B-ALL patients. A total of 42 patients were brought into the cohort studies. Our findings revealed that patients who appected CAR-T followed by HSCT had a 1-year overall survival (OS) rate of 70 % and a 1-year leukemia-free survival (LFS) rate of 95 %. Moreover, patients who underwent this combined treatment had higher OS and LFS rates compared to those who received CAR-T therapy alone. In conclusion, the results of this clinical trial provide compelling evidence for the safety and efficacy of using CAR-T therapy as a bridging strategy to allo-HSCT in patients with R/R B-ALL.

Real-World Safety and Effectiveness of Letermovir in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: Final Results of Post-Marketing Surveillance in Japan.

Cytomegalovirus (CMV) is a common opportunistic infection after allogenic hematopoietic stem cell transplantation (allo-HSCT). Letermovir, an inhibitor of CMV DNA terminase, is approved for CMV prophylaxis in allo-HSCT patients. We report the final results of post-marketing surveillance of letermovir in Japan. The case report forms were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation using data elements in the Transplant Registry Unified Management Program and sent to individual HSCT centers to decrease the burden of reporting. Hematopoietic stem cell transplantation patients who received letermovir between May 2018 and May 2022 were registered. Data collected included physician-assessed adverse events/adverse drug reactions and clinical effectiveness (development of CMV disease, CMV antigen status, and use of preemptive therapy). A total of 821 HSCT patients were included in the safety analyses. Adverse drug reactions occurred in 11.33% of patients, with serious adverse drug reactions in 3.05%. The five most common adverse drug reactions were nausea (1.58%), renal impairment (1.46%), and acute graft versus host disease, CMV test positive, and hepatic function abnormal (0.61% each). A total of 670 patients were eligible for effectiveness analyses. Among these patients, 16.57% and 28.66% required preemptive therapy through week 14 and week 48, respectively. In addition, relatively few patients developed CMV disease throughout the follow-up period (1.34% at week 14 and 3.85% at week 48). This final analysis of post-marketing surveillance with up to 48 weeks follow-up period in Japan provides further evidence supporting the safety profile and effectiveness of letermovir for CMV prophylaxis in patients undergoing allo-HSCT in real-world settings.

CD56bright NK cell expansion correlated with EBV reactivation control post allogeneic hematopoietic stem cell transplantation.

Natural killer (NK) cells are equipped with anti-Epstein-Barr virus (EBV) function, however, whether EBV infection will affect NK cells reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To identify the characteristics of NK cells, we prospectively enrolled 11 patients who occurred EBV reactivation post allo-HSCT and 11 patients without EBV infection as control. We found that that EBV infection induced the expansion of CD56bright and NKG2A+KIR- NK subsets,and decreased the cytotoxicity function of NK cells. The frequency of NKG2A+KIR- NK cells were higher in patients who progressed into post-transplant lymphoproliferative disorder (PTLD) than EBV viremia patients, which also correlated with decreased proliferation and cytotoxic function. By screening the activation receptors of NK cells, we found the DNAM-1+CD56bright NK cells is significantly increased after EBV stimulation, further we demonstrated that DNAM-1 is essential for EBV induced NK cells activation as the cytokine release against EBV-transformed lymphoblastoid cell lines(EBV-LCLs) of CD56bright NK cells were significantly decreased after DNAM-1 blockade. NK cells infusion suppressed the progression of EBV-related tumor mice model. A prospective cohort indicated that old donor age was an independent risk factor for EBV infection. Rapid CD56bri expansion and high expression of DNAM-1 on CD56bri NK cells in response to EBV reactivation correlated with rapid EBV clearance post allo-HSCT in patients with younger donors. In summary, our data showed that high expression of DNAM-1 receptors on NK cell may participate protective CD56bri NK cells response to EBV infection after allo-HSCT.

Allogeneic stem cell transplantation in multiple myeloma: is there still a place?

The introduction of novel agents dramatically improved response and outcomes of multiple myeloma (MM) and led to a sharp decline in the use of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Thus, recent guidelines do not recommend anymore allo-HSCT as consolidation in the first-line treatment of newly diagnosed MM, even in high-risk patients. In a relapsed/refractory setting, allo-HSCT is not routinely recommended but should only be performed within clinical trials in young and high-risk patients. Nonetheless, allo-HSCT still represents a potential curative approach that has been used for decades in the treatment of MM and plasma cell neoplasms with favorable results and may still represent a treatment option for carefully selected patients. Despite that promising results were obtained with CAR T-cell therapies and bispecific antibodies in triple- and penta-exposed/refractory MM, these patients will inevitably relapse. To date, less is known about outcomes of allo-HSCT in patients exposed to novel immunotherapeutic drugs. Therefore, allo-HSCT could represent a reasonable treatment choice for younger and high-risk patients who have relapsed after CAR T-cell therapies and bispecific antibodies as well as an alternative for patients not eligible to these treatments and in those countries where immunotherapies are not yet available. In the choice of conditioning, reduced intensity conditioning regimens are currently recommended for the lower toxicity and mortality. Moreover, the use of alternative donors, particularly haploidentical, has progressively increased in last years with results comparable to full matched donors. Finally, post-transplantation maintenance strategies are encouraged whenever feasible.

The Application Study of Voriconazole and Its Metabolites Concentration Monitoring in Allogeneic Hematopoietic Stem Cell Transplantation Patients

To explore the application value of simultaneous monitoring of voriconazole (VRCZ) and voriconazole N-oxide (VNO) in efficacy and safety of VRCZ in the prevention and treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients before engraftment (i.e., days +1 to +30 after transplantation). The influencing factors of VRCZ, VNO concentration and MR (CVNO/CVRCZ) and the difference of VRCZ in the prevention and treatment of fungal infection and liver and kidney injury were analyzed. The receiver operating characteristic curve (ROC) was used to analyze the differences (the corresponding to the maximum of the Youden index on the curve was set as the cut-off value) to confirm the critical value. The factors affecting VRCZ concentration (CVRCZ), VNO concentration (CVNO) and MR were patient weight, VRCZ daily dose, and transplantation type (all P < 0.05). CVRCZ and CVNO in the effective group were higher than those in the ineffective group (P < 0.001), the opposite of MR (P < 0.001); the liver and renal injury group had lower MR than the normal group (P < 0.05). ROC showed that CVRCZ, C VNO and MR had important value in predicting VRCZ in the prevention and treatment of invasive fungal infections in allo-HSCT patients before engraftment, and their cutoff of concentrations were 0.95 μg/ml, 1.35 μg/ml and 1.645, respectively (AUC: 0.9677, 0.7634, 0.9564). CVRCZ and MR can assist in indicating liver ［cutoff values: 0.65 μg/ml, 1.96 (AUC: 0.5971, 0.6663)］ and renal injury ［cutoff values: 0.95 μg/ml, 1.705 (AUC: 0.6039, 0.6164)］. The great value of simultaneous monitoring of VRCZ, VNO and MR can predict in the efficacy and safety of VRCZ in allo-HSCT patients before engraftment. The prediction accuracy of CVRCZ was higher than that of MR, followed by that of CVNO. Increased CVRCZ and decreased MR increase the risk of liver and kidney injury.

Systemic inflammatory autoimmune disease before allogeneic hematopoietic stem cell transplantation is a risk factor for death in patients with myelodysplastic syndrome or chronic myelomonocytic leukemia.

Myelodysplastic syndrome (MDS) is well known to be complicated by systemic inflammatory autoimmune disease (SIADs). However, it remains unclear how the prognosis after allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS is impacted by SIADs that occur before allo-HSCT. Therefore, we hypothesized that SIADs before allo-HSCT may be a risk factor for negative outcomes after allo-HSCT in patients with MDS. We conducted a single-center, retrospective, observational study of sixty-nine patients with MDS or chronic myelomonocytic leukemia who underwent their first allo-HCT. Fourteen of the patients had SIADs before allo-HSCT. In multivariate analysis, the presence of SIADs before allo-HSCT was an independent risk factor for overall survival (HR, 3.36, 95% confidence interval: 1.34-8.42, p = 0.009). Endothelial dysfunction syndrome was identified in five of 14 patients with SIADs who required immunosuppressive therapy or intensive chemotherapy, and notably, all patients with uncontrollable SIADs at allo-HSCT developed serious endothelial dysfunction syndrome and died in the early phase after allo-HSCT. The development of SIADs in the context of MDS is thought to reflect the degree of dysfunction of hematopoietic cells in MDS and suggests a higher risk of disease progression. In addition, MDS patients with SIADs before allo-HSCT are considered to be at higher risk of endothelial dysfunction syndrome because of preexisting vascular endothelial dysfunction due to SIADs. In conclusion, SIADs before allo-HSCT constitute an independent risk factor for death in MDS patients undergoing allo-HSCT.

Fusarium, Scedosporium and Other Rare Mold Invasive Infections: Over Twenty-Five-Year Experience of a European Tertiary-Care Center.

Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem cell transplant recipients, hematological malignancies patients, solid organ transplant recipients and intensive care unit patients. In contrast with invasive aspergillosis and mucormycosis, other hyalohyphomycoses and phaeohyphomycoses remain poorly known. We conducted a retrospective analysis of the clinical, biological, microbiological and evolutive features of 92 IMD having occurred in patients in our tertiary-care center over more than 25 years. A quarter of these infections were due to multiple molds. Molds involved were Fusarium spp. (36.2% of IMD with a single agent, 43.5% of IMD with multiple agents), followed by Scedosporium spp. (respectively 14.5% and 26.1%) and Alternaria spp. (respectively 13.0% and 8.7%). Mortality at day 84 was higher for Fusarium spp., Scedosporium spp. or multiple pathogens IMD compared with Alternaria or other pathogens (51.7% vs. 17.6%, p < 0.05). Mortality at day 84 was also influenced by host factor: higher among hematology and alloHSCT patients than in other patients (30.6% vs. 20.9% at day 42 and 50.0% vs. 27.9% at day 84, p = 0.041). Better awareness, understanding and treatments are awaited to improve patient prognosis.

Abstract CT242: Phase 2b study of alloHSCT patients receiving RGI-2001, an NKT cell activator, demonstrates safety and protection from acute GVHD, correlating with increased NKT cell number in patient blood

Abstract Background: Allogeneic hematopoietic stem cell transplant (alloHSCT) has potentially curative outcomes for patients with certain hematologic malignancies but also has toxicity due to graft-versus-host-disease (GVHD), where donor-derived T cells attack the immune suppressed recipient, leading to significant mortality and morbidity. Natural killer T (NKT) and T-regulatory (Treg) cell levels in the donor product or in the recipient associate with protection from acute GVHD (aGVHD) and thus may represent therapeutic targets. RGI-2001 is a liposomal formulation of an NKT cell agonist, expanding both NKT and Tregs in animal models, resulting in prevention of aGVHD without compromising general immune function. Phase 1/2a studies of RGI-2001 demonstrated safety and potential efficacy in reducing aGVHD in alloHSCT using single doses. In this Phase 2b study, RGI-2001 was given weekly x 6 doses (100 ug/kg) in combination with standard GVHD prophylaxis. Results: RGI-2001 was given to 48 subjects undergoing matched (8/8) alloHSCT. Control data from the CIBMTR (n=207) was obtained and used as comparison. Patients receiving RGI-2001 did not have any serious infusion reactions, related serious adverse events, cases of cytomegalovirus disease, post-transplant lymphoproliferative disease, or graft failure. Compared to the CIBMTR group, the RGI-2001 group demonstrated lower grade II-IV aGVHD (day 180) and higher aGHVD-free survival (GFS) and overall survival. Relapse and cGVHD rates were similar between the groups. In addition, the number of NKT cells in the blood of the RGI-2001 group correlated with specific outcomes within this group. Grade II-IV at day 100 or d180 or GFS d180 occurred in &amp;gt;8 patients, and the mean NKT numbers at day 28 for these patients is lower than patients without occurrence. The number and percentages of Tregs, CD4+ T cells, CD8+ T cells, and NK cells did not correlate with any clinical endpoints. Conclusions: RGI-2001 given weekly x 6 doses is safe and well tolerated. Compared to matched cohort, the RGI-2001 cohort had decreased aGVHD and increased overall survival, suggesting that RGI-2001 could be added to alloHSCT regimens to reduce aGVHD while not affecting overall immune responses against infection and tumor relapse. Future studies will focus on optimizing dosage based on blood levels of NKT cells, elucidating the mechanisms of actions of RGI-2001, and identifying potential biomarkers of response. Citation Format: Jack D. Bui, Calvin Lee, Christine Caron, Dana Lee, Zachariah DeFilipp, Yi-Bin Chen. Phase 2b study of alloHSCT patients receiving RGI-2001, an NKT cell activator, demonstrates safety and protection from acute GVHD, correlating with increased NKT cell number in patient blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT242.

Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients.

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P=.002) compared with the control group. Additionally, the time duration of CMV reactivation (P=.001) and bacterial infection rate (P=.013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P=.006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.