Allogeneic Stem Cell Transplant Patients Research Articles

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.

Coordinating expensive, difficult-to-obtain prophylactic medications before discharge: A quality improvement project in an academic stem cell transplant unit.

337 Background: Infections are a significant source of morbidity/mortality in allogeneic stem cell transplant (alloSCT) patients and antimicrobial prophylaxis has reduced deaths. Between July 2022 and July 2023, 21% of new alloSCT recipients were discharged from UVA Medical Center without posaconazole or isavuconazonium +/- letermovir in-hand at the time of hospital discharge necessitating daily oral drug administration at the infusion center until medication could be obtained. This led to excess cost for UVA, burden on clinic staff, missed doses, and patient frustration. We sought to decrease the number of new alloSCT recipients discharged without appropriate prophylaxis in-hand from 21% to 10% by November 2024. Methods: Per the 2023 ASCO Quality Training Program associated with this project, a Model for Improvement and Plan Do Study Act (PDSA) methodology was utilized. The population included alloSCT patients with new prescriptions (Rxs) for posaconazole or isavuconazonium +/- letermovir. The outcome measure was percentage of newly discharged alloSCT patients requiring oral prophylaxis at the infusion center. The process measure was Time to Affordable Medication (TAM) defined as days from Rx prior-authorization (PA) request to paid claim with an affordable copay (defined as a copay the patient was able/willing to pay, including free drug approvals or assistance programs). The counter measure consisted of initiating the Rx PA process 10 days prior to planned admission via a discharge test Rx order set instead of waiting until admission. This standardized process allowed for clearer communication and more time for pharmacy technicians to process the Rx for PA, copays, free drug applications, and pharmacy logistics. Upon admission, the official Rx was released to the discharge pharmacy. If Rx shipment was required, this was set up the week prior to discharge. An I-chart (3-sigma) statistical process control (SPC) chart was used to assess the intervention. Results: The baseline TAM was assessed retrospectively in 22 Rxs over 3 months prior to intervention for a mean of 7.5 days. PDSA cycle 1 was implemented Nov. 2023. TAM for the first 35 Rxs was 4.3 days and the SPC upper control limit decreased from 26.3 days to 13.3 days demonstrating overall markedly decreased variation despite data from early 2024 having greater variability due to new insurance deductibles. Rxs requiring 10 or more days were due to free drug application processes. Importantly, no newly discharged alloSCT patients have required drug administration at the infusion center. Conclusions: PDSA #1 resulted in a decrease in TAM of 3.2 days, decreased variation in the process, and no patients discharged without drug in hand. Since we have already surpassed our aim, next steps include demonstrating sustainability of the process and a survey requesting feedback to identify balance measures.

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.

NPP-669, a prodrug of cidofovir, is highly efficacious against human adenovirus infection in the permissive Syrian hamster model.

Human adenoviruses can cause serious, disseminated infections in immunocompromised patients. For pediatric allogeneic stem cell transplant patients, the case fatality rate can reach 80%. Still, there is no available antiviral drug that is specifically approved by the Food and Drug Administration for the treatment of adenovirus infections. To fill this pressing medical need, we have developed NPP-669, a prodrug of cidofovir with broad activity against double-stranded DNA viruses, including adenoviruses. Here, we report on the in vivo anti-adenoviral efficacy of NPP-669. Using the immunosuppressed Syrian hamster as the model, we show that NPP-669 is highly efficacious when dosed orally at 1 mg/kg and 3 mg/kg. In a delayed administration experiment, NPP-669 was more effective than brincidofovir, a similar compound that reached Phase III clinical trials. Furthermore, parenteral administration of NPP-669 increased its efficacy approximately 10-fold compared to oral dosing without apparent toxicity, suggesting that this route may be preferable in a hospital setting. Based on these findings, we believe that NPP-669 is a promising new compound that needs to be further investigated.

Identifying risk factors for severe omicron infection in allogeneic hematopoietic stem cell transplant recipients with hematologic malignancies.

In December 2022, a large-scale epidemic occurred in China due to Omicron variant of SARS-CoV-2. This study explored risk factors for Omicron infection in transplant recipients at our institution and investigated the factors influencing the severity of SARS-CoV-2 Omicron infection among recipients of allo-HSCT. This single-center study investigated totally 63 allogeneic hematopoietic stem cell transplant patients infected with Omicron variant at the Beijing GoBroad Boren Hospital Transplant Center during December 2022 and analyzed their risk factors. The study included 63 allogeneic hematopoietic stem cell transplant patients who developed Omicron infection. There were 34 mild and 29 moderate to severe cases. Their median age was 22 years (range, 1-65 years), with the male-to-female ratio being 1:1.1. Acute myeloid leukemia (53.97%), acute lymphoblastic leukemia (42.86%), and non-Hodgkin lymphoma (3.17%) were underlying diseases. The median time between HCT and Omicron infection was 8.45 months. Significant predictive factors for moderate to severe Omicron infection included older age (p < .0001), cGVHD (p = .0195), concurrent bacterial infection (p < .0001), low absolute lymphocyte count (p = .026), low CD4/CD8 ratio (p = .0091), high CRP (p < .0001), high serum ferritin (p = .0023), high D-dimer (p < .0001), low CD4 absolute count (p = .0057), and low B-cell absolute count (p = .0154). A moderate to high HCT-CI score tended to be associated with moderate to severe infection (p = .0596). This study indicates that risk factors for severe Omicron infection include certain clinical characteristics, such as age, cGVHD, and inflammatory response.

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.

Comparison of intermittent intravenous tacrolimus to continuous tacrolimus in adult allogeneic stem cell transplant recipients.

Introduction: Initial continuous intravenous (CIV) tacrolimus (0.03 mg/kg/day based on ideal body weight [IBW]) has been favored for graft versus host disease (GVHD) prevention in allogeneic stem cell transplant patients due to the consistent, steady-state degree of immunosuppression; however, this method poses many logistical challenges. We implemented intermittent (IIV) tacrolimus at a starting dose of 0.015 mg/kg IBW twice daily over 4 h. To our knowledge this is the first retrospective comparison of CIV to IIV tacrolimus. Objectives: The primary objective was to evaluate the safety of IIV tacrolimus in comparison to CIV with respect to nephrotoxicity and neurotoxicity. The secondary objectives were to compare the incidence of grade II-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) at day +180, outcomes including relapse and overall survival, cell engraftment, and reactivation of cytomegalovirus and Epstein-Barr virus. Methods: This retrospective, single-center review evaluated adults who received an allogeneic stem cell transplant patients between January 1, 2020, and December 31, 2022. Results: Fifty-one unique patients were eligible for evaluation - 28 in the IIV cohort and 23 in the CIV group. The number of patients who developed nephrotoxicity and neurotoxicity were comparable between groups with no significant differences noted. No severe neurotoxicity was identified in either population. Secondary objectives revealed no significant difference in GVHD incidence or survival outcomes. Conclusion: IIV tacrolimus is comparable to CIV in terms of safety while also maintaining similar outcomes at day +180. IIV is a safe and feasible alternative to CIV in adult allogeneic stem cell transplant recipients.

Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes in Allogeneic Stem Cell Transplantation Patients with Early Coronavirus Disease 2019 Infection

Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection, with a median time to diagnosis of 100 days post-transplantation. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% confidence interval [CI], 1.26 to 13.05; P = .019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; P = .001). This was attributed mainly to higher nonrelapse mortality (NRM) among early COVID-19 patients (P = .042). Allogeneic HSCT recipients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; P = .021), CD3+CD4+ cell (95% CI, -105.35 to -11.59; P = .042), CD3+CD8+ cell (95% CI, -324.55 to -57.13; P = .038), and CD3-CD56+ cell (95% CI, -193.51 to -47.31; P = .014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impaired immune reconstitution post-transplantation.

A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies—its utility during respiratory virus pandemics

ObjectivesIn hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematologic malignancies. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent; however, its use is not straightforward. Inhaled pentamidine is the recommended second-line agent; however, aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. We evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic hematopoietic stem cell transplantation recipients and patients with hematologic malignancies during COVID-19. ResultsA total of 202 unique patients who received 239 courses of IV pentamidine, with a median of three doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The most common reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients developed an infusion reaction or experienced adverse effects from IV pentamidine. ConclusionsPentamidine administered IV monthly is safe and effective.

Clinical Study of Allogeneic Hematopoietic Stem Cell Transplantation Patients with Co-Reactivation of Cytomegalovirus and Epstein-Barr Virus

To explore the clinical characteristics and risk factors of cytomegalovirus(CMV) and Epstein-Barr virus(EBV) co-reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its influence on prognosis. The clinical data of 222 patients who received allo-HSCT from January 2015 to December 2020 were collected, and the patients were divided into groups according to the occurrence of CMV and EBV infection. Kaplan-Meier method was used for survival analysis, and Cox proportional hazard regression model was used to analyze the risk factors of co-reactivation of CMV and EBV. After allo-HSCT, there were 30 patients with co-reactivation of CMV and EBV (CMV++EBV+ group), 101 patients with CMV viremia (CMV+ group), 149 patients with EBV viremia (EBV+ group), and 28 patients with CMV and EBV inactivation (CMV-+ EBV- group). Compared with the other groups, the incidence of acute graft-versus-host disease (aGVHD) and hemorrhagic cystitis (HC) was higher in CMV++ EBV+ groups (53.3% vs 42.6%, 36.9%, 17.9%, P < 0.001; 36.7% vs 32.7%, 22.8%, 10.7%, P =0.042). The incidence of post-transplant lymphoproliferative disease (PTLD) in CMV++ EBV+ group was similar to CMV+ group and EBV+ group (3.3% vs 3.0%, 3.4%, P =0.811). Univariate and multivariate analysis showed that the persistent time of CMV and EBV after transplantation were independent risk factors for co-reactivation of CMV and EBV. Compared with the other groups, the 2-year overall survival (OS) rate and 2-year disease-free survival (DFS) rate of patients in CMV++EBV+ group were lower (46.7% vs 74.9%, 83.4%, 71.4%, P < 0.001; 46.7% vs 70.9%, 79.5%, 69.9%, P =0.002), and 2-year non-recurrence mortality (NRM) was higher (48.2% vs 22%, 13.6%, 18.7%, P <0.001). The persistent time of CMV and EBV after transplantation are independent risk factors for patients with co-reactivation of CMV and EBV. Patients with co-reactivation of CMV and EBV had lower OS and DFS rate and higher NRM, suggesting that the clinical prognosis of the patients are worse.

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.

Immunogenicity and Tolerance of BNT162b2 mRNA Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Patients.

Allogeneic hematopoietic stem cell transplantation (ASCT) induces acquired immunodeficiency, potentially altering vaccine response. Herein, we aimed to explore the clinical tolerance and the humoral and cellular immune responses following anti-SARS-CoV-2 vaccination in ASCT recipients. A prospective, non-randomized, controlled study that involved 43 ASCT subjects and 31 healthy controls. Humoral response was investigated using the Elecsys® test anti-SARS-CoV-2. Cellular response was assessed using the QFN® SARS-CoV-2 test. The lymphocyte cytokine profile was tested using the LEGENDplex™ HU Th Cytokine Panel Kit (12-plex). Adverse effects (AE) were observed in 69% of patients, encompassing pain at the injection site, fever, asthenia, or headaches. Controls presented more side effects like pain in the injection site and asthenia with no difference in the overall AE frequency. Both groups exhibited robust humoral and cellular responses. Only the vaccine transplant delay impacted the humoral response alongside a previous SARS-CoV-2 infection. Noteworthily, controls displayed a Th1 cytokine profile, while patients showed a mixed Th1/Th2 profile. Pfizer-BioNTech® anti-SARS-CoV-2 vaccination is well tolerated in ASCT patients, inducing robust humoral and cellular responses. Further exploration is warranted to understand the impact of a mixed cytokine profile in ASCT patients.

Recombinant mannan-binding lectin magnetic beads increase pathogen detection in immunocompromised patients

The microbiological diagnosis of infection for hematological malignancy patients receiving chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients relies primarily on standard microbial culture, especially blood culture, which has many shortcomings, such as having low positive rates, being time-consuming and having a limited pathogenic spectrum. In this prospective observational self-controlled test accuracy study, blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF) samples were collected from chemotherapy or allo-HSCT patients with clinical symptoms of infections who were hospitalized at Peking University First Hospital. Possible pathogens were detected by the method based on recombinant mannan-binding lectin (MBL) magnetic bead enrichment (M1 method) and simultaneously by a standard method. The analytical sensitivity of M1 method was close to that of standard culture method. Besides, the turn-around time of M1-method was significantly shorter than that of standard culture method. Moreover, the M1 method also added diagnostic value through the detection of some clinically relevant microbes missed by the standard method. M1 method could significantly increase the detection efficiency of pathogens (including bacteria and fungi) in immunocompromised patients.Key points• The detection results of M1-method had a high coincidence rate with that of standard method• M1 method detected many pathogens which had not been found by standard clinic method

Impaired Immune Reconstitution and Worse Survival Outcomes Among Allogeneic Stem Cell Transplant Patients with Early COVID-19 Infection

Impaired Immune Reconstitution and Worse Survival Outcomes Among Allogeneic Stem Cell Transplant Patients with Early COVID-19 Infection

Role of Outpatient Physical Medicine and Rehabilitation in a Multidisciplinary Prehabilitation Program for Older Adults Before Allogeneic Hematopoietic Stem Cell Transplant.

Physical rehabilitation is increasingly incorporated throughout the allogeneic hematopoietic stem cell transplant journey for older adults. This study aimed to describe physical medicine and rehabilitation-related diagnoses, exercise barriers, and management recommendations for older adults before allogeneic hematopoietic stem cell transplant. Fifty physical medicine and rehabilitation consults as part of the Enhanced Recovery-Stem Cell Transplant multidisciplinary prehabilitation program at a comprehensive cancer center were retrospectively reviewed. Many physical medicine and rehabilitation-related diagnoses (173), exercise barriers (55), and management recommendations (112) were found. Common diagnoses were musculoskeletal dysfunction (more commonly back, shoulder, then knee) ( n = 39, 23%) and fatigue ( n = 36, 21%). Common exercise barriers were also musculoskeletal dysfunction (more commonly back, knee, then shoulder) (total n = 20, 36%) and fatigue ( n = 20, 36%). Most patients ( n = 32, 64%) had one or more exercise barriers. Common physical medicine and rehabilitation management recommendations were personalized exercise counseling ( n = 37, 33%), personalized nutrition management ( n = 19, 17%), body composition recommendations ( n = 17, 15%), medications ( n = 15, 13%), and orthotics and durable medical equipment ( n = 8, 7%). Routine physical medicine and rehabilitation referral of older allogeneic hematopoietic stem cell transplant patients for prehabilitation resulted in the identification of many rehabilitative needs and substantial additional management recommendations. Increased early, collaborative prehabilitation efforts between physical medicine and rehabilitation and allogeneic hematopoietic stem cell transplant teams to optimize care for these patients is recommended.

Recovery of physical function, muscle mass, and quality of life in patients undergoing allogeneic hematopoietic stem cell transplantation.

This study aimed to investigate the recovery of physical function, muscle mass, and quality of life (QOL) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients 1 year after the procedure. A total of 71 patients who underwent allo-HSCT at our institution between February 2010 and June 2020, for whom a physical therapy assessment could be performed before allo-HSCT, at discharge, and 1 year after the procedure, were included. Exercise therapy during hospitalization was provided individually by a physical therapist, and exercise was self-administered after discharge. One year after allo-HSCT, handgrip strength and results of the 6-minute walk test recovered to pre-HSCT levels. However, muscle mass 1 year after allo-HSCT did not reach the pre-HSCT level. All subscales of QOL, 1 year after allo-HSCT, recovered to pre-HSCT levels, but only two of the eight subscales recovered to the national standard of 50. Multivariate analysis revealed factors associated with the recovery of physical function, muscle mass, and QOL, hemoglobin levels and albumin levels, especially among men. In contrast, factors that negatively affected recovery were age, acute graft-versus-host disease, and pre-HSCT intensity conditioning. The results suggest a potential recovery in handgrip strength, endurance, and QOL 1 year after allo-HSCT.

Cytomegalovirus Reactivation in Allogenic Haematopoietic Stem Cell Transplant Patients with Haploidentical Versus Fully Human Leukocyte Antigen Matched Donor

Objective: To determine CMV reactivation in hematopoietic stem cell transplant patients with haploidentical versus fully HLA matched donors Methodology: Retrospective Observational study was conducted at Armed Forces Bone Marrow Transplant Centre (AFBMTC) between March 2019 and October 2022. We enrolled a total of 60 consecutive patients.CMV DNA PCR analysis was carried out every week from day +14 to day +100 in order to monitor CMV reactivation during the 100-day post-transplantation period. The SaMag viral nucleic acid extraction kit (Sacace Biotechnologies, Como, Italy) was used to extract the DNA from two millilitres of blood collected in EDTA tubes. The kit's lower limit of detection for blood and serum was 5 copies/mL, while for other body fluids it was 500 copies/mL. An Applied Biosystems 7500 real-time PCR machine (Thermo Fisher Scientific, Waltham, MA) was used to conduct the PCR analysis. Result: The age range from 0.6 to 53 years ago was a median of 15±10.6. 39 patients had CMV reactivation (65%). With a range of 13 to 66 days, the median time to CMV DNAemia was 19.25 days.. Only two (3.3%) of the 39 patients received ganciclovir, while 26 (43.3%) received valganciclovir. Patients with aplastic anaemia had the highest rate of CMV infection (41%), followed by those with ALL (20.5%), AML (12.8%), and primary immunodeficiency (10.2%). A statistically significant connection between the underlying diagnosis and CMV infection. CMV infection was higher in haplo identical transplant recipients (66.6%) than in completely matched recipients (33.3%) and was statistically significantly. Sadly, 14 people passed away, yielding a mortality rate of 23.3%. Primary graft failure was the most frequent cause of mortality, resulting in neutropenic sepsis in 6 patients (42.85%), but 3 of these patients also had CMV reactivation. The rate of overall survival (OS) was found to be 76.7%. The rate of disease-free survival (DFS) was estimated at 71.7%. Notably, neither OS nor DFS in our analysis showed a statistically significant connection with CMV infection. Conclusion: The findings demonstrated a statistically significant association between haploidentical transplantation and CMV reactivation, with higher rates observed in the haploidentical group compared to fully matched recipients. Various factors, including underlying diagnosis, conditioning regimen, and GVHD prophylaxis, were also found to be correlated with CMV reactivation. However, while CMV reactivation was associated with specific factors, it did not impact overall survival or disease-free survival in the study population.

Venous Thromboembolism in Hematopoietic Stem Cell Transplantation

Background: Venous thromboembolism (VTE) is an underappreciated complication seen amongst allogeneic and autologous hematopoietic stem cell transplant (HSCT) patients and a major cause of morbidity and mortality. Despite these challenges, VTE in HSCT remains understudied, with a paucity of established guidelines on thrombosis surveillance, prevention, and treatment. Balancing risk of bleeding and thrombosis is particularly challenging as HSCT patients are concurrently pancytopenic and coagulopathic. We aimed to describe the incidence, predictors, and adverse events of VTE amongst patients at 90 days post-HSCT. Methods: We conducted a retrospective cohort study of adult patients, age &amp;gt;18-years-old, who underwent HSCT for a hematological malignancy between January 1, 2011 and December 31, 2021 at a tertiary care centre in Canada. Patients were followed from transplant until Day 90 post-transplant, or death. Baseline, transplant, laboratory, and cancer characteristics were analyzed. Results: Four Hundred and Seventy Six (476) HSCT patients were included (age range 18 - 74), 285 (59.9%) of our patients were male, and 191 (40.1%) were female. Three Hundred and Seventeen (317) (66.6%) patients underwent autologous transplant, and 159 (33.4%) patients underwent allogeneic transplant ( Table 1). Forty Seven (47) patients (9.8%) suffered from VTE within 90 days post-HSCT; 74.5% were catheter related. 9.43% of allogeneic, versus 10.09% autologous patients were diagnosed with VTE (p=0.820). 11.9% of allogeneic, versus 4.1% of autologous patients (p=0.001) suffered from bleed unrelated to anticoagulation. There was significant association of VTE post-HSCT with history of unprovoked DVT (p = 0.026), previous treatment with steroids (p = 0.032), infectious complications (including bacteremia (p = 0.025), and skin and soft tissue infection (p &amp;lt; 0.001)), use of peripherally-inserted central catheters (PICCs (p &amp;lt;0.001), left-sided CVC placement (p = 0.007), second central venous line insertion (due to complications from the first) (p &amp;lt; 0.001), and blocked or malfunctioning central venous catheter (p = 0.003). There was no significant association of VTE post-HSCT with transplant graft (autologous versus allogeneic), underlying hematological malignancy, age, BMI, or sex. Mortality rate at 90 days amongst VTE patients was 14.89%, versus 3.27% in non-VTE patients (p &amp;lt; 0.001) ( Figure 1). Conclusion: The majority of VTE post-HSCT were catheter-related and were more frequently associated with use of PICCs. VTE post-HSCT was associated with higher mortality. VTE prophylaxis or active surveillance could be considered in patients with the above-mentioned risk factors balancing the risk of bleeding, particularly in allogeneic stem cell transplant patients, and those who are concurrently thrombocytopenic.

Statin Use and Its Effects on Survival Outcomes and Rates of Gvhd in Allogeneic Stem Cell Transplant Patients: Results from Real-World Cohorts

Introduction: The effect of statin use in allogeneic stem cell transplant remains unclear. There have been conflicting results in studies examining the impact of statins on engraftment, graft-versus-host-disease, survival, and long-term outcomes in stem cell transplant recipients. Methods: Retrospective data was extracted using the TriNetX database. The primary endpoint was overall survival at 5 years, risk of death, and graft-versus-host-disease in the two cohorts. Results: 5045 patients were identified in cohort-1 (statin cohort) and 10,181 patients were identified in cohort-2 (non-statin cohort). Table-1 shows patient characteristics at baseline. Propensity-score-matching was used to balance the two cohorts. Patient count in each group after matching was 3702 (Table-2). Overall survival was 59.32% in cohort-1 versus 48.55 % in cohort-2, with HR of 0.685 (95% CI 0.634, 0.740) in favor of cohort 1 (Figure-1). Median OS for cohort-1 was not reached versus 1593 days for cohort-2. Risk of death in cohort-1 and 2 was 0.311 and 0.4 respectively (Figure-2), with a risk difference for the death of -0.089 (95% CI, -0.110, -0.067, p-value &amp;lt;0.001), in favor of cohort-1. Risk of graft-versus-host-disease was 0.648 and 0.674 in cohort-1 and 2 respectively (Figure-3), with a risk difference of -0.026 (95% CI -0.054, 0.002, p-value 0.065), and risk ratio of 0.961 (95% CI 0.921, 1.003). Survival-probability was higher at 5 years in cohort-1 regardless of presence or absence of GVHD. Conclusions: Our retrospective analysis of a large patient cohort showed improved OS and decreased risk of death with statin use in allogeneic stem cell transplant patients, regardless of presence or absence of GVHD, even though the average total and LDL cholesterol levels were higher in statin-group. The difference in graft-versus-host-disease was not statistically significant in both cohorts, however, there was a trend towards decrease GVHD in statin-cohort. To the best of our knowledge, this is the first large database based study evaluating the effect of statin use on outcomes in patients undergoing allogeneic stem cell transplant. Phase 3 clinical trials are needed to further answer this question.

Bleeding Risk Factors in Thrombocytopenic Patients with Hematologic Malignancies

Introduction Despite prophylactic platelet transfusions, World Health Organization (WHO) grade ≥ 2 bleeding occurs in 50 to 70% of patients with hematologic malignancies and hypoproliferative thrombocytopenia secondary to therapy and/or underlying disease (Gernsheimer et al, Blood 2022). Anemia (hematocrit, HCT ≤ 25%), coagulopathy (activated partial thromboplastin time ≥ 30s, international normalized ratio ≥ 1.2), and platelet count ≤ 5000/µl were independently associated with increased risk of bleeding in the PLADO (platelet dose) trial of 1272 patients with hypoproliferative thrombocytopenia treated between 2004 to 2007 (Uhl et al, Blood 2017). Updated data on bleeding outcomes and risk of bleeding is lacking. Methods We performed a post-hoc analysis of bleeding outcomes and bleeding risk factors in 330 patients with hematologic malignancy and hypoproliferative thrombocytopenia from therapy and/or underlying disease randomized at 3 institutions to receive either tranexamic acid (TXA) or placebo in the double-blinded, multicenter American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A-TREAT) (Gernsheimer et al, Blood 2022). Patients received prophylactic platelet transfusions for a platelet count of ≤ 10,000/µl and WHO grade bleeding was assessed daily for 30 days after a platelet count ≤ 30,000/µl and study drug was started. Study drug was discontinued when platelet count was ≥ 30,000/ul for 46 hours without platelet transfusion support or until a maximum of 30 days after treatment activation, whichever came first. Red blood cell (RBC) transfusion was given according to local standard of care. Cox proportional hazards regression with time-varying covariates was used to assess the association of patient characteristics with the risk of a first major (grade 2+) bleeding event. HCT, platelet count, inpatient vs. outpatient status, steroid treatment, and fever were recorded daily. Patients were censored at the first of time of withdrawal, death, or day 30. Results WHO grade ≥ 2 bleeding occurred in 46% of patients overall with no difference between the TXA and placebo groups (TXA 44% versus placebo 47%, p=0.66). Bleeding rates were highest in allogeneic stem cell transplant patients, followed by chemotherapy, followed by autologous stem cell transplant. Overall bleeding rates by organ system showed oral and nasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%) bleeding (Table 1). WHO grade ≥ 2 vaginal bleeding occurred in 28% of patients of childbearing potential despite widespread use of hormonal suppression. In a proportional hazards regression model of time to first bleeding event, undergoing allogeneic stem cell transplant was associated with a non-significant increased hazard of bleeding vs chemotherapy (HR 1.32, 95% CI 0.92-1.89), whereas autologous transplant had significantly lower hazard of bleeding vs chemotherapy (HR 0.39, 95% CI 0.20-0.76) (Table 2). HCT &amp;lt; 21% was associated with increased bleeding risk even after adjusting for severe thrombocytopenia (HR 2.71, 29% CI 1.37, 5.36). Platelet count &amp;lt; 5000/µl was also associated with increased risk (HR 3.33, 95% CI 1.67-6.61). Inpatient status, presence of fever, and age did not significantly impact risk of first bleed. Conclusions The overall rate of WHO grade &amp;gt;2 bleeding was similar to historical literature with lower rates of gastrointestinal bleeding than previously reported (31% in PLADO). Vaginal bleeding was common despite standard use of hormonal suppression in patients of childbearing potential. Platelet count &amp;lt; 5000/µl remains a risk factor for bleeding. Regardless of platelet count, bleeding risk increased with HCT &amp;lt; 21% suggesting a red blood cell transfusion threshold higher than 21% is unlikely to mitigate bleeding. More investigation is needed on strategies to reduce bleeding in this patient population.