Stem Cell Transplantation In Patients Research Articles

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

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

Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Fanconi Anemia: Results of a Single Center with a Fludarabine-Based Conditioning Regimen

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the only curative treatment for bone marrow failure (BMF) and hematologic complications of Fanconi anemia (FA). The evolution remains affected by the toxicity, the risk of graft failure, and clonal evolution. This study aimed to identify factors affecting outcomes in FA patients after allo-HSCT. We included FA patients who underwent allo-HSCT between January 2006 and December 2021. The conditioning regimen was cyclophosphamide/fludarabine (Cy/Flu) ± rabbit anti-thymocyte globulin (ATG). Bone marrow was the stem cell source from HLA-matched related donors in all transplants. Twenty-three patients, 19 with BMF and 4 with MDS/clonal evolution, were included. The median age was 11 years (5-39 years). Five patients (22%) received serotherapy with the conditioning regimen. Engraftment occurred in all patients without severe regimen-related toxicity. The 100-day cumulative incidence (CI) of grade II-IV acute GvHD (a GVHD) and 5-year CI of chronic GvHD (cGVHD) were 17% and 32%, respectively. The 5-year CI of late secondary graft failure was 10.5%. Two patients developed clonal evolution (AML; n = 2) and one patient developed nephrotic syndrome (n = 1). The 10-year overall survival (OS) and event-free survival (EFS) were 80% and 75%, respectively. There was a trend toward a better EFS in patients aged <10 years compared to patients aged ≥10 years (100% versus 61%; p = 0.06). At the last follow-up, 18 patients were alive, and 4 expired. Causes of death were infections with refractory GVHD (n = 1), graft failure (n = 2), and renal failure (n = 1). Despite the small patient population, we show excellent outcomes, particularly for those transplanted in the first decade.

Knowledge, attitude, and perception of exercises among post-hematopoietic stem cell transplant patients: A cross-sectional study.

Exercise rehabilitation is crucial for the recovery after hematopoietic stem cell transplantation (HSCT). This study aimed to investigate knowledge, attitude, and perception (KAP) of exercise among post-HSCT patients. This cross-sectional study was conducted at Zhujiang Hospital, Southern Medical University between January 2020 and December 2022 among post-HSCT patients, using a self-designed questionnaire. A total of 192 patients were included, with the mean age of 37.90 ± 11.96 years; 116 (60.42%) reported to exercise before. The mean KAP scores were 9.22 ± 2.05 (possible range: 0-12), 43.51 ± 5.47 (possible range: 12-60) and 51.79 ± 7.45 (possible range: 15-75), respectively. Patients previously inactive in exercise exhibited significant differences in KAP scores from active patients: attitude total score, positive attitude, perception total score, willingness to exercise, aerobic exercise, breathing training (all P < .001), with a noteworthy distinction in resistance exercise (P = .018). According to structural equation modeling, perception was directly influenced by knowledge (β = 0.87, P < .001), attitude (β = 0.26, P = .007), and exercise habits (β = 3.36, P = .001), as well as indirectly by education (β = 0.44, P = .010) and knowledge (β = 0.18, P = .029). Post-HSCT patients had adequate knowledge, moderate attitude and perception of exercises, even 1 year after HSCT. Patients inactive in exercises exhibited significant differences in knowledge and exercise perception from active patients. Healthcare professionals should tailor education, target attitude, and personalize exercise plans to facilitate effective recovery post-HSCT.

Busulfan and cyclophosphamide for autologous stem cell transplantation in patients with multiple myeloma after proteasome inhibitor and/or immunomodulatory drug treatment.

High-dose melphalan at 200mg/m2 (MEL-200) is the standard conditioning regimen before autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Busulfan (BU) and cyclophosphamide (CY) can be used as alternatives when MEL is unavailable. However, most studies on BU/CY conditioning regimens were conducted before proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) were available. This non-interventional comparative cohort study compared progression-free survival (PFS) between the MEL-200 and BU/CY in patients with MM treated with PIs and/or IMIDs. A total of 137 patients were analyzed (MEL-200,113 patients; BU/CY, 24 patients). The BU/CY group had a higher rate of PI and/or IMID use and very good partial response (VGPR) or complete remission (CR) at ASCT and post-ASCT maintenance. Median PFS was 29.7 and 46.8months in the MEL-200 and BU/CY groups, respectively. In the multivariate analysis, PFS was significantly better in the BU/CY group. International Staging System Stage I and VGPR or CR at ASCT were significantly associated with longer PFS. No treatment-related mortality was observed in either group by day 100. The BU/CY conditioning regimen may be a viable alternative to the MEL-200 regimen in patients with MM who undergo ASCT after treatment with PIs and/or IMIDs.

The benefits of prophylactic defibrotide: Are the tides turning?

Veno-occlusive disease (VOD) is a life-threatening endotheliopathy that can occur after stem cell transplant (SCT). Numerous risk factors contribute to the development of VOD during SCT, and the role of prophylactic defibrotide (DF) in mitigating these risks remains unclear. We compare not only the incidence of VOD development, but also the severity of VOD and survival outcomes between patients who did and did not develop VOD and did or did not receive prophylactic DF. In this single-center retrospective study of 58 pediatric SCT patients from 2008 to 2022, we compare the demographics, risk profiles, and outcomes within three cohorts: Group 1: prophylactic DF and no VOD (n=5), Group 2: prophylactic DF and development of VOD (n=6), and Group 3: treatment DF for patients who developed VOD (n=47). Patients with VOD who did not receive prophylactic DF had higher severity classification of disease at onset (very severe 80.9% vs. 66.7%, p=.592) and at maximum severity (very severe 89.4% vs. 83.3%, p=.532), as opposed to mild, moderate, or severe categorization compared to those who did not receive prophylactic DF. Patients who developed VOD and did not receive prophylactic DF had a lower 1-year survival probability compared to those who received prophylactic DF and still developed VOD (51.1% vs. 75% alive at 1year, excluding the two subjects without adequate follow-up time, p=.266). Although, not statistically significant in our small retrospective study, there is potential overall survival and decreased VOD severity benefits of prophylactic DF.

Elevation of NT-proBNP Levels in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Patients with Endotheliopathy

Background/Objectives: Hematopoietic stem cell transplantation (HSCT) in pediatric and young adult (YA) patients can lead to endotheliopathy, such as thrombotic microangiopathy (TMA), sinusoidal obstruction syndrome (SOS), and diffuse alveolar hemorrhage (DAH). Natriuretic peptides have been studied as markers of endotheliopathy and critical illness. We hypothesized that an elevation in NT-proBNP was associated with the development of endotheliopathy (DAH, SOS, or TMA) in the first 100 days following HSCT in pediatric and YA patients. Methods: IRB-exempt status was obtained. This retrospective case–control study reviewed HSCT at our institution from 2016 to 2020. Cases were selected based on an endotheliopathy diagnosis in the first 100 days after HSCT. Cases were matched with controls. Baseline and near-event NT-proBNP levels were compared between cases and matched controls. The effect of NT-proBNP levels on developing endotheliopathy was estimated using conditional logistic regression. Results: Sixty-two patients were included (31 cases, 31 controls). Near-event NT-proBNP was significantly higher in cases compared to controls (median: 473 vs. 187 pg/mL, p = 0.03, Wilcoxon rank–sum test), in contrast to comparison in baseline NT-proBNP (median: 86 vs. 86 pg/mL, p = 0.51). After adjusting for covariates, an association between near-event NT-proBNP and odds of developing endotheliopathy did not achieve statistical significance. However, trends from most common transplant indications suggested an association between an elevated near-event NT-proBNP level and endotheliopathy, particularly in acute lymphoblastic leukemia (ALL) patients. Conclusions: NT-proBNP should be studied further as a biomarker for endotheliopathy in pediatric and YA patients undergoing HSCT. This may be particularly relevant for patients undergoing HSCT for ALL.

Proceedings of the Conference “CMV Vaccine Development—How Close Are We?” (27–28 September 2023)

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children, including sensorineural hearing loss. There is interest in developing a pre-conception vaccine that could confer protective immunity on a woman of child-bearing age, hence resulting in a reduced cCMV disease burden. Other populations, including solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients, could also benefit from CMV vaccination. To review and discuss vaccines that are in clinical development, a workshop, sponsored by the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID), was empaneled. At this workshop, correlates of protective immunity against CMV, epidemiologic features of CMV transmission, and vaccine platforms in development were reviewed. Representatives from academia, pharma, and the NIH engaged in discussion on the current state-of-the-art in CMV vaccinology. A summary of the presentations from this is provided in this report.

Beyond Awareness: Hope for a CMV Vaccine! An Introduction to the Conference, “CMV Vaccine Development—How Close Are We?” (27–28 September 2023)

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children. The major theme of this National Institute of Allergy and Infectious Diseases (NIAID) workshop, “CMV Vaccine Development—How Close Are We?”, was to report progress on the development of a pre-conception vaccine that could confer protective immunity for women of child-bearing age. Such a vaccine could result in a reduced cCMV disease burden, although other populations, including solid organ transplant and hematopoietic stem cell transplant patients, could benefit as well. To frame the compelling need for a cCMV vaccine, a keynote lecture by Dr. Megan Pesch, immediate past-president of the National CMV Foundation and a leading cCMV researcher from the University of Michigan, was given. This manuscript provides a summary of Dr. Pesch’s presentation from this workshop, which was written as the introductory conference report for the meeting.

Epidemiology of Bacteremia in Patients with Hematological Malignancies and Hematopoietic Stem Cell Transplantation and the Impact of Antibiotic Resistance on Mortality: Data from a Multicenter Study in Argentina

The epidemiology of bacteremia and the antibiotic resistance profile (ARP) of Gram-negative bacilli (GNB) in hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) patients may differ according to geographic region. In addition, multidrug-resistant organisms (MDROs) may impact mortality. This is a prospective, observational, and multicenter study. The first episodes of bacteremia in adult patients with HM or HSCT were included. The risk factors for 30-day mortality were identified. One thousand two hundred and seventy-seven episodes were included (HM: 920; HSCT: 357). GNB were isolated in 60.3% of episodes, with Enterobacterales (46.9%) and P. aeruginosa (8.5%) being the most frequent. Gram-positive cocci were isolated in 41.9% of episodes, with coagulase-negative staphylococci (19.8%) and S. aureus (10.4%) being the most frequent. MDROs were isolated in 40.2% (24.4% GNB). The ARP of GNB in patients with HM vs. HSCT was cefepime: 36.8% vs. 45.7% (p = 0.026); piperacillin–tazobactam: 31.05% vs. 45.2% (p &lt; 0.0001); carbapenems: 18.9% vs. 27.3% (p = 0.012); and aminoglycosides: 9.3% vs. 15.4% (p = 0.017), respectively. Overall mortality between patients with HM and HSCT was 17.5% vs. 17.6% (p = 0.951), respectively. The risk factors for mortality were relapsed and refractory underlying disease, corticosteroids use, respiratory source, septic shock, and GNB resistant to meropenem, while 7-day clinical response was a protective factor for survival. Bacteremia was frequently caused by GNB, with a large proportion of MDROs and a high level of antibiotic resistance, especially in patients with HSCT. Carbapenem-resistant GNB bacteremia was associated with a significant increase in mortality.

Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents

BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT.MethodsThirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy.ResultsAHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function.ConclusionAHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.

Comparative analysis of single versus tandem autologous stem cell transplantation in patients with multiple myeloma in Korea: the KMM2102 study

Tandem autologous stem cell transplantation can improve the prognosis of patients with multiple myeloma. However, the precise role of tandem transplantation remains debatable. We evaluated the clinical benefits of tandem transplantation retrospectively. Of the 655 included patients, 117 underwent tandem transplantation; the remaining were assigned to the control group. After a single transplantation, the tandem group achieved a complete remission (CR) rate of 24.8%, which increased to 46.2% after a second transplantation. The tandem group had a significantly longer median PFS than the control group in patients with International Staging System (ISS) III and high-risk cytogenetics (23.1 vs. 14.7 months, p = 0.007 for ISS III; 21.7 vs. 13.2 months, p = 0.042 for high-risk cytogenetics). The tandem group exhibited significantly superior PFS to the control group (20.3 vs. 12.6 months, p = 0.003) among patients who failed to achieve CR after a single transplantation. Tandem transplantation was associated with significantly improved PFS after adjusting for maintenance therapy in patients with ISS III, those with high-risk cytogenetics, and those who did not achieve CR after a single transplantation. Following propensity score matching, the tandem group exhibited significantly longer PFS than the control group (30.3 vs. 13.5 months, p = 0.028). Tandem transplantation should be considered in high-risk patients.

Real World Predictors, Timing, and Outcomes of Autologous Stem Cell Transplantation in Patients with Multiple Myeloma

Real World Predictors, Timing, and Outcomes of Autologous Stem Cell Transplantation in Patients with Multiple Myeloma

Maribavir use in pediatric immunocompromised hosts: A case series to talk about real-world experience

Abstract Background Cytomegalovirus (CMV) is a common infection affecting pediatric immunocompromised hosts. The treatment of CMV in solid organ (SOT) or hematopoietic stem cell transplant (HSCT) patients is challenged by the toxicities associated with antiviral therapies (myelosuppression with valganciclovir, ganciclovir and cidofovir; nephrotoxicity with foscarnet and cidofovir) and the prevalence of resistant/refractory CMV. Maribavir, a novel benzimidazole, competitively inhibits CMV UL97 protein kinase to inhibit DNA synthesis and block nuclear exit of viral particles from CMV-infected cells. It is FDA approved for use in patients at least 12 years of age and weighing at least 35 kg. The use of maribavir in pediatric patients is of interest due to its availability as an oral dosage formulation and improved side effect profile. To date, there are no pediatric case series or studies describing the use of maribavir for CMV treatment. Methods This study is a retrospective case series compiling the findings the first pediatric patients at Children’s National Hospital, DC that received maribavir. We included children who received maribavir from 01/2017 – 10/2023. Patients were included if they were on maribavir monotherapy, or combination therapy with additional anti-CMV agent(s). The medical records were reviewed for indication of medication use, viral response to therapy and side effects. Side-effects review specifically evaluated for increased LFTs, increased serum creatinine, and decreased absolute neutrophil count or factors that may contribute to early discontinuation of maribavir. Results (table) Maribavir was used in three male patients with varied conditions – including solid organ transplant (SOT), hematopoietic stem cell transplant (HSCT) and Severe Combined Immunodeficiency (SCID) s/p HSCT. Two cases had signs of CMV disease, and one had CMV viremia. All cases included documented CMV resistance (n=2) or refractory CMV (n=1) and had previously been receiving at least one antiviral with CMV activity for at least 14 days and had increasing CMV DNA-emia in the blood. None of the patients had side effects such as nephrotoxicity, liver toxicity or myelosuppression that aggravated after starting maribavir. Dosing of 400mg BID (range 12mg/kg/day to 55mg/kg/day) was used. Once started, maribavir was continued until CMV quantitative levels were undetectable for two weeks. Clearance of CMV and was achieved in all the patients on maribavir or combination of maribavir with other drugs (n=1). Duration of maribavir treatment ranged from 4.2 to 6.2 weeks. Conclusion This is the first case series describing use of maribavir in a pediatric population. In this small cohort maribavir is effective and well tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.

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.

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.

Machine learning based analysis of single-cell data reveals evidence of subject-specific single-cell gene expression profiles in acute myeloid leukaemia patients and healthy controls

Acute Myeloid Leukaemia (AML) is characterized by uncontrolled growth of immature myeloid cells, disrupting normal blood production. Treatment typically involves chemotherapy, targeted therapy, and stem cell transplantation but many patients develop chemoresistance, leading to poor outcomes due to the disease's high heterogeneity. In this study, we used publicly available single-cell RNA sequencing data and machine learning to classify AML patients and healthy, monocytes, dendritic and progenitor cells population. We found that gene expression profiles of AML patients and healthy controls can be classified at the individual level with high accuracy (>70 %) when using progenitor cells, suggesting the existence of subject-specific single cell transcriptomics profiles. The analysis also revealed molecular determinants of patient heterogeneity (e.g. TPSD1, CT45A1, and GABRA4) which could support new strategies for patient stratification and personalized treatment in leukaemia.

Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma With Deletion 17p

Despite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. The aim of this study was to evaluate real-world outcomes in patients with newly diagnosed MM (NDMM) with del(17p) undergoing upfront autologous hematopoietic stem cell transplantation (auto-HCT). We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being hematological response and measurable residual disease (MRD) status postauto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10-5 cells. One hundred and fifteen patients were included (55% male). Median age at auto-HCT was 62 years (range 34 to 83). The median del(17p) clone size was 20%, with 51 (53%) patients having clone sizes >20% and 15 (15%) patients having clone sizes >55%. Additional high-risk cytogenetic abnormalities included t(4;14) in 15 (13%) patients, t(14;16) in 8 (7%) patients, and 1q21+ in 25 (22%) patients. After induction, 10% of patients achieved ≥ CR, and 50% achieved ≥ VGPR, with 25% having MRD-negative ≥ VGPR. Post-transplant, 42% achieved ≥ CR, and 83% achieved ≥ VGPR as best response, with 55% (48/87) having MRD-negative ≥ VGPR. With a median follow-up of 31.4 months (range 3.1 to 199.1), median PFS and OS for the entire cohort were 19.9 and 71.5 months, respectively, and 5-year OS was 53%. Concurrent del(17p) and t(4;14) were associated with significantly worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. In multivariable analysis (MVA), female sex was associated with worse PFS (HR [95% CI] 2.87 [1.75 to 4.72], P < .001), while MRD negative CR post-transplant (0.35 [0.18 to 0.68], P = .002) and maintenance therapy (0.46 [0.27 to 0.77], P = 0.003) were associated with better PFS. In MVA for OS, female sex (2.22 [1.18 to 4.17], P = 0.013) and the presence of t(4;14) (2.55 [1.09 to 5.95], P = 0.030) were associated with worse OS, whereas Karnofsky Performance Status of ≥90 (0.47 [0.23 to 0.94], P = 0.034) was associated with better OS. This study affirms del(17p) as a high-risk abnormality with unfavorable outcomes despite modern therapies. The co-occurrence of del(17p) and t(4;14) was associated with particularly poor outcomes. Novel approaches are needed for this high-risk subgroup.

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.

Improving discharge times for patients admitted for allogeneic stem cell transplantation.

290 Background: Among patients admitted for allogeneic stem cell transplant (SCT) at University of Virginia (UVA) Health from 01/2022 through 12/2022, 0% were discharged by noon, even when discharge was anticipated. The discharge of SCT recipients is dynamic, impacted by events occurring throughout admission. Delays in discharge can result in patient/provider dissatisfaction, postponed admissions, additional costs, and poor utilization of healthcare resources. Methods: A multidisciplinary team of licensed providers, pharmacists, nurses and key stakeholders in the SCT program attended ASCO’s Quality Training Program in 2023, with the aim of increasing the percentage of patients discharged by noon to 20%. After review of baseline data and development of current and ideal process maps, the team distributed a survey to the department to identify perceived sources of delay. Results were corroborated with baseline data and arranged into a pareto chart and priority matrix to synthesize an action plan. The most commonly identified causes for discharge delay included: medication delivery time, complex medication issues, and delay in placing the discharge order. Results: From 10/2023 through 12/2023, the first PDSA cycle focused on anticipation of discharge and prompt placement of the discharge order, which was identified as a process measure. A discharge checklist was created via EPIC smartphrase and incorporated into daily progress notes. Data analysis demonstrated no change in the percentage of patients discharged by noon, but did show numerical improvement in the average time of discharge order placement and discharge time. The second PDSA cycle from 01/2024 through 05/2024 involved standardization of the team responsible for discharging SCT patients, with continued use of the smartphrase. Subsequently, the percentage of patients discharged by noon increased to 14.3%, with significant improvement in the time of discharge order placement and discharge time from baseline (see Table). Conclusions: Through implementation of quality improvement concepts, our team was able to improve our process measure of discharge order placement time. While we have made strides in regards to our outcome measure of percentage of patients discharged by noon, we have not met our goal yet. With continued progress and consistent auditing, we may see improvements in length of stay, bed availability, and financial burden. Future PDSA cycles are planned with an emphasis on medication delivery time. Key times during discharge for patients admitted for allogeneic stem cell transplantation. Mean Baseline PDSA 1 PDSA 2 p-value (PDSA 1 and PDSA 2) Discharge Order Time 11:46 AM 11:09 AM (p ≤ 0.304) 9:32 AM (p ≤ 0.0001) p ≤ 0.023 Discharge Time 4:20 PM 4:03 PM (p ≤ 0.559) 3:08 PM (p ≤ 0.022) p ≤ 0.239 Length of Stay (days) 26.8 25.9 (p ≤ 0.647) 26.6 (p ≤ 0.898) p ≤ 0.663 Medication Delivery Time 2:18 PM 1:00 PM (p ≤ 0.054) 12:18 PM (p ≤ 0.002) P ≤ 0.402

Stem cell transplantation in cerebrovascular accidents: A global bibliometric analysis (2000-2023).

Cerebrovascular accident (CVA) is a major global contributor to death and disability. As part of its medical management, researchers have recognized the importance of promising neuroprotective strategies, where stem cell transplantation (SCT) is thought to confer advantages via trophic and neuroprotective effects. To evaluate the current state of research on SCT in patients with CVA, assess key trends and highlight literature gaps. PubMed was screened for SCT in CVA-related articles in October 2023, for each country during the period between 2000 and 2023. Using the World Bank data, total population and gross domestic product were collected for comparison. VOSviewer_1.6.19 was used to create the VOS figure using the results of the same query. Graphs and tables were obtained using Microsoft Office Excel. A total of 6923 studies were identified on SCT in CVA, making 0.03% of all published studies worldwide. Approximately, 68% were conducted in high-income countries, with a significant focus on mesenchymal stem cells. The journal "Stroke" featured the largest share of these articles, with mesenchymal SCT having the highest rate of inclusion, followed by hematopoietic SCT. Over time, there has been a noticeable shift from in vitro studies, which assess stem cell proliferation and neurogenesis, to in vivo studies aimed at evaluating efficacy and safety. Additionally, the number of reviews increased along this approach. This bibliometric analysis provides a comprehensive guide for physicians and researchers in the field through an objective overview of research activity, and highlights both current trends and gaps. Having a potential therapeutic role in CVA, more research is needed in the future to focus on different aspects of SCT, aiming to reach a better treatment strategy and improve life quality in patients.