Allogeneic Transplant Patients Research Articles

Long-term remission with allogeneic transplant in patients with refractory/relapsed cutaneous cytotoxic T-cell lymphoma

Long-term remission with allogeneic transplant in patients with refractory/relapsed cutaneous cytotoxic T-cell lymphoma

Spike-Specific Memory B Cell Response in Hematopoietic Cell Transplantation Recipients following Multiple mRNA-1273 Vaccinations: A Longitudinal Observational Study.

Preventing SARS-CoV-2 infection is of utmost importance in allogeneic hematopoietic cell transplantation patients (allo-HCT), given their heightened susceptibility to adverse outcomes associated with SARS-CoV-2 infection. However, limited data are available regarding the immune response to COVID-19 vaccines in these subjects, particularly concerning the generation and persistence of spike-specific memory response. Here, we analyzed the spike-specific memory B cells in a cohort of allo-HCT recipients vaccinated with multiple doses of the mRNA-1273 vaccine and monitored the spike-specific antibody response from baseline up to one month after the fourth dose. After the primary vaccine series, the frequency of spike-specific B cells, detected within the pool of Ig-switched CD19+ cells, significantly increased. The booster dose further induced a significant expansion, reaching up to 0.28% of spike-specific B cells. The kinetics of this expansion were slower in the allo-HCT recipients compared to healthy controls. Spike-specific IgG and ACE2/RBD binding inhibition activity were observed in 80% of the allo-HCT recipients after the first two doses, with a significant increase after the third and fourth booster doses, including in the subjects who did not respond to the primary vaccine series. Additionally, 87% of the allo-HCT recipients exhibited positive cross-inhibition activity against the BA.1 variant. Our findings provide evidence that allo-HCT recipients need repeated doses of the mRNA-1273 vaccine to induceSARS-CoV-2 specific immune response similar to that observed in healthy individuals. This is particularly crucial for vulnerable individuals who may exhibit a limited response to the primary series of SARS-CoV-2 vaccination.

Nephrons and non-relapse mortality: simplified comorbidity index and acute kidney injury are associated with NRM in adults undergoing allogeneic hematopoietic cell transplant

The Simplified Comorbidity Index (SCI) is a recently published 5-component, pre-transplant tool to predict non-relapse mortality (NRM) in allogeneic hematopoietic cell transplantation (alloHCT) patients. The SCI captures chronic kidney disease (CKD) using estimated glomerular filtration rate (eGFR) based on the CKD-EPI equation (KDIGO 2021 CKD-EPI), which may be more sensitive to predict risk of NRM than the creatinine cut-off in the 16-component, Hematopoietic Cell Transplant—Comorbidity Index (HCT-CI). We retrospectively assessed the ability of the SCI to risk-stratify patients and the impact of acute kidney injury (AKI) to NRM in adults who underwent alloHCT at the University of Minnesota. We included 373 patients who underwent their first alloHCT between 2015 and 2019. Through multivariate analysis, we found that patients with an SCI of greater than 4 had a higher risk of NRM. Additionally, we noted that AKIs stages 2–3 prior to day +100 was independently associated with a 3-fold greater NRM than patients who did not experience clinically significant AKI.

Preoperative BMI and Hb levels are important predictors of massive bleeding in liver transplant patients.

This study aims to compare intraoperative bleeding during liver transplant procedures and analyze the predictive role of preoperative laboratory indicators in significant intraoperative bleeding. A retrospective analysis was conducted on 271 cases of allogeneic liver transplant patients from January 2018 to June 2023. Patients were categorized into the massive bleeding (MB) group and the non-massive bleeding (non-MB) group based on the occurrence of significant intraoperative bleeding. Preoperative laboratory parameters between the MB and non-MB groups were compared, and univariate and multivariate regression analyses were performed. ROC curves were performed to analyze the value of these parameters in distinguishing the MB and non-MB groups. In the MB group, body mass index (BMI), hemoglobin (Hb), platelet count (PLT), fibrinogen (Fib), and total protein (TP) levels were significantly lower than those in the non-MB group (p < 0.05). Conversely, prothrombin time (PT), international normalized ratio (INR), total bilirubin (TBIL), creatinine (CRE), blood urea nitrogen (BUN), the model for end-stage liver disease (MELD) score, length of stay, and hospital stay were significantly higher in the MB group compared to the non-MB group (p < 0.05). Univariate and multivariate logistic regression analyses revealed that preoperative BMI and Hb were independent risk factors for massive bleeding during liver transplantation. ROC curve analysis for predicting massive intraoperative bleeding showed that the area under the curve (AUC) of Hb was considerable (AUC: 0.83). Preoperative BMI and Hb levels are critical predictors of massive bleeding during liver transplantation, emphasizing the importance of proactive management based on these indicators for improved patient outcomes.

Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide

Introduction: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers. Methods: Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT. Serum samples were analyzed for 2,925 protein levels by antibody-based proximity extension assay (PEA). Mean differences in the log-transformed abundance values were compared using t tests in a volcano plot. Results: Five patients with very severe SOS/VOD and 5 control patients were compared. Ten proteins were identified that showed a statistically significant and log-transformed 3-fold increase in concentration. They were CALCA, CCL20, GPR37, IGFBP4, IL1RL1, SLC39A14, SPINK4, FABP3, MYL3, and CHCHD10. Four different proteins, namely, CD83, leukocyte associated immunoglobulin-like receptor 2 (LAIR2), CD7, and HEM6 showed a significant decrease with defibrotide treatment. SOS/VOD resolved in 80% (n = 4) of patients, while 1 patient deceased due to SOS/VOD. Conclusion: PEA technology identified 10 proteins that were significantly elevated in patients with very severe SOS/VOD. Prospective studies in a larger cohort using this technology may be able to conclusively identify diagnostic protein biomarkers for SOS/VOD.

Bone Density Screening, Treatment and Fracture Rates in Allogeneic Hematopoietic Cell Transplant Patients

Bone Density Screening, Treatment and Fracture Rates in Allogeneic Hematopoietic Cell Transplant Patients

Impact of Renally Adjusted Methotrexate Dosing on Safety and Efficacy Outcomes in Allogeneic Hematopoietic Cell Transplant Patients

Impact of Renally Adjusted Methotrexate Dosing on Safety and Efficacy Outcomes in Allogeneic Hematopoietic Cell Transplant Patients

Bloodstream Infection in Allogeneic Transplant Patients Treated with Post-Transplant Cyclophosphamide

Bloodstream Infection in Allogeneic Transplant Patients Treated with Post-Transplant Cyclophosphamide

Incidence, management and outcome of Hepatic Veno-Occlusive disease /Sinusoidal Obstruction Syndrome after hematopoietic stem cell transplant in Thalassemia major patients: A prospective study of Pakistani BMT.

Hepatic Veno occlusive disease (VOD), also known as sinusoidal obstruction syndrome (VOD/SOS), is a post-transplant life threatening complication. In this study, we aimed to discuss the incidence, management and outcome of VOD in post allogenic transplant patients of beta thalassemia major (BTM). A prospective study was conducted in Armed Forces Bone Marrow Transplant Center, between 2001-2022. A total of 385 fully Human Leucocyte Antigen (HLA) matched BTM patients, with Ursodeoxycholic acid for prophylaxis, were included in the study. Incidence of VOD was calculated through cumulative incidence estimates. Chi square test and Mann Whitney test were used to compare discrete and continuous variables respectively. VOD was diagnosed and graded according to European Society for Blood and Marrow Transplantation EBMT Pediatric diagnostic criteria. Risk factors for VOD were grouped as recipient, transplant and donor related. Univariate analysis was performed by log-rank test. All patients who developed VOD were managed primarily with fluid restriction and strict input output monitoring. Statistical analyses were performed using SPSS v 25.0. Out of 385 transplant patients, forty developed VOD. Median time from date of transplant till onset of VOD was 14 days (range 6-30). Cumulative incidence of all grade VOD was 10.39% (95% CI, 7-14). Eleven out of 40 patients who developed VOD died. Cumulative incidence of Transplant related mortality (TRM) for patients with and VOD was 20.5% (95% CI, 16.6-25.1) vs 27.5% (95% CI, 16.1-42) (p value 0.318) respectively. Among risk factors, age of recipient and fibrosis (p value of 0.04 and 0.000 respectively) were found to be significantly associated with VOD. Careful selection of transplant candidates before transplant can help reduce the incidence of VOD.

Genetic features and outcomes of allogeneic transplantation in patients with WT1-mutated myeloid neoplasms

Genetic features and outcomes of allogeneic transplantation in patients with WT1-mutated myeloid neoplasms

Fluoroquinolone-Resistant Enterobacteriaceae Prevalence for Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (aHSCT) in the Treatment of Multiple Myeloma (MM)

Background: Fluoroquinolones (FQL) are commonly used in antimicrobial prophylaxis in immunocompromised cancer patients (pts) during prolonged neutropenia. A possibly high and increasing proportion of pts harboring FQL-resistant Enterobacteriaceae (FRE) challenges the assumption that prophylaxis with FQLs is still of benefit in preventing sepsis. Previous studies reported that colonization of FRE in allogeneic transplant patients may be an infection risk factor (cf. Satlin et al. Clin Infect Dis 202;73:1257-65). This prospective study aims to determine the prevalence of FRE in defined pt populations in two metropolitan areas treated with dose-intense melphalan with autologous peripheral blood stem cell (PBSC) transplantation, and to determine the possible clinical effects of FRE in the host microbiome on transplant outcomes. Methods: Pts eligible for this prospective, ongoing study have a diagnosis of MM and are undergoing autologous PBSC transplantation after conditioning with dose-intense melphalan 200 mg/m 2 at Hackensack University Medical Center (HUMC) and MedStar Georgetown University Hospital (MGUH). Peri-rectal swabs are scheduled before chemotherapy mobilization of PBSC given with FQL prophylaxis, before transplant admission with initiation of antimicrobial prophylaxis, at time of hospital discharge, and 3 months after aHSCT. Prophylaxis is discontinued with fever or hospital discharge. Blood cultures are obtained at time of fever (&amp;gt;38 °C) with adjustments in antibiotics per standard of care. A central catheter is placed for venous access in all patients throughout their transplant course. Pts are discharged after achieving neutrophil (ANC) engraftment and control of conditioning regimen toxicities. Bacterial cultures from perirectal swabs (fresh or frozen for shipping) were purified on CHROMagar™ Orientation Plates and grown in the presence of ≥5 ug/ml ciprofloxacin to select for quinolone-resistant organisms. Results: To date, 39 pts are evaluable (Table 1). PBSC were mobilized using filgrastim/plerixafor (G-Moz) or cyclophosphamide/etoposide/dexamethasone (CDE) followed by filgrastim with levofloxacin prophylaxis. The quantity of CD34+ cells infused is in Table 1. All pts achieved ANC engraftment at a median of 10.8 days (range 9-14) and were hospitalized for a median of 13 days (range 11-24). 37/39 pts collected swabs before transplant admission (and swabs were obtained at discharge for the other 2 pts). 13/37 (35%) admission swabs demonstrated FRE colonization (Table 2). 6/33 swabs at time of discharge were positive for FRE including for 4 pts negative for FRE on transplant admission with a total of 17/39 pts (44%) showing FRE colonization at some point during the transplant admission. Samples collected at 3 months after transplantation for 24 pts reaching that timepoint showed FRE colonization for 4 pts including 2 pts not previously testing positive at time of transplantation. 27/107 samples tested positive for FRE and 21/39 pts (54%) had at least one FRE positive culture. Seven pts (20%) developed neutropenic fever but no pt experienced a blood-stream infection (BSI). One pt developed Clostridium difficile colitis during the period of neutropenia. One pt tested positive for MRSA colonization at admission but did not develop fever or BSI. One pt was readmitted after initial hospital discharge for evaluation of fever without a source of infection determined. Ten pts (5 FRE colonized during transplant course) were given prednisone for persistent diarrhea attributed to engraftment syndrome (cf: Spitzer TR. Bone Marrow Transplant 2001;27:893-8) commencing at a median of 10 (range, 8-13) days after aHSCT and not associated with CDE mobilization or detection of FRE. Nineteen other patients, 8 of whom tested positive for FRE, did not receive corticosteroids for management of regimen-related toxicities (an additional 7 pts received preplanned corticosteroids starting at day +8). No center effect is yet evident. Conclusions: FRE are detected in a high proportion of pts undergoing aHSCT in the treatment of MM. However, FQL prophylaxis is not associated with FRE BSI in this ongoing study. FRE colonization is not predictive of delayed engraftment or prolonged hospitalization, and does not appear predictive of non-infectious diarrhea.

Janus Kinase (JAK) 1 Inhibition Results in Significant Changes in Serum Proteins and Peripheral T-Cell Populations That Correlated with Clinical Scores in Chronic Graft Versus Host Disease (GVHD) Patients (an Analysis from GRAVITAS-309)

Background: Chronic GVHD (cGVHD) occurs in 30-70% of allogeneic hematopoietic cell transplantation patients, and the rate has increased over the past 2 decades. Based on the degree of organ involvement, cGVHD is classified as mild, moderate, or severe. Standard treatment includes systemic corticosteroids (CS), together with immunosuppressive agents. GRAVITAS-309 (NCT03584516) was designed as a 2-part, multicenter, randomized trial to assess efficacy and safety of itacitinib, an orally bioavailable, selective JAK1 inhibitor, in combination with CS as first-line treatment for moderate to severe cGVHD. The dose-finding, open-label, randomized portion of the study initially investigated itacitinib at 200 mg once daily (qd) and 300 mg qd in combination with CS (methylprednisolone or prednisone); both doses were well tolerated. The trial was expanded to test itacitinib 400 mg qd and 300 mg twice daily (bid); the initial 300 mg qd cohort was expanded and a CS monotherapy cohort was added. Results from the expanded portion of the study (n=139 patients) showed improved overall response rate (ORR) at 6 months in patients treated with itacitinib + CS vs CS alone (Im, et al. Blood 2022;140[Suppl 1]:1870). Here, we analyzed samples collected from patients in 4 cohorts (cohort A [300 mg qd], cohort B [400 mg qd], cohort C [300 mg bid], and cohort D [CS alone]) for systemic proteins and immune cell populations, to support investigation into the itacitinib mechanism of action and to correlate with clinical outcomes. Methods: Peripheral blood mononuclear cells (PBMCs) and serum were collected before treatment (baseline, day 1), and day 7, day 14 (PBMCs only), and day 28 following treatment initiation. Serum proteins were analyzed using the OLINK Target 96 platform, and circulating T-cell subsets were measured using flow cytometry of PBMCs and presented as a percentage of parent population. Samples were assessed irrespective of patients' response. Most of the patients (70-100% per cohort) with samples available for analysis were responders (achieved complete or partial responses). Results: Serum levels of proteins, including several proposed as potential prognostic cGVHD biomarkers, changed significantly at day 28 relative to baseline following treatment with itacitinib (Table 1). Levels of elafin, a marker of acute GVHD of the skin, were significantly reduced and levels of dickkopf-3 (DKK3), a marker of sclerotic and nonsclerotic cGVHD, were significantly increased in itacitinib cohorts only. Based on a repeated measures correlation analysis, both markers significantly correlated with overall clinical skin scores (elafin: r=+0.43; DKK3: r=-0.53; both P&amp;lt;0.001). Serum levels of other reported markers of cGVHD, including osteopontin, C-X-C motif chemokine ligand (CXCL) 9 and CXCL10, were significantly decreased exclusively in itacitinib-treated cohorts, and not in the CS only cohort. Some proteins, including matrix metalloproteinase (MMP) 3, increased in all cohorts, suggesting that changes in these proteins cannot be attributed to itacitinib alone, but may reflect response to CS; other proteins, such as suppression of tumorigenicity (ST2), remained unchanged in response to treatment in all cohorts. CS treatment alone resulted in an increase in naive CD4 T cells (CD4 +CD8 -&amp;gt;CD45RA +CCR7 -) and a corresponding reduction of CD4 effector memory T cells (CD4 +CD8 -&amp;gt;CD45RA -CCR7 +) within 28 days (Figure 1, cohort D). Changes in naive CD4 T cells following CS monotherapy were significantly attenuated by itacitinib ( P&amp;lt;0.05 vs CS at day 28), particularly at the 400 mg qd dose (Figure 1, cohort B), which demonstrated the best ORR at 6 months (53% with 400 mg qd vs 36% with CS). Conclusions: Analysis of patient samples from GRAVITAS-309 revealed that serum elafin and DKK3 levels significantly correlated with skin GVHD scores, possibly reflecting the systemic origin of observed skin manifestations. Serum levels of osteopontin, CXCL9, and CXCL10 were specifically reduced by itacitinib in patients with cGVHD and may represent potential pharmacodynamic markers. Observed changes in different peripheral T-cell populations in patients' samples following itacitinib treatment were consistent with those reported in murine GVHD models, suggesting a potential role of naive CD4 + T cells in driving this disease. Planned future analyses will include identification of novel biomarkers that correlate with organ involvement.

Survival of Hematopoietic Stem Cell Transplantation in the National Institute of Neoplastic Diseases, Lima-Perú between 2012 to 2022: 10 Years of Experience

Introduction: Hematopoietic stem cell transplantation (HSCT) is part of standard treatment in a great number of hematologic malignancies and some solid tumors. The National Institute of Neoplastic Diseases (INEN) started the HSCT program in 2012, performing over 600 HSCT so far. In this study, we report the overall survival (OS) at 5 years of patients who undergone this procedure in our institution through 10 years of experience. Methods: We analyzed retrospectively the survival of all patients admitted to the HCST program at INEN between 2012 and 2022. Clinical and pathological data were collected from the medical records and the unit's transplant patient registry. The OS was determined through the Kaplan-Meier method and the comparisons of survival curves were performed using the log-rank or Breslow test. Results: During the study period, a total of 647 transplants were performed. The median age was 39 years (range: 1 - 70), 73.4% of patients were between 18 and 60 years, and 57.1% were men. Most transplants (n = 591, 91.3%) were performed in the adult population and 8.6% (n = 56) in pediatric population. According to the type of transplant, 68% (n=440) were autologous and 32% (n=207) allogeneic from related donor. The most frequent diagnosis were acute leukemia (n = 221, 34.2%), multiple myeloma (n = 190, 29.3%), non-Hodgkin lymphoma (n = 105, 16,2%; of these, 22 were T- cell lymphomas), Hodgkin lymphoma (n = 69, 10.7%) and germinal cell tumor (n = 33, 5.1%); in the pediatric population, leukemia was the most common diagnosis (66.1%). The median follow-up of the patients was 3.7 years (95% CI: 3.4, 3.9), 25.2% (n = 163) of the patients died due to disease progression. The median overall survival (OS) for the entire cohort was not reached and the OS rate at 5 years was 68.3%. The 5-year OS rate by transplant subtype was 53.9% and 75.3% (p &amp;lt; 0.001) for allogeneic and autologous transplants, respectively; and according to the pathology, the patients who had a better 5-year OS were HL (87.5%) and NHL (77.5%), while in leukemias it was 56.1%. Survival by age group (&amp;lt;40 vs &amp;gt;40) and sex (female vs. male) did not present a significant difference (p &amp;gt; 0.05). Conclusions: The survival of the transplanted patients was similar to that reported in other series. Leukemia was the most frequent hematological malignancy admitted to the HSCT program. HL and NHL were the malignant tumors with the highest survival rates at 5 years. Nearly a third of transplants were allogeneic, all from matched related donors. HSCT in our series has shown an improvement in OS at 5 years in both autologous and allogeneic transplant patients compared to non-transplanted patients, according to international reports.

Cytokine release syndrome after bronchoalveolar lavage

BackgroundImmunosuppressed bone marrow transplant patients with pulmonary infiltrates routinely undergo bronchoscopy with bronchoalveolar lavage (BAL) to investigate potential etiologies. Cytokine release syndrome after BAL is unreported in the literature in general and in this patient population.Case presentationWe report on an allogeneic bone marrow transplant patient with non-infectious organizing pneumonia of the lungs who developed delayed and rapidly progressive shock and hypoxia post-procedure over the course of 12 h resulting in intensive care unit admission for supportive care. BAL was characterized by a marked lymphocytic, cytotoxic T cell infiltrate on pathology and flow cytometry without clear evidence of infection. The patient’s clinical status improved quickly only after the initiation of high dose intravenous steroids and returned to baseline as an outpatient.ConclusionThe patient’s clinical data and course suggest a cytotoxic T cell response from the lung and BAL as the etiology. With an increasing number of cellular therapies for cancer entering the clinic, the potential for unusual but morbid complications from routine bronchoscopy should be considered.

Hematopoietik Kök Hücre Nakli Türüne ve Nakil Öncesi Mevcut Polifarmasiye Bağlı Olarak İlaç-İlaç Etkileşimi Farklılıkları

Introduction: Drug drug interactions can effect the success of stem cell transplantation process. Therefore, analyzing the risk of these interactions would be helpful for practitioners. This study was conducted to identify drug-drug interactions in allogeneic and autologous stem cell transplantation patients before and after transplantation. &#x0D; Methods: Patients who underwent allogeneic stem cell transplantation and autologous stem cell transplantation were included in the study. Patients’ treatment sheets were collected ten days before transplantation day, on the transplantation day, and ten days after transplantation day. Drug-drug interactions were analyzed by using four drug-drug interaction checking databases.&#x0D; Results: 50 patients from both transplantation types were included. The mean ages for allogeneic and autologous transplants were 42.4 and 51.8, respectively. 52% of allogeneic transplants and 28% of autologous transplants were on ≥5 drugs at tenth day before transplantation. The means of interactions in allogeneic and autologous stem cell transplantation patients were 75.42 and 43.62, respectively. The detection of at least one contraindicated interaction in allogeneic and autologous transplant patients were 94% and 92%, respectively. In 48% of allogeneic transplants and 36% of autologous transplants, two or more contraindicated interactions were detected.&#x0D; Conclusion: Allogeneic stem cell transplantation patients experienced almost two times more drug-drug interactions than autologous stem cell transplantation patients. Transplantation type, being in the pre and post-transplantation period and the drug number at the beginning of the transplantation process matter in terms of the number of drug-drug interactions. Identifying interactions in terms of transplantation type and existing medications is very important.

Reciprocal associations between beliefs about medicines, health locus of control and adherence to immunosuppressive medication in allogeneic hematopoietic cell transplant patients: Findings from the ADE-TRAM study

PurposePatients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are required to strictly adhere to immunosuppressive medications to avoid rejection and infective complications. Since medication adherence is among the most important modifiable behaviors to achieve better outcomes, the aims of this study were to measure the baseline and longitudinal trends of medication adherence and investigate the psychological factors associated with medication adherence in allo-HSCT patients. MethodsThis was a single-center, longitudinal study of patients who underwent allo-HSCT to treat hematological malignancies at the University hospital of Florence (Italy). Adherence was measured with the Immunosuppressive Medication Self-Management Scale; psychological factors (i.e., beliefs about medicines and health locus of control) were measured with the Beliefs About Medicines Questionnaire and Multidimensional Health locus of Control Scale. Data were collected 1, 3, 6 and 12 months after discharge. A mixed effects model was performed after adjusting for demographic characteristics. Results50 adult patients were included in this study. Adherence to immunosuppressant was optimal and increased significantly 3 months after bone marrow transplantation (B = 0.23, p = 0.041). Patients with lower concerns about immunosuppressive medications were more likely to be adherent (B = 0.02, p = 0.040), while those having beliefs that their disease was due to external factors were less likely to be adherent (B = −0.02, p = 0.026) than their counterparts. ConclusionsThese results underline the importance of psychological factors in affecting adherence to immunosuppressants of allo-HSCT patients. Healthcare providers and researchers should target medication beliefs and reorient locus of control with appropriate interventions, in order to improve adherence.

Treatment strategy at the decision for allogeneic transplantation in patients with myelodysplastic syndrome in the era of azacitidine: A KSGCT prospective study

The optimal bridge strategy at the decision for allogeneic hematopoietic stem cell transplantation (HSCT) in patients with myelodysplastic syndrome (MDS) is unclear. We performed a prospective observational study in which 110 patients with MDS who were decided to undergo HSCT were enrolled. Among these 110 patients, 77 patients were enrolled in this study within 1 month from the decision for HSCT. Among these 77 patients, 13 patients had a human leukocyte antigen (HLA)-matched sibling, 54 patients started an unrelated donor search, and the other 10 patients directly selected cord blood (CB) at the decision for HSCT, and 13 (100%), 38 (70.4%), and 9 (90%) patients actually underwent HSCT within 1 year, respectively. The overall survival (OS) at 1 year from their enrollment was 70.9%, and the selection of azacitidine use at the decision for HSCT was not associated with OS. Among 60 of the 77 patients who actually underwent HSCT within a year from their enrollment, a lower relapse rate after HSCT was observed in those who selected CB at the decision to undergo HSCT. However, this preferable effect of CB selection disappeared when patients who were enrolled in this study in > 1 month from the decision for HSCT were additionally included in the analyses.In conclusion, the selection of bridge strategy at the decision for HSCT did not affect outcomes in patients with MDS. The immediate performance of HSCT may be associated with better outcomes.

“Democratizing” cancer care: City of Hope’s national enterprise model for delivering cancer care.

103 Background: Despite progress in cancer care, many patients do not have access to innovative care including participation in clinical trials. In 2021, City of Hope (COH), as part of a national expansion of its established cancer services, acquired Cancer Treatment Centers of America in the Chicago, Atlanta, and Phoenix regions to offer a standardized system of care to patients in those regions. The goal is to integrate academic and community-based practices into a single enterprise focused on improving access to care. Physicians collaborate to enhance patient care and connect patients and families to innovative treatments. Initial priorities included integrating patient conferences, developing common quality programs and metrics, new physician recruitment, integrating clinical pathways, developing new specialty programs, integrating EHRs, contracting, branding/marketing, operating as non-profit organizations and other organizational structures. Methods: We describe changes made at a single site as a model to improve local cancer care. Phoenix (PHX), Arizona is the 5th largest city in the United States. Most patients with hematologic malignancies currently receive care in the community setting and lack access to clinical trials. Results: In collaboration with our parent center in Duarte, we have instituted a variety of changes designed to enhance patient care. The hiring process for physicians (who become COH faculty). in the hematologic malignancy program includes stakeholders from Duarte and Phoenix. All potential transplant, cellular therapy and complex patients are presented and discussed with related COH faculty at regularly scheduled interdisciplinary rounds. To date, over 50 have been presented, 20 have proceeded to autologous transplant. Quality programs are integrated with active participation in QA conferences at each facility. Second opinions are returned to their primary oncologist with recommendations. Patients who would benefit from a trial or innovative therapy not available at the Phoenix site are referred to the Duarte campus and return to Phoenix following that intervention. The first shared allogeneic transplant patient performed in Phoenix is pending. In the next phase of integration, trials will be offered at COH PHX. An integrated approach to determine eligibility for older myeloma transplant candidates piloted by COH PHX is under development. Conclusions: The ability to remain in their local community while obtaining an opinion from an NCI designated cancer center, democratizes care for hematologic malignancy patients. Ongoing discussions throughout their treatment determine the best options including clinical trials if appropriate. The majority of patients will receive therapy locally, especially as the number of clinical trials grows. This model once fully integrated, improves access to care and can be easily replicated at other sites.

TFF3 as a Diagnostic Biomarker in Kidney Transplant Patients.

Intestinal trefoil factor 3 (TFF3) is a protein secreted by many cell types, and its serum and urine levels vary in patients with kidney disease. Therefore, the present study aimed to determine the diagnostic value of TFF3 in allogeneic kidney transplant patients included in the one-year follow-up. To analyze the influence of the diagnostic method used, we studied the type of biological material and the time elapsed since renal transplantation on the parameter's value. The study also aimed to investigate the relationship between TFF3 levels and creatinine and estimated glomerular filtration rate (eGFR) values in the serum and urine of the patients studied. The study used blood and urine samples from adult patients (n = 19) 24-48 h, 6 months, and 12 months after kidney transplantation. We collected one-time blood and urine from healthy subjects (n = 5) without renal disease. We applied immunoenzymatic ELISA and xMap Luminex flow fluorimetry to determine TFF3 in serum and urine. There was a significant difference in TFF3 levels in the serum of patients collected on the first one or two days after kidney transplantation compared to the control group (determined by ELISA and Luminex) and six months and one year after kidney transplantation (ELISA). We observed a correlation between creatinine concentration and urinary TFF3 concentration (ELISA and Luminex) and a negative association between eGFR and urinary (ELISA) and serum (Luminex) TFF3 concentration in patients on the first and second days after kidney transplantation. We noted significant correlations between eGFR and TFF3 levels in the serum and urine of patients determined by the two methods six months and one year after transplantation. In women, we observed that urinary TFF3 concentration increased significantly with increasing creatinine and that with increasing eGFR, urinary TFF3 concentration determined by two methods decreased significantly. In the present study, the choice of diagnostic method for the determination of TFF3 in serum and urine significantly affected the concentration of this biomarker. The values of this parameter determined by ELISA were higher than those assessed using the Luminex assay. Based on the presented results, we can conclude that TFF3 has great potential to monitor renal transplant patients. Determination of this protein in parallel with creatinine and eGFR levels in serum and urine may provide helpful diagnostic information.

Demographic comparison of survival outcomes after bone marrow transplantation in adolescent and young adult patients: A single institution cohort study.

e18522 Background: Bone marrow transplant (BMT) has become an increasingly common treatment modality for both malignant and non-malignant conditions. However, BMT requires significant healthcare and financial resources, which can result in allocation disparities across socioeconomic, demographic, and racial/ethnic groups. The data exploring how demographic disparities impact survival after BMT is limited, particularly within the adolescent and young adult (AYA) population, defined as patients between the ages of 15 and 39 years. The goal of this study was to assess overall survival of AYA patients undergoing transplant at our institution and to gain insight into if demographic factors impact the likelihood of mortality after transplantation. Methods: Patients aged 15-39 who underwent transplant at the Wilmot Cancer Institute in Rochester, NY between 2012-2020 were identified. Information regarding demographic characteristics, indication for transplant, and mortality was collected. The primary endpoint was overall survival (OS), defined as the time from transplant to the date of death from any cause or the date of last in-person contact. Survival criteria were estimated using the Kaplan-Meier method and compared using mortality odds ratios. These analyses were stratified by indication for transplant, recorded race/ethnicity, gender, and by age. Results: 169 patients met inclusion criteria, and median OS for the entire cohort was not reached. Of 108 allogenic transplant recipients, median OS was 7.85 years (95% CI [3.3, not estimated]). Median OS for patients receiving transplant for solid tumor pathology was 3 years (95% CI [0.4 years, not estimated]), compared to other indications for transplant where survival exceeded the median. For allogenic transplant patients, median OS for Black patients was 4.8 years (95% CI [0.7 years, not estimated]), 7.8 years for Caucasian patients (95% CI [3.3 years, not estimated]), median OS was not reached for Hispanic patients, and 1.1 years for all other minorities (95% CI [0.4 years, not estimated]) (p = 0.28). There was no significant difference in mortality based on insurance type or gender for either type of transplant. There was a significant difference in mortality for allogenic transplant patients based on average median household income when compared at an average income of $60,000/ year (OR 2.6, 95% CI [1.164, 5.6] p = 0.0097). Conclusions: Overall survival for AYA patients who had a transplant for any indication at our institution was better than expected. There were no significant differences for either transplant type based on gender, racial/ethnic background, gender, age, or indication for transplant. There was a significant difference based on median household income. Larger multi-institutional studies are likely needed to accurately identify further demographic disparities.