Autologous Stem Cell Transplantation In Patients Research Articles

At-Home Care Versus Total Hospital Care Model for Autologous Stem Cell Transplantation in Adult Lymphoma Patients: A Pilot Case-Control Study.

Lymphoma is the second most prevalent cancer treated with autologous stem cell transplantation (ASCT). Additional resources are required to enhance the provision of care for these patients. To explore the complications and economic costs of home versus hospital care models for ASCT in patients diagnosed with lymphoma and to describe the experience of home care patients. This was an observational pilot case-control study with 1:1 matching, in which all patients assisted at home were included. Data were obtained by reviewing medical records and data from the hospital's financial and resource management service. The IEXPAC scale version 11 + 4 was used to assess the care process experience as perceived by home care patients. The study included 34 patients, in which there was a significant decrease in neutropenic fever, both in frequency and duration (P = .001 and P < .001, respectively), in mucositis days (P = .038), and the rate of red cell concentrate transfusion (P < .001); however, there was a longer neutrophil recovery time (P = .044) in home care versus hospitalized patients. The overall cost was higher in the hospital care model (P = .001). Home care patients obtained high scores on the perceived experience of the care process scale. The home ASCT model is associated with fewer complications, shorter hospital stays, and more significant cost savings. The experience of the home care process was rated satisfactorily. This study provides evidence for a model that offers high-quality care and a comfortable experience for ASCT patients. Preparing more nurses for this home care model is imperative.

Invasive fungal infections are rare in pediatric and young adult autologous hematopoietic stem cell transplant patients.

Pediatric and young adult patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) face a crucial, yet understudied, risk of invasive fungal infections (IFI), especially compared to allogeneic transplants. This gap underscores the need for research in pediatric patients undergoing auto-HSCT. Our objective was to evaluate the incidence of IFI in pediatric and young adult patients during the first year after auto-HSCT. We conducted a single-center retrospective analysis of 150 pediatric and young adult auto-HSCT patients who underwent transplant from January 2013 to January 2023. We focused on IFI incidence within the first-year post transplant, using the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria for IFI identification. Among the 150 patients analyzed, with 240 unique transplant episodes, the primary indication was neuroblastoma (37.3%), and micafungin was extensively used for prophylaxis (82.7%). There was an absence of IFI from yeast and mold species, suggesting a low IFI risk in this cohort. The incidence of IFI in pediatric auto-HSCT recipients receiving micafungin primary antifungal prophylaxis is rare. The findings advocate for further research to refine prophylaxis guidelines and highlight the need for individualized risk assessment to optimize post-transplant care.

Rising Prevalence of Low-Frequency PPM1D Gene Mutations after Second HDCT in Multiple Myeloma.

Multiple myeloma (MM) first-line treatment algorithms include immuno-chemotherapy (ICT) induction, high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) consolidation, followed by lenalidomide maintenance. After these initial therapies, most patients suffer a disease relapse and require subsequent treatment lines including ICT, additional HDCT and ASCT, or novel immunotherapies. The presence of somatic mutations in peripheral blood cells has been associated with adverse outcomes in a variety of hematological malignancies. Nonsense and frameshift mutations in the PPM1D gene, a frequent driver alteration in clonal hematopoiesis (CH), lead to the gain-of-function of Wip1 phosphatase, which may impair the p53-dependent G1 checkpoint and promote cell proliferation. Here, we determined the presence of PPM1D gene mutations in peripheral blood cells of 75 subsequent myeloma patients in remission after first or second HDCT/ASCT. The prevalence of truncating PPM1D gene mutations emerged at 1.3% after first HDCT/ASCT, and 7.3% after second HDCT/ASCT, with variant allele frequencies (VAF) of 0.01 to 0.05. Clinical outcomes were inferior in the PPM1D-mutated (PPM1Dmut) subset with median progression-free survival (PFS) of 15 vs. 37 months (p = 0.0002) and median overall survival (OS) of 36 vs. 156 months (p = 0.001) for the PPM1Dmut and PPM1Dwt population, respectively. Our data suggest that the occurrence of PPM1D gene mutations in peripheral blood cells correlates with inferior outcomes after ASCT in patients with multiple myeloma.

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and postprotocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and postprotocol groups, respectively (P < .001). Recurrent fever (14.2% versus 16.0%, P = .726), documented infection (1.7% versus 6.7%, P = .068), and readmission (13.3% versus 22.7%, P = .091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% versus 1.3%, P = .736) nor 90-day NRM (0.8% versus 1.3%, P = .736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the preprotocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

Engraftment Syndrome in Autologous Hematopoietic Stem Cell Transplant Patients: Incidence, Associated Risk Factors, Features, and Outcomes.

BACKGROUND Autologous stem cell transplantation (ASCT) is the standard treatment for multiple myeloma (MM) and refractory/relapsed (R/R) lymphoma patients. Engraftment syndrome (ES) is a non-infectious febrile syndrome during ASCT. This study focused on the incidence, risk factors, manifestations, and outcomes of patients with ES receiving ASCT. MATERIAL AND METHODS This retrospective cohort study included MM and R/R lymphoma patients who underwent ASCT at Chiang Mai University Hospital from January 2014 to September 2020. ES was diagnosed by the consensus of independent reviewers based on clinical manifestations, laboratory, and radiological findings. RESULTS We included 124 patients, of whom 67 (54.1%) had lymphoma. The mean age was 48.0±12.3 years. The incidence of ES was 36.3%. The ES group had a significantly higher proportion of patients with fever, elevated liver enzymes, elevated bilirubin, hypoalbuminemia, and weight gain compared to the non-ES group. TNC more than 10×10⁸ cells/kg was an independent risk factor for ES (odds ratio 2.94 with a 95% confidence interval of 1.15-7.50, P=0.024). ES was associated with longer length of stay (22.5±8.2 vs 16.9±6.4 days, P<0.001) but was not associated with overall survival (OS). CONCLUSIONS The incidence of ES in this cohort was 36.3%. Features observed in ES patients were fever, elevated liver enzymes, elevated bilirubin, and hypoalbuminemia. TNC of more than 10×10⁸ cells/kg was an independent risk factor. ES was associated with longer length of stay but not survival outcomes.

The effect of breathing exercises on chemotherapy-induced nausea and vomiting in autologous hematopoietic stem cell transplantation patients: A randomized controlled trial

PurposeThis research was conducted as a randomized controlled study to examine the effect of breathing exercises on managing chemotherapy-related nausea and vomiting in patients who underwent autologous hematopoietic stem cell transplantation. MethodsA randomized controlled trial design was used, including an intervention group doing breathing exercises and a control group receiving standard care for chemotherapy-induced nausea and vomiting. The sample was selected from patients hospitalized in the bone marrow transplantation unit. A total of 70 autologous hematopoietic stem cell transplantation patients (35 intervention and 35 control participants).Several variables were evaluated, including the frequence and degree of nausea and vomiting, the patient's nutritional status, and the need for antiemetics. Data were analyzed and interpreted using Mann Whitney U, Pearson chi-square test, Independent t-test, Mann Whitney U, and multiple linear regression. ResultsIt was found that there was a negative relationship between the number of breathing exercises, the number of nausea and vomiting and the severity of nausea. As the number of breathing exercises increased, the number nausea and vomiting, and severity of nausea decreased significantly (p < 0.05). It was found that the use of antiemetics decreased in the intervention group. Furthermore, it was found that the intervention group had higher daily food consumption on the 3rd, 7th, and 9th days (p < 0.05). ConclusionBreathing exercises were a practical approach to managing chemotherapy-related nausea and vomiting.

The Efficacy and Safety of Tandem Transplant Versus Single Stem Cell Transplant for Multiple Myeloma Patients: A Systematic Review and Meta-Analysis.

While high-dose therapy and autologous stem cell transplant (ASCT) remain integral to the primary treatment of newly diagnosed transplant-elble multiple myeloma (MM) patients, the challenge of disease progression persists. The primary objective of this meta-analysis is to evaluate the efficacy and safety of tandem ASCT compared to single ASCT. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing tandem ASCT with single ASCT in patients with newly diagnosed MM. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases for studies published up to January 2024. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and treatment-related mortality (TRM). We used a random-effects model to calculate pooled hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs). Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa Scale. Twelve studies involving 5057 patients met the inclusion criteria. Tandem ASCT was associated with a significantly higher CRR compared to single ASCT (HR 1.33, 95% CI 1.03-1.71, I2 = 15%), but no significant differences were observed in PFS (HR 0.75, 95% CI 0.42-1.34, I2 = 14%), OS (HR 0.60, 95% CI 0.33-1.10, I2 = 27%), or the ORR (RR 0.80, 95% CI 0.59-1.08, I2 = 33%). However, tandem ASCT was associated with a significantly higher risk of TRM (RR 1.78, 95% CI 1.00-3.18, I2 = 0%). Tandem ASCT improves the CRR but does not provide significant benefits in terms of PFS, OS, or ORR compared to single ASCT in patients with newly diagnosed MM. Moreover, tandem ASCT is associated with a higher risk of TRM. The decision to pursue tandem ASCT should be made on an individual basis, carefully weighing the potential benefits and risks in light of each patient's unique clinical situation. Future research should focus on identifying patient subgroups most likely to benefit from tandem ASCT and exploring strategies to optimize the efficacy and safety of this approach in the context of novel agent-based therapies.

Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group

BackgroundDecisions regarding maintenance therapy in patients with multiple myeloma should be based on both treatment efficacy and health-related quality of life (HRQL) consequences. In the CARFI trial, patients with first relapse of multiple myeloma underwent salvage autologous stem cell transplantation (salvage ASCT) before randomization to carfilzomib-dexamethasone maintenance therapy (Kd) or observation. The primary clinical endpoint was time to progression, which was extended by 8 months by Kd. The aim of this paper is to present the all HRQL endpoints of the CARFI trial including the HRQL effect of Kd maintenance therapy relative to observation. The primary HRQL endpoint was assessed by EORTC QLQ-C30 Summary score (QLQ-C30-sum) at 8 months follow-up. A key secondary HRQL endpoint was quality-adjusted progression-free-survival (QAPFS).MethodsHRQL was assessed with EORTC QLQ-C30, EORTC QLQ-MY20 and FACT/GOG-Ntx at randomization and every second month during follow-up. HRQL data were analyzed with linear mixed effect models until 8 months follow-up. QAPFS per individual was calculated by multiplying progression-free survival (PFS) by two quality-adjustment metrics, the QLQ-C30-sum and EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The QAPFS per treatment group was estimated with the Kaplan-Meier method. P < 0.05 was used for statistical significance, and a between-group minimal important difference of 10 points was interpreted as clinically relevant for the QLQ-C30-sum.Results168 patients were randomized. HRQL questionnaire compliance was 93%. For the QLQ-C30-sum, the difference of 4.62 points (95% confidence interval (CI) -8.9: -0.4, p = 0.032) was not clinically relevant. PFS was 19.3 months for the Kd maintenance group and 16.8 months for the observation group; difference = 2.5 months (95% CI 0.5; 4.5). QAPFS based on the QLQ-C30-sum for the Kd maintenance group was 18.0 months (95% CI 16.4; 19.6) and for the observation group 15.0 months (95% CI 13.5; 16.5); difference = 3.0 months (95% CI 0.8–5.3). QAPFS based on the QLU-C10D for the Kd maintenance group was 17.5 months (95% CI 15.9; 19.2) and 14.0 months (95% CI 12.4; 15.5) for the observation group; difference = 3.5 months (95% CI 1.1–5.9).ConclusionsKd maintenance therapy after salvage ASCT did not adversely affect overall HRQL, but adjustment for HRQL reduced the PFS compared to unadjusted PFS. PFS of maintenance therapy should be quality-adjusted to balance the benefits and HRQL impact.

Invasive Fungal Infections Are Rare in Pediatric and Young Adult Autologous Hematopoietic Stem Cell Transplant Patients

Invasive Fungal Infections Are Rare in Pediatric and Young Adult Autologous Hematopoietic Stem Cell Transplant Patients

Gemcitabine-based conditioning compared to BEAM/BEAC conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: No difference in outcomes.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL. A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results. Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC). The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.

Safety and efficacy of a new high-dose regimen of panobinostat, gemcitabine, busulfan, and melphalan for 1st or 2nd salvage ASCT for refractory/relapsed or high-risk myeloma: Matched-pair comparisons with concurrent control cohorts.

Improvement of autologous stem-cell transplantation (ASCT) for myeloma is needed. Building on our prior work, we prospectively evaluated panobinostat and gemcitabine/busulfan/melphalan (GemBuMel) with ASCT in this population. Patients aged 18-65 years with relapsed/refractory or high-risk myeloma and adequate end-organ function were eligible. Treatment included panobinostat (20 mg/day, days -9 to -2) and GemBuMel (days -8 to -2). Patients were enrolled in 1st (ASCT-1) or 2nd ASCT (ASCT-2) cohorts. We compared their outcomes with all our other concurrent ASCT patients who met eligibility criteria but received melphalan or BuMel off study, matched for age, prior therapy lines, high-risk cytogenetics, and response at ASCT. We enrolled 80 patients, 48 and 32 in the ASCT-1 and ASCT-2 cohorts, respectively; in these two cohorts, high-risk cytogenetics were noted in 33 and 15 patients, respectively; unresponsive disease in 12 and 11 patients, respectively, after a median of 2 and 3 therapy lines, respectively. Transplant-related mortality (TRM) occurred in two ASCT-2 patients. One-year PFS rates were 69% (ASCT-1) and 72% (ASCT-2); 1-year OS rates were 79% (ASCT-1) and 84% (ASCT-2). Minimal residual disease negativity improved after ASCT-1 (8.5%-23%, p < .0001) and ASCT-2 (34%-55%, p = .02), which correlated with improved outcomes. Trial patients and controls (N = 371) had similar TRM and post-ASCT maintenance. Trial patients had better PFS after either a 1st (p = .02) or a 2nd ASCT (p = .04) than matched-paired control patients. In conclusion, panobinostat/GemBuMel is effective for relapsed/refractory or high-risk myeloma patients, with better PFS than concurrent matched controls receiving melphalan or BuMel.

Economic Burden Associated with ASCT in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Nationwide Health Insurance Claims Database Study in Japan during 2012-2022

Introduction: Autologous stem-cell transplantation (ASCT) is a standard of care for transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). ASCT-related costs and cost drivers remain unknown in Japan, thus restricting economic evaluation comparisons of newer innovative therapies with ASCT. Japan has universal health insurance coverage with a copayment system, which provides a nationwide snapshot of the current treatment landscape in Japan through health insurance database analysis. To capture continuous follow-up data of DLBCL patients who received stem-cell transplantation (SCT) in Japan, we conducted this study using a Japanese health insurance association (HIA) claims database. Methods: This is a retrospective observational study of patients with DLBCL who received SCT using the Medical Data Vision, Co. Ltd. (MDV; Tokyo, Japan) HIA claims database. The MDV HIA database contains inpatient, outpatient, and pharmacy claims from 149 health insurance societies in Japan. The database comprises approximately 7.84 million unique patient identifiers and covers about 3.0% of the Japanese population (as of August 2022). Patients who received treatment during the identification period from October 2012 to February 2022, inclusive, were selected using the DLBCL ICD-10 codes C83.3, C83.8, C85.1, and C85.2. Patients were required to have data for at least 6 months before and after the index date, which is the date of the first recorded ASCT procedure. The total cost included the costs of SCT-related lab tests, stem cell harvests, conditioning regimens during the lookback period, and all costs during the follow-up period including SCT-related hospitalization. Structural Equation Modelling (SEM) is ongoing to estimate the relationships of observed and latent variables having direct and indirect effects on pre-assumed causal relationships. Results: A total of 108 patients (3.8%) among all DLBCL patients who received SCT met the eligibility criteria, and all were ASCT patients. Of those patients, 41.67% were female and 97.22% were aged between 18 to 65 years old with a median age of 55. Subsequent therapy after the index date was received by 13.89% of the 108 patients, of which 2 (1.85%) patients received CAR-T cell therapy. Among the 108 ASCT patients, the median (Q1-Q3) length of SCT-related hospitalization was 34 days (28.50-42.00 days). During SCT-related hospitalization, CT scan was the most common test (22, 50.93%) among all ASCT patients, followed by MRI (12, 11.11%) and PET (3, 2.78%); and no patients were admitted to the ICU or emergency room during SCT-related hospitalization. There was 1 (0.93%) patient who received radiation therapy during SCT-related hospitalization. The median (Q1, Q3) of the total cost for ASCT patients during the lookback and follow-up period (index date inclusive) was $78,718.63 ($57,175.90, $141,108.38). Conclusions: This is the first study to examine the total cost and healthcare resource use of ASCT among patients with DLBCL in the Japan nationwide setting with a follow-up period of up to 24 months. While it is not directly comparable to our study, the median of the total cost for ASCT with a 6-month follow-up period in the US, as reported by Cui et al. (2022), was more than $86,408. The data presented in this study will be a benchmark when considering new innovative therapies for patients with DLBCL. Identifying the cost drivers of ASCT-related costs for DLBCL patients may provide insights for optimizing clinical practice for patients with DLBCL undergoing ASCT and for delivering better care for patients.

Autologous Stem Cell Transplantation Remains a Curative Option As Second Line Treatment for Patients with Relapsed/Refractory Large B Cell Lymphoma: Spanish Multicenter Geth-TC/Geltamo Study

Introduction: High dose therapy and Autologous Stem Cell Transplantation (ASCT) has remained the treatment of choice for transplant-eligible patients with relapsed/refractory (R/R) large B cell lymphoma (LBCL) and chemosensitive disease. Recently, CART therapy has been approved in second line for patients with primary refractory disease or early relapse (&amp;lt;1 year of first-line therapy) and the current role of ASCT has been questioned. However, several studies have shown that despite early failure of first line, patients with chemosensitive disease after salvage therapy can be cured with ASCT consolidation. Our objective was to analyze the efficacy of ASCT in patients with R/R LBCL after a long-term follow up and try to define the optimal role of ASCT. Patients and methods: We performed a retrospective multicenter study based on GETH-TC database of ASCT. We included patients from centers of GETH-TC/GELTAMO with R/R LBCL who underwent ASCT from January 2010 to December 2021. All the patients received rituximab and anthracycline-based frontline therapy. Diffuse LBCL NOS, high-grade B-cell lymphoma double/triple hit and NOS, primary mediastinal, transformed follicular lymphoma (tFL) and other less frequent LBCL subtypes were included. Plasmablastic and primary central nervous system lymphoma were excluded. Patients who underwent ASCT in first CR were also excluded except patients with tFL who had received previous anthracycline-based frontline therapy for the indolent lymphoma. The primary endpoints were progression-free survival (PFS) and overall survival (OS) in the overall series and according to different prognostic factors, including disease status at ASCT. Disease status was defined as complete remission (CR), partial response (PR) and refractory disease (stable disease or progression) assessed by PET/CT. Results: Seven-hundred and ninety-one patients fulfilled the inclusion criteria. Patients characteristics are summarized in Table 1. After a median follow-up of 74 months (95%CI 68-81), 65% of the patients were alive and 84% of them free of disease. Six-year-PFS and OS were 51% (95%CI 47-54) and 63% (95%CI 60-67), respectively. Non-relapse mortality at 1 year was 9% (95%CI 7-11). The main causes of death were progression in 161 (58%), ASCT-related toxicity in 18 (6%) and other causes in 98 (35%). PFS was significantly influenced by age at ASCT, treatment lines prior to ASCT and disease status at ASCT (p&amp;lt;0.01). OS was influenced by age at diagnosis, R-IPI at diagnosis, age at ASCT, treatment lines prior to ASCT and disease status at ASCT (p&amp;lt;0.01). In the multivariate analysis, age &amp;gt;60 years at ASCT [HR 1.31 (95%IC: 1.06-1.62), p=0.011], ASCT as ≥3 th line [HR 1.81 (95%IC: 1.42-2.31), p&amp;lt;0.001] and PR versus CR at ASCT [HR 1.46 (95%IC: 1.18-1.81), p&amp;lt;0.001] were the only independent variables influencing PFS, Figure 1. Age &amp;gt;60 years at ASCT [HR 1.62 (95%IC: 1.24-2.12), p&amp;lt;0.001], ASCT as ≥3 th line [HR 1.77 (95%IC: 1.32-2.37), p&amp;lt;0.001] and PR versus CR at ASCT [HR 1.58 (95%IC: 1.22-2.05), p&amp;lt;0.001] were the only independent variables for OS. From 307 (39%) patients who relapsed after ASCT, 59 received CART therapy (median PFS 8.9 months) and 69 allo-SCT (median PFS 10.8 months). Refractory disease or early relapse did not significantly influenced survival. Analyzing this population separately (n=477), disease status at ASCT (PR versus CR) and ASCT as ≥3 th line were the only independent variables for both PFS [HR 1.46 (95%IC: 1.11-1.92), p=0.007; HR 1.79 (95%IC: 1.32-2.43), p&amp;lt;0.001, respectively] and OS [HR 1.92 (95%IC: 1.38-2.67), p&amp;lt;0.001; HR 1.91 (95%IC: 1.35-2.69), p&amp;lt;0.001, respectively]. Conclusions: To our knowledge, this is the largest series analyzing the efficacy of ASCT in patients with R/R LBCL after rituximab-containing frontline therapy. Our results indicate that ASCT is a curative option for patients with chemosensitive disease (especially in CR after salvage), regardless of the timing of relapse after frontline treatment. These data support that ASCT could be considered in patients with primary refractory or early relapse, provided the disease is sensitive to salvage therapy.

A 5-Stage System for ASCT Multiple Myeloma

652. Multiple Myeloma: Clinical and Epidemiological INTRODUCTION: In the last three decades, significant advancements in multiple myeloma (MM) treatment, including immunomodulators, targeted therapies, chemotherapy combinations, autologous stem cell transplantation (ASCT), and CAR-T therapy, have emerged. ASCT offers hope for MM patients by using high-dose chemotherapy with stem cell support. However, it carries risks of severe toxicity. Despite evaluating factors like age, performance status, and co-morbidities for ASCT eligibility, outcomes for MM patients still vary greatly. Various models, such as the ISS-series systems, have been developed to assess risk factors for progression-free and overall survival We conducted a study on 5,259 ASCT patients since 1989, identifying 7 easy variables (ISS stage, diagnosis-transplant interval, ferritin, transferrin, LDH, age, and gender) and creating a 5-stage system. This system helps evaluate the risk of MM patients before ASCT. METHODS: In this retrospective study, data from 5,259 MM patients receiving ASCT (1989-2022) were collected (median follow-up: 57 months). We assessed 30 clinical variables pre-ASCT. Multiple imputation was used to deal with the missing values. Patients were split into a 70% training set and a 30% validation set. Univariate/multivariate Cox regression analysis identified 7 clinical and demographic signatures. Signatures were scored based on hazard ratios normalized to ISS III vs. ISS I&amp;II. K-adaptive partitioning generated a 5-stage system, ATM5S, evenly distributed and validated in the training set. Harrel's c-index was used to compare ATM5S with the current myeloma systems. RESULTS: 3683 patients (70%) in the test cohort had a median age of 59.6, median PFS 38.8 month and median OS 56.1 month. IgG was the most common isotype (55%). Univariate Cox analysis showed that 27 variables were significant predictors for both PFS and OS. Multivariate Cox analysis showed that time from diagnosis to transplant, ferritin, transferrin, LDH, ISS stage, lymphocytes, platelets, calcium, gender and age were independent prognostic factors for both OS and PFS. We selected the most easy, understandable and well-distributed (with high-risk group&amp;gt;20%) 7 variables: ISS, time from diagnosis to transplant, ferritin, transferrin, LDH, age and gender and developed a score system, which resulted into a 5-stage system (ATM5S) by k-adaptive partitioning. This staging system also demonstrated a significant discriminatory effect in the validation set (30%, 1576 patients). CONCLUSIONS: The Arkansas Transplant-Myeloma 5-Stage System (ATM5S) showed a promising performance in both training and validation cohorts.

Long-Term Outcome of Multiple Myeloma Patients Receiving Autologous Stem Cell Transplantation (ASCT) - Impact of Therapeutic Strategy Following ASCT

Introduction Despite all the therapeutic progress made in multiple myeloma (MM), the standard of care for eligible patients remains an intensive induction therapy followed by high dose melphalan and autologous stem cell transplantation (ASCT). Material and methods This present retrospective study included MM patients treated in Lyon between 1997 and 2020. All patients received induction chemotherapy followed by intensive chemotherapy and ASCT, with or without consolidation and maintenance therapy. Number and type of therapeutic lines administered for relapse after ASCT were analyzed. All data were reported in the European blood and marrow transplantation (EBMT) PROMISE registry. Statistical analysis Descriptive analyses were used for demographic variables, biological parameters, and treatment characteristics. Overall survival (OS) and progression-free survival (PFS) were presented using the Kaplan-Meier method and log-rank tests were performed to compare survival curves. Univariate and multivariate analyses were computed using Cox regressions and the multivariate analyses considered the variables for which the univariate ANOVA p-value was≤ 10%. Statistical analyses and graphics were computed with R v4.1.2, with the help of ‘survival’ and ‘ggplot2‘ packages. Results Before ASCT A total of 342 patients were included in the study (median 60 years (range: 28-73), 58% were male, 89.4% were diagnosed with a type III myeloma according to the Salmon and Durie classification. No genetic analysis was performed at that time. Most patients (92.5%) had a performance status (PS) of 0 or 1. The type of myeloma was heavy chain and light chain myeloma for 75.7% patients (68.9% of IgG kappa) and light chain myeloma in 23.1%. The median delay between diagnosis and ASCT was 4.8 months. Before ASCT, patients received an induction therapy with VTD in 54.1% of cases, VD in 30.1%, and more recently VRD in 16.1%. Disease status before ASCT was complete remission (CR) for 17.5% of the patients, partial remission (PR) and very good partial remission (VGPR) for 79.2% of patients and progressive disease or relapse for 3.0% of them. After ASCT The median duration of aplasia was 11 days. At day 100, the response was CR in 166 patients (50.5%), 182 patients (54.7%) received a consolidation treatment and 71 patients (20.8%) a maintenance therapy (Revlimid® for 90% of them). Overall, 227 (66.4%) patients relapsed. The median delay between ASCT and relapse was 22.5 months (0.89-229.13) and the median follow-up duration was 46.7 months (0.33-287.97). Among the 227 patients who relapsed, 6 patients were not treated, 79 patients (23.1%) received one chemotherapy line, 32 patients (9.4%) received two lines, 38 (11.1%) received 3 and 72 (21.1%) received at least 4 lines and up to 8. Overall survival and progression free survival The median OS was 132 [95% CI 110.6; NR] months from diagnosis and 122.8 [100.9; NR] months from ASCT. The median PFS was 39.35 [36.25; 43.37] months from diagnosis and 31.07 [28.42; 35.91] months from ASCT (Figure 1 A, B). In multivariate analysis on OS, the shorter aplasia duration (p&amp;lt;0.001) and consolidation and maintenance (p&amp;lt;0.001) were significantly associated with a significant better OS. The median OS was not reached from ASCT for patients who have received both consolidation and maintenance treatments and no death was reported. (Figure 1 C). For patients receiving chemotherapy lines for relapses after ASCT (Figure 1D) regardless of the number of lines the median OS was102.4 months and the 10-year OS probability was 45.6%. The OS of patients who received 3 lines of treatment was identical to that of patients who received one or 2 lines after ASCT. The median OS after 1 to 2 lines of chemotherapy after ASCT was not reached and was 127.15 months [70.6-NR] for those receiving 3 lines (Figure 4B). The OS of patients who received more than 4 chemotherapy lines after ASCT was significantly lower compared to the OS (p=0.0096) with a median [95%CI] OS of 85.5 months [65.61-106.15]. In conclusion this study showed the significant positive impact on OS of the association consolidation and maintenance. We have also studied the impact of number of chemotherapy lines and the impact on OS and PFS of kind of treatment will be discussed.

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.

BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial

Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic. This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300mg/m2 BCNU on day-6), in BendaEAM, BCNU was replaced by 200mg/m2 bendamustine given on days-7 and-6. Eligible patients were aged 18-75 years and had mantle cell lymphoma, diffuse large B-cell lymphoma, or follicular lymphoma in first or second remission or chemosensitive relapse. The primary endpoint of the study was to evaluate whether replacement of BCNU by bendamustine reduces lung toxicity, defined as a decrease of the diffusion capacity of the lung for carbon monoxide by at least 20% at three months after ASCT. Data analyses were performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02278796, and is complete. Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n=8, 19.5%; BEAM: n=11, 25.6%; risk difference=-6.1%: 95% confidence interval:-23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed. Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM. Mundipharma.

High Neoantigen Load Confers a Major Benefit from Autologous Stem Cell Transplantation Compared to Consolidation in Newly Diagnosed Multiple Myeloma

Autologous stem cell transplant (ASCT) is the current standard of care for eligible patients with multiple myeloma (MM). The UK national trial CARDAMON investigated whether, following carfilzomib, cyclophosphamide, and dexamethasone (KCD) induction, ASCT was of benefit compared with further cycles of KCD as consolidation. All patients received carfilzomib maintenance. KCD consolidation did not show non-inferiority, but the difference was marginal, and we previously concluded “that further studies are warranted to explore deferred autologous HSCT in some subgroups.” Whilst some of the benefit of ASCT derives from the myeloablative effect of melphalan, there is evidence that immune reprogramming has an important role. It has also been reported that neoantigen burden has prognostic significance in MM, with patients with a high neoantigen load having worse outcomes. Taken together, we hypothesized that patients with higher neoantigen load would gain most benefit from ASCT, due to immune reprogramming. We therefore developed a pipeline to predict neoantigen load in myeloma patients ( Fig. 1A) and explored whether this had prognostic significance in the context of consolidation or ASCT in patients enrolled in CARDAMON. We collected paired tumour and germline whole exome sequencing and RNA-Seq data. We called nonsynonymous and frame-shift mutations using MuTECT2 and calculated RNA-Seq expression using Salmon. We used ARCAS-HLA for HLA genotyping. We translated high-confidence mutations within a sliding window and predicted HLA allele binding using NETMHCpan-4.0, predicting binding when the IC50 was less than 200nM, per the standard definition of a strong binding peptide. We removed any neoantigens that were not expressed, using the RNA-Seq data. Neoantigen load for an individual patient was taken as the number of predicted expressed neoantigens. We chose a neoantigen cut-off based on mutation rates distinguishing immunologically “cold” or “hot” tumours. Consequently, patients with &amp;lt;= 130 neoantigens were defined as low antigen load, and those with &amp;gt;130 were defined as high neoantigen load. We observed a total of 15,162 high affinity neoantigens across 58 patients, with a median of 200 neoantigens per patient (range 34 - 653). Forty-six neoantigens were shared across patients, mostly NRAS, KRAS, and BRAF. We first compared patients by randomization group. For patients who received consolidation, there was no significant difference in progression-free survival (PFS) between high and low antigen loads (p=0.32). For patients in the ASCT arm, a high antigen load was associated with a longer PFS (p=0.013). This was surprising, as high antigen load has previously been shown to be a poor prognostic factor, although our numbers were small and confirmation in independent data is ongoing. We then considered patients split by antigen load. For those with low antigen load, we saw no difference in PFS between those who received ASCT and those who received consolidation. However, for patients with a high antigen load, there was a marked improvement in PFS for those undergoing ASCT ( Fig. 1B Upper; median PFS not reached vs. 25 months; hazard ratio 0.50, 95% confidence interval 0.20-0.65; p=0.0039). This difference translated to overall survival ( Fig. 1B Lower; median OS not reached in either group; hazard ratio 0.12, 95% confidence interval 0.014-0.50; p=0.028). The marked benefit of ASCT over consolidation in this subgroup analysis is in contrast to the marginal difference between the two therapies for allcomers in the CARDAMON trial. Whilst upfront ASCT remains the treatment of choice for eligible patients, the risk/benefit ratio may be less clear in the more frail and in the context of deep response to induction. In summary: We have developed a bioinformatic pipeline to predict neoantigen burden in newly diagnosed myeloma, which suggests higher neoantigen load is associated with a major benefit from ASCT. This approach provides novel insight into the biology of ASCT and could be used to stratify patient need for ASCT in the future, although the immunological mechanisms implicated in these findings remain to be identified. Neoantigen subtype effect (frameshift vs SNV) and validation in a larger cohort is ongoing.

Responses and Outcomes after Second-Line Therapy in Transplant-Eligible Patients with DLBCL Relapse over 1 Year after First-Line Therapy

Introduction Chimeric antigen receptor T-cell therapy (CAR T) is approved as second-line therapy in patients with large B cell lymphoma (LBCL) that is refractory to, or relapsed within 1 year of, initial therapy. In patients with LBCL that relapses more than 1 year after completion of initial therapy, salvage chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients. However, data on the outcomes of salvage chemoimmunotherapy with intent for ASCT for this specific population are lacking. Methods We retrospectively reviewed patients with relapsed LBCL more than 1 year after 1 st line therapy who received salvage treatment. We included patients seen at our institution prior to the start of salvage therapy, who began therapy between 1/2008 and 1/2023, and were treated with stated intent to proceed to ASCT. We excluded patients with CNS involvement at relapse and those not evaluable for response. The primary outcome was progression-free survival (PFS), defined as the time from initiation of salvage therapy to LBCL progression or death. Event-free survival (EFS) was defined as time from salvage initiation to change in lymphoma therapy, disease progression, or death. Additional key outcomes included overall survival (OS), overall response rate (ORR) and complete response rate (CRR) to salvage therapy, and outcomes after subsequent CAR T. Outcomes for important subgroups using baseline characteristics were compared. ORR and CRR were compared using Fisher's exact test. PFS, EFS and OS were estimated using the Kaplan-Meier method, and differences were tested by the log-rank test. Results A total of 78 patients met inclusion criteria, with characteristics summarized in Table 1. Median time from completion of initial therapy to relapse was 31.2 months (range, 12.3 - 177 months). CRR to salvage therapy was 76%, with a 94% ORR. In 60 patients who completed ASCT, CRR was 85%. With a median of 45 months' follow-up from salvage initiation, median PFS was 50 months (95% confidence interval (CI) of 25 - NR), and median EFS was 29.2 months (95% CI, 19.6 - NR)( Figure 1). Median OS was 132 months (95% CI 108 - NR). On subgroup analysis, factors significantly associated with shorter PFS were time from last treatment to relapse &amp;lt; 36 months, Ann Arbor stage 3-4, LDH above normal, and increased international prognostic index at relapse. Other factors such as age, gender, salvage regimen, extranodal disease, cell of origin, transformation from indolent lymphoma, bulky disease, and marrow involvement at relapse, were not significantly associated with PFS. Comparing response to salvage in 60 ASCT recipients, patients in CR (n=52) had longer median PFS than those in PR (n=8) (108 vs 33 mo), but this was not statistically significant (p = 0.4). In 33 patients who received 3 rd line therapy or beyond, 16 (48%) received CAR T therapy; 7 proceeded directly to CAR T after inadequate response to salvage, and 9 had progression after completion of ASCT and received CAR T. Among all patients, CRR after CAR T was 81% and ORR 94%, with median PFS and OS not reached; PFS and OS at 24 months after CAR T were 63% and 81%, respectively. Discussion To our knowledge, this is the first study to specifically evaluate outcomes of ASCT-eligible patients with relapsed LBCL more than 1 year after initial therapy, who did not meet FDA criteria for CAR T-cell therapy. We observed highly favorable outcomes, with longer PFS and OS compared to studies that evaluated late LBCL relapses (Hilton LK., JCO 2023, Harrysson S., BJH 2022), possibly reflecting the exclusive use of modern salvage regimens with intent for ASCT, improvements in subsequent therapies, or bias related to the single-center design. In patients who received CAR T in 3 rd line or later, frequent and durable responses were seen. However, due to the small sample size, whether CAR T should be considered as an alternative to ASCT in patients with late LBCL relapse remains unknown. Our data represent a benchmark for patients with LBCL relapses &amp;gt;12 months after completion of frontline therapy and may help inform patient counseling and future clinical trial designs.

Development of a Combined Risk Assessment Model for Venous Thromboembolism and Bleeding in Hematopoietic Stem Cell Transplantation Patients

Background: Venous thromboembolism (VTE) and bleeding are common complications amongst allogeneic and autologous hematopoietic stem cell transplant (HSCT) patients. Balancing risk of bleeding and thrombosis in this population is particularly challenging as HSCT patients are concurrently pancytopenic and coagulopathic. However, risk factors for bleeding and thrombosis in HSCT patients are understudied. We aimed to derive a combined bleeding and VTE risk assessment tool to be used in the immediate post-transplant period (90 days). Methods: We conducted a retrospective cohort study of adult patients who underwent allogeneic or autologous HSCT between January 1, 2011 and December 31, 2021 at a tertiary care centre in Canada. The risk models patients were followed from transplant until occurrence of the event of interest with last follow up at Day 90 post-transplant, or death. Primary outcome for VTE was the occurrence of a confirmed thrombosis including proximal upper and lower extremity deep vein thrombosis, pulmonary embolism, or thrombosis of unusual sites, including cerebral and splanchnic. Primary outcome for bleeding was the occurrence of a major or clinically significant non-major bleeding event, not related to anticoagulation, as per the definition of the International Society of Thrombosis and Hemostasis. Group characteristics were compared using chi-square, Fisher's exact, or Student's T-tests as appropriate. Potential predictors for VTE and bleed amongst our patients were evaluated using single variable logistic regression and confirmed with multiple variable logistic regression with forward selection. For continuous variables, optimal cut-off points were estimated using ROC curves. Final VTE and bleed risk scores were derived based on weighted variables and compared using Cox regression with non-parametric bootstrapping used for internal validation. Results: A total of 476 patients (317 autologous, 159 allogeneic) were included. 47 patients (9.8%) suffered from VTE, and 32 patients (6.7%) suffered from bleed unrelated to anticoagulation within 90 days post-HSCT. A VTE risk assessment tool was derived, and internally validated, and it included: second central venous catheter insertion (due to complications from first central line) (2 points), and previous cancer treatment with steroids (1 point). The overall cumulative incidence of VTE was 31.8% in the high-risk group (&amp;gt;2 points) versus 7.6% in the low-risk group (0-1 points). The high-risk group was associated with higher mortality at 90 days (15.9% versus 3.2%, p &amp;lt;0.001; Figure 1). A bleeding risk assessment tool was also derived, and internally validated, and it included: baseline (day 0 of transplant) platelet count of &amp;lt;90 (1 point), and baseline hemoglobin of &amp;lt;96 (1 point). The overall cumulative incidence of bleed was 17.2% in the high-risk group (2 points), versus 4.3% in the low-risk group (0-1 points). The high-risk group was associated with higher mortality at 90 days (12.6% versus 2.6%, p&amp;lt;0.001). Amongst the low-risk bleed group, overall cumulative incidence of VTE was 10.03%, with 31.03% in the high-risk VTE group versus 8.33% in the low-risk VTE group (p&amp;lt;0.001). The positive VTE group was associated with higher mortality at 90 days (10.26% versus 1.72%, p=0.001; Figure 2). Amongst the high-risk bleed group, overall cumulative incidence of VTE was 9.19%, with 33.33% in the high-risk VTE group, versus 4.17% in the low-risk VTE group (p&amp;lt;0.001). The positive VTE group was associated with higher mortality at 90 days (37.5% versus 10.13%, p=0.026). Conclusion: We derived a predictive score, VTE and Bleeding in Marrow Transplant (VBMT) - risk score, for both VTE and bleeding in the immediate post-transplant period (90 days), to be used in conjunction with other criteria for bleeding and thrombosis. Amongst the low-risk bleed patients, we recommend strong consideration of chemical VTE prophylaxis, especially amongst the high-risk VTE group. These risk assessment models will help stratify patients based on bleed and thrombosis risk, and ultimately help guide VTE prophylaxis and surveillance strategies amongst HSCT patients.