Autologous Hematopoietic Stem Cell Transplantation In Patients Research Articles

Results of Levofloxacin Prophylaxis Timing in Autologous and Allogeneic Stem Cell Transplantation: A Retrospective Cohort Study.

Background Despite preventive measures and varying antibiotic recommendations, bacterial infections continue to pose a significant threat to individuals undergoing hematopoietic stem cell transplantation (HSCT).Levofloxacin prophylaxis is commonly used, but the optimal timing for initiation is debated. This study aims to assess infection outcomes based on timing of levofloxacin prophylaxis (initiation at the first day of conditioning vs. after infusion of stem cells) in autologous and allogeneic HSCT patients. Methods We compared infectious episodes, responsible pathogens, and clinical outcomes based on the implementation of levofloxacin prophylaxis in patients receiving autologous or allogeneic HSCT procedures. This retrospective single-center study involved a review of the medical records of autologous and allogeneic HSCT patients treated at our adult stem cell transplantation unit between 2018 and 2020. The study included 23 patients who underwent autologous HSCT and 12 patients who underwent allogeneic HSCT. We compared the demographic data, febrile neutropenia, proven bacterial infections, and 30-day survival among the autologous and allogeneic transplant groups, including those who received oral levofloxacin 500 mg/day prophylaxis. Results Positive blood cultures (26.1% vs. 75%; p = 0.011), mean neutrophil engraftment (10.6±1.2 vs. 14.8±1.3; p<0.001), and mean platelet engraftment (11.2±1.1 vs. 15.4±3.2; p = 0.004) were all lower in autologous transplant patients versus their allogeneic counterparts. When each type of HSCT was evaluated within the same type, there were no observed differences in infection frequency, infection type, or 30-day mortality between the patient groups with different levofloxacin initiation times. Conclusion Healthcare professionals should choose the most appropriate timing for initiating levofloxacin prophylaxis based on individual patient factors and clinical circumstances while considering the cost-effectiveness implications. Further research with a larger sample size and prospective design is needed to support our findings.

Analysis of laboratory parameters before the occurrence of hepatic sinusoidal obstruction syndrome in children, adolescents, and young adults after hematopoietic stem cell transplantation

PurposeHepatic sinusoidal obstruction syndrome (SOS) is a serious complication following hematopoietic stem cell transplantation (HSCT) in which early diagnosis improves patient outcome. The aim of our study was to detect laboratory parameters following HSCT that can predict the occurrence of SOS.MethodsThis retrospective study included 182 children, adolescents, and young adults who underwent allogeneic or autologous HSCT for the first time (median age 7.2 years). The diagnosis of SOS was based on the pediatric criteria of European Society for Blood and Marrow Transplantation (EBMT). We investigated 15 laboratory parameters after HSCT before the onset of SOS.ResultsThe overall incidence of SOS was 14.8%. SOS developed in 24 of 126 allogeneic (19.1%) and in 3 of 56 autologous (5.4%) HSCT patients at a median time of 13 days after HSCT. We observed a low SOS mortality rate of 11.1% within 100 days after HSCT. International normalized ratio (INR) ≥ 1.3, activated partial thromboplastin time (aPTT) ≥ 40 s, reptilase time ≥ 18.3 s, factor VIII ≤ 80%, antithrombin III ≤ 75%, protein C ≤ 48%, D-dimer ≥ 315 µg/L, bilirubin ≥ 9 µmol/L, and ferritin ≥ 3100 µg/L showed significant associations with the onset of SOS in the univariate analyses. In the multivariate analysis, INR ≥ 1.3 [odds ratio (OR) = 8.104, p = 0.006], aPTT ≥ 40 s (OR = 10.174, p = 0.001), protein C ≤ 48% (OR = 5.215, p = 0.014), and ferritin ≥ 3100 µg/L (OR = 7.472, p = 0.004) could be confirmed as independent risk factors after HSCT before SOS. If three of the four significant cut-off values were present, the probability of developing SOS was more than 70%. The probability of SOS was 96%, if all four laboratory parameters were changed according to the cut-off values. The values of factor XIII, von Willebrand factor (vWF), von Willebrand factor activity (vWF activity), protein S, fibrinogen, and alanine aminotransferase (ALT) were not relevant for the occurrence of SOS.ConclusionIn summary, the laboratory parameters INR, aPTT, protein C, and ferritin were very useful to predict the occurrence of SOS. In addition, this is the first report on a significant association between SOS and high values of INR and aPTT after HSCT before SOS.

Co-Expression of C-MYC/BCL2 Is Associated with Inferior Survival Outcomes in Relapsed/Refractory Diffuse Large B-Cell Lymphoma after Autologous Stem Cell Transplantation - a Nationwide Retrospective Analysis in Singapore

Introduction Co-expression of C-MYC and BCL2 in diffuse large b-cell lymphomas (DLBCL), also termed double-expressor lymphomas (DEL), has been shown to be associated with poorer outcomes after standard R-CHOP induction therapy. Approximately 70% of DEL will relapse within 5 years. The subsequent traditional approach with potential for cure has been high dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT). Whilst factors such as remission status after front-line treatment and early relapse have been associated with poorer outcomes after ASCT, data are limited regarding significance of DEL status on survival outcomes post-ASCT. We retrospectively studied the prognostic impact of DEL status on outcomes in patients with relapsed or refractory (R/R) DLBCL who underwent ASCT. Methods This was a retrospective, nationwide study of adults patients, &amp;gt;18 years old, with R/R DLBCL who underwent autologous hematopoietic stem cell transplantation (ASCT) between 2010 and 2022 at the only 2 transplant centers in Singapore - Singapore General Hospital and National University Cancer Institute. Patients with double/triple hit lymphoma, defined as concurrent rearrangements of MYC and BCL2 and/or BCL6 by fluorescence in situ hybridization (FISH) analysis, were not included in this study. Patients with transformed indolent B-cell NHL (non hodgkin lymphoma), primary mediastinal B-cell lymphoma, primary CNS (central nervous system) lymphoma, or Richter transformation of chronic lymphocytic leukemia were excluded. Only patients that had available MYC and BCL-2 immunohistochemistry (IHC) were included in this study. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess associations between covariates of interest and OS or PFS. Results A total of 72 patients were included, 44 (61.1%) non-double expressor DLBCL (non-DEL) and 28 (38.9%) double expressor DLBCL (DEL). Patient demographics and disease characteristics at relapse were similar in both groups aside from a higher incidence of CNS involvement in the non-DEL group as compared to DEL group, 34.1% vs 10.7% (Table 1). Both groups achieved a &amp;gt;90% response (CR and PR) after second-line salvage chemotherapy as well as a &amp;gt;90% response post-transplant (CR and PR). Patients with DEL however were more likely to relapse post-transplant, 69.7% vs 40.9% (p = 0.032) and were also associated with increased odds of all-cause mortality, 60.7% vs 36.4% (p=0.043). This significance was maintained on multivariable analysis, HR 4.22 95% CI 1.20 - 14.84 (p=0.025) and HR 4.32 95% CI 1.10 - 17.15 (p=0.038) respectively. The median follow up for survivors were 42 months (range, 26 to 64 months) in the DEL patients and 60 months (range, 46 to 88 months) in the non-DEL patients. The 5-year PFS in patients with DEL was inferior to non-DEL patients, 23.3% vs 49.6% respectively, p=0.022. DEL patients were also associated with inferior 5-year OS, 40.2% vs 65.7%, p=0.041. In multivariable model, DEL status remained significantly associated with inferior PFS and OS. We also observed that patients with CNS involvement at relapse had inferior PFS and OS. Male gender and a less than complete metabolic response (CR) status prior to transplant, assessed on PET-CT, was also associated with inferior OS. Conclusion Co-expression of C-MYC/BCL2 was associated with inferior outcomes after ASCT in patients with R/R DLBCL. While ASCT has been the standard curative approach in the R/R setting, considerations for novel targeting therapies to achieve a deeper response prior to transplant or the upfront use of chimeric antigen receptor T-cell therapy at first relapse may be further explored in this high-risk subset of patients.

Analysis of Laboratory Parameters before the Occurrence of Hepatic Sinusoidal Obstruction Syndrome in Pediatric Patients after Hematopoietic Stem Cell Transplantation

Introduction: Hepatic sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease of the liver, is a serious complication following hematopoietic stem cell transplantation (HSCT). Early diagnosis and treatment with defibrotide can improve patient outcome. The pathogenesis is not fully understood, but it is obvious that some laboratory parameters are already changed before the onset of SOS. The aim of our retrospective study was to detect laboratory parameters following HSCT that can predict the occurrence of SOS. Methods: We analyzed 182 children with a median age of 7.2 years who underwent allogeneic or autologous HSCT for the first time and without defibrotide prophylaxis. Our study population consisted of 126 patients who received allogeneic HSCT (69.2%) and 56 patients who underwent autologous HSCT (30.8%). The stem cell sources were peripheral blood stem cells (50.5%) or bone marrow (49.5%) and the most frequent underlying diseases were solid tumors (34.1%), genetic diseases (19.2%), acute lymphoblastic leukemia (18.1%), and acute myeloid leukemia (13.7%). The diagnosis of SOS was based on the pediatric criteria of European Society for Blood and Marrow Transplantation. We investigated the following 15 laboratory parameters after HSCT before the onset of SOS: international normalized ratio (INR), activated partial thromboplastin time (aPTT), reptilase time, factor VIII, factor XIII, von Willebrand factor (vWF), von Willebrand factor activity (vWF activity), fibrinogen, antithrombin III, protein C, protein S, D-dimer, alanine aminotransferase (ALT), bilirubin, and ferritin. The last laboratory values within one week before the onset of SOS were analyzed in the SOS patient group. In the non-SOS patient group, we investigated the parameters for four weeks after transplantation and calculated the median. We selected cut-off values for the continuous parameters based on receiver operating characteristic curves analyses and existing reference values. We performed Mann-Whitney U test, univariate and multivariate analyses to find significant ( P &amp;lt; .05) associations between the values of laboratory parameters and the occurrence of SOS. The probability of developing SOS was calculated using the significant independent variables. Results: The overall incidence of SOS was 14.8% at a median time of 13 days after HSCT. SOS developed in 24 of 126 allogeneic (19.1%) and in 3 of 56 autologous (5.4%) HSCT patients. Only 3 out of 27 patients (11.1%) who suffered from very severe SOS died within 100 days after HSCT. In the univariate analysis, we found significant associations between the onset of SOS and the following parameters: INR ≥ 1.3, aPTT ≥ 40 sec, reptilase time ≥ 18.3 sec, factor VIII ≤ 80%, antithrombin III ≤ 75%, protein C ≤ 48%, D-dimer ≥ 315 µg/L, bilirubin ≥ 9 µmol/L, and ferritin ≥ 3100 µg/L. In multivariate analysis, we confirmed INR ≥ 1.3 [odds ratio (OR) = 8.104, P = .006], aPTT ≥ 40 sec (OR = 10.174, P = .001), protein C ≤ 48% (OR = 5.215, P = .014), and ferritin ≥ 3100 µg/L (OR = 7.472, P = .004) as independent risk factors after HSCT before SOS. If three of the four significant cut-off values were present, the probability of developing SOS was more than 70%. The probability of SOS was 96%, if all four laboratory parameters were changed according to the cut-off values. The values of factor XIII, vWF, vWF activity, protein S, fibrinogen, and ALT were not relevant for the occurrence of SOS. Conclusions: In summary, the laboratory parameters INR, aPTT, protein C, and ferritin were very useful to predict the occurrence of SOS. These four parameters can enable earlier diagnosis and treatment leading to an improved outcome. In addition, this is the first report on a significant association between SOS and high values of INR and aPTT after HSCT before SOS.

Prospective longitudinal analysis of clinical and immunological risk factors associated with oral and gastrointestinal mucositis following autologous stem cell transplant in adults.

The study aimed to characterize the incidence of both oral and gastrointestinal (GI) mucositis, its' associated temporal changes in local and systemic pro-inflammatory cytokines, and to explore predictive clinical and immunological factors associated with their occurrences in hematopoietic stem cell transplant (HSCT). Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood and saliva were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month. Baseline and inflammatory predictors in a repeated time measurement of moderate-severe mucositis were assessed by multiple logistic regression and generalized estimating equations, respectively. Of the 142 patients analyzed, oral mucositis and diarrhea (representing GI mucositis) were reported as 68.3% and 95.8%, respectively. Predictive factors for moderate-severe oral mucositis were BEAM or busulphan-based regimens (odds ratio (OR)=9.2, 95% confidence interval (CI)=1.16-72.9, p-value (p) = 0.005) and vomiting (OR=4.6, 95% CI 1.68-12.3, p= 0.004). Predictive factors for moderate-severe GI mucositis were BEAM or busulphan-based regimens (OR=3.9, 95% CI 1.05-14.5, p= 0.023), female sex (OR = 3.3, 95% CI 1.43-7.44, p= 0.004) and body mass index (OR=1.08, 95% CI 1.02-1.15, p= 0.010). Cytokines analyses were performed in 96 patients. Saliva and plasma interleukin-6 (OR=1.003, 95% CI 1.001-1.004, p< 0.001 and OR=1.01, 95% CI 1.001-1.015, p= 0.029), and plasma tumor necrosis factor-alpha (OR=0.91, 95% CI 0.85-0.99, p= 0.019) were predictive of moderate-severe oral mucositis in a time-dependent model. This study provides real-world evidence and insights into patient- and treatment-related factors affecting oral and GI mucositis in HSCT.

Oral and Gut Microbiota Dysbiosis is Associated with Mucositis Severity in Autologous Hematopoietic Stem Cell Transplantation: Evidence from an Asian Population

Mucositis is a debilitating complication of hematopoietic stem cell transplant (HSCT). It is unclear how changes in the composition of microbiota, which are modulated by geographical location and ethnicity, may influence immune regulation leading to the development of mucositis, and the study of both oral and gut microbiota in a single population of autologous HSCT in the Asian region is lacking. The study aimed to characterize the oral and gut microbiota changes, and the impact on both oral and lower gastrointestinal (GI) mucositis, with its associated temporal changes in a population of adult autologous HSCT. Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood, saliva and fecal samples were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month post-transplant. Longitudinal differences in alpha and beta diversities were determined using Wilcoxon signed-rank test and Permutational Multivariate Analysis of Variance, respectively. Changes in relative abundances of bacteria across timepoint were assessed using the Microbiome Multivariate Analysis by Linear Models function. The combined longitudinal effects of clinical, inflammatory and microbiota variables on mucositis severity were measured using the generalized estimating equation. From the 96 patients analyzed, oral mucositis and diarrhea (representing lower GI mucositis) were reported at 58.3% and 95.8%, respectively. Alpha and beta diversities were significantly different between sample types (p<0.001) and across timepoints, with alpha diversity reaching statistical significance at Day 0 in fecal (p<0.001) and Day+7 in saliva samples (p<0.001). Diversities normalized to baseline by 6-month. Significant microbiota, clinical and immunological factors were associated with increasing mucositis grades. Increasing relative abundances of saliva Paludibacter, Leuconostoc and Proteus, were associated with higher oral mucositis grades, whilst increasing relative abundances of fecal Rothia and Parabacteroides were associated with higher GI mucositis grades. Meanwhile, increasing relative abundances of saliva Lactococcus and Acidaminococcus, and fecal Bifidobacterium were associated with protective effects against worsening oral and GI mucositis grades, respectively. This study provides real-world evidence and insights into the dysbiosis of the microbiota in patients exposed to conditioning regimen during HSCT. Independent of clinical and immunological factors, we demonstrated significant associations between relative bacteria abundances with the increasing severities of oral and lower GI mucositis. The findings presented in our study offer a potential rationale to consider the inclusion of preventive and restorative measures targeting oral and lower GI dysbiosis as interventional strategies to ameliorate mucositis outcome in HSCT patients.

Mel-200 Or Mel-140 , Which One İs More Advantageous? Retrospectively Analysis Of The Multiple Myeloma Patients Treated With Autologous Hematopoetic Stem Cell Transplantation

Background Autologous hematopoietic stem cell transplantation (AHSCT) is one of the standard treatment modalities for patients with multiple myeloma (MM) under 65 years of age. Renal failure, significant disease comorbidity, significantly affects treatment choices. There are conflicting data in the literature regarding the dose of melphalan to be used for AHSCT in patients with renal failure and comorbid conditions. This study aimed to compare the efficacy and side effect data of different melphalan doses in patients with renal failure.&#x0D; Material and Methods The study included 107 patients older than 18 years of age with a diagnosis of MM who underwent AHSCT in our center between January 2010 and January 2019. The data of the patients were analyzed retrospectively. Patients were grouped according to estimated glomerular filtration rate (eGFR:

Low Non Relapse Mortality and Good Hematological Response after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients with Renal Insufficiency at Transplant: A Prospective Société Francaise De Greffe De Moelle-Thérapie Cellulaire Observational Study

Background: High dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (ASCT) is widely used in newly diagnosed multiple myeloma (NDMM) patients as upfront therapy. However, the safety and efficacy of ASCT in patients with renal insufficiency (RI) is controversial, which have led to an inconsistent arbitrary cut-off for creatinine clearance (CrCl) for performing ASCT. Here, we analyzed prospectively the outcomes of NDMM patients with severe RI who underwent ASCT. Methods: We enrolled prospectively, from April 2018 to Sept 2020 in 17 SFGM-TC centers, 50 NDMM patients who had a serum CrCl of <40 mL/min (CKD-EPI) at the time of ASCT. They all received bortezomib-based induction therapy and had achieved at least a partial response before proceeding to ASCT. The recommended dose of melphalan was 140 mg/m2 and it was infused at least 3 x106/kg autologous CD34+ cells. Consolidation/maintenance post-ASCT was according to the physician's choice. The primary endpoint was non-relapse mortality (NRM). Overall survival (OS) and progression free survival (PFS) were estimated with Kaplan-Meier method, and cumulative incidence of relapse (CIR) and NRM were estimated using cumulative incidence function to account for competing events of death without relapse or death unrelated to myeloma. Results: At diagnosis, a renal biopsy was done in 9 (no amyloidosis, 6 cast nephropathy and 3 others). 82% were male. The median medullary plasmocytosis was 42% (11-80), light chain MM was frequent in 28 patients (56%), IgG in 13 (26%), IgA in 8 (16%) and 1 IgD. Seven (16%) had extra medullary disease. The ISS score was I (1), II (7) and III (34) (8 missing). At enrollment at the time of ASCT: median age was 56 years (33-68). Induction chemotherapies had included bortezomib plus IMiDs in 28 (56%) patients, CyBorDex in 17 (34%), bortezomib dex in 4 (8%) and 1 other (2%). Thirty nine patients (80%) had received 4 or less cycles of chemotherapy and 13 (26%) had ≥2 lines of chemotherapy. The pre-transplant disease status was sCR in =3 (6%), CR in =7 (14%), VGPR in =22 (45%), and PR in =17 (35%) of patients (1 not evaluable ( NE)). The number of days of cytapheresis was 2 or less in 93% of cases and the median number of CD34+ cells collected was 5.4 x 106 (1.1-15.1) (3 missing).The HCT-CI score was 0 (4), 1 (8), 2 (11), 3 (11), missing (16) and 97% had a Karnofsky score ≥70%. HDM was 100 mg/m2 in 1, 140 mg/m2 in 44/50 patients and 200 mg/m2 in 5/50 with 6 patients receiving a tandem ASCT. Seventy three percent received consolidation post ASCT (1 missing) and 69% had maintenance therapy (lenalidomide: 53%, thalidomide: 26%, bortezomib: 21%). Toxicity: We observed one death during the first 100 days post-ASCT, secondary to a septic shock on day 42. The median time to neutrophil engraftment (>500/mm3) was 13 days (10-136) and to platelet engraftment (>20 000/mm3) 16 days (8-136). Among patients receiving RBC transfusions (43%) and platelet transfusions (49%), the median number of RBC transfusions was 3 (2-14) and that of platelet transfusions was 2 (1-44). Response: Nine patients (60%) achieved dialysis independence from the time of diagnosis: 15 patients were on dialysis at diagnosis, 6 at the time of ASCT and 4 three months post-ASCT. At 100 days post-ASCT, the hematological response had improved in 62 % of patients, from PR to VGPR (15%), from PR to CR/sCR (15%), from VGPR to CR/sCR (30%) and from CR to sCR (2%). The best response obtained was 4 (9%) PR, 18 (39%) VGPR, 19 (41%) CR and 5 (11%) sCR with one patient relapsing and 3 NE. At 2 years, the NRM was 4% (95% CI: 0%-12%), the OS was 84% (95% CI:74%-95%), the PFS was 70% (95% CI:58%-84%) and the CIR was 30 % (95% CI:17%-43%) (Figure). Conclusions: HDM with ASCT proved to be safe and effective in NDMM patients with RI at transplant. NRM was 4% at 2 years and 62% improved their hematological response. Renal response will be reported. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Estimating the Incidence-Based Cost of Illness Due to Hematopoietic Stem Cell Transplantation Using One-Year Insurance Claim Data in Korea.

Long-term follow-up data are required for incidence-based cost-of-illness (COI) studies, and it is difficult to carry out such assessments. To overcome this limitation, we estimated the acute and maintenance-state costs of hematopoietic stem cell transplantation (HSCT) using 1-year claim data. Using Korean National Health Insurance (NHI) data from 2016, 2017, and 2018, we identified patients receiving HSCT based on the procedure code "X5*" (i.e., HSCT). The post-HSCT group was defined as patients without the "X5*" code, but with the code "Z948 (other transplanted conditions)" and indications of HSCT (referring to those who had received HSCT). Mean annual medical use and costs were computed using the monthly values available for each patient. The mean number of hospitalizations/year, outpatient visits per year, hospitalization days/year, and length of stay (LOS)/hospitalization were 8.14, 35.80, 97.16, and 14.72, respectively, for allogeneic HSCT patients (n = 56); 8.08, 33.58, 73.04, and 10.63, respectively, for autologous HSCT patients (n = 89); 2.93, 29.40, 50.95, and 20.84, respectively, for post-allogeneic HSCT patients (n = 40); and 1.72, 16.38, 30.11, and 19.29, respectively, for post-autologous HSCT patients (n = 252). The estimated annual NHI-covered medical costs (US dollars) were $38,833-$40,876 for the allogeneic HSCT group, $1749-$6744 for the post-allogeneic HSCT group, $21,231-$22,863 for the autologous HSCT group, and $3954-$5352 for the post-autologous HSCT group. This study describes an alternative method for conducting incidence-based COI studies using cross-sectional claims data.

Autologous Hematopoietic Stem-Cell Transplantation in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

IntroductionIn 1995, the use of autologous hematopoietic stem-cell transplantation (AHSCT), which was previously used to treat hematological tumors, was introduced for severe autoimmune diseases such as multiple sclerosis (MS). AHSCT has proven its safety over the past few years due to technical advances and careful patient selection in transplant centers. While most studies have reported that AHSCT led to decreased Expanded Disability Status Scale (EDSS) scores, some patients reported increased EDSS scores following the procedure. Given the contradictory results, we aimed to conduct a comprehensive systematic review and meta-analysis to investigate the efficacy and safety of AHSCT.MethodsPubMed, Web of Science, and Scopus were searched in March 2022 using a predefined search strategy. We included cohort studies, clinical trials, case–control studies, and case series that investigated the efficacy or safety of AHSCT in patients with MS. PICO in the present study was defined as follows: problem or study population (P): patients with MS; intervention (I): AHSCT; comparison (C): none; outcome (O): efficacy and safety.ResultsAfter a two-step review process, 50 studies with a total of 4831 patients with MS were included in our study. Our analysis showed a significant decrease in EDSS score after treatment (standardized mean difference [SMD]: −0.48, 95% CI −0.75, −0.22). Moreover, the annualized relapse rate was also significantly reduced after AHSCT compared to the pretreatment period (SMD: −1.58, 95% CI −2.34, −0.78). The pooled estimate of progression-free survival after treatment was 73% (95% CI 69%, 77). Furthermore, 81% of patients with MS who received AHSCT remained relapse-free (95% CI 76%, 86%). Investigating event-free survival, which reflects the absence of any disease-related event, showed a pooled estimate of 63% (95% CI 54%, 73%). Also, the MRI activity-free survival was 89% (95% CI 84%) among included studies with low heterogeneity. New MRI lesions seem to appear in nearly 8% of patients who underwent AHSCT (95% CI 4%, 12%). Our meta-analysis showed that 68% of patients with MS experience no evidence of disease activity (NEDA) after AHSCT (95% CI 59%, 77). The overall survival after transplantation was 94% (95% CI 91%, 96%). In addition, 4% of patients died from transplant-related causes (95% CI 2%, 6%).ConclusionCurrent data encourages a broader application of AHSCT for treating patients with MS while still considering proper patient selection and transplant methods. In addition, with increasing knowledge and expertise in the field of stem-cell therapy, AHSCT has become a safer treatment approach for MS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00389-x.

P1610: IMPACT OF COVID-19 ON PATIENTS TREATED WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION - A RETROSPECTIVE COHORT STUDY

Background: Early studies of COVID-19 reported high mortality rates in patients with malignancy and who were immunocompromised. The immunosuppression related to autologous hematopoietic stem cell transplantation (ASCT) together with the risk of contracting severe SARS-CoV-2 lead to modifications in the therapy recommendations and, in many cases, to postponed treatment. Aims: To describe how Coronavirus Disease 2019 (COVID-19) affect patients with hematological malignancies treated with ASCT. Methods: This retrospective observational cohort study includes all patients with hematological malignancies treated with ASCT in Sweden from 1 January 2020 until 31 December 2020. Patients who subsequently tested positive for SARS-CoV-2 until 31 March 2021 were analyzed for morbidity, mortality, need for supportive care and risk factors involved in COVID-19. Results: The study identified 442 patients who underwent ASCT in Sweden in 2020, among whom 20 (4.5%) subsequently contracted COVID-19. The overall mortality was 15% and the COVID-19 related mortality 10%. The absolute risk of COVID-19 related mortality was 0.45% among patients treated with ASCT. Six (35%) patients were hospitalized, among which four (24%) needed supplementary oxygen and two (12%) intensive care. Image:Summary/Conclusion: ASCT patients have a higher risk of severe outcome of COVID-19 compared to the general population. The risk of death, need for hospital care, oxygen and intensive care was lower in this study compared with most previous studies, possibly because of less missing asymptomatic patients. The risk of contracting SARS-CoV-2 was comparable with the general population. This study support performing ASCT for treatment of hematological malignancies despite the COVID-19 pandemic.

Financial incentives to increase stool collection rates for microbiome studies in adult bone marrow transplant patients.

In order to study the role of the microbiome in hematopoietic stem cell transplantation (HCT), researchers collect stool samples from patients at various time points throughout HCT. However, stool collection requires active subject participation and may be limited by patient reluctance to handling stool. We performed a prospective study on the impact of financial incentives on stool collection rates. The intervention group consisted of allogeneic HCT patients from 05/2017-05/2018 who were compensated with a $10 gas gift card for each stool sample. The intervention group was compared to a historical control group of allogeneic HCT patients from 11/2016-05/2017 who provided stool samples before the incentive was implemented. To control for possible changes in collections over time, we also compared a contemporaneous control group of autologous HCT patients from 05/2017-05/2018 with a historical control group of autologous HCT patients from 11/2016-05/2017; neither autologous HCT group was compensated. The collection rate was defined as the number of samples provided divided by the number of time points we attempted to obtain stool. There were 35 allogeneic HCT patients in the intervention group, 19 allogeneic HCT patients in the historical control group, 142 autologous HCT patients in the contemporaneous control group (that did not receive a financial incentive), and 75 autologous HCT patients in the historical control group. Allogeneic HCT patients in the intervention group had significantly higher average overall collection rates when compared to the historical control group allogeneic HCT patients (80% vs 37%, p<0.0001). There were no significant differences in overall average collection rates between the autologous HCT patients in the contemporaneous control and historical control groups (36% vs 32%, p = 0.2760). Our results demonstrate that a modest incentive can significantly increase collection rates. These results may help to inform the design of future studies involving stool collection.

A Propensity Score Matching Study of Autologous Hematopoietic Stem Cell Transplantation and New Drug Chemotherapy for Newly Diagnosed Multiple Myeloma

To compare the clinical efficacy, survival, and prognosis of autologous hematopoietic stem cell transplantation (ASCT) with new drug chemotherapy in the treatment of newly diagnosed multiple myeloma (NDMM) in the new drug era. The clinical data of 149 patients with NDMM treated with new drug induction regimen in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2012 to December 2019 were retrospectively analyzed. Twenty-four patients who received ASCT were in ASCT group, and 125 patients who did not receive ASCT were in non-ASCT group. The median follow-up time was 43 (1-90) months. The propensity score matching (PSM) method was used to balance confounding factors, then depth of response, overall survival (OS), and progression-free survival (PFS) between the two groups were compared and subgroup analysis was performed. After matching, the covariates were balanced between the two groups. Fifty-one patients (15 cases in ASCT group and 36 cases in non-ASCT group) were included. ASCT patients had a better complete response (CR) rate than non-ASCT patients receiving maintenance therapy (93.3% vs 42.3%, P=0.004), while there were no statistical differences in deep response rate and overall response rate (ORR) between the two groups (93.3% vs 65.4%, P=0.103; 93.3% vs 96.2%, P=1.000). Before matching, the 3 and 5-year PFS rate and median PFS (mPFS) in ASCT group and non-ASCT group were [89.6% vs 66.5%, P=0.024; 69.8% vs 42.7%; non-response (NR) vs 51.0 months], and the 3 and 5-year OS rate and median OS (mOS) were (100% vs 70.6%, P=0.002; 92.3% vs 49.6%; NR vs 54.0 months). After matching, the 3 and 5-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.6% vs 61.7%, P=0.182; 62.7% vs 45.7%; NR vs 51.0 months), the 3 and 5-year OS rate and mOS were (100% vs 65.6%, P=0.018; 88.9% vs 46.9%; NR vs 51.0 months). Subgroup analysis showed that patients with mSMART 3.0 high risk stratification, the 3-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.3% vs 41.5%, P=0.091; NR vs 34.0 months), and the 3-year OS rate and mOS were (100% vs 41.5%, P=0.034; NR vs 34.0 months). Patients with mSMART 3.0 standard risk stratification, the 3-year PFS rate and OS rate in ASCT group and non-ASCT group were (83.3% vs 76.8%, P=0.672; 100% vs 87.2%, P=0.155). The 3-year PFS and OS rate in MM patients who achieved deep response within 3 months after transplantation compared with non-ASCT patients who achieved deep response after receiving maintenance therapy were (83.1% vs 56.7%, P=0.323; 100% vs 60.5%, P=0.042), and the 3-year PFS and OS rate in patients who achieved overall response in both groups were (83.1% vs 62.5%, P=0.433; 100% vs 68.1%, P=0.082). After matching, Cox multivariate regression analysis showed that mSMART 3.0 risk stratification and ASCT were independent prognostic factors for OS. In the new drug era, ASCT can increase CR rate and prolong OS of NDMM patients. ASCT patients who are mSMART 3.0 high risk stratification or achieved deep response within 3 months after transplantation have better OS than non-ASCT patients receiving new drug chemotherapy. ASCT and mSMART 3.0 risk stratification are independent prognostic factors for OS in NDMM patients.

Application of Conditioning Regimen with Busulfan and Cyclophosphamide in Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

To evaluate the safety and efficacy of BUCY (busulfan and cyclophosphamide) conditioning regimen for autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM). The clinical data of 72 MM patients received transplantation in the Hematology Department of the First Affiliated Hospital of Soochow University from May 2012 to June 2015 were retrospectively analyzed. Among them, 36 patients received BUCY conditioning regimen while the others received high-dose melphalan (HDM) conditioning regimen. The complication, post-transplantation hematopoietic reconstitution and efficacy between the two groups were compared. There were no significant differences in sex, age, isotype, stage, induction therapy, mobilization method and proportion of conditioning regimen with Bortezomib between the two groups. The median time of neutrophil engraftment for the patients in BUCY and HDM groups was 10 (8-17) and 10 (9-13) d (P=0.046), and the median time of platelet engraftment was 10 (8-18) and 11 (9-47) d (P=0.017), respectively. The transplant related mortality of the patients in both groups was 2.7%. The CR rates of the patients after ASCT (38.9% and 50.0%) were higher than those before ASCT (27.8% and 19.4%) in the two groups. For the patients in BUCY group, the median follow-up time was 45 (0-61) months. Fifteen patients (41.7%) achieved disease progression. While for the patients in HDM group, the median follow-up time was 52(0-75) months. Twenty-two patients (61.1%) achieved disease progression. The BUCY conditioning regimen is a safe and effective therapy for ASCT in patients with MM. Besides, in terms of safety and efficacy, BUCY regimen is not inferior to HDM regimen. BUCY regimen may replace HDM regimen as a standard conditioning regimen for ASCT in MM.

P-195: Salvage autologous stem cells transplantation and maintenance therapy in relapsed refractory multiple myeloma

<h3>Background</h3> Multiple myeloma (MM) is an incurable hematological neoplasm. However, new therapies have improved overall survival (OS). In relapsed/refractory MM (RRMM) and a resource-limited environment, optimizing treatment options is essential. Autologous hematopoietic stem cell transplantation (ASCT) is an available strategy, frontline and at relapse <h3>Objective</h3> to analyze overall survival (OS2) and progression-free survival (PFS2) in RRMM patients comparing second-line consolidation strategies. <h3>Methods</h3> This retrospective survival analysis study, based on the Uruguayan Multiple Myeloma Registry, included all RRMM adult patients <66 years diagnosed in 2010-2020 who received second-line therapy. RRMM was defined according to international criteria. OS2 and PFS2 were measured from the identification of relapse until death/last control and progression, respectively. We used SPSSv.25 for statistical analysis. Survival was analyzed using Kaplan-Meier model with Log-Rank test, and Cox regression model along with hazard ratios (HR) <h3>Results</h3> Fifty-nine patients were included, with a median age at diagnosis of 56 years (IQR 12), 49.1% were male, 70.10% IgG, 84.75% were Durie-Salmon stage (DS) III and 37.3% ISS-III, 27.1% ISS-II, and 30.5% ISS-I. Age, ISS, and DS were not statistically different between therapeutic groups. Most (69.5%) patients had received a first ASCT, and 35.6% received maintenance as first-line therapy. Maintenance therapy was lenalidomide in 20.3%, thalidomide in 6.8%, and 8.5% other options. Eleven patients (18.6%) received salvage ASCT and maintenance, 18.6% received only ASCT, 16.9% received only maintenance and 45.8% neither ASCT nor maintenance. The median OS2 was 34 months, and PFS2 was 26 months. The 3-year OS2 and 3-year PFS2 were 47.2% and 32.2% for the entire cohort, respectively. The combination of ASCT and maintenance achieved a 3-year OS2 of 75.0% whereas OS2 in the non-combined therapy (NCT)(ASCT or maintenance) was 50.7% (HR 0.1, CI95% 0.01 to 0.6, p=0.01). ASCT and maintenance achieved a 3-year PFS2 of 43.1% whereas PFS2 was 37.6% for the NCT (HR 0.2, CI95% 0.1 to 0.7, p=0.01). The 3-year OS2 was 50.7% for those who received ASCT or maintenance vs. 28.4% for those without second-line consolidation (HR 0.3, CI95% 0.2 to 0.9, p=0.02). The 3-year PFS2 was 37.6% for patients who received any of the consolidative strategies vs 19.1% (HR 0.4, CI95% 0.2 to 0.9, p=0.02) in those who did not receive salvage ASCT or maintenance <h3>Conclusion</h3> ASCT has been recommended for patients relapsing after primary therapy, including an ASCT with an initial remission duration of >18 months. The role of salvage ASCT in patients who received lenalidomide maintenance has not been determined. In our analysis, the combination of ASCT and maintenance improved the OS2 and PFS2 compared to those treated with only ASCT or maintenance. Not receiving second-line consolidation was associated with inferior PFS2 and OS2.

Hematopoietic Stem Cell Transplantation for Children with Neurological Diseases Improves the Outcomes and Not Leads to Significant Late Effects — Report from Russian Group

Strong evidence of safety, tolerability, efficacy and low rate of late effects presence after hematopoietic stem cell transplantation (HSCT) required for children with severe refractory cases of neurological diseases.We aimed to analyze the effectiveness of both allogenic and autologous hematopoietic stem cell transplantation for all cohorts of patients with neurological diseases based on safety, tolerability and late effects rate.Sixty three patients enrolled to the analysis transplanted 2004 - 2017. Diagnosis: Hurler syndrome (HS) - 40 patients, multiple sclerosis (MS) - 13 patients, metochromatic leukodystrophy (ML) - 4 patients, neuromyelitis optica (NMO) - 3 patients. Median of age 11,8 years old (3 months - 17,4 years old). Most of the patients were girls (n=39, 61,8%). All patients were with confirmed diagnosis by clinical and laboratory testing, imagining. Patients with autoimmune disorders (AD) were treated with different immunosuppressive drugs without effect. MS patients received autologous hematopoietic stem cell transplantation (HSCT) with peripheral blood stem cells (PBSC), other patients - allogenic HSCT both from related and unrelated donors. For allogenic HSCT bone marrow (BM) was used in 32 cases, PBSC - in 13 and cord blood (CB) - in 2 cases (for HS only). In 34 cases HSCT from unrelated donor were done. MS patients received Cyclophosphamide and ATG based chemotherapy before autologous HSCT, NMO and ML patients received Treosulfan, Fludarabine, Rituximab and ATG (if unrelated donor). In case of HS myeloablative conditioning (MAC) regimen was used for 29 patients and reduced intensity conditioning (RIC) - for 11 patients. RIC: Fludarabine, Melphalan, ATG. MAC: Busulfan/Treosulfan, Fludarabine, Thiotepa/Melphalan and ATG with Rituximab (in case of unrelated donors). Patients received CsA/Tacro-based with MMF/MTX GvHD prophylaxis for all allogenic cases. In 3 RIC HSCT for HS immunomagnetic СD3/СD19+ depletion of PBSC was used.All MS patients improved fast. Median follow-up of MS pts. 48,7±2,4 months (10-84 months). Two MS patients relapsed (clinical and MRI). Median of engraftment day - +10. No severe complications registered. All patients after allogenic HSCT engrafted (full donor chimerism on day +30). Median of engraftment day - 21 (11-30 days). Thirty nine patients after allogenic HSCT survived. Reasons of death: infections - 4 pts., TRALI - 1 pt., aGvHD - 1 pt. TRM improved, over the years, with improving of supportive care and donor selection as well as pre-transplant screening. No early severe toxicity revealed. GvHD: grade II - 17 patients, grade III-IV - 3 patients, local cGVHD - 3 patients. No patients had extensive cGvHD. All 5 rejected patients were with HS (MAC and RIC rejection rate was same). At median follow up of 60 months (8-160 months), the estimated probability of 5 years OS is 87%. All patients with complete donor's chimerism have good neurological response (best response correlated with early HSCT for all patients). Better status before HSCT correlated with better outcome. Cardio-vascular effects (EF decreasing) were most common for MS patients (n=7), progressive skeletal deformation - for HS patients (totally 17 cases), in one of them operative reconstitution was performed, endocrine (thyroid dysfunction, growth hormone deficiency) - for MS, NMO and HS patients (n=8), late immune reconstitution - for 1 case (NMO patient). Median period of late effects arising after HSCT was 21 month (12-27 months). All survived patients (MS, HS, ML, NMO) improved deficit in neurocognitive sphere in different grade but needed in special rehabilitation.Thus, this is the first analysis of outcomes and late effects of a group of children received HSCT for neurological diseases, especially for AD. HSCT is successful approach for patients with such diseases. In-time HSCT can significantly improve the outcome. Most of the patients remain in remission during the long time of follow-up. Long-time follow-up showed that these patients require the special observational protocol including estimation of cardio-vascular, skeletal, endocrine and neurocognitive risks. Better neurocognitive response correlated with intensive rehabilitation using computer model. Russian Joint study showed effective cooperation for treatment of such patients in the national setting. DisclosuresNo relevant conflicts of interest to declare.

Autologous Hematopoietic Stem Cell Transplantation (AHSCT): An Evolving Treatment Avenue in Multiple Sclerosis.

Autologous hematopoietic stem cell transplantation (AHSCT) is considered as the novel approach to improve multiple sclerosis (MS) patients with disease-modifying therapies (DMTs)-resistance. The results obtained from different studies indicate that AHSCT increases the life quality of MS patients. Several factors are known to be influenced on the successful rate of AHSCT in patients with MS. The individuals aged <40 years with a short duration of MS disease have been demonstrated to show a better response to AHSCT administration. Furthermore, this treatment approach was more effective in relapsing remitting MS (RRMS) patients than progressive MS (PMS). Different clinical trials revealed that AHSCT with a low density conditioning regimen could be suggested as a suitable candidate approach in the management of MS. Several molecular and cellular mechanisms are known to be involved in the resetting of the immune system following the AHSCT infusion in MS patients. These mechanisms play a role in the depletion of auto-reactive lymphocytes and immune system renewal. In the present review, we discuss different clinical and molecular aspects of AHSCT application in the alleviation of MS symptoms.

Use of Backup Stem Cells for Stem Cell Boost and Second Transplant in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient stem cells in case there is a need for stem cell boost for delayed/poor engraftment or for future second ASCT. However, collecting and storing backup stem cells in all patients requires significant resources and cost, and the rates of backup stem cell utilization are not well studied. We sought to examine the utilization of backup stem cells (BSCs) in patients with MM undergoing ASCT. Patients with MM aged ≥18 years old who underwent first ASCT at our institution from January 2010 through December 2015 and collected sufficient stem cells for at least 2 transplants were included in this single-center retrospective study. This timeframe was selected to allow for adequate follow-up. A total of 393 patients were included. The median age was 58 years (range, 25-73). After a median follow-up of 6 years, the median progression-free survival (PFS) of the cohort was 3 years. Sixty-one percent (n=240) of patients progressed or relapsed. Chemotherapy-based mobilization was used in almost all patients (98%). The median total CD34+ cells collected was 18.2×106/kg (range, 3.4-112.4). A median of 5.7×106 CD34+ cells/kg (range, 1.8-41.9) was infused during the first ASCT, and a median of 10.1×106 CD34+ cells/kg (range, 1.5-104.5) was cryopreserved for future use. Of the patients, 6.9% (n=27) used backup stem cells, with 2.3% (n=10) using them for stem cell boost, 4.6% (n=18) for a second salvage ASCT, including 1 patient for both stem cell boost and second ASCT. Rates of backup stem cell use among patients aged <60, 60-69, and ≥70 years were 7.8%, 5.7%, and 5.9%, respectively. There was a trend toward higher rates of backup stem cell use for second ASCT in patients who were younger, had suboptimal disease control at time of first ASCT, and longer PFS. The median dose of stem cell boost given was 5.6×106 CD34+ cells/kg (range, 1.9-20). The median time from stem cell boost to neutrophil, hemoglobin, and platelet engraftment was 4 (range, 2-11), 15 (range, 4-34), and 12 (range, 0-34) days, respectively. Lower CD34+ dose and older age at time of ASCT predicted need for stem cell boost. With new salvage therapies for relapsed MM, the rates of second ASCT are very low. The low rates of use suggest that institutional policies regarding universal BSC collection and long-term storage should be reassessed and individualized. However, need for stem cell boost in 2.3% of patients may present a challenge to that.

449 - Efficacy of Oral Ribavirin in Respiratory Syncytial Virus Infection in Hematopoietic Stem Cell Transplant Patients: A Single-Centre Experience

Background: Respiratory syncytial virus (RSV) is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematological malignancy or a hematopoietic stem cell transplantation (HSCT). In immunocompromised patients including HSCT recipients, RSV can progress to a more severe lower respiratory infection (LRI), often complicated by respiratory failure leading to increased morbidity and mortality. Little is known about the best management strategy in this immunocompromised group and strategies to manage RSV is challenging. Data on aerosolized ribavirin to treat RSV infections in HSCT recipients come from small, retrospective studies with heterogeneous treatment combinations but nevertheless, have shown to prevent poor outcomes. There is very little data on oral ribavirin treatment but the retrospective data so far has been promising. Aim: To evaluate the effectiveness of oral ribavirin in HSCT patients with RSV infection at our centre in London, Ontario. Methods: Eighteen HSCT patients with RSV were analyzed retrospectively. In 2012, there were 5 patients treated with supportive care alone. After 2012, there were 13 patients treated with oral ribavirin. RSV diagnosis was established by polymerase chain reaction assay via nasopharyngeal swabs. Oral ribavirin was initiated at 15 mg/kg/day in three divided doses for 7-10 days with possibility of extension in persistently symptomatic patients. An immunodeficiency scoring index (ISI) was used to classify patients as low, moderate, or high risk for progression to lower respiratory infection (LRI) or death. Findings: An outbreak of RSV occurred in our oncology unit in early 2012 where 5 HSCT patients ((3 autologous HSCT and 2 allogeneic HSCT patients) contracted RSV infection as well. No definitive treatment options were available during this period and patients were managed with supportive care alone. 4/5 HSCT patients died of RSV infection leading into an 80% mortality rate. This experience led to the development of a protocol for the HSCT patients focusing on prevention of nosocomial transmission, early PCR testing and treatment with oral ribavirin for those confirmed with RSV infection and signs of pneumonia or LRI. Since 2012, 13 HSCT patients (4 autologous HSCT patients and 9 allogeneic HSCT patients) were diagnosed with RSV infection and promptly treated with oral ribavirin. The median treatment duration was 10 days (range: 7-12). All patients treated with oral ribavirin survived the infection. Oral ribavirin was well tolerated with minor adverse effects. Conclusion: We found that HSCT patients with lower respiratory RSV infections can be successfully managed by use of prevention strategies and oral ribavirin. Although, our experience reflects a small sample size, the protocol was associated with decreased mortality compared to patients who received supportive care alone. Our experience supports the use of oral ribavirin for the early treatment of HSCT patients with RSV associated LRI and may be an alternative to aerosolized RBV. But ongoing review of our experience with this protocol is necessary and large prospective studies are needed to determine the optimal therapy in this patient group. Disclosures No relevant conflicts of interest to declare.

Safety and Efficacy of Consolidation Therapy with Ipilimumab Plus Nivolumab after Autologous Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation (ASCT) is a standard-of-care treatment for many hematologic malignancies. Progression of disease after ASCT is the primary cause of treatment failure. In this Phase Ib trial, we studied the safety and clinical effect of combined checkpoint inhibition therapy (CPIT) with ipilimumab and nivolumab as a consolidation strategy after ASCT for patients with high-risk diffuse large B cell lymphoma (DLBCL), mature T cell lymphoma (TCL), and multiple myeloma (MM). Starting at 14 to 28 days after ASCT, patients received ipilimumab (1 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 16, and 22) and nivolumab (3 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, and 26). Patients received a median of 5 doses of ipilimumab and 8 doses of nivolumab. Thirty-five patients were included in the intent-to-treat population. Ninety-four percent of the patients experienced immune-related adverse events (irAEs) of any grade. Ninety-seven percent of irAEs resolved spontaneously or after holding study drugs and instituting high-dose corticosteroid therapy. Progression-free and overall survival at 18 months post-ASCT for each disease cohort were 85.7% and 100% for primary refractory DLBCL, 28.6% and 57.1% for relapsed DLBCL, not evaluable and 80% for frontline TCL, 25% and 75% for relapsed TCL, 57.1% and 87% for high-risk transplant-naïve MM, and 40% and 100% for MM relapsed within 3 years of first ASCT. We conclude that combined CPIT appears to be tolerable as a consolidation strategy after ASCT and in addition to the potential clinical efficacy observed in some subsets of disease, T cell receptor repertoire, T regulatory cell phenotype, and gut microbiota profiles provide a biologic rationale warranting further study of this approach.