Wolf, Robert Christian

e19008 Background: Cytokine release syndrome (CRS) is typically reversible in CAR-T therapy, while hyperinflammatory syndromes like macrophage activation-like syndrome (MAS-L) and high-grade immune effector cell-associated hemophagocytic syndrome (IEC-HS) are associated with significant morbidity and mortality. Early interventions are critical for improving outcomes. We aim to analyze clinical cytokine assays and cellular phenotypes early in hyperinflammatory syndromes to identify profiles for severe cases to inform management decisions. Methods: This study included 113 CAR-T patients (pt) (September 2019-March 2024) with cytokine profiles (CP) performed at the second tocilizumab dose or with suspected hyperinflammatory states (CP1), followed by assessments at 24 hours (CP24) and 48 hours (CP48). 52 pts consented to blood (PB) and bone marrow (BM) cell immune phenotyping at pre-treatment (pre-LD) and day 1 for PB. Results: Among the 113 pts, CRS pts (N=74), when compared to MAS-L(N=19) & IEC-HS (N=20) at CP1, had lower levels of TNF (median in pg/mL; 31, 62.9, 47.7) , IL-18 (794, 1353, 2011), and MCP-1 (689, 2722, 2485.5). While MAS-L and IEC-HS had similar CP1 profiles, CP24 and CP48 differed between them: TNF & MCP-1 levels decreased in MAS-L but remained elevated or increased in IEC-HS. IL-18 was stable in MAS-L but increased steadily daily in IEC-HS. Infections were more frequent in IEC-HS (CRS: 43%; MAS-L: 58%; IEC-HS: 85%; p=0.002). Notably, patients who died with persistent E. faecium bacteremia had higher IL-18 in CP48. In the 52 pts with cell phenotypes available by flow, 33 had CRS, 18 MAS-L and 8 IEC-HS. The correlation between cell phenotypes and cytokine levels showed that elevated TNF at CP1 correlated with increased non-classical monocytes in pre-LD BM and higher NK and NK-T cells in pre-LD PB. Similarly, elevated IL-18 CP48 levels correlated with increased CD8 T-cells, NK-T cells, and intermediate monocytes in pre-LD PB, as well as increased NK cells at both pre-LD and day 1 (Table). Conclusions: We report distinct cytokine profiles in IEC-HS early in the inflammatory course post-CAR-T therapy. These elevated cytokines correlate with specific immune cell subsets, including BM-resident monocytes, intermediate monocytes with heightened cytokine trafficking and inflammatory capacity. This study demonstrates the feasibility for identifying potential biomarkers for early risk stratification and targeted interventions. Cytokine Sample source Immune cells R P value TNF CP1 BM pre-LD Non-classical monocytes (CD14loCD16+) 0.38 0.025 PB pre-LD Monocytes (All) 0.47 0.022 NK cells (CD56+CD16+) 0.34 0.024 NK-T cells (CD3+CD56+CD16-) 0.29 0.04 IL-18 CP48 PB pre-LD CD8+ T-cells 0.59 0.0093 NK-T cells (CD3+CD56+CD16-) 0.53 0.023 Intermediate monocytes (CD14+CD16+) 0.58 0.012 PB pre-LD NK cells (CD56+CD16+) 0.56 0.49 0.015 0.024

ABSTRACTTransplant‐associated thrombotic microangiopathy (TA‐TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high‐risk features on the clinical outcomes of adult patients meeting the updated TA‐TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA‐TMA at Mayo Clinic Rochester (incidence 6.2%) after a median of 137 days post alloHCT (IQR: 34–283 days). The development of TA‐TMA was associated with an inferior overall survival posttransplant (HR: 3.8, 95% CI: 2.97–4.72). High‐risk features, including concomitant infection, acute graft‐versus‐host disease (GVHD), and organ dysfunction, were associated with poor survival, while LDH elevation was not associated with inferior outcomes. The most common treatment strategy for TA‐TMA was discontinuation of calcineurin or mTOR inhibitors in 80 (81%) patients. Thirty (37.5%) patients experienced worsening of GVHD with this strategy, of which 26 (86.7%) patients had died at last follow‐up. The most common cause of death among these patients was worsening GVHD (69%; n = 18), followed by infection (11%; n = 3), disease relapse (8%; n = 2), other/unknown causes (8%; n = 2), or TA‐TMA (4%; n = 1). Objective response rate (ORR) to initial treatment for the cohort was 56.6%. Eculizumab was used in 11 patients with an observed ORR of 70%, including 5 complete responses. In conclusion, TA‐TMA remains a significant contributor to non‐relapse mortality and is associated with worse survival following alloHCT. Not all high‐risk features, particularly LDH elevation, have consistently demonstrated a negative impact in adult cohorts. Patients with TA‐TMA may benefit from immune suppression dose adjustment, rather than a discontinuation, and the addition of complement‐directed therapy, particularly among high‐risk patients.

Background: There is an increased risk of second primary malignancies including second hematological malignancies (SHM) in multiple myeloma (MM) patients undergoing autologous stem cell transplant (auto-SCT) followed by lenalidomide maintenance. We analyzed the characteristics and outcomes of patients who developed SHM after an auto- SCT for MM. Methods: A retrospective study of all MM patients who underwent auto- SCT at Mayo Clinic, Rochester between January 1, 1990, and 31 August 2023 and later developed SHM. Demographic, clinical and pathologic data were collected retrospectively. Overall survival (OS) was calculated from the date of auto-SCT to the date of last follow up. Statistical analyses were performed using GraphPad prism 9.0. Chi-square test was used to calculate the difference between categorical variables. Kaplan Meier method and log rank test were used to estimate OS. Results: Among 3513 patients who underwent at least 1 auto-SCT, 104 (2.9%) developed a SHM at a median follow up of 59 (range, 0.2-265) months. Patients who developed SHM, more frequently received pretransplant alkylating agents (37.5 vs 24.2 %, odds ratio [OR], 1.87; P=0.003) and topoisomerase II inhibitors (anthracyclines/etoposide) (17.3% vs 10.4%, OR [1.79]; P=0.03) compared to a control group of MM patients without SHM. Further, exposure to lenalidomide (77.8% vs 57.6%, OR[2.59]; P <0.0001) and radiation therapy (32.6% vs 23.1%, [1.54]; P=0.04) were more often seen in the SHM cohort compared to control group. Among the 381 patients who underwent > 1 auto- SCT, 3.1% developed SHM. Therapy related myeloid neoplasms (t-MN) accounted for 90.3% of cases [n=94; t-myelodysplastic syndrome (t-MDS=64), t-acute myeloid leukemia (t-AML=12), t-MDS transformed to AML(n=16), chronic myeloid leukemia (n=1), MDS/myeloproliferative neoplasm overlap syndrome (n=1)]. Eight patients (7.6%) developed therapy related B- cell acute lymphoblastic leukemia (t-ALL); Philadelphia (Ph) negative ALL (n=7) and Ph- like ALL (n=1). One patient each developed mixed phenotype acute leukemia and acute leukemia, not otherwise specified. Sixty patients (57.6%) were males and the median age at diagnosis of SHM was 70 (range, 43-84) years. The median time from auto-SCT to diagnosis of SHM was 58.5 (range, 7-236) months. In a multivariate analysis, receiving an alkylating agent (hazard ratio [95% confidence interval]: 2.51 [1.54 to 4.01]; P = 0.0002) and/or topoisomerase II inhibitor as induction for MM (3.12 [1.59 to 5.88]; P = 0.0006), exposure to lenalidomide (7.08 [3.92 to 13.50]; P = <0.0001) and radiation therapy (1.60 [1.02 to 2.44]; P = 0.03) were independent predictors of developing SHM. At diagnosis, 57% (n=37) of t-MDS and 71% (n=20) with t-AML had high risk disease per R-IPSS and 2022 European Leukemia Net respectively. Clonal abnormality in chromosome 5 and/or 7 was present in 45% (n=42) of patients. Complex and monosomal karyotype was seen in 32% (n=30) with t-MN. The most frequently mutated genes based on next generation sequencing data included TP53 (n=33), DNMT3A (n=9), RUNX1 (n=5), TET2 (n=4) and CEBPA (n=4). In the t-MDS/AML cohort, 3 patients (3.1%) underwent second auto-SCT and 9 (9.5%) received allogenic SCT (allo-SCT) for SHM. After a median follow-up of 27.2 months, the median OS from t-MDS/AML diagnosis was 8.04 months (95%CI, 6.1-11.0 months) and there was no difference in median OS for allo-SCT recipients versus nonrecipients (9.1 vs 6.8 months, P =0.19). In the t-ALL (n=8) cohort, all of them received lenalidomide based induction and five received lenalidomide maintenance. Most of the t-ALL patients had adverse risk cytogenetics [IKZF1 deletion (n=2), complex karyotype (n=2), TP53 mutation (n=1) and P2RY8-CRLF2 fusion (n=1)]. Three patients with t-ALL underwent allo-SCT and the median OS for allo-SCT recipients versus non recipients were 8.3 vs 7.9 months respectively, P=0.50. Among patients with SHM, 92.3% (n = 96) have died with SHM (72%) being the most common cause of death. MM patients who developed SHM had an inferior OS when compared to those without SHM (median OS, 75 vs 90 months, P =0.006). Conclusion: SHM following auto-SCT tends to have aggressive disease biology with poor outcomes. Short term follow up underestimates the risk of SHM and the higher incidence noted in our study may be due to longer follow up. As the OS in MM patients continues to improve, SHM remains an important challenge in improving long term outcomes.

Background and Methods: IEC-HS is a hyperinflammatory state with high morbidity and mortality. Effective interventions to reverse the process early in the clinical course may be critical to improve outcomes. We previously examined cytokine differences between IEC-HS and other secondary hemophagocytic lymphohistiocytosis, and found significant differences in the patterns and outcomes.(1) This study examines cytokine profiles (CP) of patients treated with CAR-T from 9/2019 to 3/2024 who developed CRS, MAS-L and IEC-HS. Demographics and lab results were compared among the three groups and correlated with outcomes. Results: CP was tested in 113 of 366 CAR-T patients: 74 with CRS, 19 with MAS-L, and 20 with IEC-HS. The racial distribution was 93% White/Caucasian, 2% Black or African American, 1% Asian, 1% Native American and 3% other or unavailable. No differences were seen in demographics between groups except a higher percentage of patients with ECOG performance status ≥2 in IEC-HS (p=0.037). Incidence of IEC-HS by disease: 3.6% (7/193) in lymphoma, 5% (8/159) myeloma and 28.5% (4/14) B-acute lymphoblastic leukemia (p=0.0002). Incidence of IEC-HS by CAR-T product: 3% (4/150) in Axi-cel, 23% (6/26) in Brexu-cel, 8% (1/13) in Tisa-cel, 5% each (3/60) in Cilta-cel and Ide-cel, and 0/17 in Liso-cel (p=0.001). Prior to lymphodepletion, labs were already different among the CRS, MAS-L, and IEC-HS groups: hemoglobin (g/dL: 11.1, 9.6, 8.45); platelets (x109/L: 168, 116, 52.5); ferritin (µg/L: 115, 946, 1944). CP was started when patients needed a second dose of tocilizumab or concern for developing MAS-L/IEC-HS, and continued daily until clinical improvement or resolution of inflammatory state. Tocilizumab and dexamethasone use were similar across groups. Other therapies used were vasopressors (3%, 10.5%, 45%; p<0.0001), Methylprednisolone (20%, 31.6%, 50%; p=0.027), Anakinra (12%, 63%, 85%; p<0.0001), Siltuximab (9.5%, 16%, 30%; p=0.06), Basiliximab (30% of IEC-HS), and continuous veno-venous hemofiltration (30% of IEC-HS). Among the first CP, the CRS group had lower levels of cytokines (in pg/mL) compared to MAS-L and IEC-HS groups: TNF (31, 62.9, 47.7), IL-10 (29.3, 97.7, 169), IL-18 (794, 1353, 2011), IFN-gamma (74, 281, 250), MCP-1 (689, 2722, 2485.5), MIP-1 alpha (220, 234, 247.5), IL-6 (>315: 45%, 79%, 70%), soluble IL-2R alpha (>4000: 45%, 84%, 70%). The percentage of patients who received anakinra before CP1 were 4% (CRS), 21% (MAS-L) and 25% (IEC-HS) (p=0.007). IL-1 beta was below threshold among all patients who received anakinra in CRS and MAS-L and 75% in IEC-HS, suggesting rapid and effective IL-1 suppression by anakinra except in IEC-HS. Cytokines trends 24 hours and 48 hours after the first CP differed between MAS-L and IEC-HS. MAS-L had decreased TNF (62.9, 40.4, 18.5) and MCP-1 (2722, 355, 104) while these cytokines remained elevated or increased in IEC-HS (TNF: 47.7, 105.5, 62.6; MCP-1: 2486, 2276, 1585). IL-18 was minimally elevated in MAS-L (1353, 1955, 3068) and significantly increased in IEC-HS (2011, 2420, 4048). Notably, CP2 and CP3 levels of these cytokines in IEC-HS were statistically significantly higher than corresponding CPs among CRS and MAS-L. In addition, patients who died with persistent E. faecium bacteremia had higher IL-18 on CP3. Infections occurred in 43%, 58%, and 85% respectively (p=0.002), including E. faecium bacteremia (3%, 5%, 35%; p=0.0004), CMV viremia (30% of IEC-HS patients vs. 11% of non-IEC-HS; p=0.025), and invasive fungal infections (15% of IEC-HS patients; p=0.0001). Between the IEC-HS and non-IEC-HS groups, day 100 non-relapse mortality was 35% vs. 0 (p<0.0001), day 100 all-cause mortality was 45% vs. 3% (p<0.0001), and E. faecium bacteremia-related deaths were 50% vs. 1% (p<0.0001). Conclusions: CRS, MAS-L andIEC-HS are known complications of CAR-T. Cytokine-directed therapy can modify the cytokine milieu and control the inflammatory process. However, excess immunosuppression may result in life-threatening infections. Further studies are needed to identify optimal biomarker-guided immunosuppressive strategies to control the inflammatory cascade, while avoiding excess immunosuppression. References: 1. Leung, Nelson, et al. “Outcomes of patients who received CAR T cell therapy and developed IEC-HS treated with cytokine directed therapy.” (2024): 7516-7516.

7516 Background: Immune effector cell hemophagocytic lymphohistiocytosis IEC-HS is a complication of CAR T cell therapy (CART). This study aims to look at the outcomes of CART patients who develop IEC-HS. Methods: Patients who developed IEC-HS after receiving CART and patients who developed IEC-HS without (nonCART) between December 2020 and March 2022 were included. Results: The 20 CART patients were older than the 25 nonCART patients. Peak ferritin, fibrinogen, CRP, serum creatinine and transaminases were similar between the 2 group. CART patients had lower white blood cell count and platelets and bilirubin than the nonCART patients. CART patients were more like to have markedly elevated IL-6 levels (> 315 mg/ml), higher IL-18, higher MCP-1, and suppressed IL-1β and GMCSF than nonCART patients (Table). Treatment of IEC-HS included tocilizumab (n = 19), anakinra (n = 18) siltuximab (n = 4) and basiliximab (n = 4), dexamethasone (n = 18) methylprednisolone (n = 6), etoposide (n = 1) and ruxolitinib (n = 1). A significant response defined by a 90% reduction or normalization of the cytokine was observed with IL-10 and IFN-ϒ in 92.3% and 84.6% of the CART patients respectively. An intermediate response was noted with TNF, IL-6, MCP-1 and MIP-1 in 38.4%, 30.8% and 61.6% and 38.5% of the patients respectively. No patient had a significant response in IL-2Rα or IL-1β and only 7.7% had a significant response in IL-18. Of the 5 patients who had a MIP-1 response, 4 were on basiliximab +/- high flow continuous venovenous hemofiltration and the only patient that had an IL-18 response was on both modalities. The 100-day mortality after IEC-HS in the CART patients was 40% and was associated with higher peak and lower best ferritin but not the percentage reduction (Table). Higher TNF (90.3 pg/ml vs 37.2 pg/ml, p = 0.05), markedly elevated levels of IL-6 (92% vs 50%, p = 0.03) and IL-10 (33% vs 0%) and an IL-6 response (44.4% vs 0%) were associated with survival at day 100. IL-6 responders had lower peak ferritin vs IL-6 nonresponders (14066 mcg/L vs 45051 mcg/L, p = 0.08). Enterococcus faecium bacteremia developed in 75% of the nonsurvivors vs 16.6% of the 100-day survivors (p = 0.009). Survivors cleared the enterococcus bacteremia within days while nonsurvivors had protracted bacteremia. Conclusions: IEC-HS is devastating complication of CART. Anti-cytokine therapy can reduce some cytokines and ferritin but overimmunosuppression may lead infectious complication, in particular with E. faecium. Better biomarkers are needed to finetune immunosuppressive therapy in order to avoid over-immunosuppression. [Table: see text]

Introduction: Fludarabine combined with melphalan 140 mg/m2 (FluMel140) is a commonly used reduced-intensity conditioning (RIC) regimen in patients undergoing matched related (MRD) and unrelated donor (MUD) allogeneic stem cell transplant (alloSCT). Ciurea et al Blood 2020, described outcomes of Flu 160 mg/m2 and Mel 100 mg/m2. In this study, we describe our experience of attenuated melphalan dosing 100-120 mg/m2 versus 140 mg/m2 with fludarabine 125 mg/m2 (attenuated FluMel versus regular dose FluMel). Methods: We retrospectively reviewed patients from November 2016 to April 2023 with AML, ALL or MDS undergoing alloSCT who received fludarabine and melphalan. Patients who received the lower dose of melphalan were considered to be the attenuated FluMel cohort, whereas patients receiving the melphalan 140 mg/m2 were considered to be the control cohort. Kaplan-Meier and log-rank tests were used to estimate OS. NRM and relapse incidence (RI) was calculated using competing risk analysis. R 4.2.0 (R Foundation for Statistical Computing) was used for statistical analyses. Results: A total of 134 patients [92 (68.7%) males] were evaluated. Thirty-seven (27.6%) patients received attenuated FluMel and 97 (72.4%) patients received regular dose FluMel (controls). Among the patients in the attenuated FluMel cohort, 5 (13.5%) patients also received fludarabine at doses less than 125 mg/m 2 [median 20 mg/m 2 (range 87.5-112.5 mg/m 2]. Median age at transplant was 65 years (range 30 - 76 years). The most common disease was AML [75 (56.0%) patients] ( Table 1). Patients in the attenuated FluMel group had comparable iothalamate clearance compared to control cohort (clearance <65 ml/min/1.73 m2: 18.9% vs. 12.4%, P = 0.52). Patients in the attenuated FluMel group had comparable rates of high/very high DRI to those in control cohort (51.4% vs. 43.3%, P = 0.91). Compared to the control cohort, patients in the attenuated FluMel group were less likely to have a matched related donor (21.6% vs. 45.4%, P = 0.02) and were more likely to receive PTCy for GVHD prophylaxis (37.8% vs. 16.5%, P = 0.02). Among the patients receiving attenuated FluMel, the median melphalan dose administered was 100 mg/m2. The median time to neutrophil engraftment was 19 days (IQR 16-21 days), and median time to platelet engraftment was 18 days (range 12-25 days). Eleven (29.7%) patients developed post-alloSCT mucositis, and 3 (8.1%) patients developed grade 3-4 mucositis. All the patients in the attenuated FluMel group achieved 100% CD33 donor chimerism at day +30 (n=35) and day +100 (n=28) after alloSCT. Similarly, 26 (74.3%, n = 35) patients achieved ≥ 95% CD3 donor chimerism at day +30 after alloSCT and 23 (82.1%, n = 28) patients achieved ≥ 95% CD3 donor chimerism at day +100 after alloSCT. Median follow-up of the entire cohort after alloSCT was 2.3 years (95% CI 2.1-2.5 years). Median follow-up was 1.5 years in the attenuated FluMel cohort and 2.5 years for the control cohort ( P<0.001) . Survival was similar among patients receiving attenuated FluMel vs. control cohort (2-year OS 74.7% vs. 65.0%, P = 0.28). At 2 years post-alloSCT, the attenuated FluMel and control cohort had similar non-relapse mortality (19.9% vs. 24.4%, P=0.58) and relapse (22% vs. 15.2%, P=0.51). The attenuated FluMel was not associated with an increased incidence of relapse (HR 1.36, 95% CI 0.50-3.73, P=0.55) or NRM (HR 0.74, 95% CI 0.28-1.95, P = 0.55). GVHD-free relapse free (GRFS) survival was also similar among the attenuated Flu/Mel and control cohort (1-year GRFS rate 41.1% vs. 45.6%, P = 0.8). Among the patients receiving PTCy for GVHD prophylaxis, the 2-year OS in patients receiving attenuated FluMel was higher than the control group, but it was not statistically significant (2-year OS rate: 90% vs. 55%, P=0.37, Figure 1). Compared to the control group, the attenuated FluMel group had similar rates of NRM at 100 days (10% vs. 12.5%), 1 year (NA vs. 25%) and at 2 years after alloSCT (NA vs. 25%, P=0.54). GRFS at 1 year was also similar between the attenuated FluMel and control group (68.6% vs. 43.8%, P = 0.69). Conclusion: The attenuated dosed FluMel conditioning is a safe and effective regimen for elderly patients with acute leukemia and MDS, and is non-inferior to regular dose FluMel. Among patients receiving PTCy for GVHD prophylaxis, the lower dose of melphalan was non-inferior to regular dose FluMel for survival outcomes. Larger studies are needed to confirm our findings.

Introduction Orally administered tacrolimus is widely used in hematopoietic cell transplant patients, but multiple clinical situations may arise rendering oral administration infeasible. The undesirable sequelae of intravenous administration, including toxicity, challenges with administration and cost call for innovative solutions to conserve existing supply and optimize safety and efficacy of medication delivery. We sought to demonstrate feasibility of sublingual tacrolimus use and estimate a sublingual-to-oral (SL:PO) conversion ratio in the hematopoietic cell transplant setting. Methods Ten adults undergoing allogeneic hematopoietic cell transplant received tacrolimus 0.04 mg/kg/dose twice daily. Initial doses were given via sublingual route and a steady state trough level was collected after 4 consecutive doses. Participants were then switched to oral tacrolimus, the dose adjusted for a goal trough 8-12ng/mL, and another steady state trough was drawn. Total daily dose was divided by trough concentration for each route to determine the dosing ratio of SL:PO. Results Median trough level following sublingual administration was 11.3 ng/mL. Three of these were within goal, 3 were low (4.7–6.4 ng/mL) and 4 were elevated (15.9–18.6 ng/mL). Median SL:PO ratio was 1.02. In 5 participants the SL:PO ratio was <1 (range 0.57–0.94) and in 5 the ratio was ≥1 (range 1.10–1.92). No significant barriers or intolerance to sublingual tacrolimus use were noted. Conclusions Results demonstrate reliable absorption with sublingual tacrolimus use in patients undergoing hematopoietic cell transplant. Sublingual administration may allow for avoidance of the undesirable complications of IV tacrolimus, such as increased toxicities, required hospitalization for continuous infusion, risk of dose conversion and dilution errors and increased cost. Trial Registry name: Use of Sublingual Tacrolimus in Adult Blood and Marrow Transplant Patients, NCT04041219 https://clinicaltrials.gov/ct2/show/NCT04041219?term=NCT04041219&draw=2&rank=1

Introduction: The bone marrow plasma cell (BMPC) clone burden is typically low in light chain (AL) amyloidosis and some patients do not have a detectable serum monoclonal spike (M-spike). Increased BMPC% and serum free light chain (FLC) are associated with poorer outcomes. However, the outcomes of patients with AL amyloidosis based on the presence or an absence of a measurable serum M-spike before autologous stem cell transplantation (ASCT) has not been explored. Methods: This was a retrospective review of patients who had a diagnosis of AL amyloidosis and received ASCT between March 1996 and September 2017. The serum M-spike was recorded before ASCT and patients were divided according to the presence or absence of a measurable serum M-spike. Progression-free survival (PFS) was defined as time from ASCT to disease progression, relapse or death of any cause. Overall survival (OS) was calculated from time of ASCT to death of any cause. Univariate and multivariate analysis for PFS and OS were done using the following variables: age&gt;65 vs. ≤65 years, Mayo 2012 stage 3/4 vs. 1/2, BMPC ≥ 10% vs. &lt;10%, organs involved &gt;2 vs. ≤2, melphalan conditioning 200mg/m2 vs. 140 mg/m2 ,ASCT year &gt;2010 vs. ≤2010, and presence vs. absence of a measurable serum M-spike. Results: Seven-hundred and sixteen patients were identified and 521 (73%) had a measurable serum M-spike. Patients who had a measurable serum M-spike were more likely to have BMPC≥ 10% than patients without a measurable serum M-spike (46% vs. 34%, P=0.002) and they were more likely to have a difference in FLC ≥18 mg/dl (47% vs. 29%, P=0.0001). Overall, PFS and OS were significantly shorter in patients who had a measurable serum M-spike compared to patients without a measurable serum M-spike (Figure 1 A,B). The shorter survival was irrespective of the administration of induction therapy before ASCT. We also evaluated the difference in survival in patients with Mayo 2012 stage 3/4 based on the presence or absence of a measurable serum M-spike. The PFS and OS were also significantly different in these patients (Figure 1 C,D). Predictors for PFS included Mayo 2012 stage 3/4 vs. 1/2 (hazard ratio (HR): 1.5, P=0.003), BMPC ≥ 10% vs. &lt;10% (HR: 1.4,P=0.004), melphalan conditioning 200mg/m2 vs. 140 mg/m2 (HR:0.6, P=0.001), ASCT year &gt;2010 vs. ≤2010 (HR: 0.8, P=0.03), and the presence vs. absence of a measurable serum M-spike (HR: 1.82, P&lt;0.0001). For OS, Mayo 2012 stage 3/4 vs. 1/2 (HR: 2, P&lt;0.0001), melphalan conditioning 200mg/m2 vs. 140 mg/m2 (HR:0.4, P&lt;0.0001), ASCT year &gt;2010 vs. ≤2010 (HR: 0.6, P=0.002), and the presence vs. absence of a measurable serum M-spike (HR:1.9, P=0.003) were predictive. Conclusion: The presence of a measurable serum M-spike before ASCT is a negative independent predictor for PFS and OS in AL amyloidosis. Figure 1 Disclosures Sidiqi: Amgen: Honoraria; Celgene: Honoraria, Other: Travel grant; Janssen: Honoraria. Dingli:Karyopharm Therapeutics: Research Funding; Apellis: Consultancy; Alexion: Consultancy; Janssen: Consultancy; Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Sanofi-Genzyme: Consultancy. Kapoor:Amgen: Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Janssen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; GlaxoSmithKline: Research Funding. Dispenzieri:Intellia: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Kumar:Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Tenebio: Other, Research Funding; Genecentrix: Consultancy; MedImmune: Research Funding; Cellectar: Other; Dr. Reddy's Laboratories: Honoraria; Merck: Consultancy, Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Novartis: Research Funding; Adaptive Biotechnologies: Consultancy; Kite Pharma: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Carsgen: Other, Research Funding; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding. Gertz:Proclara: Other; Abbvie: Other; DAVA oncology: Speakers Bureau; Aurora Bio: Other; Prothena: Other: personal fee; Teva: Speakers Bureau; Physicians Education Resource: Other: personal fee; Annexon: Other: personal fee; Ionis/Akcea: Other: personal fee; Sanofi: Other; Appellis: Other: personal fee; Amgen: Other: personal fee; Janssen: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Medscape: Other: personal fee, Speakers Bureau; Research to Practice: Other; Alnylam: Other: personal fee; Johnson and Johnson: Speakers Bureau; Springer Publishing: Patents & Royalties; Celgene: Other.

Abstract Introduction: The Bone Marrow Transplant Program at Mayo Clinic (Rochester, Minnesota) developed a multidisciplinary approach (involving physicians, nurses, pharmacists, dietitians, and financial specialists) for outpatient management of patients undergoing stem cell transplantation. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Table. Patient Characteristics (N=716) Characteristic Value Male, no. of patients (%) 426 (59) Age, median (IQR), y 59 (53–65) Creatinine, median (IQR), mg/dL 1.0 (0.9–1.2) b2-Microglobulin, median (IQR), mcg/mL 2.5 (1.9–3.7) Gammopathies, no. of patients (%) Measured by serum immunofixation or immunoelectrophoresis IgA 148 (21) IgG 414 (58) IgM 6 (1) IgD 12 (2) Light chain 83 (12) Biclonal 6 (1) None 47 (7) Measured by urine immunofixation or immunoelectrophoresis k light chain 402 (56) l light chain 226 (32) Biclonal 1 (0) None 79 (11) Not performed (anuric) 8 (1) Status at stem cell transplant, no. of patients (%) Untreated 4 (1) Plateau 436 (61) Primary refractory 113 (16) Relapse after therapy 93 (13) Relapse during therapy 70 (10) Characteristic Value CD34+ cells, median (IQR), ×106/kg Collected, no. 10.0 (7.6–12.6) Infused, no. 4.7 (3.9–6.2) Sessions of apheresis, median (IQR) 3 (2–5) Engraftment, median (IQR), days after transplantation Neutrophils, 0.5×109/L 13 (12–15) Platelets, 50×109/L 16 (14–22) Duration of hospitalization, median (IQR), d 4 (0–10) Abbreviation: IQR, interquartile range. Results: During a 45-month period after implementation of the program (2005-Sept 2007), the day-100 survival rate was 99.5% for low-risk myeloma patients (transplantation during first plateau; n=202) and 97% for high-risk myeloma patients (refractory, relapsing or second or greater plateau; n=71). The overall day-100 survival rate was 99%(270/273). Analysis of hospitalization trends since inception of the program showed that 39% of patients completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization Conclusion: Outpatient stem cell transplantation is feasible for patients with multiple myeloma with a therapy mortality of 1%. Nearly 40% of our patients completed the procedure without hospitalization. Age and serum creatinine levels predicted a higher likelihood of hospitalization. Implementation of out patient transplant requires affordable housing in the community since many third party payers do not support hotel costs despite the reduction of hospital days. The hospital physical plant and patient registration process has to support use of designated hospital rooms for purely out patient practice. The transplant team must have process owners to standardize across all disease categories collection protocols, conditioning regimens, infusion SOP’s and post infusion supportive care guidelines for standard antibiotics, narcotics, laboratory work and transfusion thresholds. A care team meeting between physicians, nursing, dietary, pharmacy, business office, data base and appointment coordinators is essential to coordinate all the multidisciplinary efforts. Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL