ALBERT

Description: TRM, drug toxicities, life-threatening infections, poor quality of life, and graft versus host disease (GVHD) are significant risks of hematopoietic cell transplantation (HCT). In addition to the risks of HCT, existence of pre-transplant comorbidities can have significant impact on transplant outcomes. A comparison of CCI and the HCT-CI revealed that HCT-CI was prognostic and better at predicting TRM and overall survival (OS). However, the HCT-CI and CCI results have been inconsistent in predicting the TRM and OS in validation studies. In subgroup analyses of a large retrospective trial, HCT-CI did not predict TRM or OS for UCB recipients. Patient heterogeneity in age, disease, disease-risk, comorbidities, and conditioning regimens may have limited validation in these UCB recipients. The design of this research was to explore whether or not the HCT-CI and/or CCI can accurately predict post-transplant outcomes in young patients with high risk hematologic malignancies undergoing uniform RIC UCB transplantation. A retrospective chart review was performed on 52 consecutive young (age 〈 55) UCB transplant recipients receiving the RIC regimen fludarabine, cyclophosphamide, ATG, and 200 cGy TBI. All patients had received cyclosporine and mycophenolate mofetil for GVHD prophylaxis. Information on pre-transplant comorbidities was obtained from the CIBMTR pre-TED form for each patient and retrospective chart reviews. Demographic information, ECOG performance status (PS), identification of comorbidities, and post-transplant outcomes were obtained. Between 2005 and 2011, 52 patients age 19 – 54 (median 38) years, 30 males (58%) and 22 females (42%), underwent RIC UCB transplantation with the above regimen. Most patients had advanced stage or high risk hematologic malignancies; 28 patients had MDS/AML (54%), 8 patients had ALL (15%), while 16 patients had other hematologic malignancies. 39 patients had a PS = 0, while 13 had a PS = 1. Half of the patients were in CR 〉 2, with the same number receiving more than 2 prior therapies. 8 patients had received a prior autologous HCT, 8 a prior allo-HCT, and one patient had failed a previous UCD transplantation. 11 patients did not achieve engraftment. Median time to neutrophil engraftment was 26 days (95% CI: 24 – 28 d) and median time to platelets engraftment was 38 days (95% CI: 31 – 45 d). No patient developed grade 4 acute GVHD. Grade 3 acute GVHD was seen in 12 / 52 patients (23%). Chronic GVHD was seen in likewise seen in 12 patients (23%). To date 16 patients (30%) have relapsed. OS was 42% and PS was 37% at one year. Median PFS and median OS were 5 months and 7 months, respectively (PFS 95% CI: 1 – 11 months, OS 95% CI: 1 – 13 months). Neither CCI, nor HCT-CI were significant predictors of OS and PFS, however the ECOG PS was significantly associated with an improved OS and PFS (Table).OSPFSN1 yr2 yrs4 yrsp1 yr2 yrs4 yrspECOG PS03946%36%21%0.02644%36%21%0.0311331%0015%00CCI≤ 23944%26%10%0.2238%26%10%0.2〉 21338%31%31%38%31%31%HCT-CI02236%31%5%0.3632%32%5%0.3211443%14%14%29%14%14%≥21643%31%31%44%31%31%TRM occurred in 18 patients (35%). Neither comorbidity indices, nor the performance status were correlated to TRM (p 〉 0.05). For ECOG PS, OR 1.6 p = 0.49, CI 0.42 - 5.93; CCI OR = 2.4, p = 0.09, CI 0.86 - 6.59, HCT-CI OR = 0.6, p = 0.46, CI 0.19 - 2.08. In a previous presentation our group concluded that CCI performs better than HCT-CI in elderly patients undergoing UCB transplant. When tested in a population younger than 55 years old though, we were unable to validate the generally accepted prognostic indices. It is unclear whether this is due to a selection bias: it appears most of the patients were essentially health from a non-hematological stand-point, and as such the “classic” cardiac or pulmonary risk factors were underrepresented. The excess TRM is likely due to the severity of their underlying disease, and the majority were in CR ≥ 2 and had received multiple previous courses of antineoplastic chemotherapy. As umbilical cord transplants become more utilized, a new prognostic index needs to be developed, more fitting to the patients 〈 55 years old. Disclosures: No relevant conflicts of interest to declare.

Description: B ackground: Current therapies for CLL/SLL have frequent toxicities, are non-curative, and several trials have demonstrated that early treatment of the disease doesn't result in longer overall survival. In high doses, both curcumin (CM), from turmeric, and vitamin D (VD) have been shown to be safe in multiple clinical trials of solid tumors. Curcumin was shown to disrupt CLL cell interactions with the microenvironment, induce apoptosis independent of DNA damage, and upregulate vitamin D receptor (VDR) in malignant lymphoid cells. We hypothesized that the combination of CM and VD is safe and active in CLL/SLL and would delay disease progression. Methods: This was an open-label phase II trial for previously untreated patients with asymptomatic,Rai stage 0-II CLL/SLL not currently meeting National CancerInstitute Working Group (NCI-WG) Criteria for treatment. All patients received 8 gm of CM and 10,000 IU of vitamin D3 (VD) orally daily. VD was started 1 week after CM and both agents were maintained for up to six 4-week cycles. The primary endpoint was the overall response rate (ORR) based on NCI-WG criteria. Secondary endpoints were event-free (EFS), overall survival (OS), and time to next treatment (TTNT). VD-25-OH and CM major metabolites; CM glucuronide (COG) and CM sulfate (COS), were measured in plasma by liquid chromatography-tandem mass spectrometry. Phosphorylated-NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), a validated pharmacodynamic marker of CM activity, as well as VDR, were measured in CLL cells by flow cytometry. Results: A total of 35 patients (pts), 51% males, were accrued to the trial, 30 (86%) were evaluable for response. Median age was 60 years (range 45-80). Most had CLL (97%); 51% were Rai stage 0 and 49% were Rai stage 1. Cytogenetic abnormalities included del13q14 (37%), trisomy 12 (11%), del 11q22 (11%) and del 17p (3%); 20% had ZAP-70 levels 〉20%. Median number of cycles received was 5 (range 1-6) and treatment was well tolerated overall. The most frequent adverse effects (AE) were diarrhea/gastrointestinal upset in 69% of patients (14% were grade 3). No serious AEs were observed. Eighteen pts (51%) completed all 6 cycles of treatment; 10 (29%) withdrew consent, 4 (11%) discontinued treatment because of diarrhea, and 3 (9%) patients progressed on treatment. Best response was stable disease in 28/30 (93%) evaluable pts. After a median follow up of 29 months, EFS was 72.0% (95% CI 52.1 - 84.7%), 74.1% (95% CI 58.7-89.6%) had not started new CLL treatment, and OS was 100%. Median VD-25-OH levels were 28.75ng/ml (range 12.5-55.6) at baseline and 49.5 ng/ml (24.8-69) at 28 days. Median COG/COS levels were 15.8 (2.73-75)/6.71(0-33.5) and 18 (0-75.9)/7.21(0-35.2) ng/ml at 8 and 28 days, respectively. Flow cytometric analysis of CLL cells showed no significant change in VDR or Phosphorylated-NF-κB with CM-VD treatment. Conclusion: Curcumin and high-dose vitamin D combination is safe and well tolerated in patients with early stage CLL. Although no responses were seen, the majority of patients maintained stable disease on treatment. Longer follow up is planned on this study to determine long - term CLL progression rates of patients treated with CM-VD. Disclosures Afable: Eli Lilly: Employment. Lazarus:Pluristem Ltd.: Consultancy. Nagabhushanam:Sabinsa Corporation: Employment. Grote:BTR Group Inc: Employment. Kunati:Symrise AG: Employment.

Description: Venous thromboembolic events (VTE) are common after the diagnosis of lymphoma. Although various risk factors have been associated with VTE in cancer patients, there is no specific VTE risk prediction score for diffuse large B cell lymphoma (DLBCL) patients. The Khorana score is a prediction-model of VTE in cancer patients receiving chemotherapy that incorporates clinical and laboratory parameters. We evaluated the risk factors for VTE, the effect of VTE on the outcomes of DLBCL patients and the utility of the Khorana score in DLBCL patients. Methods: We searched the Hematologic Malignancies Database of University Hospitals Seidman Cancer Center for newly diagnosed DLBCL patients between 2002 and 2014. Data on patient characteristics including risk factors, disease characteristics, treatment, outcomes and VTE was collected. The Khorana score was calculated using clinical (disease type, body mass index) and laboratory (hemoglobin level, platelet and leukocyte count) parameters. Risk factors identified as having statistical significance on univariate Cox proportional hazards analysis (p 12g/dL), increased white cell count (〉11,000/mcl), hemoglobin (800/mcl) and chromosomal translocations involving MYC presented statistically significant increases in hazard of VTE (Table 2). On multivariate analysis only bone involvement (p=0.017) and anemia (p=0.035) retained statistical significance as risk factors for VTE. Three-year OS for patients presenting with VTE within 1 year of DLBCL diagnosis was 46.7 % (95% CI 30-63.3) vs. 72.3% (95% CI 67.4-77.3) in subjects without early VTE (p=0.05) (Figure 2). Presence of VTE at any time after DLBCL diagnosis was also associated with worse OS rates, with estimated 3-year OS of 52.2 % (95 % CI 39.8-64.7) for subjects experiencing VTE and 74 % (95 % CI 69-79) for those without VTE after DLBCL diagnosis (p

Description: Background: Patients (pts) diagnosed with non-Hodgkin lymphoma (NHL) have increased risk of venous thromboembolic event (VTE). Retrospective studies have observed the risk of VTE is not the same across lymphoma subtypes, with aggressive subtypes having higher risk than indolent lymphomas. Current VTE prediction models such as the Khorana score (K-Score) consider all lymphomas as having equal risk of VTE. We conducted retrospective time - based analyses to develop a VTE prediction model that includes lymphoma subtype as a risk factor. Methods: We accessed the Hematologic Malignancies Database at University Hospitals Seidman Cancer Center and collected records of pts diagnosed with diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL) between 2000 and 2016. Pts with CNS involvement or active anticoagulation were excluded. FL grade 3B pts were included in the DLBCL cohort. Information retrieved included demographic characteristics, baseline disease and laboratory parameters, as well as comorbidities and diagnosis of VTE, including radiographic confirmation. Time to VTE was measured from the date of NHL diagnosis to the date of VTE incidence or censored at the date of last follow-up for those without VTE. Cumulative incidence of VTE was estimated using Kaplan-Meier method and its difference among groups was examined by log-rank test. Cumulative incidence of VTE was also calculated considering death as competing risk and comparisons done using the Gray test. Cox proportional hazards model was used to evaluate the effect of continuous and categorical covariates on cumulative incidence of VTE and to identify prognostic factors of VTE. Fifty percent of the study participants were randomly assigned to training cohort or reserved as an independent validation cohort. Performance of multivariate models was evaluated using the Akaike Information Criterion (AIC) and Concordance Index (C-Index). The final models built using the training dataset were further validated using the validation cohort. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Results: We identified 627 pts with DLBCL (n=421) or FL (n=206) with available baseline characteristics, (Table 1). After a median follow up of 48 months (range 1-191), 77 pts experienced a VTE after NHL diagnosis. The cumulative incidence of VTE at 4 years for the whole cohort was 10.5% (95% CI 8.3-13.2). DLBCL pts had a significantly higher 4 - year cumulative incidence of VTE: 13.7% (95% CI 10.8-17.5) vs. 4.0% (95% CI 2.0 - 7.9) in FL pts (p

Description: Introduction: CD25 is expressed on the cell surface of many lymphomas, including classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma. ADCT-301 (camidanlumab tesirine [Cami-T]) is an antibody drug conjugate comprising a human monoclonal antibody against CD25 conjugated to a potent pyrrolobenzodiazepine dimer (PBD) toxin. We report here a first-in-human clinical trial of Cami-T, focusing on patients (pts) with relapsed/refractory (R/R) cHL treated in dose-escalation and subtype-specific dose-expansion cohorts. Methods: This was a Phase 1, open-label, dose-escalation and dose-expansion multicenter study in pts with R/R cHL. The objectives of the study were to assess the safety and tolerability, determine the recommended dose(s) for expansion, and evaluate pharmacokinetics and pharmacodynamics. The clinical activity of Cami-T was measured by overall response rate (ORR; per 2014 Lugano Classification), duration of response (DoR), progression-free survival (PFS), and overall survival. Pts received Cami-T intravenously every 3 weeks (Q3W; 1 Cycle). Dose escalation was performed according to a continual reassessment method. Results: As of June 15, 2018, 60 pts with cHL have been enrolled. Baseline characteristics include median age: 38.5 years (range 19-80); median number of prior therapies: 5 (range 2-15). Cami-T doses ranged from 5 to 300 µg/kg (median number of cycles: 3 [range 1-15], with a median treatment duration of 43 days [range 1-354]). Treatment-emergent adverse events (TEAEs) were reported in 57/60 (95%) pts; most common TEAEs (≥20%) were fatigue (25, 41.7%), maculopapular rash (20, 33.3%), increased gamma-glutamyltransferase (GGT; 18, 30%), pyrexia (18, 30%); increased alanine aminotransferase (ALT; 14, 23.3%), dyspnea (13, 21.7%), nausea (13, 21.7%), increased aspartate aminotransferase (AST; 12, 20.0%), increased blood alkaline phosphatase (ALP; 12, 20.0%), and cough (12, 20.0%). As part of immune-related AEs, there were 2 (3.3%) cases of Guillain-Barré syndrome (1 each at dose 45 and 60 µg/kg) and 1 (1.7%) case of thyroiditis. Also, there were 16 (26.7%) cases of peripheral edema or effusion, which are AEs thought to be associated with PBDs. Grade ≥3 TEAEs occurred in 37/60 (61.7%) pts; the most common Grade ≥3 TEAEs (≥5% of pts) were liver function abnormalities (increased GGT [16.7%], ALT [10.0%] AST [5.0%], and ALP [5.0%]), maculopapular rash (13.3%), anemia (8.3%), and decreased platelet count (5.0%). TEAEs leading to treatment discontinuation occurred in 17/60 (28.3%) pts. Most pts (72%) tolerated at least 3 cycles before an AE leading to a dose reduction/delay occurred. Exposure to the conjugated antibody was dose-related and at a ≥45 µg/kg dose was sustainable throughout the dosage interval at a mean concentration of 0.0826 µg/mL (coefficient of variation [CV] 49.9%) and mean minimum concentration of 0.0092 µg/mL (CV=81.7%; n=25). The maximum tolerated dose was not reached; however, the recommended dose for expansion was identified as 45 µg/kg Q3W. Response data for 55 evaluable pts with cHL are shown in the Table. The ORR was 69.1% (38/55 pts) and the complete response (CR) rate was 43.6% (24/55 pts). In the 45 µg/kg dose group (dose escalation + expansion), the ORR was 80.8% (21/26 pts) and the CR rate was 50% (13/26 pts) (Table). ORRs by prior treatment were 80.8% (21/26) in pts who previously received brentuximab vedotin (BV), 80.0% (12/15) in those who previously received both a checkpoint inhibitor (CHPi) and BV, 81.8% (9/11) in those who had a prior hematopoietic cell transplant (HCT), and 85.7% (6/7) in those who had a prior CHPi, BV, and HCT. Median DoR and PFS were 7.7 and 6.7 months, respectively (Figure). Conclusions: In pts with R/R cHL, therapy with Cami-T provided impressive ORRs and CR rates in a heavily pretreated pt population. A 45 µg/kg dose of Cami-T was identified as having optimal activity with an acceptable safety profile. Enrollment of pts with HL is now complete and initial response data for all pts with HL will be available later this year. This data supports further investigation in a planned Phase 2 study. Study sponsored by ADC Therapeutics. http://clinicaltrials.gov/show/NCT02432235. Disclosures Hamadani: Celgene Corporation: Consultancy; Cellerant: Consultancy; Janssen: Consultancy; ADC Therapeutics: Research Funding; Ostuka: Research Funding; MedImmune: Consultancy, Research Funding; Merck: Research Funding; Takeda: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau. Collins:BMS: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Celgene Corporation: Research Funding; Amgen: Research Funding; Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Celleron: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Samaniego:ADC Therapeutics: Research Funding. Spira:AstraZeneca: Consultancy; AbbVie: Consultancy; BMS: Consultancy; Roche: Consultancy; ADC Therapeutics: Research Funding. Davies:GSK: Research Funding; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ADC Therapeutics: Research Funding; Pfizer: Research Funding; Gilead: Honoraria, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Consultancy. Radford:ADC Therapeutics: Consultancy, Research Funding; Celgene: Research Funding; Pfizer: Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; AstraZeneca: Equity Ownership; Novartis: Consultancy, Speakers Bureau; GlaxoSmithKline: Equity Ownership; BMS: Consultancy, Speakers Bureau. Caimi:Celgene: Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Menne:ADC Therapeutics: Research Funding; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. Boni:ADC Therapeutics: Employment, Equity Ownership. Cruz:ADC Therapeutics: Employment, Equity Ownership. Feingold:ADC Therapeutics: Employment, Equity Ownership. He:ADC Therapeutics: Employment, Equity Ownership. Wuerthner:ADC Therapeutics: Employment, Equity Ownership. Horwitz:Portola: Consultancy; Corvus: Consultancy; Mundipharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Trillium: Consultancy; Aileron Therapeutics: Consultancy, Research Funding; Spectrum: Research Funding; Kyowa-Hakka-Kirin: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Innate Pharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding.

Description: Background: BL is associated with a high risk of primary or secondary CNS involvement, warranting intrathecal (IT) and/or systemic therapy that penetrates the blood-brain barrier (BBB). The lower-intensity DA-EPOCH-R regimen has recently shown high survival rates in BL (Dunleavy, NEJM 2013), but it omits drugs traditionally used for CNS prophylaxis (like high-dose methotrexate [HDMTX]). The objective of this multi-institutional retrospective study was to examine treatments, risk factors, and CNS-related outcomes among patients (pts) with BL. Methods: We collected data from 26 US centers on adult BL pts diagnosed (dx) in 6/2009-6/2018. Using institutional expert pathology review and 2016 WHO criteria, we excluded other high-grade lymphomas (including BL-like/unclassifiable), or cases with inadequate clinicopathologic data. We studied factors associated with baseline CNS involvement (CNSinv) using logistic regression reporting odds ratios (OR). Progression-free (PFS), overall survival (OS), and cumulative incidence function of CNS recurrence (in a competing risk analysis) were examined in Cox or Fine-Gray models reporting hazard (HR) or subhazard ratios (SHR), respectively. All estimates report 95% confidence intervals (in square brackets). Results: Among 557 BL pts (median age, 47 years [yr], 24% women, 23% HIV+), 107 (19%) had CNSinv at dx, including 89 (16%) with leptomeningeal, and 15 (3%) with parenchymal CNS disease. In a multivariable model, factors significantly associated with CNSinv at dx included stage 3/4 (OR, 11.2 [1.47-85.9]), poor performance status (PS; OR, 2.12 [1.22-3.69]), ≥2 extranodal sites (OR, 3.77 [2.02-7.03]), or marrow involvement (OR, 2.44 [1.35-4.39]), whereas intestinal involvement conferred low risk of CNSinv (OR, 0.27 [0.11-0.65]). CNSinv at dx was not significantly associated with use of specific chemotherapy regimens (Fig. A,P=.75) or receipt of IT chemotherapy (91% vs 84%, P=.065). Pts with CNSinv were less likely to achieve a complete response (62% vs 76%, P=.005), had worse 3 yr PFS (47% vs 69%; P3x]; see Evens AM et al, ASH 2019 for further details). With median follow up of 3.6 yrs, 33 pts (6%) experienced a CNS recurrence (82% within 1 yr from dx; 79% purely in CNS, and 21% with concurrent systemic BL). The cumulative risk of CNS recurrence was 6% [4-8%] at 3y (Fig. D). Univariate significant predictors of CNS recurrence included baseline CNSinv, HIV+ status, stage 3/4, poor PS, LDH〉3x, involvement of ≥2 extranodal sites, marrow, or testis. However, in a multivariate model only baseline CNSinv (SHR, 3.35 [1.53-7.31]) and poor PS (SHR, 2.24 [1.03-4.90]) retained significance. The 3 yr risk of CNS recurrence varied from 3% for pts with no risk factor, to 10% with one, and 17% with both factors (Fig. E). In addition, the risk of CNS recurrence differed according to chemotherapy regimen, and was significantly higher for pts treated with DA-EPOCH (12% at 3y [8-18%]; Fig. F) compared with CODOX-M/IVAC (4% [2-8%]) or hyperCVAD/MA (3% [1-6%]; SHR for DA-EPOCH vs. others, 3.50 [1.69-7.22]). All pts recurring after DA-EPOCH had received IT chemotherapy. Higher risk of CNS recurrence persisted with DA-EPOCH regardless of baseline CNSinv (Pinteraction=.70), poor PS (Pint=.14), or HIV status (Pint=.89). Baseline CNSinv was the strongest factor associated with CNS recurrence after DA-EPOCH (3 yr risk, 30% vs 8%, P

Description: Abstract 2019 High-dose chemotherapy (HDC) followed by autologous hematopoietic cell transplantation (AHCT) has been shown to result in better outcomes than conventional salvage chemotherapy for treatment of relapsed Hodgkin (Lancet 2002;359:2065–71) and non – Hodgkin lymphoma patients (N Engl J Med 1995;333:1540–5). The relative efficacy of different conditioning regimens is still uncertain. Our center has had extensive experience with BEP, consisting of BCNU (600mg/m2), etoposide (2400mg/m2) and cisplatin (200mg/m2) (Lazarus HM, J Clin Oncol 1992;10:1682–9) with more than 150 patients transplanted using this conditioning regimen. We have observed it to be efficacious and associated with a low incidence of transplant-related mortality (Biol Blood Marrow Transplant 2005;11:13–22). The purpose of this analysis is to compare the outcomes of patients transplanted with BEP with a contemporaneous cohort of patients transplanted with BEAM (BCNU 300mg/m2, etoposide 800mg/m2, cytarabine 1600mg/m2, melphalan 140 mg/m2). We performed a retrospective analysis of 55 consecutive relapsed lymphoma patients who had either BEAM or BEP preparative therapy for AHCT between 2005 and 2010 at our institution. Given the potential for nephrotoxicity and ototoxicity of cisplatin, patients were selected to receive BEAM if they had previous renal dysfunction (any elevation of serum creatinine) or had previous hearing loss. All patients received corticosteroids for prophylaxis of BCNU – induced pneumonitis. The Mann – Whitney test was used for analysis of continuous variables, Fisher's exact test for categorical data, while survival analysis was performed with the Kaplan – Meier method. Twenty-four patients received BEAM and 31 received BEP. The median age was higher in BEAM-treated patients (51 vs. 43 years, p = 0.0392). Other baseline characteristics were comparable between both cohorts: gender (male 54 vs. 58%, p = 0.791); diagnosis (NHL 75 vs. 77.4%, p = 1.000); status of disease at transplant (partial remission or worse 33.3 vs. 35.5%, p = 1.000); median number of previous therapies (2 in both groups, p = 0.51). The rate of non-renal comorbidities was higher in the BEAM cohort, but the difference was not statistically significant (45.8 vs. 32.3%, p = 0.403). The median CD34 cell dose was similar in both groups (6.252 x106 vs. 6.475 x106 CD34 cells/μL, p = 0.842). The rate of complications, including bacteremia, other infections, mucositis, diarrhea and renal dysfunction were not statistically different (Table 1). The small sample size may have prevented us from observing a statistical difference in cardiac toxicity.Table 1.Complications observed after BEAM or BEP conditioning for Autologous Hematopoietic CellBEAM (%)BEP (%)Bacteremia45.835.5p = 0.580Non – bacteremic infections37.541.9p = 0.787Mucositis54.258.1p = 0.791Diarrhea79.164.5p = 0.370Increase in serum creatinine 〉 50%12.516.1p = 1.000Cardiac complications16.73.2p = 0.153BCNU pneumonitis4.26.4p = 1.000 The median follow up time for the whole cohort was 31 months (28 vs. 34 months, p 0.267). Relapse free survival (RFS) after 36 months was 81.1% and 82.9% for BEAM and BEP, respectively (p = 0.693) (Figure 1). Overall survival at 24 months was 89.6% for BEAM and 90.8% for BEP (p = 0.371) (Figure 2). Among patients transplanted in partial response or worse, the median RFS was 57 months after BEAM and 66 months after BEP (p = 0.3173). There were no deaths in the first 100 days after transplant for both cohorts. There were no differences in the median number of days from hematopoietic cell infusion to discharge (12.5 vs. 12.0 days, p = 0.600) or achievement of ANC 〉500/μL (10 days for both cohorts, p = 0.415). In conclusion, BEP conditioning achieved comparable engraftment, toxicity and survival outcomes to those achieved by BEAM for treatment of relapsed lymphoma patients. BEP is therefore a valid alternative for treatment of this patient population. The BCNU dose in BEP is twice that in BEAM, but we continue to observe limited rates of BCNU – induced pneumonitis. BEP may be preferable over BEAM in patients with underlying cardiac comorbidity. Longer follow up and prospective trials will help in identifying variables that aid in the selection of patients for the most appropriate conditioning regimen. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Autologous hematopoietic cell transplant (HCT) is frequently used to treat plasma cell dyscrasias. High-dose melphalan is the most commonly utilized preparative regimen. Frequently seen non-hematologic adverse effects include oropharyngeal mucositis and GI toxicity. Reported incidence rate of overall and severe (grade 3-4) mucositis is 60-90% and 30-40%, respectively. Amifostine is a thiol derivative, which has been used for protection of normal tissues in radiation and chemotherapy. Amifostine has a relatively safe profile with hypotension, nausea, vomiting and diarrhea (N/V/D) as main side effects. We explored the efficacy of amifostine to reduce overall incidence and severity of mucositis after high-dose melphalan therapy. Methods: We conducted a retrospective study of 126 autologous HCT (110 patients) with high-dose melphalan performed from January 2007 to July 2014 at our center for plasma cell myeloma. Twelve patients underwent tandem transplants and four had second autologous transplants after relapsed disease and were excluded from survival analysis. Patients' characteristics (n=110) as listed in Table 1. All but one patient received two doses of Amifostine given as 740 mg/m2 IV bolus on days T-2 and T-1. Melphalan was administered as IV bolus on T-1 at the dose of 200 mg/m2, except for 4 patients who received 140 mg/m2 due to impaired renal function. All patients received ice chips peri-melphalan infusion. All patients received cryopreserved autologous hematopoietic cell infusion on T-0. We graded mucositis and GI toxicities as per CTCAE v4.0 and recorded patient controlled analgesia (PCA), total parenteral nutrition (TPN), transplant and disease outcomes. Results: Severe (grade 3-4) mucositis and diarrhea rates were 14% and 12%, respectively (Table 2). PCA was used in 10% of transplants at a mean duration of 0.9 days and TPN was utilized in 5% of transplants for a mean duration of 0.45 days. Median length of stay for transplant was 15 days (range 3-44 days). Median time to neutrophil and platelet engraftment was 10 and 19 days, respectively (Table 3). Three patients died within 100 days after transplant (2 due to infections and 1 due to renal amyloidosis). At a median follow up of 39 months, median PFS is 25 months and OS is greater than six years. All patients were able to receive amifostine at prescribed doses except for one patient who received only one dose due to intractable N/V/D. Conclusion: Amifostine is effective in reducing high-dose melphalan-induced severe mucositis. Our data would suggest a decrease in severe mucositis and GI toxicity rates when compared to historically reported incidences. In addition, amifostine does not appear to have a deleterious effect on engraftment and/or survival and response rates (Table 3). Table 1. Patients characteristics Median Age (years) 59 (36-71) Gender (%) Male 54Female 46 Performance status (ECOG) 1 (0-2) Median time to transplant from diagnosis (years) 0.97 Median number of treatment regimens prior to transplant 2 (1-6) Response prior to transplant (%) Partial remission (PR)Very good partial remission (VGPR)Complete remission (CR)Stable disease (SD) 60%21%18%0.8% Table 2. Toxicity Overall (grade 1-4) Severe (grade 3-4) Median grade Median Duration (days) Mucositis 55% 14% 2 2 Diarrhea 92% 12% 2 7 Nausea 89% 4% 1 8 Vomiting 67% 3% 1 2 Table 3. Engraftment and post-HCT disease response Engraftment Median (days) Range (days) Neutrophils 10 6-21 Platelets 19 8-71 Post-HCT disease responses (%) Stringent complete response (sCR) 13% Complete response (CR) 32% Very good partial response (VGPR) 24% Partial response (PR) 25% Not evaluated 6% Disclosures Off Label Use: Amifostine use to prevent mucositis.