Gastineau, Dennis A.

Abstract Introduction: Immunotherapy is most likely to work in a setting of low tumor burden, making vaccine strategies attractive as maintenance therapy post autologous peripheral blood stem cell transplantation (PBSCT) for multiple myeloma (MM). However, it is difficult to ascertain the effects of the vaccines from delayed responses to the transplant. A novel immunotherapeutic, APC8020 (Mylovenge), was studied as consolidation therapy after for MM post PBSCT (Mayo vaccine trial). Mylovenge is prepared from autologous antigen presenting cells, including dendritic cells, partially purified from an unmobilized leukapheresis product by gradient density isolation and then incubated for two days with autologous serum containing M protein obtained pretransplant. We report long term results of the Mayo vaccine trial compared retrospectively to a consecutive cohort of MM patients who underwent autologous stem cell transplant at Mayo Clinic during the same time period. Methods: The Mayo vaccine trial patients had transplants between July of 1998 and May of 2001. Using these cutoff dates we analyzed 151 total MM patients, 27 from the vaccine trial (9 newly diagnosed and 18 relapsed) and 124 from database (DB) (50 newly diagnosed patients and 74 relapsed). The median (range) of follow-up for alive patients in vaccine trial is 6.5 years (2.9 – 8), and in the DB is 7.1 years (6 – 8). Two-sided Fisher’s exact tests and stratified log rank tests (with newly diagnosed or relapsed as the stratum) were used to compare baseline patient characteristics and time to event distributions (overall survival – OS, progression free survival – PFS, and time to progression – TTP) between the two groups. Results: The median (range) of age in vaccine trial and DB was 56 (30–69) and 57 (36–71) years respectively. There were no significant differences in the known prognostic factors including PCLI, B2M, and CRP. The median (95% confidence interval - CI) TTP for the vaccine trial and DB patients was 1.5 years (1.3 – 2.4) and 1.6 years (1.3 – 1.8); stratified log rank p value = 0.46. The median (95% CI) PFS for the vaccine trial and DB patients was 1.5 years (1.3 – 2.4) and 1.5 years (1.1 – 1.8), stratified logrank p value = 0.30. The median (95% CI) OS for the vaccine trial and DB patients was 5.3 years (4.0 -N/A), and 3.4 years (2.7 – 4.6); stratified logrank p value = 0.02. Conclusions: Despite the fact that no difference was seen in TTP or PFS, post-transplant vaccine therapy was associated with prolonged survival. This is similar to what has been reported in other tumor systems including prostate cancer and glioblastoma multiforme. This approach warrants further investigation, including preclinical studies aimed at optimizing the immune response and randomized trials to define the role of vaccine therapy in myeloma. Figure Figure

Abstract Introduction: We retrospectively analyzed outcomes of 716 patients with multiple myeloma who were mobilized using cyclophosphamide and growth factor (n=370) or growth factor alone (n=346) before stem cell transplantation. Table. Patient Characteristics (N=716) Variable Cyclophosphamide (n=370) Growth Factor Only (n=346) P Value Abbreviation: IQR, interquartile range. *Or equivalent dosage. Men, No. of patients (%) 224 (61) 202 (58) .50 Age, median (IQR), y 58 (52–64) 60 (53–65) .11 b-2 Microglobulin, median (IQR), mcg/mL 2.7 (1.9–4.0) 2.3 (1.9–3.2) .01 Creatinine, median (IQR), mg/dL 1.1 (0.9–1.3) 1.0 (0.8–1.2) .002 Apheresis, median (IQR) collections, No. 2 (1–3) 4 (3–6) .001 Marrow plasma cells, % 17 (5–34) 5 (1–13) .001 CD34+cells, median (IQR), cells/kg Total collected 10.3x106(7.2x106–14.6x106) 9.9x106(7.6x106–11.9x106) .01 Infused 5.6x106(4.5x106–7.6x106) 4.2x106(3.8x106–5.0x106) <.001 Duration of hospitalization, median (IQR), d 4 (0–10) 4 (0–9) .92 Nonstaphylococcal bacteremia, No. of patients (%) 48 (13) 25 (7) .01 Melphalan dosage, No. of patients (%) .04 200 mg/m2* 337 (91) 298 (86) 140 mg/m2* 33 (9) 48 (14) Exposure before mobilization, No. of patients (%) Melphalan 45 (12) 44 (13) .50 Lenalidomide 14(4) 63(18) .01 Results: Patients receiving cyclophosphamide had higher stem cell yields than the growth factor only group (median number of apheresis sessions needed to achieve stem cell collection goals, 2 vs 4 sessions, respectively [P=.001]). However, patients treated with cyclophosphamide required more time for engraftment of platelets and neutrophils (P<.001 for both). For patients receiving cyclophosphamide, 75% achieved engraftment (defined as a platelet count of 50x109/L) by day 39, whereas 75% of patients not receiving cyclophosphamide achieved engraftment by day 18. Similar results were observed for neutrophil engraftment. These differences did not affect the duration of hospitalization, but patients treated with cyclophosphamide had a higher incidence of posttransplant nonstaphylococcal bacteremia. For cyclophosphamide-mobilized patients, considerably faster platelet engraftment (5 fewer days) resulted if stem cell reinfusion occurred more than 30 days after the first apheresis session. Conclusion: Our data suggested that cyclophosphamide damaged the microenvironment and slowed engraftment. By lengthening the period between the completion of apheresis and stem cell reinfusion, the microenvironment may recover and result in faster engraftment. We suggest that the cyclophosphamide used for mobilization may affect the marrow microenvironment. Cyclophosphamide improves yields but increases bacteremia rates after transplantation. Cyclophosphamide increases time required to collect stem cells and slows engraftment. Figure Figure

Abstract The infused autograft absolute lymphocyte count (A-ALC) is an independent prognostic factor for survival after autologous hematopoietic stem cell transplant (AHSCT) in non-Hodgkin’s lymphoma (NHL). Previous studies have shown that A-ALC directly correlates with the peripheral blood absolute lymphocyte count (PC-ALC) at the time of apheresis collection. However, factors affecting the PC-ALC at apheresis remain undefined. We hypothesized that one possible factor impacting PC-ALC may be the time interval from last chemotherapy to stem cell collection (TILC). Data from 160 patients who underwent AHSCT for treatment of relapsed NHL at Mayo Clinic between 1993 and 2001 were collected and analyzed. The primary end point of this study was correlation between TILC and PC-ALC, and our analysis revealed a strong correlation (r = 0.67, p < 0.0001). Further analysis revealed higher PC-ALC numbers in patients with TILC ≥ 60 days versus TILC < 60 days (median of 7.44 x 109/L in the ≥ 60 day group versus 3.87 x 109/L in the < 60 day group, p < 0.0001). Both the median overall survival (figure below) and the progression-free survival were longer in the TILC ≥ 60 days group versus the TILC < 60 days group (76 versus 21 months, p < 0.0037; 76 versus 11 months, p < 0.018, respectively). These findings were independent of other prognostic indicators for relapsed NHL patients undergoing APHSCT. The data supports our hypothesis that TILC affects PC-ALC and survival post-AHSCT in NHL. Figure Figure

Abstract Aim: The autonomic nervous system plays an essential role in homeostasis and the response to stress. The peri-transplant period can be a challenging time for homeostatic responses due to the fluid shifts, sepsis and cardiac dysrhythmias that can occur. Patients with AL amyloidosis may have significant autonomic neuropathy (AN) that renders the peri-transplant care problematic. The purpose of this study was to compare a cohort of patients with AL amyloidosis complicated by AN with a matched cohort without AN to determine the outcome of patients with AN during and after stem cell transplantation (PBSCT). Methods: We performed a nested case-control study by searching the Mayo Clinic dysproteinemia transplant database for all patients with AL amyloidosis who underwent autologous PBSCT. Patients with proven AN were identified and compared to a large cohort of matched controls. We have complete follow-up on all the patients. The main outcome variables were overall survival (OS), the duration of hospitalization, incidence of sepsis, peri-transplant atrial fibrillation (AF) and engraftment kinetics. Comparisons between groups were performed with the Mann Whitney U test for continuous variables and the chi squared test for nominal variables. Overall survival was determined by the Kaplan-Meier method. A stepwise Cox proportional hazards model was used to evaluate the impact of various parameters on OS. Results: We identified 13 patients with AN who underwent PBSCT and compared them to a control group of 94 patients. The two cohorts were well matched for many of the relevant clinical and laboratory characteristics prior to PBSCT. Notable differences included (i) patients with AN tended to have more organs involved (2.5 versus 1, p<0.001) and as a result (ii) the conditioning dose of melphalan was often reduced (p=0.0015). There was no difference in the number of apheresis sessions required for CD34+ cell collection (2.5 versus 2.0, p=0.99), or the number of CD34+ cell collected (6.75 versus 8.15 x106/kg, p=0.99) between the two cohorts. The median hospital duration was 10 (1 – 78) and 8 (0 – 78) days (p=0.99) respectively. Engraftment kinetics, as measured by the time to reach a neutrophil count > 500/ml (p=0.85), a platelet count > 20,000/ml (p=0.99) and a platelet count > 50,000/ml (p=0.99) were similar in the two cohorts. Culture positive sepsis was more common in patients with AN (75% versus 47%, p=0.014). Atrial fibrillation occurred in all patients with AN but in only 1 patient from the control group (p<0.0001). The median OS from PBSCT was 45.2 months for all the combined groups. However, the median OS for patients with AN was 29 months but not yet reached for the controls (p<0.0001). On univariate analysis, cardiac involvement (p=0.0132), AN (p=0.0011), GFR (p=0.038), number of organs involved (p=0.0064) and NT-pro-BNP (p=0.039) all had an impact on OS. On multivariate analysis, AN remained an independent adverse determinant of OS. Conclusion: Patients with autonomic neuropathy secondary to AL amyloidosis can undergo PBSCT safely with similar engraftment kinetics. They are at a higher risk of peri-transplant atrial fibrillation and sepsis although their hospitalizations are not longer compared to controls. Patients with AN generally have more organ involvement by AL amyloidosis. However, AN is an independent, adverse determinant of OS in AL amyloidosis.

Abstract Abstract 636 Cellular vaccine may offer additional benefit as consolidative therapy after autologous stem cell transplant (ASCT) for multiple myeloma (MM). We have reported previously from two phase II studies the survival of MM patients who received APC8020 (autologous antigen presenting cell vaccine) after ASCT (Lacy, AJH '09, (84): 799; Lin, ASH annual meeting 2010, abstract 1958). To determine if there was an outcome advantage for additional consolidative vaccine therapy after ASCT, we performed this matched case control analysis comparing the survival of patients who received ASCT only (control) at Mayo Clinic to those who received APC8020 after ASCT in the same time period. Forty-three study patients accrued between July 1998 and March 2002 were eligible for matching. To reduce bias from disease risks and transplant-related mortality, control patients were required to be alive and progression free six months after transplant and have a M-spike value of < 2g/dL at 4 mos (1st study) or 9 mos (2nd study) after transplant, similar to post-ASCT patients who were enrolled in the two APC8020 studies. A total of 111 control patients were eligible for matching. Control patients were matched to study patients by age (+/− 5 yrs), ISS (International Staging System) stage, and plasma cell labeling index (PLCI, either >= 3 or < 3). A matched control was not identified for one study patient. Of the remaining 42 study patients, all had at least one matched control patient. Thirty-two patients had 2 matched controls. Cox proportional hazards analysis showed that there was no statistically significant difference in time to progression between the study and control patients (HR 1.54, 95% CI 0.92 – 2.58, p = 0.1). However the overall survival is significantly improved among the study patients (HR 0.54, 95% CI 0.30 – 0.99, p = 0.05). This analysis is the only known report of long-term follow-up of the largest group of MM patients treated with APC8020 vaccine. While many current prognostic tests were not available at the time of the initial vaccine studies, the control patients in this analysis were matched by known disease risks that are still in use today. The survival advantage in study patients remained statistically significant compared to matched controls. Interestingly, the time to progression is unchanged between study and control patients. This is similar to other reports of vaccine therapy such as in sipuleucel-T (Provenge™) in prostate cancer where an overall survival benefit is seen without change in progression-free survival. A larger, randomized phase III study is needed to confirm the encouraging survival benefit of this treatment modality in MM. Further insight into the mechanisms of action of APC8020 is needed to improve our understanding of the role of this therapy in the context of current practice of MM maintenance therapies. Disclosures: Sims: Dendreon Corporation: Employment.

Background: Therapy-related MDS/AML (t-MDS/AML) is a common and devastating complication of treatment with alkylating agents and topoisomerase II inhibitors, often employed with curative intent, in standard or high-doses, in the treatment of hematological malignancies and solid tumors. Allogeneic HSC transplant is considered the standard treatment for t-MDS/AML but its applicability is limited by the unavailability of donors, comorbidities in the recipient and risk of acute and chronic graft-versus-host disease. Patients carrying diseases commonly treated with high-dose chemotherapy and autologous HSC transplant (such as multiple myeloma and non-Hodgkin lymphoma) who latter develop t-MDS/AML occasionally have stored HSC harvested prior to the diagnosis of the secondary malignancy (hereafter called early-stored HSC). The benefit of using early-stored HSC to support myeloablative therapy for the treatment t-MDS/AML is unknown. Methods: Retrospective, single center analysis of patients with t-MDS/AML receiving myeloablative chemotherapy with or without irradiation supported with early-stored HSC. Results: Six patients received early-stored HSC transplant for treatment of t-MDS/AML between 2000 and 2007. Median age at the time of the transplant was 57 years (range 15–71). Three patients had been primarily diagnosed with follicular lymphoma, 2 with multiple myeloma and 1 with Ewing’s sarcoma. One patient had received prior autologous HSC transplantation. Two patients developed AML, 1 patient CMML, 1 patient RCMD, 1 patient RAEB1 and 1 patient RAEB2. Median time from diagnosis of primary malignancy to HSC harvesting was 26 (2–122) months and from harvesting to development of t-MDS/AML 44 (7–79) months. Conditioning regimen was Cy/TBI in three patients, BuCy in 2 patients and Samarium + Melphalan in one patient. Five patients engrafted neutrophils and 4 patients engrafted platelets 10–34 and 13–126 days after transplant respectively. In 3/6 patients there was disappearance of the pre-transplant chromosomic abnormality (2 patients -7 and 1 patient -7 and t(1;7)). Two patients obtained hematologic CR and two patients obtained CR without full recovery of platelets. One patient died of sepsis 230 days after transplant, one died with refractory disease on day 103 after transplant and one patient is alive with recurrence of t-MDS. Three patients are alive and free of disease 7, 73 and 87 months after transplant. Conclusion: Myeloablative conditioning followed by autologous, early-stored HSC transplant can provide prolonged survival to patients with tMDS/AML not suitable to allogeneic SCT.

Abstract Abstract 3095 Background: Although HDM is the standard conditioning for pts with MM undergoing ASCT, it is not sufficient for cure. In an effort to improve upon this standard, we added escalating doses of Y-90 Zevalin (a murine IgG1 kappa monoclonal antibody Ibritumomab conjugated to Y-90) to HDM in a standard 3+3 phase I trial design. Y-90 is a beta-emitting radioisotope with a path length of 5 mm allowing it to target CD20+ cells and bystander cells within 5 mm. Methods: Eligibility included being a candidate for ASCT. Consenting patients (pts) received: day -22, rituximab 250 mg/m2 with In2B8 for scanning; day -14, rituximab 250 mg/m2 with escalating doses of Y90-Zevalin; day -2 and -1, melphalan 100 mg/m2/day; day 0, at least 2 × 10(6) CD34/kg stem cells; and GM-CSF until ANC engraftment. The 6 dose levels (DL) were (in Gy): 10; 12; 14; 16; 18; and 20. Dose limiting toxicity (DLT) was defined as: sustained pulmonary or liver toxicity (grade3; 96 hours duration or VOD that does not resove by day 30); delayed engraftment (ANC < 500 at day 21 or platelet transfusion dependence at day 35); and non-hematologic grade (gr) 4 toxicity excluding gastrointestinal or constitutional. Responses were according to IMWG criteria. Accrual was between May 2005 and June 2011. Data was frozen as of August 2, 2011. Results: Thirty pts have been accrued: DL1, 3; DL2, 3; DL3, 3; DL4, 6, DL5, 6; DL6, 6. The median age of patients was 59 (range 32, 73), and 70% were male. 60% had ASCT as primary therapy. The other patients were transplanted in chemosensitive relapse (n=3), chemoresistant relapse (n=7), and untested relapse (n=2). Median time from diagnosis to protocol therapy was 10.4 months (range 3.5, 94.3). Five pts had prior radiation therapy, and 11 had prior ASCT. Maximum tolerated dose (MTD) of Zevalin with fixed dose melphalan 200 mg/m2 was DL 5 (18 Gy) which amounted to 168 mCi (124, 182) administered. No DLTs were observed at DL 1, 2, 3, or 5. There was 1 DLT at DL 4, comprising hepatic failure (gr 5) CMV viremia (gr 3), and delayed engraftment, in a 73 yo patient with chemoresistant relapsed disease, and 2 DLTs at DL 6. These DL 6 DLTs included: 1) fatal bowel necrosis (day 12 post ASCT) in a 67 yo patient with relapsed refractory MM and history of CAD, ischemic colitis, DM; and 2) fatal biopsy proven venoocclusive disease (gr 5), which began day 91 post ASCT in a 62 yo patient with primary refractory MM, peri-mobilization S. aureus bacteremia with septic embolic, and line associated venous thrombosis. Overall, gr 3 or higher AEs were observed in 100% of pts. Non-heme gr 4 AEs were seen in: DL1, 1; DL2, 2; DL3, 0; DL4, 1; DL5, 0; DL6, 4. Median time to ANC >=500 and plts>=50 was 11 (range 8, 17) and 15 days (range 11, 89). Confirmed response rates from immediately pre-protocol to best confirmed response were: CR, 5; VGPR, 5; continued VGPR, 4, and continued PR, 7. If one includes best confirmed response from baseline for those patients using transplant as primary consolidation, 4 PRs are upstaged to VGPRs. Median follow-up for all pts is 24.5 months (0.8, 64.8), and 10 pts have died. The median PFS for pts proceeding to early and delayed ASCT was 30.4 months (95%CI 4.1-NR) and 10.3 months (95%CI 2.8–21.7), respectively. The median OS for pts proceeding to early and delayed ASCT was not attained and 11.4 months (95%CI 2.8-NA), respectively. Conclusions: For patients with multiple myeloma, the MTD of Zevalin with fixed high-dose melphalan is 18 Gy. The combination of a VGPR plus continued VGPR rate of 60%, a median PFS of 13.1 months, and a 73% 1 year OS rate make this a regimen worthy of further study. Disclosures: Kumar: Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract Abstract 2992 Background: Patients with myeloma receiving initial therapy with lenalidomide-based regimens can have difficulty collecting adequate stem cells for an autologous transplant. Stem cell collection in these patients can be significantly enhanced by addition of the CXCR-4 antagonist plerixafor to the mobilization regimen. Plerixafor is typically given subcutaneously (SQ), with collection approximately 11 hours after injection to obtain maximum yield. Intravenous administration can potentially allow more rapid and predictable mobilization compared to the SQ route. We designed this trial to prospectively assess the efficacy of intravenous plerixafor administration in patients undergoing lenalidomide therapy. Patients and methods: Patients who were receiving initial therapy with a lenalidomide-based regimen and were undergoing stem cell collection within 12 months of their myeloma diagnosis were enrolled. Patients received GCSF at 10 μg/kg/day for 4 days followed by addition of plerixafor at 0.24 mg/kg/dose starting on day 5. Plerixafor was administered intravenously early morning (6–7 am) followed by apheresis beginning 4–5 hours later. Plerixafor was administered for a maximum of 4 days; but patients could continue apheresis beyond the 4th day at treating physician discretion. The aims of the study were to determine the proportion of patients reaching a stem cell yield of at least 3 million CD34 cells/kg by second day of apheresis, the safety and tolerability of intravenously administered plerixafor, and the overall rate of failure to mobilize (defined as less than 2.5 million CD34 cells/kg in 4 collections). Results: Thirty-seven patients were accrued between December 2009 – April 2011, and 36 were eligible for analysis. The median age was 61 years (range; 28–73); 61% were male. The median time from start of initial therapy to enrollment was 4.6 months (range; 2.6 to 11.1) and the median cycles of lenalidomide were 4 (range; 3–11). Thirty-four (94%) of the patients achieved at least 3 million CD34 cells/kg within 2 days of apheresis. The median CD34 cells/kg after 1 day of collection was 3.9 million (range; 0.7 to 9.2) and after two days of collection was 7.02 million (range: 1.1–16.5). Two patients failed the mobilization (<2.5 million CD34 cells/kg). There were no grade 3 or 4 non-hematological adverse events and one patient experienced grade 4 thrombocytopenia. The most common grade 1 or 2 adverse events seen were gastrointestinal, namely nausea, diarrhea and abdominal pain or bloating. Grade 1 dizziness was reported in 8 patients. Overall, the infusion was well tolerated. Conclusion: Intravenously administered plerixafor is an effective strategy for mobilization in this patient group with low rate of failure to mobilize. It is well tolerated with toxicity comparable to the SQ administration. It also offers flexibility in patient scheduling with a convenient schedule for early morning infusion followed by apheresis later in the day. Disclosures: Kumar: Merck: Consultancy, Honoraria; Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Genzyme: Research Funding; Novartis: Research Funding. Off Label Use: Use of the investigational agent MLN9708 for the treatment of previously untreated multiple myeloma. Lacy:Celgene: Research Funding.

Abstract Background Allogeneic stem cell transplantation (allo-SCT) is a potentially curative option for patients with myelodysplastic syndromes (MDS). However, allo-SCT can be associated with significant morbidity and mortality along with a risk for post-transplant disease relapse. While many MDS prognostic models exist, a prognostic model specifically designed to predict post-transplant disease relapse is yet to be developed. Therefore, we carried out this single institution study. Methods After due IRB approval, the Mayo Clinic MDS database (1995-2012) was retrospectively reviewed. This database contains comprehensive information on MDS clinical and pathological characteristics, treatments and SCT. Primary outcomes analyzed included disease free survival (DFS), overall survival (OS) and relapse rates at five years post allo-SCT. In addition, we evaluated transplant related mortality (TRM), non-relapse mortality (NRM), and rates of acute and chronic graft versus host disease (GVHD). DFS and OS were calculated from the time of transplantation. The prognostic relevance of several disease and transplant specific characteristics were analyzed, including: age, gender, World Health Organization (WHO) categories, therapy related MDS, cytogenetics, International Prognostic Scoring System (IPSS) and IPSS-Revised (IPSS-R) at the time of MDS diagnosis, transfusion dependence, bone marrow and circulating blast count at transplant, serum ferritin levels, SCT Co-morbidity Index, donor source, HLA matching, CMV serostatus, and conditioning regimen. Multivariate analysis was performed using the Cox Proportional Hazard Model. Survival was estimated and compared using the Kaplan Meier and Log Rank tests, respectively. Results From 1995 through 2012, 96 consecutive patients with MDS underwent allo-SCT at the Mayo Clinic, Rochester. Of these, 62 were male (65%) with a median age of 54 (24-68 years). The median follow up was 31 (1-181) months. Twenty seven patients (28%) had therapy related MDS and 39 (40%) had MDS with a monosomal karyotype. IPSS-R risk stratification identified 55 (57%) patients with very high, 20 (21%) with high and 21 (22%) with intermediate/good risk disease. Fifty (52%) patients received a reduced intensity conditioning. The TRM was 8% and NRM at 5 years was 22%. Acute (grade 2 to 4) GVHD developed in 57 (59%) patients and chronic extensive GVHD was noted in 52 (54%) patients. Five-year relapse, DFS and OS rates were 24%, 42%, and 44%, respectively. In a univariate analysis, IPSS-R (high/very high, P=0.005), therapy related MDS (P=0.009), bone marrow blast count at transplant (≥10%, P=0.01), and the presence of a monosomal karyotype (P=0.05) were significantly associated with worse DFS. On a multivariable analysis, only high or very high risk IPSS-R category (HR 7.8, P=0.005) and therapy related MDS (HR 3.9, P=0.04) retained their negative prognostic impact. Based on this finding, we developed a prognostic model that assigned one point to each of these two factors (low risk-0, intermediate-1 and high risk-2). This model successfully stratified patients based on DFS, with a 5-year DFS of 67%, 40% and 23% for low, intermediate and high risk categories respectively, P=0.0012. This model was also successful in risk stratifying patients with regards to OS (table 1, figure 1). The presence of chronic GVHD was associated with a significantly improved DFS (62% vs 24%, P<0.0001) and OS (78% vs 19%, P<0.0001), however, as this is a post-transplant outcome, it was not included in the analysis/model. Conclusions Although the IPSS-R has not been validated in therapy related MDS or in patients who have received MDS directed therapy, the high/very high risk categories along with therapy related MDS, serve as independent predictors of OS and disease relapse after allo-SCT. Using these two variables, our prognostic model efficiently stratified patients with regards to DFS, relapse rates, and OS. Given the smaller sample size validation in a larger patient cohort will be needed. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 4120 Introduction: Autologous stem cell transplantation (ASCT) remains an effective treatment for immunoglobulin light chain (AL) amyloidosis but its high treatment related mortality is a concern. The development of acute renal failure can strongly affect the survival of these patients. This study looks at the impact of the timing of dialysis initiation on the overall survival (OS). Methods: AL patients who underwent ASCT from 3/96 to 1/10 were selected. Patients were placed into 4 groups: I - never dialyzed, II - initiated dialysis prior to ASCT, III - dialysis began within 30 days of ASCT and IV - dialysis was started after 30 days of ASCT. Results: Four hundred and ten patients were selected for study and 75 (18.3%) received dialysis. Baseline characteristics are listed in Table 1. In univariate analysis, serum creatinine (Scr) and b-2 microglobulin (b2m) were associated with dialysis post-ASCT. Both became non-significant in the multivariate model suggesting they are co-dependent. Dialysis had a strong influence on survival, p < 0.001 (Fig 1). This was most evident when dialysis was started after ASCT (group III (p = 0.003) and IV (p = 0.004)), but not before (II, p = 0.19).To explore the interactions of dialysis with cardiac biomarkers in their relationship with OS, cardiac troponins T (cTnT) and N terminal-pro-brain natriuretic peptide (NT-pro-BNP) were analyzed with timing of dialysis in a proportional hazard model. Timing of dialysis (p < 0.001), cTnT (p = 0.03) and NT-pro-BNP (p = 0.03) all were associated with OS. Using Receiver Operator Characteristic (ROC) curves, best cut points were chosen for cTnT (0.01 ng/ml) and NT-pro-BNP (1350 pg/ml) for survival. When treated as categorical variables, the proportional hazard model found that only NT-pro-BNP (p = 0.002) and timing of dialysis (p < 0.001) were independent predictors of OS but cTnT had loss its significance (p = 0.07). Using Kaplan Meier method, dialysis was a significant risk factor in patients with low cTnT and both high and low NT-pro-BNP (p < 0.001) but not in patients with elevated cTnT (p = 0.25). Discussion: The timing of acute renal failure strongly affects the OS of AL patients undergoing ASCT. In our study, patients who started dialysis prior to ASCT did not have an inferior OS compared to patients who never needed dialysis. On the other hand, starting dialysis after ASCT significantly shortened OS. The timing of dialysis was an independent predictor of OS even when combined with cardiac biomarkers. NT-pro-BNP appears to be the stronger marker when timing of dialysis is considered in the multivariate analysis. Disclosures: No relevant conflicts of interest to declare.