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Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age

The t(11;14)(q13;q32) translocation is seen in 15%-20% patients with multiple myeloma (MM). It generally is not associated with worse outcomes. We studied the impact of t(11;14)(q13;q32) on outcome in patients with MM who received high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT). Eligible patients underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between February 2000 and August 2010, and had conventional cytogenetic (CC) or fluorescence in situ hybridization (FISH) results available before auto-HCT (n = 993). The cohort was divided into 3 groups of patients: (1) normal (diploid by CC and negative by FISH; n = 869); (2) t(11;14)(q13;q32) by CC or FISH (n = 27); and (3) high-risk (HR) abnormalities by CC or FISH (n = 97). Of the 27 patients with t(11;14)(q13;q32), 18 had isolated t(11;14)(q13;q32) and 9 had concurrent HR abnormalities. The primary objective was to compare outcomes in patients with t(11;14)(q13;q32) and patients with diploid or HR markers detected by CC or FISH studies. The median duration of follow-up in surviving patients was 37 months. The 3-year progression-free survival (PFS) was 47% for the normal group, 27% for the t(11;14)(q13;q32) group, and 13% for the HR group (P 3.5, and relapsed disease at the time of auto-HCT were associated with shorter OS. In conclusion, patients with t(11;14)(q13;q32) had worse outcomes than patients with normal CC or FISH studies, but better outcomes than patients with HR markers detected by CC or FISH studies.

Background The optimal regimen for peripheral blood stem cell (PBSC) mobilization in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) has not been established. Experience at The University of Texas MD Anderson Cancer Center suggests in addition to single-agent cyclophosphamide (Cy), modified cyclophosphamide, vincristine, doxorubicin, and dexamethasone (mCVAD), and modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone (mCBAD) may be successful chemomobilization regimens. Methods This retrospective review included 167 patients (66 with Cy, 74 with mCVAD, and 27 with mCBAD) with multiple myeloma undergoing mobilization for auto-HCT between January 1, 2006 and September 30, 2013. The primary objective was to evaluate and compare the successful mobilization of CD34+ cells among high-dose Cy, mCVAD or mCBAD. Results Successful mobilization (≥2×106 CD34+ cells/kg) was achieved in all patients, while 65 (98%), 72 (97%), and 27 (100%) patients achieved an optimal mobilization (≥4×106 CD34+ cells/kg) in the Cy, mCVAD, and mCBAD groups, respectively. There was no significant difference in the number of apheresis sessions (P=.63), incidence of febrile neutropenia (P=.57), or hospital admission rates (P=.55). Conclusion Either Cy, mCVAD, or mCBAD can yield successful PBSC mobilization in patients with multiple myeloma undergoing auto-HCT.

Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. However, little is known about the risk of HBV reactivation after autologous hematopoietic stem cell transplantation (auto-HCT). We evaluated the incidence of HBV reactivation, liver toxicity, and survival in patients with multiple myeloma (MM) who received auto-HCT at our institution. We retrospectively identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control subjects) who were matched for age, timing of auto-HCT from diagnosis, cytogenetics, disease status at transplant, induction therapy, and preparative regimen. All patients underwent auto-HCT between 1991 and 2013. Primary endpoints were HBV reactivation, defined as HBsAg positivity or ≥10-fold increase in HBV DNA, and hepatotoxicity, as defined in the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. In the resolved HBV infection group, 52 patients (49%) were HBsAb positive and 24 (22%) had detectable HBV DNA before auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with lamivudine, whereas 4 patients received lamivudine (n = 3) or tenofovir (n = 1) at reactivation after auto-HCT for a median duration of 12 months. HBV reactivation occurred in 7 of 107 patients (6.5%) in the resolved HBV group. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or greater hepatotoxicity was 30% in the resolved HBV infection group and 22% in the control group (hazard ratio, 1.3; 95% confidence interval, .7 to 2.3; P = .4). Nonrelapse mortality for the 2 groups was not statistically different at 2 years (P = .06), although it trended higher in the control group than in the resolved HBV infection group (8% versus 1%). The median progression-free survival (PFS) and overall survival (OS) durations in the resolved HBV infection and control groups were 21 versus 18 months (P = .5) and 53 versus 67 months (P = .2), respectively. Our data suggest that resolved HBV infection in patients undergoing auto-HCT for MM is associated with a low risk of HBV reactivation and hepatotoxicity; these complications were reversible and did not adversely affect the PFS or OS.

The role of donor lymphocyte infusion (DLI) in mediating the graft-versus-myeloma (GvM) effect after allogeneic hematopoietic stem cell transplant (allo-HCT) is not clearly defined. We evaluated the safety and utility of DLI in patients with either persistent or recurrent multiple myeloma (MM) after allo-HCT. Twenty-three patients with MM received DLI after allo-HCT at the University of Texas M. D. Anderson Cancer Center between July 1996 and June 2008. Eight patients received preemptive DLI for residual disease (RD) while 15 patients received DLI for the treatment of recurrent or progressive disease (PD). We evaluated the response to DLI and the factors that may predict a response. Median DLI dose was 3.3 × 10(7) CD3 + cells (range 0.5-14.8 × 10(7)). Grade II-IV acute graft-versus-host disease (GvHD) was seen in five patients (22%). Median follow-up in surviving patients was 24 months. Five of 23 patients (22%) achieved a complete or a very good partial response (two CR, three VGPR), while eight patients (34%) had stable disease (SD) after the DLI. Patients who received DLI for RD had a higher response rate (≥ VGPR 50% vs. 7%, p = 0.03), a longer overall survival (28.3 vs. 7.6 months, p = 0.03) and a trend toward longer progression-free survival (11.9 vs. 5.2 months, p = 0.1). In this largest single institution study, we conclude that the use of preemptive, non-manipulated DLI for RD after reduced-intensity conditioning allo-HCT is encouraging, and it was associated with a higher response rate and a longer overall survival when given preemptively. The role of DLI needs to be further explored in prospective clinical trials.

BACKGROUND: High-dose chemotherapy with autologous hematopoietic cell transplant (auto-HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto-HCT for relapsed patients, particularly in the era of novel therapeutics, is not well defined. METHODS: The authors performed a retrospective analysis of all 44 myeloma patients (24 men, 20 women) who received a second auto-HCT as salvage between January 3, 1992 and November 4, 2008 at The University of Texas MD Anderson Cancer Center. RESULTS: Median interval between the first and salvage auto-HCT was 30 months (range, 2-78 months). Median age at salvage HCT was 54 years (range, 38-73 years), and median number of salvage treatment regimens was 2 (range, 0-5). Eleven (25%) patients had high-risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto-HCT. Ten patients (23%) experienced grade 3 or higher nonhematologic toxicity after the salvage auto-HCT. One patient died within 100 days, for a treatment-related mortality of 2%. Best responses after salvage chemotherapy + salvage auto-HCT were as follows: complete response (CR) + near CR, 11%; partial response, 79%; overall response rate, 90%. Eighteen (41%) patients received post auto-HCT maintenance therapy. Median follow-up from salvage HCT was 41 months. Kaplan-Meier estimates of median progression-free survival (PFS) and overall survival (OS) from time of salvage auto-HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression after first auto-HCT, greater number of prior therapies, African American race, and immunoglobulin G subtype were significantly associated with worse OS. CONCLUSIONS: In selected myeloma patients, a second auto-HCT for salvage therapy is well tolerated, with acceptable toxicity. The overall response rate and PFS are comparable to other salvage regimens. Cancer 2012;3549–3555. © 2011 American Cancer Society.

Autologous hematopoietic stem cell transplantation in light chain amyloidosis (AL) with renal involvement

There is limited information on the outcome when organs other than heart or kidneys are involved by immunoglobulin light-chain amyloidosis (AL). We report the outcome of 53 patients with AL with gastrointestinal (GI), peripheral nerve (PN), liver, lung, or soft-tissue involvement, who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution between 1997 and 2013. The median age at auto-HCT was 56 years (range, 35 to 74). One, 2, 3, or 4 organs were involved in 43%, 22%, 28%, and 4% of patients, respectively. Concurrent cardiac, renal, or both were involved in 24 (45%) patients. Forty-six patients received induction therapy before auto-HCT. The 100-day and 1-year treatment-related mortality (TRM) were 3.8% (n = 2) and 7.5% (n = 4), respectively. Forty-one (80%) patients achieved a hematologic response. Organ response at 1 year after auto-HCT was seen in 23 (57%) of the 40 evaluable patients. With a median follow-up of 24 months, the median progression-free survival and overall survival (OS) were 36 and 73 months, respectively. Auto-HCT was associated with a low TRM, durable organ responses, and a median OS of > 6 years in selected patients with AL and GI, PN, liver, lung, or soft-tissue involvement.

Th e last two decades have seen tremendous progress in the treatment of multiple myeloma, including the use of high-dose melphalan (HDM) with autologous hematopoietic stem cell transplant (auto-HCT) and the availability of various novel agents [1]. Th e incidence of cardiotoxicity after HDM is not known, even though there have been case reports of cardiac arrhythmias with HDM [2,3]. In this study, we evaluated the incidence of cardiac adverse events (AEs) in 325 patients within 30 days of undergoing auto-HCT using HDM at M. D. Anderson Cancer Center for multiple myeloma between January 2006 and December 2009. We excluded 78 patients with concurrent immunoglobulin light chain amyloidosis (AL). In the group who experienced cardiac AEs, melphalan doses of 200 mg/m 2 (19 patients) and 180 mg/m 2 (one patient) were used. Similarly, melphalan doses of 200 mg/m 2 (215 patients), 180 mg/m 2 (six patients), 160 mg/m 2 (one patient) and 140 mg/m 2 (two patients) were used in the group without cardiac AEs. In two patients without cardiac AEs the melphalan dose was missing. All patients received granulocyte colony stimulating factor (G-CSF), 5 μ g/kg/ day from day 1 until the absolute neutrophil count (ANC) was 0.5 109/L for 2 consecutive days, as per departmental guidelines. Supportive care measures, including blood product transfusion and electrolyte and weight management were done as per institutional guidelines. Cardiac toxicity was defi ned as any cardiac AE reported from the day of administration of melphalan to day 30 after auto-HCT. Th ese cardiac AEs included congestive heart failure (CHF), arrhythmias, ischemic chest pain and sudden cardiac death. CHF was defi ned as any structural or functional cardiac disorder that impaired the ability of the ventricles to fi ll or eject blood, with associated symptoms of fatigue, dyspnea and fl uid retention. Sudden cardiac death was defi ned as cessation of cardiac activity leading to unresponsiveness and demise of the patient. Ischemic chest pain was defi ned as typical substernal chest pain that was precipitated by exertion, radiating to the jaw and the inner aspect of the arms or shoulders, and relieved by nitroglycerin. Prior cardiac history was defi ned as a history of coronary artery disease, arrhythmias, valvular heart disease or cardiac light-chain amyloidosis before auto-HCT. Th e primary endpoint of the study was to evaluate the incidence of cardiac AEs after HDM and auto-HCT. We also evaluated the variables that could aff ect cardiac AEs. Th ese variables included a prior history of hypertension, diabetes, tobacco smoking, prior chemotherapy, interval between diagnosis and auto-HCT, cardiac biomarkers (troponin and brain natriuretic peptide [BNP]) and echocardiogram. Cardiac biomarkers are routinely collected as a part of pre-transplant evaluation.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment for multiple myeloma (MM); however, because of high treatment-related mortality (TRM), its role is not well defined. Patients with newly diagnosed, relapsed, or primary refractory myeloma were enrolled in a randomized phase II trial of 2 reduced-intensity conditioning regimens: fludarabine 120 mg/m2 + melphalan 100 mg/m2 (FM100) versus fludarabine 120 mg/m2 + melphalan 140 mg/m2 (FM140) before allo-HCT from related or unrelated donors. Fifty patients underwent allo-HCT using FM100 (n = 23) or FM140 (n = 27) conditioning between April 2002 and 2011. There were no significant differences between FM100 and FM140 in time to neutrophil engraftment (P = .21), acute grade II to IV graft-versus-host disease (GVHD) (P = 1.0), chronic GVHD (P = .24), response rate (P = 1.0), TRM (13% versus 15%, P = 1.0), median progression-free survival (PFS), 11.7 versus 8.4 months, P = .12, and median overall survival (OS), 35.1 versus 19.7 months, P = .38. Cumulative incidence of disease progression in FM100 and FM140 was 43% and 70%, respectively (P = .08). Recurrent disease was the most common cause of death for both FM100 (26%) and FM140 (44%), P = .24. On multivariate analysis, disease status at allo-HCT, complete response or very good partial response (VGPR) was significantly associated with longer PFS (15.6 versus 9.6 months in patients with

A total of 149 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with myeloablative (MAC; n = 38) or reduced-intensity conditioning (RIC; n = 110) regimens at MD Anderson Cancer Center were evaluated. Of the total, 120 (81%) patients had relapsed or had refractory disease. Median age of MM patients was 50 (28–70) years with a followup time of 28.5 (3–164) months. The 100-day and 5-year treatment related mortality (TRM) rates were 17% and 47%, respectively. TRM was significantly lower with RIC regimens (13%) vs. 29% for MAC at 100 days (P = 0.012). The cumulative incidence of Grade II–IV acute graft-versus-host disease (GVHD) was 35% and chronic GVHD was 46%. PFS and OS at 5 years were 15% and 21%, respectively. In multivariate analysis, allo-HCT for primary remission consolidation was associated with longer PFS (HR 0.35; 95% CI, 0.18–0.67) and OS (HR 0.29; 95% CI 0.15–0.55), while absence of high-risk cytogenetics was associated with longer PFS only (HR 0.59; 95% CI 0.37–0.95). We observe that TRM has decreased with the use of RIC regimens, and long-term disease control can be expected in a subset of MM patients undergoing allo-HCT. Further studies should be conducted in carefully designed clinical trials in this patient population. Am. J. Hematol., 2012. © 2011 Wiley Periodicals, Inc.

We retrospectively analyzed the outcomes of all consecutive patients with myeloma (n = 84) aged ≥70 years who had received autologous hematopoietic stem cell transplant (auto HCT) between July 1999 and June 2010 at our institution. The median age at auto HCT was 72 years, the median number of prior therapies was 2.5 and the median time from diagnosis to auto HCT was 10.2 months. The conditioning regimen consisted of melphalan at 140 mg/m(2) in 10%, 180 mg/m(2) in 25% and 200 mg/m(2) in 65% of patients. The day-100 non-relapse mortality was 3%. The overall response rate at day 100 was 85% (complete response 18%, very good partial response 12%, partial response 55%). After a median follow-up of 25 months among surviving patients, the estimated progression-free survival and overall survival at 5 years were 27% and 67%, respectively. The incidence of grade II-IV toxicity, response rate and survival were similar across three melphalan dose levels. These results indicate that high-dose melphalan plus auto HCT is safe and feasible for patients with multiple myeloma aged ≥70 years and age alone should not be an exclusion criterion for auto HCT.

Abstract 4569 Background: Allogeneic hematopoietic cell transplantation (allo HCT) is a potentially curative therapy for multiple myeloma (MM), but has high treatment-mortality (TRM). In addition, disease relapse occurs in a significant number of patients. We sought to evaluate if the recent advances in the field of HCT and MM have impacted the results of allo HCT for MM. We present the results of allo HCT performed at a single center over last 25 years. Methods: 149 patients with MM who underwent allo HCT between 11/1985 and 6/2010 using myeloablative (MA) N= 52, or reduced intensity conditioning (RIC) N=97 at our institution were retrospectively analyzed. Results: Patient characteristics and pertinent outcomes are summarized in the Table. 62 (42%) were female. Median age was 50 (28-70) years. Median follow up is 2.4 years [11.3 years for the patients who received allo HCT prior to year 2000( Conclusion: Allo HCT for MM can offer long term disease control in a subset of MM patients. TRM has declined and outcomes have significantly improved over the last decade. Maintenance therapy may have a role post allo HCT. Disclosures: Shah: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding. Weber:novartis-unpaid consultant: Consultancy; Merck- unpaid consultant: Consultancy; celgene- none for at least 2 years: Honoraria; millenium-none for 2 years: Honoraria; celgene, Millenium, Merck: Research Funding. Qazilbash:Celgene: Speakers Bureau.

8538 Background: High-dose melphalan at 200 mg/m2 (Mel) is the standard for autologous hematopoietic stem cell transplantation (auto-HCT) for multiple myeloma. Two recent retrospective analyses sug...

8601 Background: The incidence of renal insufficiency at presentation is approximately 30% in patients with multiple myeloma (MM). 5% of these patients are dialysis dependent. Presence of renal dysfunction is associated with increased treatment related toxicity and poor survival. Methods: We retrospectively analyzed our transplant database from July 2000 to June 2012 to identify myeloma patients who received autologous hematopoietic stem cell transplantation (autoHCT) while they were dialysis dependent. Univariate Cox proportional hazards regression was performed to assess the association between survival and covariates of interest. Kaplan Meier curve was used to estimate progression free survival (PFS) and overall survival (OS). Results: 2,091 patients underwent autoHCT during this interval. 24 (1.1%) were dialysis dependent (21 on hemodialysis and 3 on peritoneal dialysis). Median age was 53 (29-70) years. 63% were male. ISS stage at diagnosis was I & II in 4%, III in 54%, and unknown in 38%. Median dur...

Background Bortezomib and high-dose melphalan was associated with a higher complete remission (CR) rate in a phase II trial by the IFM group. Four doses of bortezomib 1 mg/m2 IV were given on days -6, -3, +1 and +4. (Roussel M et al. Blood 2010. 115:32-37).In a randomized phase II trial we reported that the addition of bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA), and melphalan followed by autologous hematopoietic stem cell transplantation (auto-HSCT) failed to demonstrate a statistically significant improvement in CR rate or survival in patients (pts) with newly diagnosed or relapsed multiple myeloma (Sharma M et al. Cancer. 118:2507-15).This study was limited by a short follow up (median 36 months) and inclusion of pts with relapsed and refractory disease. In this retrospective analysis, we evaluated the long-term (5-years) impact of the addition of bortezomib to this preparative regimen in pts who underwent auto-HCT in first remission or with primary refractory disease. Methods Forty-three pts underwent auto-HCT in first remission or with primary refractory disease. All patients received ATO 0.25 mg/kg intravenously on days -9 to -3, AA 1000 mg intravenously on days -9 to -3, and melphalan 100 mg/m2 intravenously on days -4 and -3. Pts received either no bortezomib (n=13), or bortezomib at a dose of either 1 mg/m2 of 1.5 mg/m2 on days -9, -6, and -3. The primary endpoint was CR rate and secondary endpoints were progression free survival (PFS) and overall survival (OS). Results Pt characteristics are shown in the attached Table. The median follow-up for all surviving pts was 61.4 months (range, 15-80 months). Pts in the bortezomib and non-bortezomib arms were matched for age, gender, high-risk cytogenetic abnormalities, time to auto-HSCT, use of bortezomib in induction, and disease burden at auto-HSCT (Table). Only 5 (17%) pts in the bortezomib and 4 (30%) in the non-bortezomib group received maintenance therapy. There was no significant difference in the time to neutrophil engraftment or treatment-related mortality TRM between the bortezomib and non-bortezomib groups. The CR rate in the bortezomib group and the non-bortezomib group was 20% and 53%, respectively (p=0.03). There was no significant difference in rates of CR + very good partial remission (VGPR), or CR + VGPR + partial remission (PR) between the bortezomib and non-bortezomib groups (p=0.72 and 1.00, respectively). The median PFS in the bortezomib group and the non-bortezomib group was 25.4, and 40.0 months, respectively (p=0.13, Figure 1). The median OS was 61.6 months in the bortezomib group and not reached in the non-bortezomib group (p=0.22, Figure 2). There was no significant impact of high-risk cytogenetics, lactic dehydrogenase (LDH) or b2 microglobulin levels, or maintenance therapy on PFS or OS. Conclusions After long-term follow up of 5 years, the addition of bortezomib to a preparative regimen of ATO, AA, and high-dose melphalan did not result in a significant improvement in CR rate, PFS, or OS. The lack of benefit with bortezomib may be due to the inclusion of ATO and AA in the regimen, or the schedule of bortezomib, which was only given before melphalan. Disclosures: Shah: Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees Other; Millenium: Membership on an entity’s Board of Directors or advisory committees, Membership on an entity’s Board of Directors or advisory committees Other.

Background Peripheral blood stem cell (PBSC) mobilization in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) is commonly carried out using growth factors alone. Approximately 10-15% of patients receive chemomobilization, which assists with cytoreduction and improving the cell yield; however, an optimal regimen has not been established. Here we report our experience with three chemomobilization regimens that have been used at our center: i) cyclophosphamide alone (Cy) ii) modified cyclophosphamide, vincristine, doxorubicin, dexamethasone (mCVAD) and iii) modified cyclophosphamide, bortezomib, doxorubicin, dexamethasone (mCBAD). Methods This is a single-center, retrospective chart review of patients with multiple myeloma undergoing mobilization for an auto-HCT with Cy, mCVAD, or mCBAD between January 1, 2006 and September 30, 2012. A total of 120 patients were identified as initiating stem cell mobilization with Cy (n=39), mCVAD (n=66) or mCBAD (n=15) for multiple myeloma within the defined time period. For the purpose of this study, we combined mCVAD and mCBAD into one group (n=81). The primary objective of this study is to compare successful mobilization and collection (≥ 2 x 106 CD34+ cells/kg collected) between high dose Cy (2-4 g/m2 x1) and mCVAD (cyclophosphamide 350 mg/m2 q12h x 4 days, vincristine 0.4mg continuous infusion daily x 4 days, doxorubicin 10 mg/ m2 continuous infusion daily x 4 days, dexamethasone 40 mg IV daily x 4 days) + mCBAD (same as previous, except using bortezomib 1.3 mg/m2 bolus x 4 days instead of vincristine). Secondary objectives include optimal mobilization (≥ 4 x 106 CD34+ cells/kg), median number of leukapheresis sessions required, use of plerixafor, post-transplant time to neutrophil engraftment, disease status at day 100, time to progression, and incidence of febrile neutropenia, hospitalization, and ICU admissions with each mobilization regimen. Results The groups were well-matched with regard to demographic characteristics. [Table] All 120 achieved a successful mobilization (≥ 2 x 106 CD34+ cells/kg collected) and 118 achieved an optimal mobilization (≥ 4 x 106 CD34+ cells/kg collected). There was no significant difference in the number of leukapheresis sessions (median 2, range 1-7) or plerixafor use (20.5% Cy vs. 8.6% mCVAD or mCBAD, p=0.08). There was no significant difference in the incidence of febrile neutropenia (10.3% Cy vs. 12.4% mCVAD or mCBAD, p=1.00), hospital admissions (18% Cy vs. 21% mCVAD or mCBAD, p=0.81), or ICU admissions (0% Cy vs. 1.2% mCVAD or mCBAD, p=1.00) between the groups. All 14 patients who had an episode of febrile neutropenia were hospitalized. One patient in the mCVAD or mCBAD group was admitted to the ICU with sepsis and renal failure, but was eventually discharged. There were no mobilization-related deaths in either study group. There was no significant difference in the time to neutrophil engraftment for the two groups (median 11 days, range 9-13). The median time to progression was 11.8 months in the Cy group and 9.1 months in the mCVAD or mCBAD group. Conclusion Cy, mCVAD or mCBAD can be used for successful PBSC mobilization in patients with multiple myeloma undergoing an auto-HCT without any unexpected toxicity. These approaches may be further evaluated in a randomized, prospective trial. Disclosures: Off Label Use: Cyclophosphamide, mCVAD, and mCBAD will be discussed as mobilization regimens used for patients with multiple myeloma. Vincristine and doxorubicin do not have specific indications for use in multiple myeloma. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees; Millennium: Membership on an entity’s Board of Directors or advisory committees.

Abstract 2027 Background: High-dose melphalan (HDM), 200 mg/m2, is the standard regimen for autologous hematopoietic stem cell transplant (auto-HCT) for multiple myeloma (MM). Although HDM-induced cardiotoxicity is reported, its incidence is not well known. In this retrospective analysis we evaluated the incidence of cardiotoxicity and its impact on outcome in patients undergoing auto-HCT for MM. Methods: Three-hundred and sixty-nine consecutive patients who received melphalan 200 mg/m2 for auto-HCT ASCT between January 2006 and December 2009 were included in these analyses. Cardiac toxicity was defined as any cardiac adverse event reported from the day of administration of melphalan to day+ 30 after auto-HCT. Results: Patient characteristics are summarized in Table 1. Median age at auto-HCT was 59 years (32–78 years). Median time from diagnosis to auto-HCT was 8.0 months (1.8–266.3). Patients undergoing auto-HCT had a left ventricular ejection fraction (LVEF) of >40%, and no symptomatic cardiac disease. Thirty-five patients had concurrent or AL amyloidosis, and 43 patients had a prior history of cardiac disease. By day +30 after auto-HCT, 34 patients (9.2%) developed one or more adverse cardiac adverse events (AE). Twenty-seven patients experienced a single cardiac AE: atrial fibrillation (a fib): 16, congestive heart failure (CHF): 3, supraventricular tachycardia (SVT): 3, ischemic chest pain: 2, ventricular bigeminy: 1, diastolic dysfunction: 1 and sudden cardiac death in a patient with AL amyloidosis: 1. Seven patients had a combination of 2 or more cardiac adverse events: CHF + a fib: 4, ischemic chest pain + QT prolongation: 1, ischemic chest pain + left bundle branch block (LBBB): 1, ischemic chest pain + premature ventricular contractions (PVCs): 1. Overall, supraventricular arrhythmias were responsible for cardiac AE in 6.2% (23/369) of the patients. Twenty-eight patients (82%) fully recovered from the cardiac AE. Four patients required long term pharmacologic treatment of a fib, and one patient with a fib developed a cerebellar infarct without residual neurologic deficits. Patients with cardiac AE were older (median age: 62 vs. 59, p=0.014) and had a prior history of cardiac disease (17/34 vs. 20/335, p=0.0001) compared to patients without cardiac AE. Gender, concurrent AL amyloidosis, interval between diagnosis and auto-HCT, or transplant before or after the year 2000 were not associated with cardiac AE. Median overall follow up was 28 months (1–369). 100-day non-relapse mortality (NRM) was 3% (1/34) vs. 0% (0/335) in patients with or without cardiac AEs (p=0.09). Kaplan-Meier estimates of 3-year OS were 70% vs. 84% in patients with or without cardiac AE (p=0.084). Conclusions: HDM and auto-HCT was associated with cardiac AEs in 9% of patients. A fib and CHF were the most common cardiac AEs, but >80% fully recovered without long-term sequelae. Patients with cardiac AE were relatively older and had a prior history of cardiac disease. There was no significant difference in NRM or OS in patients with or without melphalan-associated cardiac AEs. =VGPR: includes Complete Remission (CR);, Very Good Partial Response and Partial Remission (VGPR), PR: Partial remission. RBBB (Right bundle branch block). Disclosures: No relevant conflicts of interest to declare.

Abstract 4533 Purpose: The role of autologous stem-cell transplantation (auto-HCT) in Waldenström macroglobulinemia (WM) is not clearly defined. The aim of this study was to analyze the results of auto–HCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome. Patients and Methods: We analyzed 16 adult patients (10 males and 6 females) with WM who underwent high-dose chemotherapy and auto–HCT at MDACC between 1/89 and 2/11. Median age at diagnosis was 55 years (range 43–74) and median age at auto-HCT was 55.5 years (range 43–75). Concurrent AL amyloidosis was seen in 6 patients (37%). Median interval from diagnosis to time of progression was 3.1 years (range 0.4– 9.5) and patients had received a median of 2 lines of therapy (range: 1–6) prior to auto-HCT. Seven patients (44%) had either primary refractory disease or were in first remission, while 9 patients (56%) had relapsed disease. Median follow-up in the surviving patients was 3.5 years (range, 1.1– 12.2). Preparative regimens were as follows: 9 patients received Melphalan alone; 2 received Melphalan + Rituximab; 1 underwent Melphalan + total body irradiation (TBI); 2 received Thiotepa + Busulfan + Cyclophosphamide; and 2 received BCNU + Etoposide + Cytarabine + Melphalan + Rituximab (BEAM-R). Results: Non-relapse mortality was 6.2% at 1 year. All 15 evaluable patients achieved engraftment with a median time to neutrophil engraftment of 11 days (10–46). Fourteen patients were eligible for response evaluation. One patient died within 30 days and one was lost to follow up. Three (21%) patients achieved a CR, while 9 (64%) achieved a PR. The overall response rate was 85%. Progression-free survival (PFS) and overall survival (OS) at 5 years were 36.7% and 56.4%, respectively. Median PFS and OS from auto-HCT were 2.5 and 8.3 years, respectively. The median OS from diagnosis was 12.3 years. On univariate analyses, disease status at auto-HCT (first remission or primary refractory disease) was the strongest predictor of progression (p=0.05; HR 0.1, 95% CI 0.01–1.04), PFS (p=0.01, HR 0.1, CI: 0.01–0.6) and OS (p=0.01). Similarly, the melphalan-based regimens were associated with a longer OS in patients with relapsed disease at auto-HCT (p=0.002). On univariate analyses, LDH level at auto-HCT, number of prior chemotherapy regimens, use of prior cladribine, concurrent AL amyloidosis or International Staging System score (ISSWM) did not have a significant impact on the outcome. Conclusion: Auto-HCT is a feasible procedure in patients with advanced WM, even when performed later in the course of disease, after a median of 2 lines of therapy. Patients with relapsed disease at auto-HCT have a significantly worse outcome and may require posttransplant therapy. Disclosures: Shah: Celgene: Membership on an entity's Board of Directors or advisory committees.

Abstract 3115 Background: The International Staging System (ISS), chromosomal abnormalities, and response to therapy are well recognized predictors of outcome in multiple myeloma (MM). However, the role of serum lactate dehydrogenase (LDH) as a prognostic marker for MM is not well established. Recently we showed that high LDH at diagnosis of MM is a predictor of shorter survival. Here we report the impact of the LDH level at the time of autologous hematopoietic stem cell transplantation (auto-HCT) on its outcome. Methods: We evaluated 1,658 patients with symptomatic myeloma who underwent auto-HCT from July 1988 to December 2010 at our institution. The primary objective was to determine the impact of high LDH (>1000 IU/L) level, obtained on the start day of the preparative regimen, on progression free survival (PFS) and overall survival (OS). Results: Patient characteristics according to LDH level at auto-HCT are summarized in Table 1. Patients in the 2 LDH groups (>1000 or ≤ 1000) were matched for age, gender, disease status, and response to prior therapy at the time of auto-HCT. Patients with LDH >1000 IU/L had a significantly higher beta-2 microglobulin (β2m) and bone marrow plasmacytosis at the time of auto-HCT. Median times to neutrophil (10 vs. 10 days: p=0.10) and platelet engraftment (11.3 vs.12.2 days: p=0.20) were not different in the 2 groups. Also, there was no significant difference in CR, VGPR, PR or overall response rates between the 2 groups. Median follow up was 35 months (1 to 244). Median OS in patients with LDH >1000 and ≤ 1000 were 49.2 and 68.0 months, respectively (p=0.03). Median PFS in patients with LDH >1000 and ≤ 1000 were 14.4 and 24.7 months, respectively (p=0.001). On univariate analyses, >10% plasma cells in bone marrow biopsy, relapsed disease, serum β2M ≥ 3.5 at auto-HCT, presence of any chromosomal abnormality, and < PR after auto-HCT were associated with significantly shorter PFS and OS. Conclusions: Having a serum LDH value of >1000 IU/L prior to auto-HCT is associated with shorter PFS and OS in patients with MM. These high risk patients may require aggressive post-transplant therapy, including consolidation, maintenance, tandem transplants or novel approaches like immunotherapy. Disclosures: Shah: Celgene: Membership on an entity's Board of Directors or advisory committees.

3094 [][1] Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment for patients with multiple myeloma (MM) but its use is limited by high non-relapse mortality (NRM). European Group for Bone Marrow transplant (EBMT) risk score is a validated predictor of outcome for patients undergoing allo-HCT for hematological malignancies. It takes into consideration patient's age, donor's gender and type, disease status and the interval from diagnosis to allo-HCT, with the score ranging from 0 to 7. We assessed the impact of EBMT risk score in MM patients undergoing allo-HCT. Methods: A total of 189 patients with MM who underwent HSCT between November 1985 and June 2010 at MD Anderson Cancer Center were included in the analysis. Results: Patient characteristics are summarized in [Table 1][2]. There were 110 males (58%) and 79 females (42%) with a mean age of 50 years (range 28–70). Donors were related in 146 patients (HLA-identical=131, 1 antigen mismatched (AGMM) = 5, 2 AGMM =1, 3AGMM=1, syngeneic=8) and unrelated in 43 patients (HLA identical= 37, 1AGMM=4, 2AGMM=1, unknown=1). One-hundred and twelve patients had prior autologous transplants (auto-HCT). Of these 83 had 1, 28 had 2 and 1 had 3 prior auto-HCT, respectively. Median time from diagnosis to allo-HCT was 24.7 months (range 3.3–232) and median overall follow up was 13 months (0.2–266). Overall 94 patients (49%) had progressed before last follow-up. Incidence of all-cause mortality was 138 (73.4%) with 69 (36%) of all deaths attributed to NRM. KM estimates of 2-year PFS and OS were 25% and 42%, and 5-year PFS and OS were 16% and 27%, respectively. Cumulative incidence (CI) of grade 2–4 and grade 3–4 acute graft versus host disease (aGVHD) was 33% and 13%, respectively. Cumulative incidence of overall and extensive chronic GVHD (cGVHD) was 47% and 17%, respectively. EBMT risk score was, 0–3 for 41 (21.7%), 4 for 72 (38.1%) 4 and 5–7 for 76 (40.2%) patients. EBMT risk score was higher for males, African-Americans and older allo-HCT recipients, patients with higher LDH levels (>618mg/dl), s2-microglobulin >3.5mg/dl and patients with bone marrow plasmacytosis. Median PFS in patients with EBMT scores 0–3, 4 and 5–7 were 10.1, 8.4 and 6.4 months, respectively (P=0.0036). Median OS in patients with EBMT scores 0–3, 4 and 5–7 were 39, 15.8 and 9.6 months, respectively (p=0.001). Cumulative NRM in patients with EBMT scores 0–3, 4 and 5–7 were 37% (15/41), 36.1% (26/72) and 37.3% (28/75), respectively (p= 0.234). Cumulative incidence of progression in patients with EBMT scores 0–3, 4 and 5–7 were 36.5% (15/41), 50% (36/72) and 56.5% (43/76), p=0.119. Compared to those with EBMT risk score (0–3), individuals with EBMT risk scores >5 had a higher risk of all-cause mortality (HR 2.34, 95% CI 1.44–3.80), and disease progression (HR 3.06, 95% CI 1.67–5.61). Addition of s2-microglobulin, BM plasma cells or prior response status alone or in combination with EBMT risk score significantly improved the discrimination properties of the model containing EBMT score alone (p/= PR | 106 | 56% | ref | | 10 | 51 | 28% | 0.88 (0.52 to 1.24) | | LDH(mg/dl) | 189 | | | | 618 | 31 | 16% | 0.33 (−0.13 to 0.78) | | s2-microglobulin(mg/l) | 182 | | | | 3.5 | 54 | 30% | 0.37 (−0.01 to 0.74) | * =PR: includes Complete Remission (CR); Complete Cytogenetic Response (CCR), Very Good Partial Response and Partial Remission (VGPR) * PR: Partial remission, BM: bone marrow Table 1: Correlates of EBMT score with relevant clinical characteristics Disclosures: Giralt: Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding. [1]: #fn-4 [2]: #T1

8102 Background: Auto-stem cell transplantation (SCT) has become the standard of care for eligible patients (pts) with multiple myeloma (MM). However, the impact of bone marrow (BM) plasma cell (PC) percentage before SCT is not yet known. Methods: Retrospective review of 1489 MM pts who underwent auto-SCT from 7/8/98 – 12/31/2010 with post-induction, pre-SCT BM biopsy information available. Pts were divided into 2 groups: 10% PC infiltration (“PC high”). Progression-free (PFS) and overall (OS) survivals were estimated by the Kaplan-Meier method. Log-rank test was performed to test differences in survival. Results: 1489 pts were studied. 1174 pts had 10% involvement. For pts in the PC low group, 32% had a CR, 20% had a VGPR, 31% had a PR, 13% had

8040 Background: Approximately 15-20% of patients with multiple myeloma (MM) present with t(11;14)(q13;q32) involving IgH and CCND1-XT genes. In this study, we report the impact of the t(11;14) on the outcome of patients with MM. Methods: We performed a retrospective chart review on patients with MM who underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between 2/2000 and 8/2010, and had conventional cytogenetic (CC) or fluorescent in situ hybridization (FISH) results available before transplant. The primary objective was to compare the progression free survival (PFS) and overall survival (OS) of patients with t(11;14) to patients without chromosomal abnormalities. Results: CC or FISH studies were available for 1239 patients: 863 normal, 28 with t(11;14), 348 with other abnormalities. Concurrent high-risk abnormalities on CC or FISH were seen in 15/28 patients with t(11;14): del(13q) in 11 , del(17p) in 3, and t(14;16)(q32;q23) in 1. Induction treatment in patients with t(11;14) was: bortezomib + dexamethasone +/- thalidomide/lenalidomide : 15 (53%), thalidomide or lenalidomide + dexamethasone: 11 (39%), others 2 (8%); they received auto-HCT after a median of one line (1-7) of therapy. Median follow up in surviving patients was 39 months. There was no significant difference in median time from diagnosis to auto-HCT from diagnosis (6.9 vs. 7.7 months, p=1.0), disease status at auto HCT (>PR1: 82 vs. 76%

Abstract 4119 Background: The outcome of multiple myeloma (MM) has improved significantly over the last 2 decades due to the availability of several novel agents and an increasing use of high-dose chemotherapy and autologous hematopoietic stem cell transplant (auto-HCT). There is considerable evidence that the response to induction therapy predicts a favorable outcome after high-dose chemotherapy and auto-HCT. In this report, we evaluated the impact of pre-transplant response to conventional agents on post auto-HCT outcomes including time to progression (TTP), progression free survival (PFS) and overall survival (OS). Methods: 1567 patients received auto-HCT at UT-MD Anderson Cancer Center between 1988 and December 2010. Pre auto-HCT disease status was divided into the following prior auto-HCT response groups: complete response (CR), very good partial response (VGPR), partial response (PR), minor response (MR), stable disease (SD) and progressive Disease (PD). The primary objective was to study the impact of prior response on the outcome. Demographics, disease-related and transplant-related variables were collected. The distributions of TTP, PFS and OS were estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups. Regression analyses of survival data was based on the univariate and multivariate Cox proportional hazards model. Results: Median age at auto-HCT was 56.8 years. Median time from diagnosis to auto-HCT was 7.9 months. Of the 1567 patients, 72 (4.6%) achieved CR before auto-HCT, 255 (16%) had VGPR, 848 (54%) had PR, 78 (5%) had MR, 189 (12%) had SD, 88 (5.6%) had PD, while the response was unknown in 37 (2%) patients. Almost 17% patients were 65 years or older at auto-HCT and approximately 7% had high-risk cytogenetic abnormalities. On univariate analysis, the response prior to auto-HCT had significant impact on TTP (p= Conclusion: Patient who achieved CR or VGPR before undergoing an auto-HCT had significantly longer TTP, PFS and OS after the transplant. These results highlight the importance of effective anti-myeloma therapy to maximize the response before proceeding to auto-HCT. Disclosures: No relevant conflicts of interest to declare.

Abstract 4108 Background: The absence of contaminating tumor cells in the graft and the potential for a graft- versus- myeloma (GVM) effect make allogeneic hematopoietic stem cell transplantation (allo-HCT) a useful treatment option for patients with multiple myeloma (MM). Reduced-intensity conditioning (RIC) allo-HCT has led to a more acceptable TRM rate of approximately 10–15%, while preserving the GVM effect. We have previously studied the feasibility of a lower dose of melphalan (100 mg/m2) for allo-HCT for acute myeloid leukemia (AML) [Estey et al. Blood 2007]. Methods: We conducted a randomized phase II trial of two RIC regimens, fludarabine + melphalan 140 mg/m2 (FM140) versus fludarabine + melphalan 100 mg/m2 (FM100) before allo-HCT from related or unrelated donors. The basic hypothesis was that a lower dose of melphalan would result in less toxicity and less GVHD without compromising the engraftment and disease control. Twenty-three patients received 4 weekly doses rituximab 375 mg/m2 as part of their preparative regimen to further reduce the risk of chronic GVHD (Kebriaei et al. BMT 2006). Patients were randomized fairly between the two treatment arms using adaptive dynamic allocation to balance on chemosensitivity and donor type (related vs. unrelated). GVHD prophylaxis consisted of tacrolimus and methotrexate. Results: Fifty allo-HCT patients were randomized between April 2002 and April 2011, 27 to FM140 and 23 to FM100. All patients had a prior auto-HCT and 80% patients had at least one relapse before allo-HCT. Patient characteristics were well matched between the 2 cohorts (Table). The FM100 had more related donors (91% vs. 65%, p=0.01). There were no significant differences between FM140 and FM100 in time to neutrophil engraftment (median 12 days; p=0.21), acute grade II-IV GVHD (22% vs. 21%; p=1.0), chronic GVHD (29% vs. 48%; p=0.24), or CR + VGPR (48 vs. 43%; p=1.0). One-year TRM was 15% in FM140 group, and 13% in the FM100 group (p=1.0). Median PFS for FM140 and FM100 were 8.3 and 11.7 months, respectively (p=0.12).The median OS for FM140 and FM100 were 1.6 and 2.9 years, respectively (p=0.38). The cumulative incidence of disease progression in FM140 and FM100 was 70% and 43%, respectively (p=0.08). Recurrent disease was the most common cause of death for both FM 140 (44%) and FM100 (26%). Eight patients (FM140 5, FM100 3) received donor lymphocyte infusions after allo-HCT, and only 6 patients (FM140 4, FM100 2) received maintenance therapy after allo-HCT. Multivariate Cox models showed patients with high-risk or standard-risk cytogenetic abnormalities had similar PFS and OS (p=0.10 and 0.64), and patients with chemoresistant (/=PR) disease at allo-HCT had similar PFS and OS (p=0.56 and 0.73). Conclusions: This single center, prospective, randomized trial illustrates that the reduction in melphalan dose had no adverse impact on engraftment, response rate, PFS or OS. RIC allo-HCT is safe and can overcome adverse impact of HR cytogenetics and chemoresistant disease in a subset of heavily pretreated patients. Disease relapse remains a problem. The use of post-transplant maintenance therapy, pre-emptive DLI and vaccines will be explored in future trials. Disclosures: No relevant conflicts of interest to declare.

Abstract 333 Impact of Non High-Risk Chromosomal Abnormalities on the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Background: Despite novel therapeutic agents and high-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HCT), most patients eventually progress and die of their disease. Recent advances in cytogenetic, molecular and genomic studies have led to identification of several chromosomal and molecular abnormalities. These abnormalities are important predictors of response to therapy, progression-free survival (PFS) and overall survival (OS). On conventional cytogenetic (CC) analyses, del 13, t(4;14), t(14;16) and del 17p are considered high-risk (HR). On Fluorescence in situ hybridization (FISH) analysis, all except del 13 are considered HR (Munshi, N et al. Blood 2011 117: 4696–4700). However there are a number of chromosomal abnormalities whose significance is not clearly identified (non-HR). In this study we report the impact of these non-HR chromosomal abnormalities on the outcome of patients who received high-dose chemotherapy and auto-HCT. Methods: We performed a retrospective review of patients with multiple myeloma who underwent high dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center. Between 10/1991 and 12/2010, 1570 patients received auto-HCT. The results of CC studies were available for 1329 patients, either at diagnosis or at relapse, but before auto-HCT. The primary objective was to study the impact of non-HR chromosomal abnormalities on PFS and OS, and to compare them to patients without chromosomal abnormalities. Results: Patient characteristics and major outcomes are summarized in the attached Table. In 1329 patients with available CC analyses before auto-HCT, chromosomal abnormalities were identified in 405 (30%) patients. One-hundred and seven (7%) patients had known HR chromosomal abnormalities, while 298 (23%) patients had non-HR chromosomal abnormalities. Fifty (17%) patients with non-HR chromosomal abnormalities and 296 patients (32%) with normal CC achieved complete or stringent complete responses (CR + sCR) (p=0.0001). Median follow up in surviving patients was 36 months. Median PFS in patients with non-HR chromosomal abnormalities and normal CC were 18.2 months (95%CI: 16–22.7) and 32.7 months (95% CI: 27.8–36.3), respectively (p= Figure 1 ). The OS in patients with non-HR chromosomal abnormalities and with normal CC were 56.5 months (95% CI: 43.2–66.9) and 87.2 months (95%CI: 80.1–102.4), respectively (p= Figure 2 ). Download : Download high-res image (40KB) Download : Download full-size image FIGURE 1 . Download : Download high-res image (42KB) Download : Download full-size image FIGURE 2 . Conclusions: In this large single center study with a long follow up, we demonstrated that non-HR chromosomal abnormalities in myeloma are associated with a lower CR rate and shorter PFS and OS after auto-HCT. Further studies are needed to better define these non-HR abnormalities and their impact on prognosis. TABLE 1 . Normal (n= 924) Non-High Risk (n= 298) Median age at auto-HCT 57 59 Age >65 at auto-HCT 137/924 (14.8%) 70/298 (23.4%) Race White = 605 (65%) Black = 148 (16%) Other = 171 (19%) W = 202 (67%) B = 44 (14%) O = 52 (19%) Gender Female = 391 (42%) Male = 533 (58%) F = 104 (34%) M = 194 (66%) Disease status at transplant First Remission = 799 (86%) Relapsed: 110 (12%) Unknown = 15 (2%) First Remission = 224 (75%) Relapsed = 72 (24%) Unknown = 2 (1%) Conditioning Regimen Melphalan or non melphalan = 198 (79%) Melphalan alone = 726 (21%) Melphalan or non melphalan = 57 (81%) Melphalan alone = 241 (19%) Final Response PD = 17 (1.8%) PD = 20 (6.7%) Progressed 447/924 (48%) 172/298 (57%) Died 278/924 (30%) 123/298 (41%) PD: Progressive Disease PR: Partial Remission CR: Complete Response VGPR: Very Good Partial Response sCR: Stringent Complete Response Disclosures: No relevant conflicts of interest to declare.

Abstract 2017 Background: Multiple myeloma (MM) remains an incurable disease and is the most common hematologic malignancy among African-Americans. In the United States, MM and its precursor monoclonal gammopathy of undetermined significance (MGUS) are twice as common in African Americans (Hari et al 2010). Analysis of the Surveillance Epidemiology and End Results (SEER) database from 1969 to 2003 demonstrated African-Americans have twice the mortality from MM compared to Caucasians. However this may be a function of the considerable difference in incidence of MM between Caucasian and African-American populations. Retrospective data from Southwest Oncology Group showed comparable outcomes between groups before the advent of autologous stem cell transplantation (auto-HCT). Recently Hari et al. determined that African-American and Caucasians have similar outcomes after auto-HCT for MM. In the age of novel therapy, Waxman et al addressed racial disparity in population based query of SEER and found disease specific survival was greater for African-Americans than Caucasians; and over time, survival improvement was much less pronounced among African-Americans than Caucasians. Nevertheless transplant specific data is sparse in the contemporary era with novel treatment options. Methods: We performed a retrospective review of 196 African-American multiple myeloma patients (pts) and 806 Caucasian patients initially seen at the M.D. Anderson Cancer Center from 1/1/2002 to 12/31/2010 who underwent autologous transplantation after high dose chemotherapy. The year 2002 was used to incorporate patients who had been exposed to novel agents. Results: A total of 1002 patients were analyzed, 196 African American and 806 Caucasian pts with multiple myeloma who underwent an autologous transplant. Median age at diagnosis was 59 years for both cohorts. Initial response prior to transplant was fairly evenly matched between groups (TABLE 1) as well as final response after transplant. 25% of Caucasian pts and 21% of African-American pts achieved a very good partial response (VGPR) while 28% of Caucasian and 21% of African-American pts achieved a complete response (CR). For evaluable patients, the International Staging System (ISS) at diagnosis was determined. The percentage of stage I, II and III patients in the African-American group was 27%, 20% and 17% respectively. The percentage of stage I, II and III patients in the Caucasian group was 26%, 19% and 17% respectively. Importantly 133/806 of Caucasians and 33/196 of African Americans were diagnosed at ISS stage III (p value=0.91). There was no measurable difference in progression free survival (figure 1) or overall survival (figure 1figure 2) with a maximum follow-up of >100 months. Conclusion: In this retrospective single-center study we demonstrated no difference in progression free survival or overall survival between African-American and Caucasian patients with MM treated in the era of novel agents and autologous stem cell transplantation. These findings concur with previous studies showing no difference in response to treatment between racial groups. In light of older SEER data this may be an effect of novel agents, improved access of care for African Americans or a combination of both. Disclosures: No relevant conflicts of interest to declare.

Abstract 4135 Multiple myeloma (MM) is the second most common adult hematologic malignancy. High dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) have become the standard of care for eligible patients. Though the impact of bone marrow (BM) plasma cell (PC) percentage has been explored in the post-SCT setting, its role before SCT is not yet known We performed a retrospective review of 1826 MM pts who underwent HDC and auto-SCT at our institution from 7/8/98 – 12/31/2010. We further identified patients who had post-induction, pre-SCT BM biopsy information available. Patients were divided into 2 groups: those with 1489 pts were studied, 605 female and 884 male. Patient characteristics are detailed in Table 1. Median time from diagnosis to auto-SCT was 247 days (range 45–7895). 1299 (87%) patients underwent auto-SCT after 2000. Nearly all patients received melphalan-based conditioning. 1174 patients had 10% involvement. The details of best responses before and after auto-SCT are also listed in Table 1. For patients in the PC low group, 32% had a CR, 20% had a VGPR, 31% had a PR, 13% had Table 1. Patient characteristics and responses All patients (n=1489) PC Extensive BM infiltration by PCs before auto-SCT is associated with a worse outcome in patients treated with HDC and auto-SCT. This finding persists when looking specifically at patients with a PR before auto-SCT. Thus, BM disease burden may further assist us in stratifying patients with a PR and may warrant further disease reduction before stem cell collection. Additionally, the differences between PC high and PC low groups are maintained in the modern era, despite the availability of several new salvage agents over the last 10 years. Further prospective study is warranted to determine the true impact of PC infiltration in the BM. Disclosures: No relevant conflicts of interest to declare.

Abstract 4522 Introduction: POEMS syndrome (polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) is a rare plasma cell disorder often associated with papilledema, extravascular volume overload, sclerotic bone lesions, Castleman disease, and high vascular endothelial growth factor (VEGF) levels. High-dose chemotherapy and autologous hematopoietic stem cell transplant (auto-HCT) can be used with good clinical response, but has significant post-transplant morbidity. Here we present our experience in 5 patients with POEMS syndrome who underwent auto-HCT at the MD Anderson Cancer Center (MDACC). Method: Between January 1999 and October 2010, 5 patients (4 males, 1 female) with POEMS syndrome received auto-HCT at MDACC. Diagnosis of POEMS was based on criteria of Dispenzieri et. al.1 All 5 patients had received systemic therapy prior to auto-HCT as follows: bortezomib+dexamethasone (dex) in 2, lenalidomide+dex in 1, cyclophosphamide+dex in 1, and pulse dex in 1. Two patients also received localized radiation for bone disease. Peripheral blood stem cells were collected with granulocyte colony-stimulating factor (G-CSF) in 4 patients and with cyclophosphamide+G-CSF in 1. The preparative regimen was melphalan 200 mg/m2 in 4 patients, while 1 patient received 180 mg/m2 due to renal insufficiency. We evaluated the response rate, toxicity, transplant-related mortality, progression-free survival (PFS) and overall survival (OS). Hematologic response was defined by the International Myeloma Working Group (IMWG) criteria2. Result: Median age at auto-HCT was 48 years (range: 39–58) and median time from diagnosis to auto-HCT was 16.6 months (6.4 – 89 months). All 5 patients had osteosclerotic bone lesions and monoclonal gammopathy: IgA lambda in 3, IgG lambda in 1, and IgG kappa in 1. Two patients had biopsy proven Castleman disease. Four patients had debilitating polyneuropathy. Other features were: skin involvement in 3, endocrinopathy in 2, ascites in 1, anasarca in 2, pulmonary hypertension in 1, and papilledema in 1. Median follow up after auto-HCT was 11.6 months (8.6 – 83.5 months). Median Karnofsky performance status was 80% (70–100) at the time of transplant and 90% (80–100) by the one year follow up visit. Two patients (40%) had complete response, 2 (40%) had a very good partial response, and 1 (20%) had a partial response by IMWG criteria. Engraftment syndrome was not seen in any of the 5 patients. Significant post auto-HCT complications were fungal pneumonia in 2 patients and pulmonary embolism in one. Patients fully recovered from these complications. One-year transplant-related mortality was 0%. All 5 patients had complete or significant resolution of their clinical symptoms after auto-HCT. Median PFS and OS have not yet been reached. With a median follow up of 11.6 months, 1-year PFS and OS were 100%. Four patients are alive and in remission, while one patient died 6 years after his auto-HCT secondary to gastrointestinal bleeding unrelated to his underlying disease. Conclusion: High-dose therapy followed by auto-HCT is safe and effective in selected patients with POEMS syndrome and is associated with durable responses and survival. Disclosures: No relevant conflicts of interest to declare.

Abstract 4156 Background: Chromosomal abnormalities detected either by conventional cytogenetics (CC) or interphase fluorescence in situ hybridization (FISH) have emerged as important prognostic markers in patients with multiple myeloma (MM) and are used to stratify patients into standard-risk (SR) or high-risk (HR) disease. HR myeloma is associated with shorter remission and survival even with novel agents and autologous hematopoietic stem cell transplantation (auto-HCT). In this report, we describe the outcome of patients with myeloma who received auto-HCT at our institution between January 2008 and December 2009, and had CC and FISH analyses available before auto-HCT to identify HR or SR disease. Methods: Primary objective was to compare the response rate, transplant-related mortality (TRM), time to progression (TTP), progression-free survival (PFS) and overall survival (OS) between HR and SR myeloma. HR myeloma was defined as having deletion of chromosomal 13 or 13q, t(4;14), and del17p by CC; or detection of t(4;14), t(14;16), or del17p by FISH in the bone marrow plasma cells (Munshi, N et al. Blood 2011 117: 4696–4700). Normal or any other CC or FISH abnormalities were considered SR. Response was assessed according to international uniform response criteria for myeloma (BGM Durie et al. Leukemia 2006 20(10):1–7). Kaplan & Meier curves were generated to calculate progression free survival (PFS) and overall survival (OS). Results: Between Jan 2008- Dec 2009, we identified 205 patients, who received auto-HCT at our institution and had pre-transplant CC and FISH analyses available. Twenty-eight patients (14%) had HR while 177 (86%) had SR myeloma. Table 1 summarizes patient characteristics and outcomes for HR and SR patients. Nine HR (30%) and 29 (16%) SR patients had international staging system (ISS) stage III at diagnosis (p=0.04). Twenty-one HR patients (70%) and 91 SR patients (51%) received induction therapy with a bortezomib-based regimen (p=0.01). Thirteen (46%) HR patients and 62 (35%) SR patients received post auto-HCT maintenance therapy (p=0.24). Nineteen HR patients (69%) and 165 SR patients (92%) achieved a CR, VGPR or PR after auto-HCT (p=0.00001). The median follow up in HR and SR patients was 14.5 months (2–30) and 12 months (1–35), respectively. Twenty-two (79%) HR and 46 (25%) SR patients had progressed at last follow up (p=0.00001). Similarly, 12 (43%) HR and 12 (7%) SR patients had died at last follow up (p Conclusion: Patients with HR myeloma had significantly worse outcome than patients with SR disease, even with novel agents and auto-HCT. In HR patients, maintenance therapy was associated with longer PFS and OS. Disclosures: No relevant conflicts of interest to declare.

Abstract 4576 Introduction: High dose chemotherapy followed by autologous hematopoietic cell transplantation (auto HCT) for multiple myeloma (MM) has shown improved survival compared to conventional chemotherapy. However, the larger clinical trials evaluating the role of auto HCT in MM have included patients who are generally younger than 65 years. Here we report the results of MM patients, age ≥70 years, who received auto HCT at our institution. Methods: We retrospectively analyzed 84 patients, who underwent auto HCT between January 1999 and June 2010 at MDACC. Conditioning regimen was Melphalan 140 mg/m2 (MEL 140) (N=9), 180 mg/m2 (MEL 180) (N=20), and 200 mg/m2 (MEL 200) (N=55). Disease response was assessed at day 100 post transplant. Results: Pertinent patient and disease characteristics are summarized in the Table. Median age at transplant was 72 (70-80) years. Median number of prior treatments was 1 (range: 1–8). Median time from diagnosis to transplant was 8.5 (2.4-151) months. No patient was in CR prior to auto HCT. Median CD34+ cell count and TNC was 4.56 (0.72-11.1) × 106/kg and 10.53 (2.25-57) ×108/kg, respectively. Median follow up is 2 (0.1-7.3) years. Grade III-IV organ toxicity was seen in 35 (51%) patients. Grade III-IV toxicity in patients who received MEL 140, MEL 180, and MEL 200 was 25%, 45%, and 44%, respectively (p value > 0.05). Non-relapse mortality (NRM) at 100 days was 2%. Two patients died in first 100 days. Disease response in evaluable patients (N=79) at day 100 was: CR=15 (19%); VGPR=7 (9%); PR=41 (52%); and SD=10 (13%). Median progression free survival (PFS) and overall survival (OS) from auto HCT was 2.1 years (95% CI 1.78–3.69) and 5.6 years (95% CI 5.51-NA), respectively. 2-year PFS and OS were 56% (95% CI 0.44–0.71) and 80% (95% CI 0.7–0.91), respectively. There was no difference in NRM, PFS, or OS in different MEL groups. Similarly there was no difference in TRM, PFS, and OS in patients ≥ 75 years compared to the patients < 75 years. Conclusion: Auto HCT in myeloma patients age ≥ 70 years is safe and feasible. Toxicity, NRM, response and survival were comparable to younger myeloma patients. The age alone should not be a contraindication for auto HCT. Disclosures: Shah: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Novartis: Research Funding. Orlowski:Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding. Weber:Novartis-unpaid consultant: Consultancy; Merck- unpaid consultant: Consultancy; Celgene- none for at least 2 years: Honoraria; Millenium-none for 2 years: Honoraria; Celgene, Millenium, Merck: Research Funding. Giralt:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

Background Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. We evaluated the incidence of hepatitis B reactivation and liver toxicity in patients with multiple myeloma (MM) who received high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution.