ALBERT

Description: Abstract 3100 The advent of reduced intensity (RI) conditioning for allogeneic stem cell transplant (HSCT) has brought the question of safe application of this therapy (tx) to older patients. This is of particular importance in CLL where the median age at diagnosis (dx) is 65 yrs. This study compares outcome post RI HSCT in those aged 60 and older (older group, n=23 pts) to those less than age 60 (younger group, n=35 pts) who received RI HSCT at the Leukemia/BMT Program of BC 2001 - June 2011 (total group n=58). Forty-two of 58 (73%) were male. Racial origin was mostly white with only 2/58 (3%) Asian pts. Max stage (Rai) pre-HSCT was advanced (III + IV) in most (31/58, 53%); 13 pts (22%) had B symptoms. Characteristics of the entire group (n=58) include (med, range): interval from dx to HSCT 7.4 yrs (0.4–29); number of prior tx 4 (1–14) and % lymphocytes in pre-HSCT marrow 71 (3–98). 22% (13/58) had bulky nodes (〉5cm). Six (10%) had Richter's transformation. HSCT comorbidity index (Sorror) was 0 in 33 (57%), 1–2 in 18 (31%) and 〉= 3 in 7 pts (12%). Most received prior nucleoside analog (57/58, 99%) and rituxan (47/58, 81%) tx. Twenty-five (43%) were resistant (RES) to last tx given; 30 of 56 pts (54%) were fludarabine (flu) RES. The younger and older group were similar apart from age at dx and HSCT (med, range) which were 47 (26–57) vs 54 (36–55) yrs and 56 (42–59) vs 63 (60–68) yrs respectively. Med donor age was 46 yrs (19–76); 39 (67%) were male; 83% of female donors were parous; 27 (47%) were unrelated (UD); and 12 (21%) mismatched. Stem cells were peripheral blood. Conditioning was non-myeloablative (flu/cy) in 14 pts (24%), and reduced intensity (fludarabine/busulfan) in the remainder (44 pts, 76%). For UD HSCT campath was added to flu/bu in 19 and thymoglobulin in 8 pts. Gvhd prophylaxis was cyclosporine and methotrexate. Count recovery occurred in 97%; 2 pts did not recover (both 1 year post 2nd RI UD HSCT. Graft failure (GF) occurred in 8 pts (14%) predominantly related to campath; 1 pt died (H1N1), 1 is well with autologous recovery 3 yrs post GF and 6 of 8 required further HSCT (including 2 older pts who survive 〉 1 yr post 2nd HSCT). Acute graft vs host disease (gvhd) grades 2–4 occurred in 83% of pts and chronic gvhd in 54% and was neither more severe nor prevalent in older pts. CR post HSCT has occurred in 26 /58 pts (45%), a med (range) of +108 days (0 days -5.4 yrs). DLI was given to 11 pts (4 older pts). At median (range) follow up of 20 months (0.3–120) post HSCT and 10.1 yrs (0.7–37) post dx 44 / 58 pts (75%) survive in the whole group, including 25/35 pts (71%) younger group and 19/23 pts (83%) older group. Death in CR occurred in only 2/14(14%) deaths or 2/58 pts (3%), both of whom were younger pts. Time of death post HSCT was similar in the younger and older groups. Pre-HSCT FISH was performed in 52 /58 pts; results were abn in 47/52 pts (90%); 28/29 (97%) younger and 19/23 (83%) older group and included: del 17p in 15 pts (26%); del 11q in 15 (26%); trisomy 12 in 11 (19%); del 13q in 29 (50%) and bi-allelic del 13q in 11 (19%). Abn FISH normalized pre-HSCT in 8 /52 (15%) and post-HSCT in 18/40 pts (45%), leaving only 22/54 (40%) with currently abnormal FISH tests. Donor chimerism 〉=90% was achieved to date in 43/50 assessable pts (86%) and occurred with similar frequency in younger and older age groups. Survival analysis for the whole group demonstrated the following had a positive impact on OS (p value): achievement of donor chimerism 〉 90% (0.006); CR post HSCT (0.010) and normal FISH or clearance of previously abn FISH (0.007). Non-significant factors included FISH (Dohner ranking); 17p del; acute gvhd gr 2–4; cgvhd; and patient age. KM estimate for OS at 1, 2, and 5 years is: whole group 85%, 73%, 73%; younger 82%, 73%, 73; older 90%, 72%; 72%. There is no difference in OS for the younger vs older group (p= 0.7). In conclusion advances have now made it possible to safely and successfully perform RI HSCT for fit older pts with CLL and obtain similar outcome and overall survival to younger pts. This allows application of this potentially curative therapy to this important patient population. Disclosures: No relevant conflicts of interest to declare.

Description: Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an autosomal dominant syndrome characterized by platelet abnormalities and a predisposition to myelodysplasia (MDS) and/or acute myeloid leukemia (AML). The disorder, caused by inherited mutations in RUNX1, is uncommon with only 14 pedigrees reported. We screened 10 families with a history of more than one first degree relative with MDS/AML for inherited mutations in RUNX1. Germ- line RUNX1 mutations were identified in 5 pedigrees with a 3:2 predominance of N-terminal mutations. Several affected members had normal platelet counts or platelet function, features not previously reported in FPD/AML. The median incidence of MDS/AML among carriers of RUNX1 mutation was 35%. Individual treatments varied but included hematopoietic stem cell transplantation from siblings before recognition of the inherited leukemogenic mutation. Transplantation was associated with a high incidence of complications including early relapse, failure of engraftment, and posttransplantation lymphoproliferative disorder. Given the small size of modern families and the clinical heterogeneity of this syndrome, the diagnosis of FPD/AML could be easily overlooked and may be more prevalent than previously recognized. Therefore, it would appear prudent to screen young patients with MDS/AML for RUNX1 mutation, before consideration of sibling hematopoietic stem cell transplantation.

Description: Chronic lymphocytic leukemia, a disease that is not curable with standard therapy, is an attractive target for allogeneic (allo) hematopoetic stem cell transplant (HSCT) with demonstrated strong graft vs. leukemia effect. However, optimal selection of patients (pts) in order to maximize outcome and minimize toxicity is still under study. We hypothesized that patient co morbidity, as measured by the HSCT adapted Charlson co morbidity index (CCI) would have a strong effect in this group of patients with older median age. At the Leukemia/BMT Program of BC the CCI has been prospectively calculated for HSCT pts since 2006, and we performed chart review to calculate scores retrospectively for the remaining CLL allo HSCT patients in order to evaluate the impact of this factor on outcome following allo HSCT. Transplant specific data was collected prospectively and entered into an electronic database. Forty pts with CLL proceeded to allo HSCT between Jan 91 and Dec 07, with myeloablative (MA) (n=21) or non-myeloablative/reduced-intensity (NMA/RIC) (n=12/7) conditioning regimen. Median (range) number of prior therapies was 4 (1–7). Twenty-four pts were refractory to fludarabine. Donors were related in 25 cases, unrelated in 15. Median age (range) was 49 yrs (32–57) (MA) and 57 yrs (52–64) (NMA/RIC), with 3 and 13 patients greater than age 55 in the 2 groups respectively. Interval from dx to HSCT was 60 months (range 7–135) (MA) and 90 months (range 18–350) (NMA/RIC). Five yr OS is 55% for the whole group; 51% for the MA group at a median follow-up (med FU) of 7.2 yrs (range 2.8–14.6) and 62% for the NMA/RIC group with med FU of 4.2 yrs (range 0.1–6.8). OS did not differ between the 2 groups (p=0.56). Related and unrelated donors had similar 5yr OS at 60.6 vs. 47.1%, p=0.23. Cumulative incidence of non-relapse mortality at 100 days and 2 years is 10 and 32% for the whole group, 14 and 38% for the MA and 6 and 26% for the NMA/RIC groups. CCI was 0, 1, 2, and 3 or greater for 21, 5, 7, and 7 patients. OS by CCI 0–2 vs. 〉=3 was 63 vs.18% for the whole group (p=0.01), 56 vs. 0% for the MA (p=0.03), and 74 vs. 27% for the NMA/RIC groups (p=0.06). Further analyses will explore the relationship between CCI and NRM, acute and chronic graft vs. host disease, and relapse. Patient numbers in this series are insufficient to evaluate the impact of specific co morbidities. In conclusion, for patients with CLL, who are in general of older age, and who may have other therapeutic options, allo SCT is optimally performed in those with a low co morbidity score. Patients with a CCI of 3 or greater may be preferential candidates for alternate less toxic therapies.

Description: Introduction: FLT-3 internal tandem duplications (ITD) and mutations in the nucleophosmin 1 (NPM1)gene appear to have negative and positive prognostic significance, respectively, in newly-diagnosed patients with acute myeloid leukemia (AML) treated with conventional chemotherapy. The prognostic significance of the D835 point mutation in exon 20 of FLT-3 is uncertain. In this study the relative importance of these abnormalities in predicting outcome was compared between patients receiving chemotherapy-based consolidation (chemo) or allogeneic stem cell transplantation (alloSCT) for AML in first complete remission (CR1). Methods: DNA was extracted from diagnostic blood or bone marrow from 267 AML patients aged 〈 60 years who achieved CR1 with induction chemotherapy and then analyzed for the presence of the ITD by PCR and NPM1 exon 12 and FLT3 exon 20 mutations by direct sequencing. Diagnostic cytogenetic abnormalities were assigned prognostic significance using Medical Research Council (MRC) UK criteria. Patients with intermediate or poor prognostic abnormalities and a sibling donor received alloSCT in CR1. If more than 1 cycle of induction therapy was necessary to achieve CR1 or poor risk cytogenetics were detected, patients without a sibling donor received unrelated donor SCT. All other patients received a minimum of one cycle of chemotherapy consolidation. Most patients received high dose cytarabine and daunorubicin induction therapy with similar consolidation. Median (range) follow-up for the entire group was 870 days (90–6003 days). Results: The overall frequency of mutations was 25%, 10% and 24% for the ITD, D835 and NPM1 mutations, respectively. On analysis of the 230 patients remaining after exclusion of acute promyelocytic leukemia (APL), ITD was significantly associated with poor disease free (DFS), event free (EFS) and overall (OS) survival. The D835 mutation was associated with poor DFS only and no effect of the NPM1 mutations could be detected. The presence of the ITD correlated with normal cytogenetics and a high presenting white cell or blast count. 92 and 138 of 230 non-APL patients received alloSCT or chemo, respectively, as consolidation in CR1.Of these 68 in the alloSCT and 95 in the chemo groups had intermediate risk cytogenetics. ITD predicted a poor EFS, DFS and OS for chemo patients regardless of the NPM1 mutation status. For ITD positive patients, relapse risk was higher with chemo in CR1 vs alloSCT (p= 0.007). Among intermediate risk cytogenetic patients 10 of 37 (27%) ITD positive vs 29 of 59 (49%) ITD negative patients are alive after chemo consolidation in CR1 (p0.5). Conclusions: FLT3 ITD predicts a poor OS following chemotherapy as consolidation for AML in CR1. In contrast the results of alloSCT in CR1 are similar for pts with and without the ITD suggesting that alloSCT can overcome the poor prognosis associated with this mutation.

Description: Background: ABL and AUL are associated with an unfavourable outcome for patients (pts) treated with standard-dose therapy alone. Although high-dose therapy has been used successfully in this population, the optimal management of pts with ABL/AUL remains unclear. Methods: A retrospective review was performed involving 24 adult pts with ABL or AUL who were treated in Vancouver between 1984 and 2006. Kaplan-Meier estimates were utilized for event-free survival (EFS) and overall survival (OAS) and a multivariate analysis was performed to determine factors predictive of outcome. Characteristics: Utilizing the WHO criteria, 18 pts had ABL and 6 pts had AUL. There were 17 males and 7 females with a median age of 37 (range 22–75) years. Median white cell count (WCC) at presentation was 10.1 × 109(range: 0.9–196 × 109)/L. Seven pts had poor-risk karyotypes (3 pts complex, 3 pts with t(9,22), 2 pts with11q23 rearrangement, and 1 pt with monosomy 7),12 pts had standard-risk karyotypes, and 5 pts had an unknown karyotype. Induction chemotherapy consisted of Cytosine arabinoside (3–6/m2/day), Daunorubicin, Vincristine and Prednisone with one pt with t(9,22) also having received Imatinib Mesylate. Thirteen pts went on to receive high-dose therapy and SCT. Stem cell source was autologous in 3 pts (all with AUL) or a related (6 pts) or an unrelated donor (4 pts). Eight of 10 pts were in complete remission at the time of SCT, one was in relapse and one had primary refractory ABL. Conditioning was TBI-based in 10 pts and Busulfan-based in 3 pts. Results: EFS and OAS estimates for all 24 patients at 3 years were 25% (95% CI 13%–50%) and 32% (95% CI 17%–58%), respectively. The non-relapse mortality (NRM) for the whole group at 3 years was 43% (95%CI 15%–61%). On multivariate analysis, when compared to pts receiving only standard-dose chemotherapy, pts who underwent high-dose therapy had significantly improved EFS [39% (95% CI 19%–77%) vs. 9% (95% CI 1%–59%), p=.03] and OAS [46% (95% CI 26%–83%) vs.14% (95% CI 3–74%), p=0.01], respectively. Age, WCC at presentation and cytogenetic risk group were not found to significantly influence outcome. Conclusion: Although patient numbers are limited, this experience would suggest that patients with ABL/AUL who achieve complete remission with standard chemotherapy should be considered for high-dose therapy and stem cell transplantation. This approach provides them with the greatest probability of long-term event- free and overall survival.

Description: Acute promyelocytic leukemia (APL) has become one of the more readily treatable subtypes of acute myeloid leukemia on the basis of its particular sensitivity to anthracyclines and the introduction of the differentiating agent all-trans retinoic acid (ATRA). Unfortunately some patients will ultimately relapse after achievement of complete remission. A PETHEMA and GIMEMA (PETH/GIM) cooperative group joint study sought to identify risk factors associated with relapse and developed a predictive model based on white cell count (WCC) and platelet count (Plt) at diagnosis. This model for relapse free survival was capable of segregating patients into low risk (WCC 〈 10 x 109/L / Plt 〉 40 x 109/L), intermediate risk (WCC 〈 10 x 109/L / Plt 〈 40 x 109/L), and high risk (WCC 〉 10 x 109/L). A subsequent follow up study demonstrated improved outcomes for intermediate and high risk group patients treated with an anthracycline and ATRA based risk adapted strategy. We reviewed 60 cases of adult de novo APL treated at Vancouver General Hospital from August 1995 to December 2003. Thirty five females (58%) and 25 males (42%) were treated with a standard induction and consolidation protocol consisting of 3 cycles of Daunorubicin (60 mg/m2 OD for 3 days), Cytosine arabinoside (100 mg/m2 BID for 7 days), and ATRA (45 mg/m2/day until complete remission or a maximum of 60 days). In 2000 maintenance therapy was introduced and ATRA and/or varying doses of Methotrexate and 6-Mercaptopurine were then instituted for up to 2 years duration. At the completion of induction chemotherapy complete morphological and cytogenetic remission was achieved in 55/60 patients (92%) with 4 induction failures and only 1 death during induction treatment. Subsequently during and after consolidation and maintenance therapy at a median follow up of 34 months there were a total of 10 episodes of relapse (18%) in these 55 patients. When the 55 patients in complete remission were stratified at diagnosis by the PETH/GIM risk group there were 18 low risk patients (33%), 26 intermediate risk patients (47%), and 11 high risk patients (20%). The number of relapses was 6 in the low risk group (33%), 4 in the intermediate risk group (15%) and no relapses were identified in the high risk group. In our experience the predictive model for relapse free survival developed by the PETH/GIM cooperative group does not identify those at most likelihood for subsequent relapse after achieving an initial complete remission. The greatest number of relapse was seen in the low risk group with no relapses in the high risk group. These variations may be explained in part by the different chemotherapy treatment protocols with variable maintenance therapy. Future investigation will focus on the prognostic role of immunophenotype, additional cytogenetic abnormalities and molecular isoforms in determining outcome in APL.

Description: A substantial proportion of lymphoid malignancy cannot be cured with conventional therapy or autografting, and a matched family donor is available for less than 1/3 of patients (pts) who may benefit from an allograft. Alternate donors (AD) were therefore utilized with curative intent for 87 pts with acute or chronic lymphoid malignancy at the Leukemia/BMT Program of BC between 1983 and 2002. Long-term results for these pts who received stem cells from unrelated donors (UD) (n=73) or mismatched related donors (MMRD) (n=14) were analyzed. UDs were HLA matched in 58 cases for HLA A, B and DR, and mismatched at 1 or 2/6 loci in 15 pts. Related donors were mismatched at 1/6 (n=13) or 2/6 loci (n=1). Diagnoses included ALL in 37 (n=12 Ph+); NHL in 28 ( n=1 Burkitt’s; n=15 aggressive; n=12 indolent); CLL in 3, PLL in 1 and myeloma in 18 pts. Transplant occurred a median (med) of 10 months (range 1.6 mos-14.7 yrs) post diagnosis at a med age of 36 years (range 12–53). The majority (n=57, 66%) were not in CR at the time of transplant; 53 (61%) were male. GVHD prophylaxis included cyclosporine + methotrexate in 72, T-cell depletion in 11, and other in 2 pts. Conditioning was TBI based in the majority (n=80, 92%), and busulfan based in 7 pts (8%). Most (n=83, 95%) received marrow (m) only; 2 received peripheral blood (pb) and 2 pb+m. The med (range) nucleated cell count was 2.6 (0.2–15)x108 CD 34 cells/kg; graft failure was seen in 5 cases (6%). Acute (A) graft-versus-host disease (GVHD) grade 0/1, 2, 3 and 4, (n= %), was seen in 24 (28%); 24 (28%); 19 (22%) and 19 (22%) pts. The majority (n=41/56, 73%) who survived past day 100 developped chronic (C) GVHD. Thirty pts (35%) are currently alive, and 57 (65%) deceased a median of 96 days (range 12 days-4.2 years) post transplant. Death from relapse (n=19) occurred at a med of 1 year (range 17 days-4 years), and from transplant related causes (n=38) at a med of 71 days (range 12 days-17 months). Overall survival (OS) is 32% (95% CI 23–43%) at a med follow-up of 6 years (range 1–15 years); the curve is flat after 50 mos, and 17/30 survivors are out more than 5 years. Cumulative incidence estimates are as follows: acute GVHD (gr 2–4) 72%; (gr 3–4) 44%; chronic GVHD 73%; relapse 27%; non-relapse mortality (NRM) 44%. In univariate analysis AGVHD (3–4) impacted negatively on OS, event-free survival (EFS) and NRM. Relapse risk was higher in pts receiving TCD stem cells. Development of CGHVD was protective against relapse (p=0.03, relative risk = 0.37). In conclusion, one-third of pts with otherwise incurable lymphoid malignancy have achieved long-term disease-free survival using alternate donor stem cell transplant. Strategies to decrease transplant-related mortality are needed. Control of underlying disease remains imperfect, but not unacceptable with 27% long-term risk of disease recurrence. No relapse has occurred after 50 mos, with a plateau seen in the risk curve after 5 years suggesting cure even in pts with ALL or MM. Interestingly, a graft-vs-malignancy effect can still be demonstrated in this population with lymphoid malignancy and alternative donors, with decreased relapse risk seen in pts developing CGVHD.

Description: Background: Autologous stem cell transplant (ASCT) is the standard treatment for relapsed aggressive diffuse large B-cell lymphoma. Studies are conflicting as to whether ASCT has comparable salvage rates in peripheral T-cell lymphoma (PTCL). Emerging evidence suggests that a graft-versus-lymphoma effect may exist in PTCL. Thus, allogeneic stem cell transplant (allo-SCT) may be a favoured approach for relapsed PTCL patients. Methods: The British Columbia Leukaemia/BMT database was reviewed to identify all PTCL patients who have undergone allo-SCT for relapsed/refractory or high risk PTCL. Twenty patients (13M, 7F) with PTCL received an allo-SCT between November 1990 and May 2007. Median age at transplant was 46.5 years (range 16–64 years). Lymphoma subtypes were PTCL-unspecified (n=7), anaplastic large cell (n=4), hepato-splenic γδ (n=4), angio-immunoblastic (n=3), enteropathy-type (n=1) and nasal-type natural killer (n=1). Seventy percent of the patients presented at diagnosis with two or three risk factors from the age-adjusted International Prognostic Index. The disease status at the time of transplant was: First complete remission (n=4; all 4 had hepatosplenic γδ PTCL); second or greater complete remission (n=6); first partial remission (n=1); first chemosensitive relapse (n=4); untested relapse (n=3); induction failure (n=2). Sixteen patients had matched sibling donors and 4 had unrelated donors (2 patients had mismatched donors). Sixteen patients received radiation-based conditioning regimens. Two patients received reduced-intensity conditioning regimens. Results: At the time of analysis, 5 patients have died. Three patients died within fifty days of transplant with treatment-related complications (2 acute graft-versus-host disease (GVHD), 1 pulmonary hemorrhage), 1 died of chronic GVHD and 1 died of high-grade sarcoma. Non-relapse mortality was 19% at 2 years. Median follow-up of surviving patients was 21 months (range, 1 to 163 months). Of the remaining 15 patients alive at the time of analysis, 3 had relapsed lymphoma and 12 remain in remission. Seven patients (35%) had grade 2 acute GVHD or greater. Thirteen patients (65%) had chronic GVHD (3 limited, 10 extensive). Univariate analysis was performed to determine the influence of gender, age, previous number of lines of therapy, acute GVHD and chronic GVHD. None of these factors were found to be of prognostic significance. Estimated 2-year event-free and overall survival at was 49% [95% CI: 28–83%] and 77% [95% CI: 59–100%], respectively. Risk of relapse at 2 years was 40% (95% CI: 3–63%). Conclusions: Allo SCT is a feasible option with encouraging results for patients with relapsed PTCL and select individuals with high-risk histologic subtypes.

Description: Abstract 4597 Introduction: Light chain deposition disease (LCDD) and light and heavy chain deposition disease (LHCDD) are plasma cell disorders characterized by pathologic aggregation and deposition of immunoglobulin components in tissues leading to organ dysfunction. Reported outcomes with conventional chemotherapy include high rates of end stage renal disease and death. High dose melphalan followed by autologous stem cell transplantation (ASCT) has been employed in an attempt to improve outcomes, but few published data are available to support this practice. Methods: We conducted a retrospective review of all patients within our institutional database treated with ASCT for LCDD or LHCDD. Diagnosis was based in all cases upon renal biopsy. Associated multiple myeloma (MM) was diagnosed if bone marrow plasma cells were 〉 10% with concomitant anemia, hypercalcemia or lytic bone disease. Filgrastim was used for peripheral blood stem cell mobilization. All patients received melphalan conditioning at a reduced dose of 140 mg/m2 (due to renal dysfunction) with the exception of one patient who received melphalan 200 mg/m2. Response to treatment was adapted from the International Consensus Criteria (Gertz et al. 2005) designed for use in AL amyloidosis except that bone marrow biopsies were not performed to confirm complete hematologic remission. A renal response was considered to have been reached if proteinura decreased from 50% of baseline with stable creatinine or if creatinine decreased by 50% from its peak value. Results: We identified eight patients (7 LCDD, 1 LHCDD) treated with ASCT between August 2006 and November 2009. The median age at diagnosis was 48 years (range 40–62). Two patients had associated MM. All patients had come to medical attention as a consequence of renal dysfunction. The median serum creatinine at presentation was 192 μ mol/L (119-444) with two patients meeting criteria for nephrotic syndrome and a third having anasarca with nephritic syndrome. No patients were found to have associated AL amyloidosis, myeloma cast nephropathy, or extrarenal LCDD. Left ventricular ejection fraction was normal in all patients and none had evidence of cardiac infiltration. Kappa light chain restriction was present in seven patients with lambda light chain restriction in the eighth. Median kappa FLC level at diagnosis was 528 mg/L (range 42–1290, normal 3.3–19.4). Induction therapy consisted of dexamethasone in five patients and dexamethasone with bortezomib in two patients; one patient proceeded directly to ASCT without induction therapy. At the time of ASCT, the median serum creatinine was 183 μ mol/L (122-298). Stem cell mobilization was uncomplicated and ASCT was tolerated with no treatment related deaths or requirement for ICU admission. Significant toxicities included engraftment syndrome requiring steroids (2), bacteremia (2), sepsis with hypotension (1), pneumonia (1), grade 3 mucositis (1) and edema requiring ultrafiltration (1). One patient with a pre-ASCT creatinine of 298 μ mol/L went on to develop end stage renal disease and dialysis dependence two months after ASCT. Hematologic response was CR in two, PR in four, and not assessable in two patients due to insufficiently elevated baseline M-protein quantity for response determination. Seven patients had a renal response. After a median follow up from ASCT of 18 months (1-39 months), only one patient had experienced disease progression with increasing kappa FLC level. With the exception of the one dialysis dependent patient, no patients had symptoms related to renal disease at last follow up. Conclusion: In selected patients with LCDD and LHCDD, high dose melphalan with ASCT produced a high rate of hematologic and renal response with acceptable toxicity. Longer follow up is needed to assess the durability of response. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4580 Background: The use of allogeneic hematopoietic stem cell transplant (alloHSCT) in the treatment of Multiple Myeloma (MM) remains controversial. Although there is hope that alloHSCT may result in a cure, relapse continues to be a significant problem. The morbidity associated with late complications of allogeneic transplantation further compounds the issues faced when addressing relapsed disease. The use of Novel Agents (NA) in this patient population has been poorly characterized. Here we present our experience of NA use in patients initially treated with alloHSCT. Patients: 108 patients underwent an allografting procedure for their MM at our center between 1989 and 2009. 84 received a fully myeloablative procedure (15 received donor lymphocyte infusion). 24 received an autologous HSCT followed by a reduced intensity allogeneic procedure. 56 have relapsed with this population making up our primary cohort for analysis. 22 patients received NAs and very few patients received them prior to transplant (4/108). Endpoints examined were post relapse survival after the initial HSCT procedure (PRS), overall survival from time of initial treatment (OS) and progression free survival (PFS) measured in months (m). Results: Of the entire cohort of 108 patients median OS was 78.6m (95% CI; 24.5–132.6). Median PFS was 23.6m (95% CI; 15.4–31.8). Of the non-relapsed patients (n = 52) the median OS was 125.9m. In this cohort 67% of the deaths occurred within 1.5 years. Of the relapsed patients (n = 56) median PFS was 18.7m (95% CI; 14.6–22.8), median PRS was 31.5m (95% CI; 17.0–46.0), and median OS was 67.0m (95% CI; 31.6–102.5). The effect of NA was examined in the cohort of relapsed patients. No significant difference was noted in PFS between those exposed to NA and those who were not exposed (19.0m (95% CI; 10.1–22.8) vs 13.7m (95% CI; 5.8–21.6); p = 0.27). Exposure to NA showed improvements in PRS (42.3m (95% CI; 7.3–77.2) vs 10.4m (95% CI; 5.2–15.7); p = 0.01, Figure 1). A trend toward superior OS was noted (71.4m (95% CI; 37.9–105.5) vs 24.6m (95% CI; 3.0–46.1); p = 0.11) although this did not reach statistical significance. Conclusion: Ongoing management of relapsed patients with multiple myeloma in the post alloHSCT setting remains a significant challenge. This retrospective study demonstrates that the use of NA is both safe and effective in treating relapsed disease. The predominant impact of these drugs is seen in the relapsed setting. Exposure to NA correlates with a 22m improvement in PRS. A 46m improvement in OS is noted however, likely due to the small cohort, it failed to reach statistical significance. Disclosures: Sutherland: Celgene: Honoraria; Orthobiotech: Honoraria. Shepherd:Celgene: Honoraria; Orthobiotech: Honoraria. Nevill:Celgene: Honoraria. Toze:Hoffman La Roche: Consultancy, Honoraria, Research Funding; Genzyme: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria.