Dingli, David

Abstract Abstract 3231 Poster Board III-168 Background Peripheral blood stem cells (PBSC) are the preferred graft type for autologous stem cell transplantation (ASCT) and mobilization is typically done using growth factor (GF) alone or a combination of chemotherapy (CTX) and GF. The success of mobilization is influenced by several factors such as prior therapy and mobilization strategy. Patients (Pts) failing to mobilize successfully often have GF dose increased and if unsuccessful, mobilization reattempted with chemotherapy + GF or G-CSF (Granulocyte Colony-Stimulating Factor) + GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor). More recently, plerixafor, a CXCR4 inhibitor, has been found to enhance G-CSF based collection allowing potential early intervention in poor mobilizers. However, this approach requires valid cut-points for peripheral CD34 counts (pCD34) for cost efficient use. Methods We studied 910 first time, G-CSF based PBSC mobilizers with MM (565; 62%), or light chain amyloidosis (345; 38%). Salvage attempts were excluded, as were first attempts using CTX+GCSF, plerixafor or GF combinations. Sensitivity-specificity analysis (ROC) was used to define ideal cut-points for predefined outcomes. We used a CD34 yield of 2 million/kg as the minimum required collection and 4 million/kg as the ideal collection for this analysis. Our current practice is to initiate collection at a pCD34 of 10/uL. Results We first determined the best day 1 pCD34 cutoff for being able to collect at least 2 million/kg PBSC to be 9.2/uL. Among those with ≥9.2/uL, only 1.6% failed to collect at least 2 million compared to 27% among the rest (P < 0.001). These numbers were 1.7% and 25% respectively using the traditional cutoff of 10/uL. We then examined how the pCD34 on day 2 predicted collection, among those failing to reach the current threshold of 10/uL. Among this group, a pCD34 on day 2 of 8/uL was the best cutoff to predict a collection of 2 million/kg. Among those with >8/uL, only 9% failed to collect at least 2 million compared to 48% among the rest (P < 0.001). Among those with day 1 pCD34 < 10, 65% achieved a count of 8/uL on day 2. We then examined what pCD34 on day 1 can best predict a pCD34 ≥ 8 on day 2 and found this to be 5/uL. Among those with day 1 pCD34 ≥ 5/uL, 92% reached day 2 pCD34 ≥ 8 compared to 36% among the rest (P < 0.001).We then determined cutoffs based on ideal targets using only those patients achieving pCD34 count > 10/uL by day 2, since these patients would have started collection without any change in the mobilization technique. We used a maximum of 5 collections to achieve the goal as being ideal, taking into account the most commonly used practice of collecting during weekdays. We examined cutoffs both for a target of 4, 8 and 12 million/kg for one, two or three transplants respectively. Among those with a day 1 or day 2 pCD34 > 10/uL 98% collected 4 million/kg in 5 collections. The best day 1 or day 2 pCD34 predicting a 8 million/kg yield in 5 collections was 21.4/uL and a 12 million/kg yield was 27.9/uL. Among those with day 1or 2 pCD34 ≥ 21.4/uL, 90% collected 8 million compared to 54% among those with pCD34 < 21.4/uL. Similarly, among those with day 1 or 2 pCD34 ≥ 27.9/uL, 79% reached 12 million in ≤ 5 days compared to 17% among those with pCD34 < 27.9/uL (P < 0.001).Finally we examined if poor collection on first day, despite a pCD34 > 10 predicts for poor overall yield. A ratio of day 1 collection (million/kg) to pCD34 day 1 or 2 < 5×104 was highly predictive of failure to get eventual yield of 2 million/kg, with 38% below the cutoff failing to reach the goal compared to 2% for those above the cutoff. Conclusions This study provides an estimate of optimal pCD34 count thresholds for early identification of patients at high risk of collection failure. It is reasonable to use the first or second day pCD34 count, since a substantial proportion of patients will achieve the threshold value by day 2 and have similar outcome as those reaching the threshold by day 1. Based on the results here, interventions such as plerixafor can be considered if pCD34 count is < 5/uL on day 1 or < 9/uL by day 2, to achieve the minimum collection of 2 million/kg. However, in order to achieve the ideal targets, a higher threshold should be considered and the recommendation would be 17/uL, and 28/uL for target of 8 or 12 million respectively. Finally, identification of poor mobilizers after start of collection potentially provides another time point for early intervention, and this needs to be prospectively studied. Disclosures Micallef: Genzyme: Research Funding. Gertz:Genzyme: Research Funding. Kumar:Celgene,Genzyme,Millenium,Novartis,Bayer,: Honoraria, Research Funding.

Abstract Abstract 1892 Background: Primary or light chain amyloidosis (AL) is a clonal plasma cell disorder characterized by a relatively low plasma cell burden and multi-organ deposition of immunoglobulin light chain derived amyloid fibrils. The survival of patients with amyloidosis is quite variable with median survival of 12–18 months in different series, and largely dependent on the number and severity of organs involved. In addition to new drugs, the combination of melphalan and dexamethasone is an effective regimen for AL and risk adapted approaches to SCT has decreased treatment related mortality. It is not clear if the recent progress in risk stratification and treatment approaches have translated into improved survival for these patients. Methods: We studied two separate cohorts of patients; the first cohort consisting of 2118 patients with AL seen at Mayo Clinic over a 40-year period between November 1967 and August 2006 was used to examine the trends in overall survival from diagnosis during this time period. The second cohort of 443 patients seen between September 2006 and August 2009 were examined only for the changes in early mortality and for validation of a model for predicting early mortality developed using the first cohort of patients. Results: The estimated median follow up for the entire group was 7.8 years (95% CI; 7.1, 8.5). The patients were divided into 4 cohorts based on date of diagnosis; 1966–1976 (n=121), 1977–1986 (n=343), 1987–1996 (n=636) and 1997–2006 (n=1017). The median OS from diagnosis for the four cohorts were 0.9, 1.2, 1.2 and 1.5 years respectively, P < 0.001 (Figure 1). More importantly there was steady improvement in the long-term survival among these patients with 4-year survival estimates of 16%, 21%, 24% and 33% respectively. Next, we specifically looked at the survival trends within the last cohort (1996-2006), dividing the patients into three time periods; 1996–1999 (n=263), 2000–2003 (n=291) and 2003–2006 (n=463). While the OS from diagnosis was relatively unchanged between the first and second time periods (28 vs. 30% 4 year survival), there was significant improvement in the last three year period (42% survival at 4 years); P =0.02. Given the high early mortality in this disease, we specifically examined the one-year mortality among the entire patient cohort and found no clear improvement in terms of one-year mortality. Using logistic regression analysis, we identified cTnT > 0.01, NT-ProBNP > 4200 and Uric Acid > 8.0 mg/dL to be the best predictors of death within one year of diagnosis. The probability of death within one year for those with none, 1, 2, and 3 risk factors was 19, 38, 61, and 78% respectively, P < 0.01 (Figure 2). This model was further validated among patients seen during the most recent three years, September 2006 and August 2009. Conclusion: Survival in AL amyloidosis has improved over time, particularly in the recent years and likely reflects the recent improvements in therapy. However, early mortality remains a problem and baseline factors can be used to identify patients at risk for early mortality, who then can be targeted for risk adapted therapy approaches in clinical trials. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Off Label Use: Lenalidomide for treatment of newly diagnosed myeloma. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria.

Abstract Abstract 2785 Poster Board II-761 Background: Cytogenetic abnormalities are common in the myelodysplastic syndromes (MDS) and carry considerable prognostic weight. One of the most common cytogenetic abnormalities in MDS is isolated trisomy 8 (∼20%). However, the impact of this abnormality on prognosis in MDS is unclear. In the following, we report on all MDS cases with isolated trisomy 8 seen at our institution and describe the natural history of this abnormality. Methods: After approval from the Institutional Review Board, the cytogenetics laboratory database at Mayo Clinic was searched for all cases of isolated trisomy 8. All patients had given written informed consent to enable use of their medical record for research. The medical records were reviewed and relevant demographic, clinical, and laboratory characteristics were abstracted. Survival was determined from diagnosis until death or last contact with the patient and measured using the Kaplan-Meier method. Univariate and multivariate analysis for survival were performed using the Cox proportional hazard method. Results: Out of a total of 23, 375 unique patient specimens evaluated over a twenty year period (January 1988 – December 2008), we identified a cohort of 106 patients (0.45%) with trisomy 8 as the sole cytogenetic abnormality (males with –Y were included). Of these patients, 89 had a classical MDS and 66 patients were males. The median age at diagnosis of MDS was 70.0 years (range: 31 – 91) for the whole cohort (females: 67 yr, males: 71.5 yr, p=0.22). All patients presented with at least one cytopenia, median Hb: 9.8g/dl (3.9 – 15.4); WBC: 4.6×103/ml (1.0 – 102.6); PLT: 119×103/ml (3.0 – 740), bone marrow blasts: 5% (0 – 22.5), LDH: 221 (62 – 1342). Considering trisomy 8 as an intermediate risk abnormality (score = 0.5), the median IPSS for the cohort was 1.0 (0.5 – 2.5) (Intermediate-1). The distribution of cases included: MDS with <5% blasts (55%), RAEB-1 (16%), RAEB-2 (18%), and CMML (11%). 85% of patients required transfusion sometime after diagnosis and 40% were treated with some form of chemotherapy. Transformation to acute myeloid leukemia (AML) occurred in 25 patients (28.1%) and of these, 22 have died. The median time from diagnosis to transformation to AML was 33 months. The median overall survival from diagnosis was 36 months, similar to what is expected for Int-1 patients (Blood 89:2079, 1997). On univariate analysis, age at diagnosis (p=0.05), LDH (p=0.017) and time to transformation (p<0.0001) were prognostic. On multivariate analysis, LDH (p=0.007) and time to transformation (p=0.009) remained independent prognostic factors. Conclusions: Isolated trisomy 8 in MDS is associated with intermediate risk disease. The risk of transformation to acute leukemia is 28% and the median survival from diagnosis of MDS is approximately 3 years. A significant fraction of patients die due to causes unrelated to their hematopoietic disorder. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1964 Background: Thalidomide (thal), lenalidomide (len) and pomalidomide (pom) have been shown to have considerable efficacy in patients with newly diagnosed as well as relapsed multiple myeloma (MM). They are often used as initial therapy in patients proceeding to stem cell transplant (SCT), and based on the initial response, are usually considered for salvage therapy during their disease course. However, the retreatment efficacy of these compounds is unknown. We conducted this study to ascertain the degree of response that can be obtained by retreatment with immunomodulatory compounds. Patients and Method: 410 patients with newly diagnosed MM who received either thalidomide-dexamethasone or lenalidomide-dexamethasone were studied. Of these, 183 patients received thalidomide, lenalidomide or pomalidomide (with or without dexamethasone) as one of the salvage regimens following relapse, and form the study group. We included all patients who received the repeat immunomodulatory therapy as salvage treatment at any time during the MM disease course. Results: The median (range) age of the MM patient group was 60 (29-80) years; 117 (64%) were male. Thalidomide and lenalidomide were used as initial therapy in 106 (58%) and 77 (42%) patients, respectively. Patients received a median of 2 treatments (range, 1–6) prior to salvage therapy; bortezomib was used as one of the salvage treatment (prior to the repeat immunomodulatory therapy) in 41 (22%) patients. An autologous stem cell transplant was performed in 118 (64%) patients after the initial immunomodulatory therapy. Almost one half (89; 49%) of the patients went off the first line therapy to undergo a SCT; whereas drug toxicity (26; 14%) and disease progression (21; 11%) were other causes requiring a treatment change. The compound used for salvage therapy was thalidomide, lenalidomide or pomalidomide in 40 (22%), 129 (70%) and 14 (8%) patients, respectively. The responses to salvage therapy based on the initial therapy and the salvage regimen are as shown in Table 1. Overall, 67 (37%) patients achieved a partial response or better and 73 (40%) patients achieved less than a partial response (stable and progressive disease) to repeat immunomodulatory therapy, while the remaining 43 (23%) had non evaluable disease response. Conclusions: Retreatment with an immunomodulatory therapy, especially a different compound, was associated with excellent response rates. Lowest response rates were seen in patients retreated with thalidomide after having received lenalidomide as their initial therapy after the diagnosis of MM. This information is valuable in deciding on the choice of repeat therapy with immunomodulatory compounds in patients with relapsed disease. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract Abstract 3211 Poster Board III-148 Although autologous stem cell transplantation (ASCT) has become standard of care for many patients with hematologic malignancies, many patients fail to collect a minimum number of CD34 + stem cells to support high dose chemotherapy and ASCT. Recently, plerixafor, a CXCR4 antagonist, was FDA approved for use in combination with G-CSF for autologous peripheral blood stem cell mobilization in patients with NHL or Multiple Myeloma. In February 2009, we commenced a risk adapted approach to the utilization of plerixafor. The study was restricted to patients mobilized with GCSF alone and patients undergoing chemotherapy primed PBSC mobilization were excluded. Peripheral blood stem cell mobilization was commenced with G-CSF at 10 mcg/kg/day. On day 4, a peripheral blood (PB) CD34 count was measured. For patients whose PB CD34 was ≥10/μL, apheresis was commenced the following morning. For patients whose PB CD34 was <10/μL, it was measured again on day 5; if ≥10/μL then apheresis was commenced the following morning. If PB CD34 was <10/μL on day 5, plerixafor (0.24 mg/kg sc) was administered on the evening of day 5 and apheresis was commenced the following day (Group A). In addition, during apheresis, for patients whose collection yield was < 0.5 × 106 CD34/kg, in the absence of instrument failure or problems with the collection procedure, plerixafor was added (Group B). Morning administration of G-CSF and evening dosing of plerixafor continued daily until apheresis was complete. From February to July 2009, 174 mobilization attempts occurred; 27 with chemotherapy and 147 with cytokines alone. The 147 pts who underwent mobilization with cytokines alone are presented here. The underlying diagnosis was as follows: Myeloma 61 pts, NHL 54 pts, Amyloid 17 pts, Hodgkin 10 pts, POEMS 4 pts and 1 pt with a solid tumor. For the entire group the median number of CD34 cells collected was 5.5 × 106 CD34/kg (range 0.1-17). The median number of apheresis was 3 (range 1-12). 67 patients (46%) received plerixafor; 37 patients started plerixafor during mobilization (Group A) and 30 patients during collections due to a poor yield (Group B). 12 pts of the 37 received plerixafor on day 4 because of prior mobilization failure or high risk of mobilization failure and are included in Group A. Table 1 outlines the details of mobilization and collection by groups. By disease category, of the 61 patients with MM, 28 (46%) received plerixafor (8 Group A and 20 Group B). Median apheresis in all the MM pts was 2 (range 1-12) with a total of 6.8 × 106 CD34/kg (2.2-16.7). In the 54 NHL pts, 32 (59%) received plerixafor (24 Group A and 8 Group B). Median apheresis for all pts with NHL was 3 (range 1-7) with a total of 4.6 × 106 CD34/kg (range 0-11.4). Overall, only 7 of 147 (5%) mobilization attempts failed to achieve a minimum of 2 × 106 CD34/kg. This compares to a 22% failure rate prior to institution of this risk adapted approach. In conclusion, implementing this risk adapted approach allows poor mobilizers to be identified promptly and for plerixafor to be initiated during mobilization and collection, thereby reducing the number of mobilization failures. In patients who predictably would not have successful collection based on a PB CD34 <10/μL, addition of plerixafor results in a majority of patients achieving an adequate collection. This risk adapted approach may be more cost effective than reattempting mobilization after a prior failure or utilizing combination G-CSF and plerixafor for upfront mobilization. Table 1. Mobilization and Collection data. All patients N=147 Group A1 N=37 Group B2 N=30 No Plerixafor N=80 PB CD34 day 4 Median 11 0 7 19 Range 0-331 0-7 0-32 0-331 PB CD34 day 5 Median 10 4.5 12 15 Range 0-51 2-9 11-23 9-51 Apheresis Yield Median 5.5 4.4 6.0 6.2 Range 0.1-17 3.1-12.7 3.0-12.2 2-17 Number of Apheresis Median 3 3 5 2 Range 1-12 1-7 4-12 1-8 Days of Plerixafor Median n/a 3 2 n/a Rang 1-7 1-8 1 Group A – Plerixafor initiated prior to apheresis 2 Group B – Plerixafor initiated during apheresis Disclosures No relevant conflicts of interest to declare.

Abstract Background: The advent of high-dose therapy and autologous stem cell transplantation (HDT-ASCT) has significantly improved response rates and survival for patients with multiple myeloma (MM). However this form of therapy is potentially toxic and does not cure patients from their disease. The response to HDT-ASCT is variable and approximately 40% of patients achieve a complete response (CR). Patients with a CR have a significantly improved time to progression (TTP) compared to patients who do not achieve CR (nCR). Optimal timing of HDT-ASCT and considerations of the relapse kinetics may assist treatment planning for this disease. We analyzed myeloma tumor burden and kinetics before and after HDT-ASCT in order to define optimal timing of this therapy for the individual patient. Patients and Methods: A cohort of 265 patients with MM who underwent HDT-ASCT at Mayo Clinic Rochester was studied. Disease burden before and after HDT-ASCT was estimated from serial M-spike measurements. The estimated tumor burden data were fitted to the Gompertz function and its parameters alpha and beta estimated using a non-linear least squares method. Cohorts of patients with CR and nCR were studied separately. Functions that coupled disease burden and kinetics with TTP were derived and used to determine the optimal timing of single and tandem transplantation. Results: The Gompertz parameters alpha and beta for patients who achieved CR and for those who did not achieve CR with HDT were determined. Our values were lower than those of Sullivan and Salmon although the ratio of alpha/beta was of a similar order (implying the same carrying capacity). Using the idealized Gompertz parameters, simulations of single versus tandem transplants were performed. Our model predicts that tandem transplantation increases CR rate by approximately 10%. When the time between transplants was studied as a variable, our model suggests that the optimal time between transplants is 7 months. Conclusions: Our modeling provides a theoretical understanding of tumor burden and kinetics for patients with MM who undergo HDT-ASCT. Patients who achieve CR with the first episode of HDT-ASCT should not be routinely offered tandem transplantation but carefully monitored and re-transplanted at an optimal disease burden. If CR is not achieved with a first cycle of HDT-ASCT, the probability of CR after a second trial of HDT is ~10% (similar to that reported by Attal et al 2003) although this depends on the tumor burden before the second transplant. TTP after tandem transplants (with its higher associated mortality) cannot be superior to TTP achieved with optimally timed serial transplants. Individualized HDT-ASCT for patients with MM is possible and may improve results.

Abstract Abstract 2803 Poster Board II-779 Background. The rate of asymptomatic amyloidosis (asym-amyloidosis) detected in patients with newly diagnosed multiple myeloma (MM) or smoldering multiple myeloma (SMM) is unknown. This topic is significant because unrecognized AL may be associated with increased mortality may change the patient's management. The objective of the present investigation was to evaluate the number and clinical significance of asym-amyloidosis in MM and SM patients at the time of the diagnostic bone marrow (BM) biopsy for MM. Materials and Methods. The study population was selected from the Mayo Clinic Dysproteinemia database and consisted of consecutive patients with an established diagnosis of MM or SMM without recognition of symptomatic AL. Bone marrow biopsies at diagnosis of MM or SMM were retrospectively stained with Congo Red and reviewed by a single pathologist. A patient was considered to have asym-amyloid if Congo Red staining with apple green birefringence was found. Results. Biopsies from 144 (M 84, F 59) patients were evaluated: 77 had a diagnosis of MM and 67 of SMM. The median age was 59 (range 26-84) years. No differences were found regarding hemoglobin, platelets, prothrombin time, serum and urine proteins, serum albumin, alkaline phosphate, creatinine and β2-microglobulin among MM and SMM patients. At a median follow-up 76 months (range 0-216), 32% patients were alive, 65% dead and 2.7% lost to follow-up. Immunoglobulin isotypes were as follows: 96/144 (67%) had IgG 23/144 (16%) IgA, 12/144 (8%) had light chain only, 1/77 (1%) had IgD, none had IgM and 12/144 (8%) had biclonal or indeterminate; 84/144 (58%) were κ restricted. The presence of amyloid was found in only 2 cases (1%, 95% CI – 0.6 to 3.2), 1 in MM and 1 in SMM group. Neither of these patients had or developed signs or symptoms suggestive of organ involvement by amyloid. Among the 142 other patients without amyloid deposition in their index bone marrow, 1 (0.7%, 95% CI -0.6 to 2.0) developed symptomatic AL after 119 months of follow-up. Characteristics of these three patients are shown in table 1. Conclusions. We found only 2 cases (1%) of amyloidosis in the 144 cases of MM or SMM. Our estimates are lower than the rates which have been reported by others, perhaps because of our high level of suspicion for amyloid at our Amyloidosis Center. These data do not support the need for searching for asym-amyloidosis in patients with newly diagnosed MM or SMM as long as they have no clinical features of AL. Disclosures: Off Label Use: Hydroxyurea use in myelofibrosis. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Witzig:Novartis: Research Funding. Kumar:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract Background: High dose therapy with autologous stem cell transplantation (HDT-ASCT) has prolonged survival in patients with multiple myeloma. Patients who achieve a complete response (CR) benefit the most from this form of therapy. Thus, achieving a CR is an important goal of therapy and it will be beneficial if the probability of achieving CR can be determined for any patient before transplant. Patients and Methods: A large cohort of patients with myeloma who received HDT-ASCT at Mayo Clinic Rochester was studied. The impact of various demographic, clinical and laboratory characteristics relating to the patients and their disease acquired were studied for their impact on response to HDT-ASCT, especially CR. Patients with a serum M-protein <0.1g/dL were excluded. Response definitions were as defined by established criteria. Survival analysis was performed according to the Kaplan-Meier method while univariate and multivariate analyses were performed with the proportional hazards method. We utilized knowledge of the rate of M-protein production by myeloma cells together with the clearance of the protein to estimate the pre-transplant disease burden. Results: We studied 224 patients with a median age of 56.5 years (32.6 – 71). Patients were transplanted a median of 8.7 months after diagnosis. Almost all patients had a response to HDT-ASCT and 78 (35%) achieved a CR. Those patients who achieved a CR had a longer time to progression (TTP) compared to those who did not achieve CR (Figure 1). The cohort was thus divided into two groups: patients who achieved CR and those that did not. The clinical and laboratory characteristics of the two groups were compared. Among the pre-transplant parameters tested, only the size of the serum M-spike was a predictor for CR (p<0.0001). A simple function that describes the probability of achieving CR based on the serum M-spike before HDT-ASCT is described. The estimated rate of tumor re-growth after HDT-ASCT in patients who obtain a CR and in patients who only get a partial response are presented. Conclusions: The pre-transplant disease burden in myeloma is the main determinant of response to HDT-ASCT. The individual probability of achieving CR can be estimated from simple clinical parameters providing a quantitative risk assessment prior to such a high-risk procedure. There is significant expansion of myeloma cells after HDT-ASCT. The design of clinical trials may benefit from knowledge of the kinetic aspects of the disease. Figure Figure

Abstract Background: Young (age < 60 years) patients with agnogenic myeloid metaplasia (AMM) are potential candidates for curative therapy with allogeneic stem cell transplantation. In such transplant-eligible patients, median overall survival (OS) is reported to be between 78 and 128 months. Because clinical course in an individual patients is markedly heterogeneous (survival ranges of months to decades), objective prognostic variables are essential for transplant decision making. Accordingly, we recently developed a modified Dupriez prognostic scoring system (PSS) that effectively discriminated between high (2 or more risk factors), intermediate (one risk factor) and low (no risk factor) risk patient groups based on the presence or absence of complete blood count (CBC)-derived adverse parameters; hemoglobin < 10 g/dl, leukocyte count < 4 or > 30 × 109/L, and platelet count < 100 × 109/L (Dingli et al. Cancer2006;106:623). In the current study, we identify absolute monocytosis of ≥ 1 × 109/L as an additional independent risk factor for survival in AMM. Methods: A consecutive cohort of WHO-defined AMM patients diagnosed before the age of 60 years was identified. The impact of various clinical and laboratory parameters on overall survival was evaluated with univariate and multivariable analysis. Results: The study included 129 patients (median age 52 years, range 18–60; 69 males) with AMM. An overall median survival of 75 months was univariately affected by platelet count < 100 × 109/L, hemoglobin level of < 10 g/dL, leukocyte count of either < 4 or > 30 × 109/L, monocytosis of ≥ 1 × 109/L, and, where cytogenetic studies were available (n=41), presence of unfavorable cytogenetic abnormalities (p < 0.01 in each instance). On multivariable analysis, all but leukocyte count maintained their significance. The independent prognostic value of monocyte count was also validated against the modified Dupriez score (see above) and thus allowed further refinement of the particular CBC-based PSS that included monocytosis of ≥ 1 × 109/L as a fourth risk factor; low-risk identified patients with none of the 4 risk factors, intermediate-risk with one risk factor, and high-risk with 2 or more risk factors (Figure 1). For comparison, Figure 2 illustrates survival curves according to the original Dupriez PSS. Conclusion: Monocytosis of ≥ 1 × 109/L is an independent risk factor for inferior survival in AMM. Figure 1. Mayo score Figure 1. Mayo score Figure 2. Dupriez score Figure 2. Dupriez score

Abstract Abstract 1858 Systemic light chain amyloidosis (AL amyloidosis) is a condition where clonal plasma cells produce misfolded insoluble immunoglobulin light chains that deposit in various organs causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT) when eligible is the standard treatment options for patients with AL amyloidosis. There are several studies who report long term outcomes of patient post ASCT. However, there is a paucity of literature describing the outcomes of patients who have received ASCT but have relapsed. We performed a retrospective study to assess the outcomes and treatment regimens employed following relapse after ASCT. Between 1996 and 2009, 410 patients received ASCT at the Mayo Clinic as first line therapy. Of those 410 patients 42 patients died within 3 months of transplant, 64 patients died without documented relapse, 158 patients were alive without documented progression, and 146 patients had documented progression. Those 146 patients are the subject of our study. The median time to hematologic relapse was 2 years (range: 0.2–15.5 years). At relapse, 59 patients were treated with IMiD based therapy, 36 with alkylator based therapy, 24 with bortezomib, 15 with steroids, and 5 with second ASCT. The respective hematologic response rates were 58%, 33%, 50%, 53%, and 60%. The remaining six patients were not evaluable for response for one other following reasons: organ transplants; no further therapy; inevaluable disease. With a median post relapse follow up of 3.6 years, the median overall survival (OS) from the first post ASCT relapse was 4.6 years. The median post transplant follow up was 6.1 years, the median OS for these patients was 7.3 years from the time of transplant. These data provide novel information about outcomes after SCT relapse, which should be useful not only for patients and doctors but also for investigators designing studies for salvage therapies post-transplant. Disclosures: No relevant conflicts of interest to declare.