Hogan, William J.

Abstract Systemic mastocytosis (SM) is a rare hematologic neoplasm characterized by abnormal growth and accumulation of tissue mast cells (MC) in various organ systems, including bone marrow (BM). Indolent and advanced forms of SM have been described. Whereas patients with ISM have a normal or near normal life-expectancy, patients with advanced SM, including those suffering from mast cell leukemia (MCL) have a poor prognosis. In these patients, neoplastic MC are usually resistant against conventional drugs and various targeted drugs. In rapidly progressive aggressive SM (ASM) and MCL, polychemotherapy followed by allogeneic hematopoietic stem cell transplantation (alloHCT) has been proposed. However, outcome of alloHCT in advanced SM is unknown, and it also remains uncertain whether clinically relevant graft-versus-SM (GVSM) effects may occur in these patients, as only sporadic case reports have been published. We performed a retrospective multi-center analysis to evaluate the outcome of alloHCT in patients with advanced SM. Fifty-four advanced SM patients receiving SCT in 32 transplantation centers in Europe and America were identified between 1990 and 2013. The median patient age was 45 years. Donors were: HLA identical siblings (31), unrelated donors (URD) (15), umbilical cord blood donors (UCB) (2), and haploidentical donors (1). In 5 patients, stem cell source was not defined (5). Thirty-four patients received myeloablative conditioning (MAC) and 18 received reduced intensity conditioning regimens (RIC). In 2 patients, conditioning regimen was not specified. Indications for alloHCT were SM with an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD) (n=32), MCL (n=13, including one with MCL-AHNMD), 8 with ASM and 1 with myelomastocytic leukemia (MML). The most prevalent AHNMD was acute myeloid leukemia (AML, n=16). With follow-up of 35-6180 (median 365) days, SM responses (defined as ≥50% decrease in BM mast cells ± decrease in serum tryptase ± regression of other organ manifestations) were observed in 39 patients (72%), including complete responses (CR) documented in 12 patients (22%). Eleven patients had stable disease, whereas 4 patients (7%) progressed immediately after alloHCT (primary resistance). In addition, 10 patients progressed (5 of them within 100 days) after an initial response. Progression was most frequently seen in MCL patients (n=6, 50%). In the AHNMD group, only 8 patients relapsed/progressed (25%). The overall survival (OS) and SM progression-free survival (PFS) at 1 year were 63% and 50% for all patients, 77% and 68% for SM-AHNMD, 63% and 50% for ASM, and 25% and 17% for MCL, respectively. The strongest predictive variable associated with inferior survival was a diagnosis of MCL. Other factors associated with poor outcome were: Karnofsky performance status ≤70%, ≥2 SM regimens given before alloHCT (e.g., steroids, cladribine, chemotherapy, tyrosine kinase inhibitor), donor source (alternative donors-UCB and haploidentical compared to sibling or URD), SM progression within the first 100 days, normal cytogenetics (compared to t(8;21) (q22;q22), and RIC (compared to MAC). The following variables were not associated with poor outcome: patient and donor age, recipient-donor sex match status, graft source (BM vs. peripheral stem cells), BM mast cell percentage at time of alloHCT, and CR status of AML or SM response at time of alloHCT. This largest multi-center analysis of results in advanced SM provides evidence for clinical efficacy of alloHCT, presumably because of a GVSM effect of alloHCT (achieving CR, and response to donor-lymphocyte infusions and RIC alloHCT). However, responses varied among different SM categories: while patients with SM-AHNMD enjoyed excellent outcomes, the OS for MCL patients in general, was poor. Nevertheless it is remarkable that 3 of 13 patients with MCL – an otherwise fatal disease with a median survival of <12 months – became long-term survivors after alloHCT. In summary, our results support development of a prospective alloHCT study, with the aim to optimize therapy and to improve overall outcome in advanced SM. Based on our pilot study, alloHCT should also be considered in practice for eligible and fit patients with SM-AHNMD (if treatment of AHNMD component needs alloHCT or SM component is aggressive), rapidly progressing ASM, MCL and MML when a suitable HLA-matched sibling donor or URD is available. Disclosures: Vercellotti: Sangart Inc.: Research Funding; Seattle Genetics: Research Funding. Akin:Novartis: Consultancy. Valent:Novartis: Consultancy, Honoraria, Research Funding.

Abstract Background Acquired factor X (FX) deficiency is associated with immunoglobulin light chain (AL) amyloidosis and may be accompanied by hemorrhage. There are limited data on the effects of autologous stem cell transplant (ASCT) on FX deficiency. We reviewed hemorrhagic complications and the effect of high dose melphalan (HDM) and ASCT on FX levels in AL amyloidosis patients with FX deficiency. Methods We conducted a retrospective chart review of patients with AL amyloid with FX levels below 60%, not on chronic anti-coagulation who underwent HDM/ASCT at the Mayo Clinic, Rochester, MN between 1995 and 2011. Results Forty-one of 358 patients (11%) met our study criteria. Median pre-ASCT FX was 45% (range: 2%, 59%). The most common bleeding complication was central line associated n=15 (37%) followed by gastrointestinal n=10 (24%) and genitourinary n=9 (22%). The most frequent and severe bleeding complications occurred in patients with FX levels less than 10%. Four patients required emergent splenectomy owing to splenic rupture; one of these patients died from hemorrhagic shock. Periprocedural prophylaxis included activated recombinant Factor VII (rFVIIa) infusions, fresh frozen plasma (FFP) infusions and platelet transfusions. rFVIIa was efficacious in controlling bleeding during splenectomy (n=5) and, in conjunction with arterial embolization, for retroperitoneal bleed (n=1). Elective splenectomy for FX deficiency (n=1) resulted in only transient improvement in FX level. No relationship between the degree of pre-ASCT FX deficiency and other laboratory values (alkaline phosphatase, AST, total bilirubin, serum albumin, total serum protein, serum creatinine, total urine protein, beta2 microglobulin, troponin T) was found. Post-ASCT FX levels were determined in seventeen patients. In four of these patients, post-ASCT FX levels were determined in the acute/subacute phase of ASCT before steady state FX levels could be achieved; the median change in FX for these patients was -6.5% (range: -19%, 3%). In the remaining thirteen patients, who were between 99 and 1920 days from ASCT, FX improved by median 26% (range: -15%, 92%). Overall post-ASCT FX increased in twelve of thirteen (92%) patients. The improvement in FX correlated with improvement in the degree of proteinuria (p = 0.04) and showed a trend towards significant correlation with improvement in serum alkaline phosphatase (p = 0.06). Conclusions Hemorrhagic complications are most frequent and severe for FX levels below 10%. rFVIIa infusions, FFP and platelets were effective prophylactic agents. In the single patient who underwent elective splenectomy, a transient improvement in FX level was seen. Splenectomy was otherwise reserved for patients with splenic rupture/hematoma. Post-ASCT FX levels increased in twelve (92.3%) of the remaining thirteen patients; five of the patients (38.5%) were no longer FX deficient after ASCT. The degree of improvement in FX levels was correlated with improvement in markers of renal or hepatic involvement by amyloid. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding.

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

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

Abstract Background The timing of SCT for treatment of AML after first relapse is controversial, i.e.,whether to proceed to SCT at the time of relapse or to proceed to chemotherapy re-induction first in an attempt to reach a second remission. The purpose of this study is to determine the optimal time of allogeneic SCT in AML patients in first relapse by comparing outcomes of allogeneic SCT between patients untreated and patients post re-induction chemotherapy. Method This retrospective study was approved by the Mayo Foundation IRB. Between February 1983 and March 2003, 60 patients with AML in untreated first relapse (REL1) or post re-induction chemotherapy (CT) underwent allogeneic SCT in Mayo Clinic, Rochester. Study outcome included overall survival (OS), disease free survival (DFS), and transplant related mortality (TRM). The outcome was compared between the patients who underwent allogeneic SCT at REL1 and CT. Survival was analyzed using Kaplan-Meier (KM) and groups were compared statistically with the log-rank test. Result Of the 60 patients receiving allogeneic SCT , 25 patients and 35 patients underwent SCT at REL1 and CT, respectively. In the group of CT, 23 patients (66%) achieved CR2 while 12 patients (34%) had refractory disease. Forty-nine of 60 patients received cyclophosphamide and total body irradiation (Cy/TBI) as a conditioning regimen and the remainder received busulfan and cyclophosphamide( Bu/Cy). Patients in REL1 were older at SCT (median age 38 vs 31 years p= 0.024 ) and had lower percentage blast cells in bone marrow at first relapse (median 15% vs 50% p=0.00095) than in CT group. Difference in other baseline characteristics were not significant. KM analysis showed that the two groups did not show statistically differences in OS (p=0.43), DFS (p=0.68), and TRM (p=0.25). However, there were trends toward longer median OS (26.2 vs 5.4 months) and DFS (11.9 vs 3.3 months) with REL1 versus CT. OS at 1 year was 56 % for REL1 and 34.3 % for CT and at 5 year 32.1 % and 28.6 %, respectively. DFS at 1 year was 48 % for REL1 and 31.4 % for CT and at 5 years 22.9 % and 24.5 % respectively. TRM at 1 year was 25% for REL1 and 40 % for CT. A univariate Cox Proportional Hazard analysis for survival showed that unfavorable cytogenetics at diagnosis and relapse, antecedent MDS, and shorter duration of CR1 were significantly associated with a higher risk of death. Higher percentage of blast cells in bone marrow at first relapse was not significantly associated with a higher risk of death. In a multivariate model, unfavorable cytogenetics at first relapse and shorter duration of CR1 were both significantly associated with an increased risk of death. In this study, even after adjusting for other factors in a multivariate model, the difference between REL1 and CT groups was not statistically significant. Conclusion This study suggests that outcome of allogeneic SCT was comparable between REL1 and CT. Patients with AML in first relapse may proceed to allogeneic SCT because there appear to be no statistical differences in REL1 versus re-induction chemotherapy before SCT. REL1 patients tended to have a better outcome than CT patients.

Abstract Abstract 4228 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, mobilization strategy, underlying disease, among others. Patients (Pts) failing to mobilize successfully often have GF dose increased and if unsuccessful, mobilization is 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 656 first time, G-CSF based PBSC mobilizers with Non-Hodgkin Lymphoma (562; 86%), or Hodgkin's Disease (94; 14%). Salvage attempts were excluded, as were first attempts using CTX+GCSF, plerixafor or GF combinations. Sensitivity-specificity analysis (Receiver operating characteristic) 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 5 million/kg as the ideal collection for the current 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/uL. Among those with ≥9/uL, only 6.6 % failed to collect at least 2 million compared to 55% among the rest (P < 0.001). These numbers were 6.3% and 50% 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 9.1/uL was the best cutoff to predict a collection of 2 million/kg. Among those with >=9.1/uL, only 22% failed to collect at least 2 million compared to 79% among the rest (P < 0.001). Among those with day 1 pCD34 < 10, 49% achieved a count of 9.1/uL on day 2. We then examined what pCD34 on day 1 can best predict a pCD34 ≥ 9.1 on day 2 and found this to be 5.2/uL. Among those with day 1 pCD34 ≥ 5.2/uL, 79% reached day 2 pCD34 ≥ 9.1 compared to 24% 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 for a target of 5 million/kg for one transplant. The best day 1 or day 2 pCD34 predicting a 5 million/kg yield in 5 collections was 17/uL. Among those with day 1or 2 pCD34 ≥ 17/uL, 4% failed to reach 5 million in ≤ 5 days compared to 96% among the rest (P < 0.001). Conclusions This study provides an estimate of optimal pCD34 count thresholds for early identification of patients with lymphoma 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 these patients appear to have similar outcome as those reaching the threshold by day 1. Based on the results here, interventions such as addition of plerixafor can be considered if pCD34 count is < 6/uL on day 1 or < 10/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 based on the current study would be 17/uL for a target of 5 million. Such a target-adapted strategy may be more appropriate. Disclosures: Kumar: Celgene,Genzyme,Millenium,Novartis,Bayer,: Honoraria, Research Funding. Gertz:Genzyme: Research Funding. Micallef:Genzyme: Research Funding.

Abstract Abstract 4152 BACKGROUND: Patients with biologically aggressive chronic lymphocytic leukemia (CLL) characterized by being refractory to purine nucleoside analogues and/or possessing the cytogenetic abnormality del (17p13) have poor clinical outcomes with a median survival of <3 years. Several groups have reported that nonmyeloablative allogeneic stem cell transplant (alloSCT) provides long-term disease control in a subset of high-risk CLL patients. The Seattle group also recently reported that alemtuzumab use prior to alloSCT may increase the risk of early relapse/progression (Sorror, ASH 2010). This is a potentially critical observation since alemtuzumab is one of the few active agents in patients with del(17p13) and is frequently used for pre-transplant debulking in patients with this genetic defect. METHODS: We performed retrospective analysis of 38 CLL patients who underwent nonmyeloablative alloSCT for CLL at the Mayo Clinic between 2003 and 2011. The relationship between transplant outcome and debulking regimen used immediately prior to alloSCT, disease status at the time of alloSCT, post transplant engraftment, GVHD development was explored. The degree of marrow involvement prior to alloSCT was assessed using the leukemia index calculated by multiplying the % involvement by CLL cells and the % cellularity. RESULTS: Median age at the time of alloSCT was 55.5 (range, 29–69) and 13 patients (34%) were female. The median duration from CLL diagnosis to alloSCT was 4.7 years. Thirty-two patients (84%) had received more than 3 prior therapies prior to alloSCT. Thirty-seven patients (97%) had received purine analog-based therapies, 18 (47%) patients had received alkylating agents and 25 (66%) had received alemtuzumab. 33 (87%) patients were purine analog refractory. On cytogenetic evaluation by FISH, 17 (45%) patients had del(17p13), 10 (26%) had del(11q23) and 1 (3%) had del(6q23). Nine patients were in complete remission (CR) by IWCLL 2008 criteria at the time of alloSCT and 7 patients were in complete remission with incomplete marrow recovery (CRi). Of the remaining 22 patients, 20 had either a partial remission or stable disease at the time of alloSCT and 2 had progressive disease. Two (5%) patients had bulky lymphadenopathy (≥ 5cm by CT imaging), 11 (29%) patients had splenomegaly, and 8 (21%) patients had more than 30% CLL involvement by the leukemia index. Fludarabine (F) and 200cGy total body irradiation (TBI) was used as the conditioning regimen for 35 patients (92%). 22 patients received unrelated donor grafts (15 matched, 7 mismatched), and 16 received related donor grafts (all matched). Patients received mycophenolate (MMF) and either tacrolimus (unrelated grafts) or cyclosporin (related grafts) for graft versus host disease (GVHD) prophylaxis. 31 out of 37 evaluable patients (84%) achieved initial 100% donor chimerism (22 within 100 days) and 24 (63%) developed ≥grade 2 GVHD. After median follow-up of 1 year (range = 0–5.4 years), 26 of 38 patients (68%) are alive, and the median overall survival is 47 months. To date, 13 (34%) have experienced CLL progression/relapse requiring accelerated taper of GVHD prophylaxis (n = 2), donor lymphocyte infusion (n = 5), or chemo/immunotherapies (n= 6). For the 12 deceased patients, causes of death was CLL relapse/progression (n = 5), GVHD (n = 2) and infectious or other complications without CLL relapse/progression (n = 5). Pre-transplant use of alemtuzumab (A) within 3 months of transplant was the only pre-transplant characteristics associated with overall survival (OS). Median OS of patients receiving A within 3 months of alloSCT was 1 year compared to not reached for those who did not receive A within 3 months of alloSCT (p = 0.011; Figure 1a). A trend was also observed between alemtuzumab use within 12 months of alloSCT; however, it did not reach statistical significance (p=0.069; Figure 1b). No statistically significant associations between residual marrow involvement at time of alloSCT (p = 0.93), type of graft (p = 0.65), or presence of del (17p13) (p = 0.13), number of prior treatments (p = 0.45), patient age (p = 0.80) or disease status at time of alloSCT (p = 0.21) were observed. CONCLUSION: In this cohort of patients with high risk CLL, alemtuzumab use prior to transplant was the greatest predictor of OS after nonmyeloablative alloSCT. Non-alemtuzumab based debulking strategies need to be developed for patients with del (17p13). Disclosures: No relevant conflicts of interest to declare.

Abstract Peripheral blood infused total autograft absolute lymphocyte count (A-ALC) correlates with day 15 absolute lymphocyte count and is an independent prognostic factor for survival after autologous stem cell transplantation (ASCT) for non-Hodgkin lymphoma (NHL). Factors to enhance A-ALC collections are not well defined. We hypothesize that the number of peripheral blood apheresis collections (PBAC) directly correlates with A-ALC. 190 consecutive NHL patients who underwent ASCT at the Mayo Clinic between 1993 and 2001 were analyzed. The primary end point of the study was to assess the correlation between the number of PBAC and A-ALC. The secondary end point was to determine if the number of PBAC affected survival post-ASCT. Of the 190 patients, 18 patients underwent 1 PBAC, 23 patients 2 PBAC, 50 patients 3 PBAC, 37 patients 4 PBAC, 50 patients 5 PBAC, and 12 patients had ≥ 6 PBAC. There was no association between the number of PBAC and the number of CD34+ stem cells collected (p= 0.25). A strong association between number of PBAC and A-ALC (Kruskall Wallis test, p <0.0001)(Figure 1) was identified. Using a cut-off of 4 PBAC, superior overall survival (OS) and progression-free survival (PFS) were observed for patients that underwent 4 PBAC or more compared to patients that underwent less than 4 PBAC (86 months vs 18 months, p <0.0001; 76 months vs 10 months, p <0.0001, respectively). Multivariate analysis demonstrated PBAC ≥ 4 is an independent prognostic factor for OS (RR = 0.654, 95%CI: 0.529–0.804, p< 0.0001) and for PFS (RR = 0.682, 95%CI: 0.561–0.826, p< 0.0001) when compared with other significant factors including performance status, lactate dehydrogenase and extra nodal disease. These data suggest that increasing the number of PBAC beyond the minimum number required to meet CD34+ collection targets may result in improved overall and progression-free survival mediated by an increase in autograft absolute lymphocyte count.

Abstract Abstract 4359 Routine serial chimerism analysis after allogeneic stem cell transplantation (Allo-SCT) has been used as a risk factor for post-Allo-SCT cancer relapse. In non-Hodgkin lymphoma (NHL) patients treated with autologous peripheral blood hematopoietic stem cell transplantation (APHSCT), a specific predictor during routine follow-up that could be used to ascertain risk for post-APHSCT relapse has not been identified. Thus, we set out to investigate if absolute lymphocyte count (ALC) measured at post APHSCT follow-up could serve as a marker of post-APHSCT NHL relapse. ALC was obtained at the time of confirmed relapse at follow-up and at last no evidence of relapse follow-up. From 1993 until 2005, 269 patients treated with APHSCT for diffuse large B-cell lymphoma (DLBCL), were included in this study. Patients at last follow-up with no relapse (N=137) had a higher ALC compared with those with confirmed relapsed at follow-up post-APHSCT (N= 132) [median ALC x 109/L of 1.66 (range: 0.13-3.69) vs 0.71 (range: 0.03-4.75), p <0.0001, respectively]. ALC at follow-up was a strong predictor for relapse with an area under the curve (AUC) = 0.86 (p<0.0001). An ALC of 1.0 × 109/L was identified as the optimal cut-off point. An ALC < 1.0 × 109/L at the time of confirmed relapse had a positive predictive value of 89% and a positive likelihood ratio of 8.4 to predict relapse post-APHSCT. Patients with an ALC ≥ 1.0 × 109/L (N = 147) had a cumulative incidence of relapse of 19% versus 92% for patients with an ALC < 1.0 × 109/L (N = 122) (p<0.0001) at follow-up post-APHSCT. This study suggests that ALC at follow-up can be used as a marker to assess risk of DLBCL relapse during routine follow-up after APHSCT. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: POEMS syndrome is a devastating syndrome, characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis, & high VEGF. We noted an unexpectedly high transplant related morbidity, which we have since postulated to be ES. Methods: 30 patients with POEMS were treated with PBSCT at Mayo Clinic Rochester. We retrospectively studied outcomes, with an emphasis on treatment related morbidity. Two definitions of ES were used: Spitzer (BMT 2001) and Maiolino (BMT 2003). Results: Two-thirds were male. Median age was 48, range 20–70. Time from first symptoms and diagnosis was 26 and 4 months, respectively. To mobilize stem cells, CTX/G-CSF was used in 5 & G-CSF in the remainder. Conditioning was Mel200 (n=19), Mel140 (n=10), and BEAM (n=1). Post-transplant 15 had GM-CSF begun day+6. Only 10% remained outpatient, and median time to discharge from hospital was transplant day 17 (range 0–175). Factors predicting for later dismissal included age (p=0.04), abnormal CXR 7 to 17 days post transplant (p<0.0001), & bolus corticosteroids (CS) beyond day 12 post-transplant (p=0.006). Ninety-three percent had fever, although only 9 had bacteremia. Eight satisfied criteria for ES according to Spitzer and 14 according to Maiolino. Another 3 patients received steroid bolus days 8, 12, and 11 for presumed ES but did not meet criteria because of delayed ANC recovery (days 16, 18, and 20, respectively). Of the 5 patients requiring endotracheal intubation, 3 satisfied Maiolino’s criteria for ES. Although these 3 received bolus CS during their course, administration was delayed at 18, 14, and 18 days. The patient whose CS bolus antedated intubation only received prednisone 30 mg/day. In toto, fourteen patients received bolus CS (daily doses between 20 and 1200 mg prednisone equivalents) commencing day 8 to 59. Those 7 patients who received CS before day 13 did better than the 7 who received them day 13 or later (Table). Conclusions: It is essential to recognize that nearly 50% of patients satisfied formal criteria for ES as defined by Maiolino. In these patients ES may run a self-limited course or lead to catastrophe. No Steroid (n=16) Steroid ≤ D12 (n=7) Steroid > D12 (n=7) P *Engraftment syndrome according to definition of Maiolino (M) or of Spitzer (S). ES M / S, n* 5 / 2 4 / 4 5 / 2 NA Wt change, % 0.6 (−.4.2–6.7) 6.7 (3.6–27.2) 11.2 (–2.1–23.2) 0.005 Rash, % 27 71 43 0.13 Diarrhea, % 73 86 86 0.71 Tmax, C 39 (37.8–41) 40.1 (39–41.1) 38.9 (38.7–40.8) 0.08 1st fever, day 10 (6–15) 8 (7–9) 12 (8–146) 0.007 Abn CXR1, % 13 71 71 0.03 Ventilator, % 0 14 71 0.004 First WBC, day 12 (8–21) 14 (12–14) 14 (12–17) 0.03 ANC500, day 15 (12–29) 16 (14–115) 18 (15–45) 0.08 PLT20, day 12 (8–41) 20 (11–115) 24 (9–170) 0.05 PLT50, day 15 (11–192) 32 (16–115) 56 (13–551) 0.03 RBCs, units 3 (2–8) 6 (4–31) 11 (6–64) 0.0008 PLTS, aph. units 2 (1–9) 9 (4–51) 18 (4–60) 0.0004 Hosp dsm, day 15 (13–36) 21 (15–69) 41 (16–175) 0.009