ALBERT

Description: Relapse remains the major cause of death in older patients transplanted for AML in first complete remission (CR1) or for patients with advanced MDS at any age. Conventional myeloablative conditioning followed by allogeneic blood or marrow transplantation is associated with significantly less relapse compared with RIC when performed in younger patients with AML or MDS, but the toxicity of this approach in older patients is prohibitive. We hypothesized that pharmacokinetic targeting to optimize busulfan (Bu) exposure, combined with the administration of AZA post transplantation would mitigate the risk of relapse while avoiding non-relapse mortality (NRM) and ultimately improve progression free survival (PFS). Here we report the results of a Bu test dose strategy targeting daily Bu exposure as determined by the area under the plasma concentration versus time curve (AUC). The primary endpoint of the study was two year progression free survival (PFS). An important secondary objective was to determine whether administration of a test dose of Bu with post test sampling would enable achievement of a daily target Bu AUC level of 4000 uM*min in at least 80% of the recipients. We used this strategy as part of a RIC regimen on a prospective multi-center phase II trial conducted by the Alliance (formerly Cancer and Leukemia Group B (CALGB)). Eligibility included patients with AML in CR1 aged 60-74 years inclusive, MDS with IPSS risk 〉 Int-2 with less than 10% marrow blasts and age

Description: Background: Autologous stem cell transplantation (ASCT) performed early in the disease course or at first relapse leads to improved progression-free and overall survival in transplant-eligible patients with multiple myeloma (MM). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF), when used after ASCT has been shown to accelerate time to neutrophil engraftment (TNE), and in some studies, it has been associated with reduced length of hospitalization, infectious complications, and antibiotic use. Strategies that reserve G-CSF administration to when neutrophil recovery is delayed, have attempted to show that there is no difference in infectious complications, length of hospitalization or TNE when compared to early administration of G-CSF on the day after stem cell infusion (DOT). However, the optimal timing for administering G-CSF has not yet been determined in patients with MM undergoing ASCT. Methods: This is a retrospective, single-center analysis of patients with MM undergoing ASCT from mobilized peripheral blood stem cells. Patients enrolled in a clinical trial of high-dose lenalidomide and melphalan as conditioning therapy which mandated the administration of filgrastim from day +1 after DOT (Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma, NCT01054196) were assigned to the early strategy group (ES). Patients receiving filgrastim as per our institutional guideline (starting on day +12 if ANC 〈 1000 cells/uL, or at the physician's discretion) were included in the delayed strategy group (DS). Patients were excluded from the analysis if their conditioning regimen included a different agent other than melphalan or lenalidomide. DOT was defined as the day of stem cell infusion. Date of neutrophil engraftment was defined as the first of three consecutive days with an ANC ≥ 500 cells/uL. TNE was calculated as the time from DOT to the date neutrophil engraftment. Total duration of neutropenia was defined as the time from onset of neutropenia (ANC 〈 500 cells/uL) to date of neutrophil engraftment. Length of hospitalization was defined as the time from DOT to the day of discharge. Results: We identified 59 patients in the ES group and 39 patients in the DS group from 08-16-2010 to 05-22-2019, for a total of 98 included in this analysis. Median age was 60 and 65 years in the ES and DS groups, respectively. Patients received a comparable dose of CD34+ cells, 5.05x106/kg in the ES group vs 4.66x106/kg in the DS group (p = 0.48). The ES group started filgrastim administration earlier (day +1 vs +9, p 〈 0.001) and received a greater median number of doses (10 vs 4, p 〈 0.001) as compared to patients in the DS group. Median time to neutrophil engraftment was shorter in the ES group compared to the DS group (10 vs 12 days, p 〈 0.001), as was the total duration of neutropenia (5 vs 6 days, p 〈 0.001). Documented infections were just as likely in both groups, 37% in the ES group and 39% in the DS group (p = 1). Length of hospitalization was shorter in the ES group as compared to the DS group (15 vs 17 days, p = 0.01). Discussion: Filgrastim use guided by an ES decreased the time to neutrophil engraftment, the duration of neutropenia and the length of hospitalization compared to a DS. Further analyses to identify predictive factors associated with a reduction in infectious complications and length of stay are underway, with the aim of developing a risk-adapted strategy for the use of filgrastim in patients with MM undergoing ASCT. Disclosures Van Besien: Miltenyi Biotec: Research Funding. Coleman:Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Rosenbaum:Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.

Description: Abstract 3561 Introduction: In patients with Hodgkin lymphoma (HL) and non-Hodgkin's lymphoma (NHL) for whom initial therapy is not curative, high dose chemotherapy followed by autologous stem cell transplantation (AutoSCT) may offer a second chance for cure or long term remission. Because of the potential toxicities of this therapy, elderly patients are usually not considered candidates for this approach. Although recent publications have suggested that AutoSCT may benefit some patients over 65 years of age, data regarding feasibility in older patients (69 or greater) are lacking. Patients and Methods: The stem cell transplant database at Weill Cornell Medical College was reviewed to identify patients with a diagnosis of lymphoma (HL or NHL) age 69 or greater who had undergone AutoSCT. Patients were included if age, date of transplant, response and survival data were available. Baseline Charlson comorbidity risk index (CCI) was calculated and correlated with outcome. Results: Twenty-one patients aged 69 or greater (range 69–86, median 71) with adequate records were identified who underwent autologous stem cell transplantation for treatment of lymphoma. Thirteen patients had diffuse large B cell lymphoma, 3 had transformed indolent lymphoma, 2 had Burkitt lymphoma, one had peripheral T cell lymphoma, one had follicular lymphoma, and one had HL. Sixteen patients underwent AutoSCT in first relapse with chemotherapy sensitive disease, 2 patients had primary refractory lymphoma, 2 were in 2nd or greater relapse, and one patient was in first complete remission (CR). Two patients underwent total body irradiation (TBI) as part of conditioning, while the other 19 patients underwent conditioning with chemotherapy alone. Sixteen patients (76%) achieved CR following autoSCT, while 3 patients did not achieve CR; 2 patients died before response assessment could be undertaken. With median follow up of 20 months, the median progression-free survival following autoSCT was 10 months and median overall survival was 18 months. Age was associated with PFS (HR 1.18, p=0.05, 95% C.I. 1.05–1.33) but not OS (HR 1.11, p=0.09, 95% C.I. 0.98–1.25). Eight of 18 patients with adequate follow up (44%) remained in remission for at least 18 months post-transplant. CCI data were available for 19 patients. Four patients (19%) died within or shortly after 100 days, all of transplant-related toxicity. Two of these 4 patients were high risk by CCI, one was medium risk, and CCI data were not available for the fourth patient. Three other patients were of medium risk; 2 are alive in CR and one died of progressive lymphoma 19 months after transplantation. Thirteen patients were of low risk by CCI. Of these patients, 9 (69%) are either alive at time of follow up or survived for greater than one year after transplant, while 4 (31%) died within one year of progressive lymphoma. Conclusion: Autologous stem cell transplantation is feasible and of potential benefit in selected elderly patients with lymphoma. Age alone need not exclude patients with good functional status and limited comorbidity from this therapeutic approach. Consideration of comorbidities may allow selection of patients most likely to tolerate and benefit from AutoSCT. Disclosures: Furman: GlaxoSmithKline: Clinical research funding, Consultancy, Research Funding, Speakers Bureau; Genentech: Clinical Research Funding, Consultancy, Research Funding, Speakers Bureau; Cephalon: Speakers Bureau, Speakers bureau; Calistoga: Consultancy, Honoraria; Celgene: Clinical Research, Consultancy, Research Funding. Leonard:Hospira: Consultancy, Honoraria; Cell Therapeutics: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Biogen IDEC: Consultancy, Honoraria; Calistoga: Consultancy, Honoraria; Johnson and Johnson: Consultancy, Honoraria; EMD Serono: Consultancy, Honoraria; Sanofi Aventis: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Biotest: Consultancy, Honoraria; Cephalon: Consultancy, Honoraria; Pharmion: Consultancy, Honoraria; Eisai: Consultancy, Honoraria; Cougar Biotechnology: Consultancy, Honoraria; Immunomedics: Honoraria; Genentech: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Description: Mucositis is a painful side effect of many transplant conditioning regimens used in HDC and PBSCT. This complication often requires treatment with potent narcotic analgesics and may even require intravenous patient-controlled analgesia (PCA) for adequate pain relief as well as total parenteral nutrition (TPN). Infections in this setting may also result from disruption of the mucosal barrier with subsequent migration of intestinal bacteria into the blood stream. Previous treatments with oral rinses and topical applications of soothing gels have largely been ineffective. Recently, a breakthrough class of drugs in the fibroblast growth factor (FGF) family holds great promise in more effectively ameliorating or even preventing oral mucositis (OM). We report on the results of a Phase I trial with CG53135-05, a novel investigational protein therapeutic (FGF-20) that promotes epithelial and mesenchymal cell proliferation in vitro and has demonstrated activity in animal models. 14 patients (ages 25–75) undergoing HDCT with PBSCT were treated with escalating doses of study drug, including 0.1 mg/kg, 0.2 mg/kg and 0.33 mg/kg (concentrations are determined by the UV method which are equivalent to 0.3, 0.6, and 1 mg/kg by the Bradford method previously used). Conditioning regimens used included melphalan (Mel 200), cyclophosphamide, carmustine and etoposide (CBV), carboplatin and thiotepa (CT), cyclophosphamide, etoposide and carmustine (CEC) and busulfan/cyclophosphamide (targeted BuCy). The primary objective of this phase I trial was to evaluate safety, tolerability and pharmacokinetics of CG53135-05. Patients (pts.) were also scored daily for presence of OM using both the WHO and OMAS (oral mucositis assessment scale) grading scales. 7/14 pts. in this study experienced no OM (including 2 Mel 200 patients), 5 pts. experienced only grade 1 OM. while 2 pts. (both treated with Mel 200) experienced grade 3 OM, and no pts. experienced grade 4 OM. 1 pt. experiencing grade 3 OM required TPN. Only 4 pts. experienced diarrhea that lasted more than 4 days and only 1 pt. had gut mucositis-associated (E. coli) bacteremia. The median day of engraftment (ANC〉500/uL) occurred on day 14 (range: day 11–19). Patients tolerated the study drug well with no significant side effects up to a dose of 0.33 mg/kg. At that dose, 2 pts. experienced an infusional reaction consisting of fevers, nausea, and mild hypotension. Pharmacokinetics were measured at all dose levels and will be presented. CG53135-05 is a member of a breakthtrough drug class (FGF family) that was well tolerated in autologous stem cell transplant patients at doses up to 0.33 mg/kg with apparent clinical effects in ameliorating or preventing OM - 12/14 pts, thus, avoided severe (grades 3–4) mucositis following HDCT. A larger Phase II clinical trial is planned.

Description: Autologous peripheral blood stem cells are harvested and cryopreserved for weeks to months or even years in advance of the autologous peripheral blood stem cell transplant (PBSCT). The stem cells are cryopreserved in dimethyl sulfoxide (DMSO), a cryoprotectant agent that prevents ice crystals from forming and puncturing the stem cell membranes during the freezing process. Infused with the thawed cells, the DMSO can cause nausea and vomiting, headaches, seizures, renal insufficiency and stem cell death. We report on the results of 103 consecutive PBSCT, in which the DMSO was washed out before reinfusion. Viability, CD 34+ cell recovery as well as clinical endpoints such as time to engraftment (neutrophil and platelet counts) and infusion reactions for the 103 cases were assessed. The cryoprotectant solution used consisted of either 10% DMSO or a combination of 5% DMSO with 6% Hydroxyethyl starch. The stem cells were frozen using a rate-controlled freezer (Cryomed™ 1010) to −180°C and then stored in the liquid phase of liquid nitrogen (kept at approximately −190°C) for up to 4.7 years (mean duration of 42 days) following collection. The sample was thawed rapidly in a 37°C water bath and then washed manually with a washing solution of 0.9% Normal Saline (NS) and 10% anticoagulant citrate dextrose solution. After the sample was resuspended, it was centrifuged (RC-3, Sorvall™) and then suspended again in NS before infusion. Endpoints examined included CD 34+ cell recovery, viability, infusion reactions, and febrile episodes within 24 hours post-infusion, time to engraftment of platelets and neutrophils, highest serum creatinine (Cr) within 4 days following the transplant, and length of hospital stay. Automated WBC differentials were performed on a Beckman Coulter™ AcT Diff Analyzer and manually (when the WBC count was 〈 1000), using Turk’s solution and a hemocytometer. Viability was assessed by exclusion of 2% Trypan blue solution. Mean CD 34+ cell recovery and viability were 85.4% and 79.38%, respectively. The mean serum Cr was 1.1. Time to neutrophil recovery was at day 12.4 (neutrophil count of 500 /uL) and platelet engraftment (defined as a platelet count of 20,000 /uL for three consecutive days without transfusion) was 14.9. Only 21% of patients experienced reactions during infusion, which included chills/rigors (9), fever (6), nausea/emesis (6), diarrhea (1), unusual body tightness or pain (3). There was also a case of mild hypotension during the infusion. 35 patients experienced neutropenic fevers during the 24-hour period post-infusion. All patients engrafted. Mean length of hospital stay was 19.4 days. In this study, fewer than 22% of the cases of PBSCT experienced infusion-related reactions. Most of these reactions were comparatively minor (chills/rigors). The percent CD 34+ cell recovery and viability were only slightly lower than historical infusions - done immediately after thawing, without washing out the DMSO. The data suggest that DMSO can be washed out of the stem cell product without notable loss of CD 34+ cells or a drop in their viability. Many DMSO-related side effects are, thus, eliminated.

Description: Standard stem cell mobilization regimens for multiple myeloma patients include G-CSF alone or in combination with high dose cyclophosphamide. Given the known in vitro and in vivo synergy between alkylating agents and proteosome inhibitors, we sought to optimize the potential for concurrent cytoreduction by adding bortezomib to the mobilization regimen. Five evaluable patients, whose prior therapy consisted of six cycles of a 21-day treatment with bortezomib/dexamethasone +/− pegylated liposomal doxorubicin, were mobilized. They received IV push bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 in combination with high-dose cyclophosphamide at 3mg/m2 and MESNA on day 8. G-CSF was given for 10 consecutive days starting on day 9. One patient began this regimen in nCR, two were in PR, and two were in CR by urine and serum immunofixation and bone marrow evaluation. Stem cells were easily harvested from each of the five patients. The number of CD34+ cells collected far exceeded the amount normally mobilized with cyclophosphamide and/or G-CSF alone, with four out of 5 patients collected in a single day. The two patients who began the mobilization cycle in PR continued to respond positively. Their protein levels dropped an additional 8.9 and 14.6 percent respectively during the last cycle. The patient who began mobilization in nCR achieved a CR by the end of treatment. Some expected toxicities associated with high dose cyclophosphamide and G-CSF occurred. All patients experienced grade 3 and 4 cytopenias, however, they recovered and were able to continue on to transplant. Serious adverse events of grade 3 chest pain (non-cardiac), grade 4 pneumonia, and grade 4 febrile neutropenia also occurred. Bortezomib in addition to high dose cyclophosphamide followed by G-CSF is a novel, well-tolerated and efficacious combination for stem cell mobilization in patients with multiple myeloma. This regimen not only yields a high number of stem cells within a short collection time, but may further cytoreduce disease as well. Stem Cell Collection Patients Days Required for Collection CD34+ Stem Cells (million/kg) 1 1 21.2 2 1 47.4 3 1 22 4 1 17.9 5 4 40.6

Description: Background Bu-based conditioning regimens are commonly used prior to autologous hematopoietic stem cell transplantation (ASCT) for lymphoma, but clinical results of an intravenous (IV) Bu-based regimen have been limited to single center studies. This multi-center, single-arm, Phase 2 study prospectively evaluated the safety and efficacy of the IV BuCyE regimen in lymphoma patients undergoing ASCT. Methods The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), transplant-related mortality (TRM) and overall response rate. TRM was defined as a death after transplant due to any cause other than disease progression. Subjects underwent first ASCT for Hodgkin lymphoma (HL) and B-cell non-Hodgkin lymphoma (NHL) that relapsed after initial therapy, was initially refractory to an anthracycline-based chemotherapy, or for high-risk NHL histology in first complete remission (CR) [International Prognostic Index (IPI) score of 4-5, or mantle cell lymphoma (MCL)]. Eligible subjects achieved CR or partial remission (PR) following salvage chemotherapy. The study initially enrolled subjects of 18-80 years, but the protocol was amended to reduce the upper age limit to 65 years due to a high TRM rate at post-transplant 100 days for the subjects 〉65 years. Therefore, we report safety for all the subjects undergoing ASCT (n=203) and efficacy from those 65 years old or younger (n=186). IV Bu doses were individually adjusted based on pre-conditioning test PK results; the area under the concentration-time curve of Bu was targeted to 20,000 mM*min. Bu was given as a 3-hour infusion once daily from Days -8 through Day -5. E (1.4 g/m2) was administered on Day -4, followed by 2.5 g/m2/day of Cy on Days -3 and -2. Results A total of 207 subjects with HL (n=66) or NHL (n=141) were enrolled from 32 centers in the US and Canada between February 2010 and April 2012. Four subjects did not proceed with ASCT due to insurance or eligibility issues; the remaining 203 underwent ASCT. The final TRM rates at Day 100 for all subjects (n=203), for those older than 65 year old (n=17), and for those 65 years old or younger (n=186) were 4.5% (95% confidence intervals (CI) 2.1-8.3%), 23.5% (95% CI; 6.8-49.9%) and 2.7% (95% CI: 0.9-6.2%), respectively. The most common grade (Gr) 3 or 4 adverse events (CTCAE v3.0) observed from Day -8 through Day 100 were febrile neutropenia (Gr 3: 58.1%; Gr 4: 3.0%), stomatitis (Gr 3: 40.9%; no Gr 4), nausea (Gr 3: 8.9%; no Gr 4), and hypophosphatemia (Gr 3:6.9%; Gr 4: 1.0%). There was no instance of seizure or hepatic veno-occlusive disease (VOD) meeting the Baltimore criteria. Efficacy was analyzed for 186 subjects ≤65 years old with HL (n=65) or NHL (n=121), which included diffuse large B-cell lymphoma (DLBCL; n=63), MCL (n=29) and follicular lymphoma (FL; n=23). The median age was 49 year old (range: 19-65); 36 % were female, 87% were white, 76% had a Karnofsky Score ≥90. Majority of the patients had CR2 or higher, or PR at transplant except that 19 MCL patients and three DLBCL patients with IPI score 4 had CR1. In addition, five patients (3 for NHL; 2 for HL) who had refractory disease to initial chemotherapy and required salvage therapy to achieve CR1 also enrolled this study. With median 20 months follow-up, the estimated 2-year PFS was 33% for HL and 58%, 77%, and 43% for DLBCL, MCL, and FL respectively [Fig. 1]. The estimated 2-year OS was 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL respectively [Fig. 2 ]. Conclusions IV BuCyE regimen provided good early disease control with acceptable safety profiles in B-cell NHL lymphoma patients 65 year old or younger, but there were early declines in PFS in HL patients. Additional comparisons of PFS and OS from the BuCyE regimen with a pre-specified, matched-control group of approximately 800 matched cases (1:4 ratio) obtained from the Center for International Blood and Marrow Transplant Research registry data who received carmustine, E, cytarabine, and melphalan (BEAM) conditioning regimen are underway, and updated results will be presented. Disclosures: Off Label Use: Busulfan, Cyclophosphamide and VP-16 for Autologous Hematopoietic Stem Cell Transplantation. Costa:Otsuka: Research Funding. Freytes:Otsuka America Pharmaceutical: Research Funding, Travel funds for scientific presentation Other. Armstrong:Otsuka: Employment. Smith:Otsuka Pharmacetical Development & Commercialization: Employment. Elekes:Otsuka Pharmaceutical: Employment. Kato:Otsuka Pharmaceutical Development & Commercialization, Inc: Employment.

Description: Haplo cord transplant combines an umbilical cord blood unit (CBU) graft with a CD34 selected adult haplo-identical graft for the purpose of establishing long term CBU chimerism, which occurs in most but not all cases. Previously we showed that excessive haplo CD34 doses impair CBU engraftment (Liu et al, Blood 2011). Since then we have utilized a fixed haplo CD34 dose of 5x106 CD34 cells/kg. We also conducted a prospective study of CBU threshold dose de-escalation and established a minimum CBU dose of 1.2 x106 TNC/kg as the threshold for further study (van Besien ASH 2014, 1093). Here- using the patients from our prospective study- we sought to identify additional predictors of CBU engraftment as measured by percentage of CBU chimerism in CD33 and CD3 lineages in patients engrafted and in remission by day 56. We focused on d56 chimerism because durable patterns of chimerism are established by then. 83 pts were enrolled, but 23 were excluded from analysis because of early death (6) relapse before day 60 (8), failure of both grafts with residual MDS (4), lost to follow up (1) and no chimerism measurements (3). 61 pts were analyzed with median age 62 (18-72 years), 41 AML/MDS, 12 NHL, 5 ALL and 4 others. 24 had ASBMT high risk, 13 intermediate and 23 low risk disease. Conditioning was Flu Mel ATG (n=46), Flu Mel TBI 400 ATG (n=14) and Flu Mel TBI 600 ATG (n=1). All pts received GVHD prophylaxis with tacrolimus until d 180 and mycophenolate until d 30. The haplo dose was fixed at 5 x 106 CD34 cells/kg. Donors targeted by recipient donor specific antibodies (DSA) were avoided if possible. CBU units were selected based on HLA matching in sequential cohorts of decreasing threshold cell dose. Coh 1(n=12), minimum 2.0 x106 TNC/kg, coh 2 min (n=14) 1.5 x106 TNC/kg, coh 3 (n=25) min 1.0 x106 TNC/kg. After min cell dose was established, further enrollment occurred with a min dose of 1.2 x106 TNC/kg (coh 4 n=10). Median CBU TNC across all cohorts was 2.27 x107/kg (1.0-8.3). CBU were matched (HR HLA) at 3/8 (n=1), 4/8 (n=7), 5/8 (n=18), 6/8 (n=14) 7/8 (n=16) and 8/8 (n=5). DSA against CBU were present in 7. Haplo graft was 4/8 (n=42), 5/8 (n=13), 6/8 (n=3) and 7/8 (n=3). DSA against haplo were present in 6. Median follow up for survivors is 16 mo (5 -34). Cord graft characteristics, matching, enrollment cohort, nor presence of DSA were associated with d56 CBU chimerism. There was a strong inverse association between degree of matching of the haplo donor and d56 CBU (Fig 1). 54 pts with ≤ 5/8 haplo HLA match had 68% d56CD33 UCB chimerism vs 14% for the six pts with 6/8 or 7/8 HLA match (p=0.004). There was also a significant association between use of TBI and cord blood engraftment. 15 pts who received TBI had 79% d56CD33 UCB chimerism vs 50% for the 46 pts without TBI (p=0.05). Decreasing d56UCB chimerism was strongly associated with cumulative relapse risk (Fig 2A). It was not associated with TRM. The associations were even stronger if only considering AML/MDS (Fig 2B). Best discrimination was with 40% CD33 and 80% CD3 (Table 1). Table 1. Relapse rate at one year Day 56 CD3 80% (39) p value CD3340% (42) p value All pts n= 61 47% 21% 0.006 52% 19% 0.0008 CD3 80% (26) p value CD3340% (28) p value AML/MDS n=41 60% 14% 0.0003 58% 16% 0.00007 Conclusions: The establishment of a durable cord blood graft is heavily influenced by HLA matching of the haplo-graft. 6/8 and 7/8 HLA-matched haplo-graft which occur by chance in about 10% of cases, should probably be avoided. More intensive conditioning with the addition of low dose TBI may further favor establishment of the cord blood graft. Cell dose or HLA matching of the cord blood graft has less effect on its long-term establishment. Increasing cord blood chimerism is associated with a much reduced risk of relapse despite- not shown here- very low rates of chronic GVHD). Low levels of cord blood chimerism are associated with very high rates of relapse. These data provide further support for the GVL effects of CBU grafts, particularly in AML/MDS. Figure 1. Relation between Haplo Graft Matching and d56 CD33 CBU chimerism Figure 1. Relation between Haplo Graft Matching and d56 CD33 CBU chimerism Figure 2. Relapse Rate in All patients (A) and AML/MDS (B) based on d56 CD33 chimerism ≥40% vs

Description: Abstract 2258 Background: Prior use of lenalidomide beyond 6 cycles of therapy in the treatment of multiple myeloma (MM) has been shown to negatively impact stem cell yield, but this phenomenon can be overcome with the addition of high-dose cyclophosphamide to standard G-CSF mobilization. We hypothesized that the use of plerixafor (Mozobil®) would compare similarly to chemotherapy in rescuing the ability to collect stem cells in lenalidomide-treated myeloma. Methods: We performed a retrospective study comparing the efficacy of plerixafor + G-CSF mobilization (PG) to chemotherapy + G-CSF (CG) (either high-dose cyclophosphamide at 3g/m2 or DCEP [4-day infusional dexamethasone/ cyclophosphamide/ etoposide/cisplatin]) in 49 consecutive stem cell collection attempts in patients with MM exposed to prior lenalidomide. The primary endpoint was the ability to collect sufficient stem cells for at least two transplants (minimum 5×106 CD34+ cells/kg), comparing results in terms of total exposure to lenalidomide and time elapsed from lenalidomide exposure until the mobilization attempt. The secondary endpoint was number of apheresis days required to meet collection goal. Resilts: Twenty-four patients underwent PG mobilization and twenty-five with CG (21 with G-CSF + cyclophosphamide, 4 with G-CSF+DCEP). The two groups did not differ in terms of total amount of lenalidomide exposure: median number of lenalidomide cycles for patients mobilized with PG was 6.5 (range 1.2–86.6), vs. 6 (range 2–21.6), for patients mobilized with CG (P = 0.663). The median time between mobilization and last lenalidomide dose was also similar between the two groups: 57.5 (range 12–462) days for PG vs. 154 (range 27–805) days for CG (P = 0.101). There was an equivalent rate of successful collection of 100% for PG and 96% for CG, P = 0.322. One patient failed collection in the CG group due to emergent hospitalization for septic shock during a period of neutropenia; no patient collected with PG had a serious adverse event that interrupted the collection process. Stem cell yield did not differ between the two arms (13.9 vs. 18.8 × 106 million CD34+ cells/kg for PG vs. CG respectively, P = 0.083). Average time to collection goal was also equal, with a median of time of 1 day required in both groups, (range 1–2 days for PG, 1–5 days for CG, P = 0.073). There was no relationship between amount of lenalidomide exposure and stem cell yield with either PG (P = 0.243) or CG (P = 0.867). Conclusion: A plerixafor + G-CSF mobilization schedule is equivalent in efficacy to chemotherapy + G-CSF in obtaining adequate numbers of stem cells for two autologous stem cell transplants in patients with MM exposed to lenalidomide; however, PG may be a less toxic approach than chemomobilization. Number of lenalidomide cycles has no impact on chances of stem cell collection success using either method. Disclosures: Mark: Celgene Corp: Speakers Bureau; Millenium Corp: Speakers Bureau. Zafar: Celgene Corp: Speakers Bureau. Niesvizky: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding.

Description: Introduction: Stem cell transplant (SCT) is a curative therapy for several advanced hematologic malignancies. In the peri-transplant period, red blood cell (RBC) and platelet (PLT) transfusions are often necessary until engraftment. Time until transfusion independence (TI) is influenced mainly by time to engraftment. Haplo-cord (HC) transplant combines an umbilical cord blood unit graft with a CD34 selected adult haplo-identical graft for the purpose of establishing long term cord engraftment. No prior studies have compared TI between HLA matched related donors (MRD), unrelated donors (MUD) and HC allotransplant recipients. Methods: Patient demographics, ASBMT disease risk classification, relapse and mortality data for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) patients undergoing MRD, MUD, and HC SCT between 1/2012-1/2015 were included. Time until TI for RBC and PLT was defined as the day of the last transfusion with no transfusions in the following 30 days (d). The cohorts were followed for 180d post-transplant. Kaplan-Meier survival method was used to compare time until RBC and PLT transfusion independence between different transplant types and ASBMT risk categories. Data were censored on disease relapse or death. Log-rank test was used to compare the survival probabilities. Statistical analyses were performed using SAS 9.4.0 (SAS Institute, Cary, NC). Results: A total of 194 AML/MDS patients received MRD (n=63, 32%), MUD (n=76, 39%), and HC (n=55, 28%) SCT. TI was achieved for RBC transfusion in 84%, 74%, and 67% of patients, and for PLT transfusion in 84%, 91%, and 85% of patients for MRD, MUD, and HC respectively. The time to attain RBC and PLT TI was not statistically different between HC and MUD transplants (log-rank p=0.16 and 0.09 respectively) (Fig. 1: A, C). Within the ASBMT high risk strata, no statistical differences in the time to attain RBC (log-rank p=0.15) and PLT (log-rank p=0.55) TI between any transplant types could be detected (Fig. 1: B, D). Conclusion: Recipients of SCT often have substantial transfusion requirements. No statistically significant difference in time to TI was seen between HC and MUD recipients. No statistically significant differences in time to TI were seen between HC, MUD and MRD recipients in the ASBMT high risk strata. Time until transfusion independence in haplo-cord transplant is comparable to matched unrelated stem cell transplant. Figure 1. Figure 1. Disclosures van Besien: Miltenyi Biotec: Research Funding.