ALBERT

Description: The optimal source of donor hematopoietic stem cells (HSC) is controversial. Granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood (G-PB) has replaced bone marrow (BM) as the most common allograft source in adults but is associated with donor morbidity and higher rates of chronic graft versus host disease (GVHD) compared to BM. The CXCR4 antagonist plerixafor (Px) mobilizes HSC into the PB (Px-PB) faster than G-CSF and preliminary data suggest both quantitative and qualitative differences in allograft content that may impact clinical outcomes. We sought to assess the efficacy and safety of transplanted allografts collected following mobilization with Px alone in HLA-identical sibling transplantation. This was a Phase II, two-strata, multi-center prospective trial (NCT01696461) to evaluate Px-PB allografts prior to reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) based hematopoietic cell transplantation (HCT). Patients aged 18-65 years with an HLA-ID sibling donor and a hematological malignancy suitable for HCT were eligible. The primary objective was to determine the proportion of donors whose cells could be successfully mobilized and collected with a sufficient CD34+ cell dose using Px as the sole mobilizing agent. Px mobilization was considered successful if ≥ 2.0x10^6 CD34+ cells/kg recipient weight were collected in no more than two leukapheresis (LP) collections. All donors receiving Px were included in the analysis of the primary objective based on the intention-to-treat principle. Secondary objectives included the incidence of acute and chronic adverse events in donors, rates of hematopoietic engraftment, donor chimerism, rates of acute and chronic GVHD, non-relapse mortality (NRM), progression free survival (PFS) and overall survival (OS) for the recipients. From July 2013 to December 2014, 64 donor/recipient pairs were enrolled at 12 centers. Donors received Px at 240μg/kg subcutaneously 4 hours prior to LP. LP was performed processing at least 4X blood volume for up to two consecutive days (a third day was allowed for low CD34+ cell yields after 2 LP procedures) to achieve a target CD34+ cell dose of ≥ 4.0 x 10^6/kg recipient weight with a minimum goal of ≥ 2.0 x 10^6/kg. All allografts were cryopreserved. GVHD prophylaxis included cyclosporine or tacrolimus in combination with methotrexate, mycophenolate mofetil, or sirolimus. G-CSF was given routinely post HCT only to MAC recipients. Patient demographics are provided in Table 1. The median donor age was 56 years (18-65). 64% of the donors were male. Donors underwent one (23%), two (72%), or three (5%) LP procedures. 63 of 64 (98%) donors achieved the primary objective. The median total CD34+ cell dose/kg recipient weight collected within 2 days was 4.6 (0.9-9.6). Maximal donor toxicity following Px injection and LP was grades 0 (30%), 1 (52%), 2 (17%), and 3 (2%). Bloating, flatulence, abdominal pain, headache, paresthesisas, injection site reaction, and dizziness were the most commonly observed toxicities. Bone pain was not observed. The one grade 3 toxicity was a vasovagal episode felt related to LP and unlikely to Px. Toxicities typically resolved within a week of LP. The median follow up is 6.3 months. Median days to ANC (〉0.5 x10^9/L) and Platelet count (〉20 x 10^9/L) recovery were 13.5 (10-148) and 19 (1-76) after MAC and 14.5 (0-25) and 18 (0-141) after RIC, respectively. The cumulative incidence of acute GVHD grades 2-4 and 3-4 at day 100 were 47% (95% CI: 30-64) and 9% (95% CI: 2-22) after MAC and 19% (95% CI: 6-38) and 5% (95% CI: 0-18) after RIC. Probability of NRM at day 100 was 4% (95% CI: 0-13) and 0% after MAC and RIC, respectively. The probability of OS at day 100 was 97% (95% CI: 88-100) and 90% (95% CI: 78-98) after MAC and RIC, respectively. In conclusion, this is the first multi-center trial to demonstrate that as an alternative to G-CSF, Plerixafor rapidly, safely, and effectively mobilizes sufficient numbers of CD34+ cells from HLA-ID sibling donors for HCT following both RIC and MAC regimens. Engraftment was generally prompt and early results of secondary endpoints in recipients are encouraging. Longer follow-up and more extensive analysis of donor allografts and recipient outcomes will be presented at the time of the meeting. Research support was provided in part by Genzyme, a Sanofi Company. Table 1. Characteristics of recipients Table 1. Characteristics of recipients Disclosures Chen: Bayer: Consultancy, Research Funding. Devine:Genzyme: Research Funding.

Description: Abstract 4127 In the age of novel targeted agents, autologous stem cell transplant (ASCT) remains the standard of care for younger patients with newly diagnosed multiple myeloma (MM), offering similar treatment responses and overall survivals as standard chemotherapeutic agents but with the added benefit of a prolonged treatment-free period. Nevertheless, a standard of care for stem cell mobilization for ASCT has yet to be determined. Even in the era of new mobilization agents such as Plerixafor, Cyclophosphamide (Cy) and G-CSF combination remains the preferred mobilizing approach for patients with MM. Several studies have shown that Cy improves the stem cell yield at the expense of increased toxicity, but whether the administration of this chemotherapeutic agent pre-transplant has any impact on the long-term event-free and/or overall survival of myeloma patients remains controversial. In this study, we present a retrospective analysis of 186 patients with newly diagnosed MM who underwent ASCT with high-dose melphalan 200 mg/m2 (HDM) between December of 2000 and 2008 at our Institution. Eighty-three patients were mobilized with single agent G-CSF and 103 patients received high dose Cy (4 gm/m2) and G-CSF combination. Patient characteristics were similar between the treatment groups, including: age, gender, disease stage, and disease status prior to transplant. However, toxicity post-mobilization with Cy/G-CSF was significantly higher compared with G-SCF alone, including: febrile neutropenia (23%), hemorrhagic cystitis (8%), GI toxicity (57%), re-hospitalization due to complications and transplant delay (14%). The overall post-transplant toxicity was similar in the 2 groups, though the treatment related mortality was slightly higher in the Cy/G-CSF arm (4% versus 2%). Post transplant responses were not significantly different in the 2 groups, with 60% of patients achieving a VGPR or better after ASCT in the G-CSF group and 49% in the Cy/G-CSF group (p = 0.33). The median event-free survivals (EFS) for the Cy/G-CSF and G-CSF cohorts were 21.6 and 22.6 months, respectively, (p = 0.62) yielding no significant difference (Figure 1). Similarly, with a median follow up for surviving patients of 34.3 and 32.7 months, the median overall survivals were 68.2 and 62.3 months (p = 0.23) for the Cy/G-CSF and G-CSF cohorts, respectively (Figure 2). This retrospective analysis confirms that the addition of high dose Cy as part of the mobilizing regimen offers no improvement on the transplant outcome for patients with newly diagnosed myeloma and should therefore only be used in cases of difficult stem cell mobilization. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Despite a well-established risk of chronic kidney disease (CKD) in 20-30% of patients undergoing AlloHCT, the benefits of treating serious infections, such as cytomegalovirus (CMV), with nephrotoxic drugs often outweigh this risk. Given a lack of consensus on the optimal management of post-transplant Human-Herpes Virus 6 (HHV6) reactivation, our center has taken an aggressive stance toward screening for and treating HHV-6 viremia with foscarnet, a nephrotoxic drug with an unknown impact on long-term renal function. Methods: To clarify the impact of foscarnet exposure on long-term renal function after transplant, we conducted a retrospective cohort study of all adult patients who underwent AlloHCT at Duke from June 2002 - Feb 2016 (n=997). HHV6 viral loads were checked weekly for the first 90 days after umbilical cord blood and haploidentical transplants, and as clinically indicated (e.g. cytopenias, encephalopathy) in others. Foscarnet treatment for HHV6 viremia was given at the physician's discretion. Data were abstracted with a web-based clinical research query tool and manual chart review. Estimated glomerular filtration rate (eGFR) was calculated with the CKD-EPI equation based on repeated measures of serum creatinine (Cr) values at baseline, 90 days (n=839), 6 months (n=720), and 12 months (n=491) after transplant. Acute Kidney Injury (AKI) and Acute Kidney Failure (AKF) were defined as 2 and 3x baseline Cr, or 〉50% and 〉75% decrease in eGFR, respectively. Multivariate logistic regression was used to estimate the association of foscarnet exposure on the probability of 〉30% decline in eGFR at 90 days, 6 months, and 12 months after adjustment for confounders. Results: Of the 997 patients included in the study, 45% (n=448) were treated with foscarnet. Patients treated with foscarnet were slightly older (median age 52yrs vs. 49yrs), less likely to receive myeloablative conditioning, and more likely to be CMV positive, receive an alternative donor graft (umbilical cord blood or haploidentical), and experience acute GvHD. The most frequent indications for treatment were CMV (n=257, 57.4%) and HHV6 (n=140, 31.3%). In the first 90 days post-transplant, when most patients were treated with foscarnet, patients exposed vs. unexposed had similar rates of AKI/AKF: AKI 59.2% vs. 59.2%; p=0.99; AKF 26.1% vs. 27.3%; p=0.67. There was no difference in eGFR at 90 days, but patients treated with foscarnet had significantly lower eGFRs at 6 months and 12 months (Figure 1). There was a significant difference in the decline in eGFR from baseline to 12 months: median -29.1 (mL/min/1.73m2) (interquartile range (IQR) -50.8 to -10.7) vs. -22.2 (-37.4 to -7.4); p=0.002. After adjustment for age, race, acute and chronic GVHD, conditioning regimen, donor type, treatment with alemtuzumab, and HHV6 status, patients treated with foscarnet were more likely to experience a 〉30% decrease in eGFR from baseline to 12 months compared to those who were not (Odds Ratio 1.8 (95% CI 1.11-2.93); p=0.02). In this multivariate model, acute and chronic GVHD were not significant predictors of eGFR decline at 12 months. Unadjusted median survival was 11.9 months (95% CI; 10.1-14.0 months) and 20.8 months (95% CI; 15.8-25.4 months) for patients treated vs. not treated with foscarnet, respectively (p30% in eGFR are strongly associated with a 10-year risk of end-stage renal disease and mortality in 〉60% and 50% of patients in the general population, respectively, (Coresh, et al. JAMA 2014), this information should be considered as one weighs the risks vs. benefits of treating HHV6 viremia following AlloHCT. Disclosures Horwitz: Gamida Cell: Research Funding.

Description: Previously we have demonstrated that multiple myeloma cell lines and primary cells express CD52, the antigenic target of Campath-1H, and that they undergo apoptosis following treatment with alemtuzumab in-vitro (Gasparetto et al. ASH #3210,2002). Based on these observations, we initiated a clinical trial where patients with advanced, multiply relapsed MM were treated with subcutaneous (sc) alemtuzumab as a single agent. Nine patients (6 men/4 women, age range 45–69 yrs) were initially treated with the standard dose of 30mg sc three times per week for up to 12 weeks. All patients had at least 4 lines of prior therapy and 8/9 patients had undergone high dose chemotherapy followed by autologous peripheral blood stem cell transplant. Treatment related toxicities included pancytopenia in all patients with grade IV neutropenia in the first four patients, necessitating withdrawal from study. Subsequently, all patients were treated with G-CSF and aggressive transfusion support and no further patients were removed from study due to cytopenias. All patients were prophylaxed with Famvir, Fluconazole and Septra and no opportunistic infections were noted during treatment. Two patients developed acute renal insufficiency that reversed when alemtuzumab was discontinued. One patient completed the entire 12 weeks of treatment. One patient had a PR with a 40% reduction in M-protein after two months of treatment, which reversed once Campath-1H was discontinued. Pharmacokinetic studies of one patient demonstrated that it required 8–10 weeks of treatment using the sc protocol to achieve serum levels of alemtuzumab of 1ug/ml, the level considered to be tumoricidal in-vivo. Based on this observation, the treatment protocol was modified so that the initial week of escalating doses was given IV to achieve more rapid therapeutic levels. Following this, sc alemtuzumab was given as above. One patient with non-secretory multiple myeloma with relapsed disease following 5 prior lines of therapy has been treated with this modified protocol. Treatment with alemtuzumab and growth factor support in this patient has been well tolerated except for the development of RSV pneumonia. At 4 weeks, a PET scan demonstrated a significant overall decrease in metabolic activity in multiple bony areas consistent with a response to treatment. These initial results suggests that alemtuzumab is associated with significant toxicities in patients with advanced multiple myeloma including pancytopenia, infections and possibly renal insufficiency but all of these were reversible and have been minimized with aggressive prophylactic therapy. Alemtuzumab does appear to have modest activity against MM in this heavily pre-treated group suggesting that it should be explored in combination with other agents and at earlier stages of disease.

Description: Abstract 4048 Introduction: Chemotherapy + GCSF mobilization and GCSF alone are the most common mobilization regimens for autologous stem cell transplant (ASCT). We examined the benefits and limitations of both regimens in terms of mobilization success, predictability and costs. Methods: A retrospective, multi-center chart review was conducted of multiple myeloma (MM) and lymphoma patients mobilized between January 1, 2006 and December 31, 2007 for ASCT. Patients were excluded if they were mobilized with plerixafor (Mozobil®) or enrolled in a clinical trial of mobilization regimens. Data collected included demographics, disease and treatment history, mobilization regimen, blood counts, aphaeresis, remobilization, cells transplanted, time to engraftment and resource use. Stem cell collection practices and related clinical outcomes were analyzed separately for patients that were mobilized with chemotherapy + GCSF vs. GCSF alone. Resource use was evaluated using US unit cost data. Results: Data were collected for 227 consecutive patients from 11 centers (143 patients that received a chemotherapy + GCSF mobilization regimen and 84 patients who received GCSF alone). Total cells collected were significantly higher in the chemotherapy + GCSF mobilization group compared to GSF alone (18.6 × 106/kg vs.7.0 × 106/kg, p

Description: Key Points NOTCH2 activation confers a marked increase in BCR responsiveness by cGVHD patient B cells that associates with increased BLNK. ATRA increases the IRF4-to-IRF8 ratio and blocks aberrant NOTCH2-BCR activation without affecting cGVHD patient B-cell viability/function.

Description: Abstract 3466 Donor cell leukemia (DCL) in the setting of bone marrow/hematopoietic stem cell transplant (HCT) has not been well characterized. We analyzed 9 cases of DCL and performed a literature review (table). The indications for transplant and subtypes of DCL are shown (table). The 6 myelodysplastic syndrome (MDS) cases included 1 case of refractory cytopenia with multilineage dysplasia (RCMD), 2 cases of refractory anemia and 3 cases which were unclassifiable. Conventional cytogenetic analysis was performed on all 9 cases of DCL (table). All 9 cases had engraftment studies performed either by short tandem repeat analysis (3) or FISH analysis for donor gonosomal complement (6) when DCL was diagnosed. Seven cases had either engraftment studies or cytogenetic analysis performed periodically after HCT to test the donor cell engraftment and engraftment was confirmed in all. FISH analysis for monosomy 7, del(7q) and del(5q) was retrospectively performed on preserved donor cells in 4 cases after DCL was diagnosed. A low level of abnormalities was observed in preserved donor cells for the cases with del(7q) (2.9%) and del(5q) (8.2%). The 2 cases of AML received chemotherapy. Of the MDS cases, 2 received donor cell infusion, 1 received 6 cycles of revlimid, and 3, along with the case of CLL, received either supportive therapy or were simply observed. Six cases have clinical follow up ≥ 5 months and of these, 1 died of disease (AML) while the other 5 are alive, including 4 MDS and the 1 CLL. The disproportionate detection of DCL in sex mismatched HCT suggests a probable under-detection in the sex-matched population. In our analysis, the interval between HCT and diagnosis of DCL (table) falls within the range of currently reported cases. When stratified by type of DCL, the T-LGL group demonstrates presentation significantly earlier than other groups (Fig. A), indicating pathogenesis of T-LGL may involve a distinct pathway. When stratified by types of primary disease, the interval of the neoplastic group is shorter than that of benign group (Fig. B), implying that pre-HCT treatment may play a role in the pathogenesis of DCL. When stratified by stem cell sources, UCB group shows shorter latency than the other sources (Fig. C), suggesting a higher risk of DCL in this cell source. The low level cytogenetic abnormalities of preserved donor cells in our series and the longer latency of the benign group suggest that donor cells with an intrinsic defect may be predisposed to evolve into DCL. Total cases (%) Reported cases (%) Current cases (%) Number of cases 83 74 9 Age (years)     Median/range 37.0/3~70 36.0/4~62 53.0/3~70 Gender     Male 43 (52.4) 38 (52.0) 5 (55.6)     Female 39 (47.6) 35 (48.0) 4 (44.4) Primary disease     Neoplasms 76 (91.6) 67 (90.5) 9 (100)     Non-neoplasms 7 (8.4) 7 (9.5) 0 (0.0) Donor     Related 59 (72.0) 54 (74.0) 5 (55.6)     Unrelated 23 (28.0) 19 (26.0) 4 (44.4)     Sex-matched 28 (34.6) 27 (37.5) 1 (11.1)     Sex-mismatched 53 (65.4) 45 (62.5) 8 (88.9) Donor cell source     BM 48 (63.2) 44 (65.7) 4 (44.4)     BHSC 16 (21.0) 13 (19.4) 3 (33.3)     UCB 12 (15.8) 10 (14.9) 2 (22.2) 2nd neoplasm (DCL)     AML 31 (37.4) 29 (39.2) 2 (22.2)     MDS/MPN* 27 (32.5) 21 (28.4) 6 (66.7)     ALL 20 (24.1) 20 (27.0) 0 (0.0)     T-LGL 4 (4.8) 4 (5.4) 0 (0.0)     CLL 1 (1.2) 0 (0.0) 1 (11.1) Interval (months)     Median/range 24.0/1~312 24.0/2~312 26.0/1~193 Cytogenetics     Normal 21 (28.0) 20 (30.3) 1 (11.1)     Abnormal 54 (72.0) 46 (69.7) 8 (88.9)     -7 or del(7q)** 15 (27.8) 10 (21.7) 5 (62.5)     +8** 2 (3.7) 2 (4.4) 0 (0.0)     Del(20)** 4 (7.4) 2 (4.4) 2 (25.0)     Del(5q)** 2 (3.7) 1 (2.2) 1 (12.5)     11q23** 3 (5.6) 3 (6.5) 0 (0.0) Other abnormalities** 28 (51.9) 28 (60.9) 0 (0.0) Follow up (months)     Median/range 8.5/1~108 9.0/1~108 6.0/1~68     Died of disease 28 (46.7) 27 (52.9) 1 (11.1) DCL, donor cell leukemia; BM, bone marrow; BHSC, blood hematopoietic stem cells; UCB, umbilical cord blood; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; ALL, acute lymphoblastic leukemia (including B-cell and T-cell ALL); T-LGL, T-cell large granular lymphocyte leukemia; CLL, chronic lymphocytic leukemia. All the numbers represent the cases with data available. * One case of myeloproliferative neoplasm is included in this category. ** The percentage is calculated using number of total cytogenetic abnormalities in each column as denominator. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2012 High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) remains a valid treatment option for patients with multiple myeloma (MM). HDC has improved response rate, event-free survival (EFS) and treatment free interval for patients with MM when compared with conventional chemotherapy. To date, Melphalan 200 mg/m2 (HDM) remains the standard ASCT preparative regimen as no other regimens have demonstrated improved outcomes with acceptable toxicity. Nevertheless, relapse remains inevitable with this approach prompting continued search for better therapies. To overcome resistance and early relapse we used a more aggressive alkylator based conditioning regimen. Here we summarize a retrospective study of the long-term follow-up of newly diagnosed MM patients treated with the preparative regimen Carmustine, 500 mg/m2 and Melphalan, 200 mg/m2 (BCNU/HDM) followed by ASCT versus a subsequent group of patients treated with HDM alone and ASCT. Methods: Between November of 1997 and December of 2008, 207 patients with MM underwent HDC followed by ASCT at our Institution, using either BCNU/HDM (n = 104, treated between 1997–2002) or HDM (n = 103, treated between 2002–2008) as the preparative regimen. Presenting patient characteristics were similar (age, gender, MM type, hemoglobin, creatinine, calcium, plasma cell infiltration, Durie-Salmon stage, and ISS stage). Patients treated with BCNU/HDM were diagnosed preceding the introduction of novel anti-MM agents such as thalidomide, lenalidomide, and bortezomib and thus did not receive these as induction therapy, while HDM patients received various combinations of novel agents as induction therapy. Results: With a median follow-up for surviving patients of 96 and 34 months for the BCNU/HDM and HDM cohorts, respectively, the event-free survival (EFS) was significantly increased with the BCNU/HDM conditioning regimen (41.7 months) as compared with the HDM regimen (21.6 months, p = 0.013) (Figure 1). Median overall survival (OS) was 83.1 months with BCNU/HDM vs. 68.2 months with HDM (p = 0.359 at current follow-up) with 34% of BCNU/HDM patients alive at 〉10 years (Figure 2). In the BCNU/HDM group, 47/104 patients achieved ≥VGPR and this subgroup had a median OS of 103 months. Nineteen patients in the BCNU/HDM group are ≥7 years from ASCT and 18 (17%) have never required treatment for progressive disease. Engraftment and transplant-related mortality were similar in both groups (3% TRM in the BCNU/HDM and 4% TRM in the HDM arm). The BCNU/HDM group had a higher incidence of pneumonitis (50%) vs. the HDM group (15%) but this was managed with short courses of steroids and was never fatal. Focusing on the subgroup of patients who proceeded to transplant immediately after only 1 induction course, the median OS was 103 months for the BCNU (80 patients) containing arm versus 69 months for the HDM (71 patients) arm (p=0.085), suggesting a clear trend further favoring this dose dense approach. Conclusions: EFS was superior with the BCNU/HDM regimen compared with HDM and a subgroup of patients treated with BCNU/HDM have achieved EFS 〉7 years without any additional therapy. Engraftment and treatment related mortality were similar in both groups despite advances in supportive care for the HDM group. Our findings suggest that BCNU/HDM should be compared in a randomized prospective fashion to HDM as an ASCT preparative regimen following optimal induction therapy with novel agents to determine whether this will lead to further improvements in EFS and OS following ASCT. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3523 A high graft failure rate and treatment-related mortality (TRM) have historically been major pitfalls of myeloablative adult umbilical cord blood (UCB) transplantation. The goal of this prospective clinical trial was to identify an approach that addresses both of these problems. There is compelling evidence that increasing cell dose with the use of two partially matched UCB grafts reduces the graft failure rate. While non-myeloablative preparative regimens reduce TRM, this comes at the cost of an increased risk of disease relapse. Therefore, there is continued clinical need for myeloablative conditioning regimens that exert potent antitumor activity and provide sufficient immunosuppression to facilitate engraftment of mismatched unrelated UCB grafts. The combination of total body irradiation (TBI) (1320cGy)/fludarabine (Flu)/cyclophosphamide (Cy) has been studied extensively by other groups. In this trial, we hypothesized that elimination of Cy would improve tolerability yet maintain comparable anti-tumor effects and engraftment potential. Methods: The conditioning regimen consisted of TBI 1350cGy and Flu 40mg/m2 × 4 days. Two cord blood units at least HLA 4/6 matched with the recipient (low resolution class I and high resolution class II), with a minimum cryopreserved cell dose of 1.5 × 106/kg were selected for transplantation. Tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis and G-CSF was administered until the neutrophil count exceeded 1000/mm3. Disease-free and overall survival was estimated using the Kaplan-Meier method. In the analysis of cumulative incidence of neutrophil and platelet engraftment, a competing event was defined as relapse or death without an event of interest, whereas in the analysis of relapse and acute and chronic GVHD, a competing event was defined as death without an event of interest. Relapse was defined as a competing risk in the analysis of TRM. The Wilcoxon signed rank test was used to evaluate the effect of cell dose on the sustained engraftment of a single cord unit. Results: 27 patients from 2 centers (Duke-24, UBC-3) with a median age of 33 (range, 20–58) years with hematologic malignancies were enrolled on the trial. Fifteen had AML (CR1-1 and CR2-14), five had ALL (CR1-2 and 2CR–3), three had MDS, one had CML, and three had NHL. The median combined total nucleated cell dose was 4.3 (range, 3.2–7.7) × 107/kg. The cumulative incidence of neutrophil engraftment (≥500/μl) was 80% (95% confidence interval (CI), 58–91%), with a median of 24 (range, 13–45) days. The cumulative incidences of platelet engraftment ≥20,000 and ≥50,000/μl was 76% (95% CI, 54–88%) and 68% (95% CI, 46–83%), respectively, and a median day of platelet engraftment ≥50,000/μl was 52 (range, 33–78). A single cord blood unit represented ≥79% of hematopoiesis by day 100. Higher cryopreserved and infused total nucleated cell dose and infused CD3+ cell dose were significant factors associated with the predominant UCB unit (P = 0.032, 0.020, and 0.042, respectively). Three patients experienced graft failure, and hematopoiesis was restored in two patients with either autologous or haploidentical hematopoietic stem cells. The cumulative incidences of grades II–IV and grades III–IV acute GVHD were 37% (95%CI, 20–55%) and 11% (95% CI, 3–26%), respectively and that of chronic GVHD was 31% (95% CI, 15–49%). With a median follow-up period of 23 months, the overall and disease-free survival rates at 2 years were 58% (95% CI, 34–75%) and 52% (95% CI, 29–70%), respectively. The 180 day and 2-year incidence of TRM was 19% (95% CI, 7–35%) and 28% (95% CI, 12–47%), respectively. The relapse rate at 2 years was 20% (95% CI, 7–37%). As an indicator of tolerability of this modified myeloablative regimen, we observed a cumulative incidence of total parental nutrition usage of just 56%. In conclusion, we find that the modified myeloablative regimen of TBI (1350cGy)/fludarabine provides dual cord blood engraftment rates comparable to more conventional myeloablative regimens. In contrast to other reports, we found that graft size predicts for the predominant UCB unit. This study supports the use of TBI 1350cGy/fludarabine as an alternative to conventional myeloablative conditioning for dual UCB transplantation and provides justification for larger studies. Disclosures: Off Label Use: Fludarabine; used as part of the stem cell transplant conditioning regimen. Chao:Genzyme: Research Funding. Horwitz:Genzyme: Honoraria, Research Funding.

Description: Abstract 2249 Background: Although high dose chemotherapy followed by autologous hematopoietic stem cell (HSC) transplantation is a potentially curative procedure for patients with hematologic and non-hematologic malignancies, a significant number are unable to mobilize sufficient cells to proceed to transplant. While the safety and efficacy of plerixafor + G-CSF is well established for front-line and salvage mobilization in patients with myeloma and lymphoma, data are limited for patients with non hematological malignancies. We now report on the safety and efficacy of remobilization with plerixafor + G-CSF in patients in this setting. Methods: This is a retrospective analysis of patients 〉18 years with non hematological malignancies enrolled in the US plerixafor compassionate use program (CUP). In the CUP, patients with previous mobilization failure (defined as the inability to collect ≥2 ×106 CD34+ cells/kg or achieve an adequate peripheral blood (PB) count, typically ≥10 CD34+ cells/μl) were remobilized with plerixafor + G-CSF with the goal of collecting 2 × 106 CD34+ cells/kg to proceed to transplant. G-CSF (10μg/kg SC) was given every morning for 5 days. Plerixafor (0.24 mg/kg SC) was given in the evening on Day 4, ~11 hours prior to apheresis the next day. Plerixafor, G-CSF and apheresis were repeated daily until patients collected ≥2×106 CD34+ cells/kg. Results: The analysis included 32 patients (median age 32.5 years) with germ cell tumor (n=21), medulloblastoma (n=4), sarcoma (n=3), breast cancer (n=2), cervical cancer (n=1) or chordoma (n=1). Previous mobilization regimens included growth factor alone in 22 patients and growth factor + chemotherapy in 10 patients; 25 patients failed to collect the minimum transplantable cell dose (median yield: 1.27 ×106 CD34+ cells/kg); 7 patients did not undergo apheresis due to low PB CD34+ cells. Remobilization with plerixafor + G-CSF resulted in a median yield of 2.8 × 106 CD34+ cells/kg; the median number of apheresis days was 2 (range 1–4). Twenty-two (69%) patients collected ≥2 × 106 CD34+ cells/kg; the median time to collect the target cell dose was 2 days (range 1–3 days). The median CD34+ cell yield for patients with germ cell tumors was 3.16 × 106 cells/kg. Twenty-four (75%) patients proceeded to transplant; 8/21 patients with germ cell tumors received tandem transplants. Median time to neutrophil and platelet engraftment was 11 and 20 days, respectively. Drug-related adverse events were observed in 12 (38%) patients; most were mild and commonly included injection site reactions (n=6), diarrhea (n=3), nausea (n=2) and bone pain (n=2). None of the patients experienced serious adverse events. Conclusions: Mobilization with plerixafor + G-CSF facilitates collection of an adequate number of HSC in the majority of adult patients with non-hematologic malignancies who have failed prior mobilization with growth factor ± chemotherapy. Using this salvage approach 75% of patients who otherwise would not have had the option could successfully undergo autologous transplantation. Disclosures: Horwitz: Genzyme Corporation: Honoraria, Research Funding. Off Label Use: Plerixafor (Mozobil®), a hematopoietic stem cell mobilizer, is approved by the US FDA in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. Huebner: Genzyme Corporation: Employment, Equity Ownership. Mody: Genzyme Corporation: Employment, Equity Ownership. Schriber: Genzyme Corporation: Speakers Bureau.