After a hospital‐wide formulary change resulted in the replacement of filgrastim with TBO ‐filgrastim for all on‐ and off‐label indications, we performed a retrospective comparison of patients with myeloma receiving 200 mg/m 2 melphalan with autologous hematopoietic stem cell transplantation to see whether the type of growth factor used post‐transplant made a difference. One hundred and eighty‐two consecutive patients with myeloma were studied, 91 receiving filgrastim immediately prior to the change and 91 receiving TBO ‐filgrastim afterward. The CD 34 + cell dose was comparable, as were other characteristics. Although the overall time to neutrophil recovery was similar for both groups, early engraftment (≤12 d) occurred more often (p = 0.05), and late engraftment (≥14 d) less often (p = 0.09) in filgrastim‐treated patients. The number of documented infections was significantly less in the TBO ‐filgrastim group. Day 100 mortality and hospital stay were similar for the two groups. These data indicate that there is no material difference between filgrastim and TBO ‐filgrastim in this clinical setting.

Growth factors are routinely used after autologous transplantation to shorten the duration of neutropenia. Tbo-filgrastim (TBO) was recently approved in the U.S. for patients with non-myeloid malignancies. The Average Wholesale Price for TBO is 20% less than Filgrastim (FGS). Whether TBO is comparable to FGS for reducing time to engraftment following HSCT is unknown. A cost-savings initiative was undertaken at Northwestern Memorial Hospital to substitute TBO for FGS in all autografts. Herein are the results of an observational study which compares TBO and FGS. FGS patients were treated from10/2013-4/14/2014 and TBO patients between 4/15/14-9/20/2014. All patients were treated for multiple myeloma with melphalan 200mg/m2. TBO and FGS were initiated day+5 after stem cell infusion, and discontinued the first day the absolute neutrophil exceeded 1000/ml. Time to engraftment was defined as the number of days from stem cell re-infusion until the first day the ANC exceeded 500cell/ml. TBO and FGS dose was rounded as follows: <80kg received 300mcg/day, >80mg<120kg received 480mcg and those >120kg received 600mcg/day. 96 consecutively treated patients were included-48 treated with TBO and 48 treated with FGS. No significant difference was observed for diagnosis, age, gender, weight, BSA, growth factor dose or dose/kg, number of stem cells infused, number of patients who developed febrile neutropenia or microbiologically proven infection or prolonged fever (>48 hours). Median time to engraftment and delayed engraftment (>14days) was significantly longer in the TBO-treated patients. There was no difference in overall length of stay or hospital mortality. TBO-filgastrim appears to be effective in reducing the time of neutropenia and stem cell engraftment. However delayed engraftment, especially as observed >14 days after stem cell infusion, was observed significantly more often in TBO treated patients compared to those treated with FGS. These results require confirmation through a large randomized trial.Table 1Filgrastim versus TBO-filgrastimCharacteristic (median/range)FilgrastimTBO-FilgastimP-valueNumber4848Age57(42-69)59(38-69)0.9299Gender (male/%)27(56)30(52)0.8395Weight (kg)76(47-120)84(50-160)0.1227Body surface area (adjusted)1.8(1.45-2.2)1.8(1.45-2.25)0.8755Melphalan dose (mg)365(290-440)365(290-45)0.99G-CSF dose(mcg/kg)389(300-600)413(300-600)0.2584Number of CD34 stem cell infused(million/kg)6.57(2.97-20.9)7.04(3.6-19.1)0.4621Documented infection (%)6(12.5)3(6)0.468Febrile neutropenia (%)27(56)20(41)0.2204Time to engraftment (days)12(9-23)13 (10-26)0.0338Engraftment > 14days (%)8(17)16(33)0.0521Total number of G-CSF doses (mean/days)9.42(6-24)9.8(5-24)0.5109Length of stay(days)16(13-51)16(12-27)0.4118Elevated temps(>100.5) for > 48 hours9(19)5(10)0.3864Hospital mortality010.99 Open table in a new tab

Background Allogeneic hematopoietic stem cell transplantation (HSCT) is an established therapy for malignant and nonmalignant hematologic disorders. Reduced-intensity conditioning (RIC) regimens have expanded the use of HSCT to elderly and higher risk patients. However, HSCT still remains associated with a significant mortality and morbidity and the careful assessment of risks and benefits before transplantation is essential. Major factors which influence non-relapse mortality (NRM) and overall survival (OS) after HSCT are diagnosis, type of transplant, remission status and the patient's risk profile, which includes age and presence of comorbidities. The use of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) has been proposed to predict the probability of NRM and OS following HSCT. However, the HCT-CI usefulness for older patients receiving a reduced intensity allogeneic HSCT remains unclear. Methods A retrospective medical record review was performed to collect data from patients who underwent an allogeneic HSCT at a large, urban, NCI Comprehensive Cancer Center during a five year period (January 2005 to December 2010). Patients 55 years and older who were transplanted using RIC for a hematologic malignancy were selected to be analyzed. Comorbidities and test results were collected to determine the HCT-CI score and other clinical data collected included disease and remission status at time of transplant. Results 85 patients aged >55 years old who received a RIC HSCT for hematologic malignancies between January 2005 to December 2010 were analyzed. The median patient age at the time of transplantation was 63 years (range: 55-75 years). The patient diagnoses included AML (39%), NHL (29%), MM (9%), MDS (11%), CLL (8%), ALL (4%). The median pre-transplantation HSCT-CI score was 2 (range: 0-9). Among 85 patients, OS at 2 years was 44%. The 2 yr OS was 31%, 37% and 44% in the low-, intermediate-, and high-risk HSCT-CI groups (p = 0.61), respectively. The corresponding NRM at 2 years was 25%, 17% and 18% (p = 0.91). We found no predictive value of HSCT-CI for either OS or NRM in older patients having an allogeneic HSCT with reduced-intensity condition. Stratification of age (55-59, 60-64, and 65+) showed no significant impact on 2 yr OS or NRM. However, there was a trend towards a better 2 yr OS for patients who had achieved a CR versus no CR at time of transplant (48% vs 41%). Conclusion Older patients with hematologic malignancies represent a highly selected cohort, with the prospect of an allogeneic HSCT often considered too high-risk. A method to reliably stratify these older HSCT candidates is greatly needed. However, the HCT-CI score in this retrospective analysis did not help predict their NRM or 2 year OS for patients 55 years and older with hematologic malignancies receiving a reduced intensity HSCT. Further research is warranted into what combination of factors may provide a reliable predictive score for older patients with hematologic malignancies. Disclosures: Mehta: Millennium: Speakers Bureau; Celgene: Speakers Bureau.

The optimal stem cell transplantation (SCT) conditioning therapy for relapsed/refractory non-Hodgkin lymphoma (NHL) is not clearly defined. In a retrospective analysis, we examined 25 patients with “high risk” relapsed/refractory NHL who received busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP16) conditioning with autologous or allogeneic SCT. The majority of patients had aggressive histology and 52% had primary refractory NHL. Furthermore, 48% of patients had chemotherapy-resistant disease at the time of SCT. Fifty-six percent of patients underwent allogeneic SCT, while 44% had autologous SCT. The median engraftment time for neutrophils and platelets was 13.5 and 14 days, respectively. The 100-day treatment-related mortality (TRM) was 16%, while the 2-year non-relapse mortality (NRM) rate was also 16%. At a median follow-up of 15 months, the estimated 2-year disease-free survival (DFS) rate was 64% (95% confidence interval (CI): 36%-82%) and the estimated 2-year overall survival (OS) was 69% (95% CI: 40%-86%). Furthermore, the 2-year disease-specific survival (DSS) rate was 73% (95% CI: 40%-90%). Using Cox proportional hazard modeling, the International Prognostic Index at time of relapse predicted DFS and OS. Altogether, Bu/Cy/VP16 was associated with early TRM; however, late toxicities (including NRM) were uncommon resulting in relatively good survival rates in a high-risk relapsed/refractory NHL population.

Abstract 4541 Background: Allogeneic stem cell transplant (SCT) is currently the standard of care in the consolidative treatment of several hematologic malignancies. Typically after a stem cell transplant the monocytes engraft first, followed by the granulocytes, macrophages and then natural killer cells. Lymphocyte recovery is considered to be an indicator of immune reconstitution during SCT and correlation between rate of recovery of lymphocyte count and patient outcome has been reported in patients after a myeloablative allogeneic transplant. Studies suggest that early lymphocyte recovery may be a predictive marker of engraftment and survival post-myeloablative SCT. However, there is minimal data on lymphocyte recovery after reduced intensity conditioning allogeneic SCT. We report our institutional experience on the correlation between rate of absolute lymphocyte recovery and survival in patients with a hematological malignancy after a reduced intensity conditioning allogeneic SCT. Methods: We performed a retrospective review of all adult patients who underwent reduced intensity conditioning chemotherapy followed by an allogeneic SCT at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University from March 2001 to March 2008. We looked at the post- allograft absolute lymphocyte count (ALC) at 3 different time points – day 15, 21 and 28. Patients were then analyzed based on ALC cutoff values of 200/mm3, 500/mm3 and 1000/mm3. For each of the cutoff values, patients were divided into 2 groups: those with absolute lymphocyte count of less than or equal to the cutoff value and those with ALC of greater than the cutoff value. Results: A total of 131 consecutive patients were included in the analysis; 46.6% were male and 53.4% were female. 51.1% patients underwent matched sibling (MSD) while 48.9% had matched unrelated donor (MUD) SCT. Overall survival was determined in 117 patients; 14 patients were excluded due to incomplete data. At day 15 and 28, patients with an ALC of greater 200/mm3 had a statistically significant overall survival compared to those that were less than 200/mm3, p= 0.016 and p=0.05, respectively. An ALC of greater than 1000/mm3 at day 15 seemed to predict for a worse outcome compared to those with an ALC of less than 1000/mm3 (p=0.008). There were however six times more people in the group with ALC less than 1000/mm3 at day 15, compared to those with ALC greater than 1000/mm3. An ALC of greater than or less than 500/mm3did not significantly appear to affect overall survival at any of the time points evaluated. Conclusion: ALC of greater than 200/mm3 at day 15 and 28 in our patient population appears to be predictive of overall survival after a reduced intensity conditioning stem cell transplant in patients with a hematological malignancy. However, the relationship between ALC and outcome is inconsistent and needs to be explored further in the context of other prognostic factors. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2028 Purpose: Current treatment of advanced stage cutaneous T cell lymphoma (CTCL) includes a number of chemotherapy agents which provide good response rates, but with often short duration. Hematopoietic cell transplantation (HSCT) has the potential to offer a durable remission due to graft-versus-lymphoma effect. We conducted a retrospective study to report the outcome of HSCT in patients with refractory CTCL. Methods: From Feburary 1997 through May 2012, twenty-one patients (22–65 yo) with advanced, refractory CTCL underwent HSCT from HLA-identical sibling (n=13), unrelated donor (n=5), umbilical cord (n=1), syngeneic (n=1) and autolougous (n=1) sources. There were 7 tumor stage MF, 6 Sézary syndrome, 2 erythrodermic MF, 1 folliculotropic MF, 1 aggressive CD8+ T cell lymphoma (Berti's type), 2 γ-δ TCL, 1 α-β TCL and 1 CD30-negative large cell peripheral TCL. The intensity of the conditioning regimen was conventional in 10 and reduced in 11. At the time of HSCT, the median disease duration was 5.4 years (1–17 y). Most patients were heavily pretreated, having failed a median number of four (1–9) lines of therapy. The stage of the disease at the time of HSCT was IIB (n=9), III (n=2), IVA (n=9), and IVB (n=1). Results: For the 21 patients evaluated there was a median follow-up of 62 months (3–186 mo). 11 patients had relapse post-transplant: 5 patients had an early relapse (<100 days) and 6 patients had a late relapse (>100 days). Relapsed disease appeared to be of a lower grade clinically than at pre-transplantation and responded to therapies they had previously failed. 1 early relapse died of disease (SS, auto-SCT) and 1 late relapse died of disease (γ-δ TCL, RIC allo-SCT). Of the nine remaining relapsed patients, 1 has died of a cerebral hemorrhage. (CD30-neg large cell peripheral TCL, alloSCT) and 1 of GVHD (γ-δ TCL, RIC allo-SCT). Of the 7 remaining relapsed patients, 4 went into CR with reduction of immunosuppression. 14 patients developed acute GVHD (fatal in 3), and 10 developed chronic GVHD. Of the surviving patients (n=15) all are in CR. Overall survival was 71%, with a median OS of 27.1 months (range, 0.5–185.9). Progression free survival (PFS) was 43% with a median PFS of 4.1 months (range, 0.5–80). Conclusions: Our results suggest that HSCT can induce durable clinical remissions in patients with refractory CTCL through graft-versus-lymphoma effect. Disclosures: No relevant conflicts of interest to declare.

Abstract 4499 Introduction Stem cell transplantation (SCT) has been shown to improve the outcome of non-Hodgkin’s lymphoma patients who fail to respond to initial therapy or have relapsed disease, but the optimal conditioning regimen prior to transplant has yet to be determined. Busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) conditioning prior to transplant has been investigated in non-Hodgkin’s lymphoma (NHL). We investigated the outcomes of patients treated with this conditioning regimen at the Northwestern University Robert H. Lurie Cancer Center. Methods A retrospective analysis of all relapsed/refractory NHL patients who received SCT from 3/2003–6/2011 at the Northwestern University Robert H. Lurie Comprehensive Cancer Center using Bu/Cy/VP-16 conditioning was performed. Detailed patient and disease-related characteristics were collected. Furthermore, we analyzed overall survival (OS), progression free survival (PFS), and disease free survival (DFS). Results We identified 25 relapsed/refractory NHL patients who received Bu/Cy/VP-16 conditioning with SCT. The median age of all patients was 49 (range: 28–71). Thirteen of 25 patients (52%) had allogeneic SCT (alloSCT) and 12/25 (48%) had autologous SCT (auSCT). Among the alloSCT, 10/13 (77%) were matched sibling donor (MSD), and 3/13 (23%) were matched unrelated donor (MUD). Six of 25 (24%) had low grade lymphoma (5 follicular, 1 marginal), 17/25 (68%) had aggressive lymphoma (9 diffuse large B-cell lymphoma (DLBCL), 1 chronic lymphocytic leukemia (CLL)/DLBCL Richter’s transformation, 2 DLBCL/follicular, 1 follicular large-cell (i.e., grade 3B), 3 mantle cell lymphoma (MCL), and 1 lymphoblastic lymphoma), and 2/25 (8%) had mixed NHL and HL disease. Of note, of the aggressive NHL patients, 13/17 (76%) had primary refractory disease or relapse less than 12 months after initial remission. The median number of prior therapies was 3 (range: 1 to 7). For all patients (n=25), median follow up time post-transplant was 12 months (range: 5 days–96 months). PFS for all patients was 71 ± 10 % (95% confidence interval (CI): 53–95%) (Figure 1). OS for all patients was 77 ± 9% (95% CI: 61–98%) (Figure 2). Four of 25 patients (16%) died less than 100 days after SCT, 2 of which were alloSCT and 2 of which were auSCT, from causes including hypoxemic respiratory failure, sepsis, and progressive disease; all of these patients had aggressive lymphoma (2 DLBCL, 1 lymphoblastic lymphoma, and 1 MCL) and primary refractory disease. Six of 25 (24%) had progressive disease at less than 12 months post transplant, and no patient has relapsed beyond 12 months. Finally, DFS for all patients was 85%. Conclusions Altogether, our experience with Bu/Cy/VP-16 conditioning prior to either auSCT or alloSCT in relapsed/refractory NHL patients suggests that this is an effective and viable conditioning regimen with excellent outcomes including high PFS of 71%, OS of 77%, and DFS of 85%. Furthermore, these outcomes were apparent despite several high risk features among these relapsed/refractory patients. Disclosures: No relevant conflicts of interest to declare.

The number of CD34+ cells infused influences the speed of hematologic recovery post-transplant. There are limited data on whether ideal (IBW) or actual (ABW) body weight should be used to calculate CD34+ cell dose. We compared the correlation between recovery to 0.5 × 109/l neutrophils and the CD34+ cell dose based upon ABW as well as IBW in 87 patients autografted for cancer. ABW was ⩾25% over IBW in 43% of patients. The median number of CD34+ cells administered was 3.6 × 106/kg ABW and 4.2 × 106/kg IBW. The time to neutrophil recovery was 8–15 days (median 10). There was a stronger inverse correlation between CD34+ cell dose/IBW and neutrophil recovery (r2=0.308; P<0.0001) than between CD34+ cell dose/ABW and neutrophil recovery (r2=0.267; P<0.0001). The median time to neutrophil recovery was comparable for those receiving ⩾2 × 106/kg CD34+ cells/kg IBW as well as ABW (10 days) and those receiving ⩾2 × 106/kg CD34+ cells/kg IBW but <2/kg ABW (10 days), but was significantly slower for those receiving <2 × 106/kg CD34+ cells/kg IBW (12 days). These data show that the CD34+ cell dose based on IBW is a better predictor of neutrophil recovery after autotransplantation.