ALBERT

Description: Advances in supportive care have reduced early treatment related mortality with ASCT to approximately 1%. Registry data has shown that relapse is the cause of treatment failure in approximately 80% of patients. However, non-relapse mortality (NRM), over time, affects 20% of transplant recipients. Delayed NRM is poorly studied. To characterize the factors associated with NRM, we reviewed 1573 consecutive autologous transplants performed at the Cleveland Clinic from 1/1992 through 12/2005. This analysis included only adult patients (pts) receiving peripheral stem cells, busulfan based preparative regimens, single transplants, and diagnoses of NHL, HD and MM (n = 856). The median age was 49, 62% were male, and 30% received prior radiation therapy. The most common number of prior chemotherapy regimens was 2 (48%); the primary diagnosis was NHL (67%), HD (18%), MM (15%); and 90% had sensitive disease at the time of transplant. 471 (55%) are alive and 385 (45%) have died. Relapse was the most common cause of death, occurring in 303 (79%) patients. Non-relapse mortality occurred in 82 patients (21% of deaths). The most common cause of NRM was pulmonary toxicity, occurring in 26 patients, followed by secondary malignancy in 19 pts, infection (12 pts), cardiac toxicity (7 pts), other organ failure (7 pts), and other causes (11 pts). Patients who died from secondary malignancy were significantly more likely to have received prior radiation therapy (p = 0.004), to require more days of pheresis to collect stem cells (p

Description: Reduced intensity conditioning for allogeneic hematopoietic cell transplantation (alloHCT) has become a standard approach for older patients and for those with co-morbidities that prohibit myeloablative conditioning. The optimal conditioning regimen for patients with AML or MDS undergoing such transplants is not clear. Therefore we performed a single center, retrospective analysis comparing busulfan (100 mg/m2/day on days -5, -4, -3, -2) and fludarabine (40 mg/m2/day on days -5, -4, -3, -2) (BuFlu) versus fludarabine (30 m2/day on days -5, -4, -3) and 400 cGy total body irradiation (200 cGy on days -1 and 0) (FluTBI) conditioning. All of the BuFlu transplants were performed as inpatient hospitalizations while all of those with FluTBI were performed as an outpatient. A total of 71 patients in two cohorts were included. The first study cohort consisted of 38 patients (23 AML, 15 MDS) who received FluTBI from 3/2004-4/2010, and the second included 33 (20 AML, 13 MDS) patients conditioned with FluBu from 6/2010-12/2013. The groups had similar disease risk and HCT comorbidity index scores. The BuFlu patients were older (median age 65 [range, 34-73] vs. 61[range, 44-70] years, P=0.03), but there were no other differences in patient or disease characteristics. All patients received peripheral blood stem cells as the graft source. The donor sources were 53% matched related (MRD) and 47% matched unrelated (MUD) for FluTBI patients and 58% MRD and 42% MUD for BuFlu patients. The BuFlu group received more red blood cell (RBC) transfusions (median 4 vs. 2, P=0.02), but there were no differences in platelet transfusion requirements. Platelet recovery was longer for patients receiving BuFlu than FluTBI (median 16 vs. 12 days, P=0.004), but there was no difference in cumulative incidence of neutrophil recovery. The respective median number of days hospitalized in the first 100 days post-transplant was 22 vs. 10 days (P

Description: We have anecdotally observed that many patients mobilized with Etoposide (VP) + filgrastim (G) collect very high numbers of CD34+ cells for autologous stem cell transplantation (ASCT). Some BMT centers have suggested that the cellular composition of an autologous graft may influence ASCT outcome. We therefore queried whether patients collecting high numbers of PBPCs (“super-mobilizers”) have a better outcome than other patients. We retrospectively reviewed 693 consecutive adult patients with Non-Hodgkin Lymphoma (NHL) or Hodgkin Lymphoma (HL) receiving an ASCT from 1/1994 through 12/2005 treated with a uniform preparative regimen of Busulfan, Cyclophosphamide and Etoposide (Bu/Cy/VP). Of these 693 patients, 350 were mobilized with VP (2 gm/m2) + G and comprised the study population. After receiving VP+G, patients were collected for a minimum of 2 days with a collection goal of 7 × 106 CD34+ cells/kg. A minimum collection of 2.0 × 106 cells was required to proceed to ASCT. Super-mobilizers were defined as collecting, and infusing, greater than 8 × 106 CD34+ cells/kg. 203 patients were super-mobilizers, while 147 collected between 2.0 and 7.95 CD34+ cells/kg. Pre-transplant performance status, LVEF, and DLCO were similar between the two groups. Super-mobilizers were slightly younger (mean 47 years old vs. 51 years old, p=0.003) and more likely to have received 2 or fewer prior chemotherapy regimens, (80% vs. 63%, p

Description: Background: HCT is physically and psychologically challenging and patients are prone to QoL impairments. AYAs are a unique population that faces hurdles due to dynamic changes in several aspects of their life, and may be particularly prone to QoL issues during HCT. The aim of this study was to determine if QoL differences exist between AYA and older adult HCT recipients pre- and post-HCT. Additionally, we aimed to determine if there has been a change in QoL for AYA transplant recipients in recent years, as more focus has been placed on supporting this unique population. Methods: QoL data were collected prospectively pre-HCT (baseline [BL]) and in follow-up post-transplant on patients undergoing HCT from Jun 2003 through Dec 2017 at Cleveland Clinic. Autologous HCT recipients are followed routinely through day +42 post-transplant, while allogeneic recipients are followed through at least one year or more. QoL was self-reported by patients using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire. FACT-BMT consists of five domain scores (Physical Wellbeing [PWB], Social Wellbeing [SWB], Emotional Wellbeing [EWB], Functional Wellbeing [FWB], and Additional Concerns [AC]) and two summary scores (trial outcome index [TOI, PWB+FWB+AC], and Total FACT Score. Scores were compared for younger AYA (age 15-29 years), older AYA (age 30-39 years) and older adults (age 40-60 years). We excluded patients 〉60 years from analysis as this group may have their own unique challenges. Repeated measures analysis of variance was used to assess differences among age groups and among time points. Pearson correlation (r) was used to determine if BL QOL had improved from 2003-2017 in AYA cohort. Separate analyses were performed for autologous and allogeneic cohorts. Results: Autologous HCT cohort included 128 AYA patients (56 younger AYA) and 355 older adults, and allogeneic HCT cohort included 136 AYA patients (76 younger AYA) and 295 older adults Autologous patients in all three groups were similar for baseline characteristics except for diagnosis (table 1). Among allogeneic patients similar rates of graft-versus host disease were seen for all three groups, and baseline characteristics were similar except for ECOG performance status (table 1). Among autologous recipients, no single QoL domain or composite score differed among the three age groups at baseline or at day +42 post-HCT (Figure 1a). In all age groups, QoL improved from baseline to D+42 in autologous HCT recipients (mean Total Score 149 vs. 152, p=0.001). Similarly, among the allogeneic HCT recipients, no single QoL domain or composite score differed among the three age groups at baseline, day +100, +180, or +365 post-HCT (Figure 1b). Among all patients compared to BL (mean 146), total FACT score improved at day +180 (150, p=0.022) and +365 (152, p=0.005), but not at day 100 (145, p=0.57). Among autologous recipients, none of the BL FACT domains improved over time since 2003. In contrast, AYA allogeneic recipients also had no significant change in BL scores since 2003 for PWB, SWB, EWB, FWB, however there was improvement in AC (r=0.26, p=0.003, TOI (r=0.23, p=0.008), and total FACT score (r=0.19, p=0.03). Conclusions: AYA HCT recipients do not have inferior QoL compared to older adults in the first 42 days after autologous HCT and the first year after allogeneic HCT. Interestingly, QoL improvements in AYA patients have occurred in recent years for allogeneic but not autologous patients. Improvements in QoL of allogeneic patients is driven by the AC domain, which addresses multiple psychosocial aspects which have been emphasized in recent years. Continued efforts to tailor treatment and support for AYA HSCT recipients is critical to improving outcomes. Disclosures Advani: Glycomimetics: Consultancy; Novartis: Consultancy; Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Majhail:Atara: Honoraria; Anthem, Inc.: Consultancy; Incyte: Honoraria.

Description: High-dose chemotherapy followed by autologous stem cell transplant (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved and pharmacologic therapies are frequently employed, but with limitations. Music therapy has been demonstrated to improve nausea and pain in patients undergoing chemotherapy, but little data are available in the transplant setting. We present Results from a randomized study of music therapy in patients undergoing ASCT. Patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy (MT) with a board-certified music therapist or no music therapy (No MT). The MT arm received two music therapy sessions: the first occurring as close to Day +1 as possible, the second occurring 48-96 hours later (listed as Day +1 and Day +5). Primary outcomes were perception of pain and nausea, measured on a visual analog scale which ranged from 0 to 10 (0 = no nausea, 10 = worst nausea). These were measured before and after the first music therapy session or at comparable interval for No MT patients and on days +5 and +7. Secondary outcomes were narcotic pain medication use, with pain medication doses converted to morphine equivalents and assessed daily from Day -1 to Day +5. Mood disturbance assessed by Profile of Mood States (POMS). POMS has six scales: depression, vigor, anger, tension, confusion, and fatigue. Categorical variables were compared between arms using Chi-square test, continuous variables were compared using Wilcoxon rank sum test. Repeat measures analysis of variance was used to compare outcomes between study arms over time. Eighty-two patients were enrolled: MT 37 patients, No MT 45 patients. MT arm had more African American patients (16% vs. 2%, p = 0.02), but otherwise patient characteristics in terms of age, gender, disease type, and preparative regimen were balanced. (Table 1). There was no difference in nausea between MT and No MT arms for Days 1 and +5, however, by Day +7, the MT arm had more nausea than the No MT arm (mean score 2.1 vs. 1.1, P=0.03). Although there was no difference in pain between MT and No MT patients, MT patients required significantly less morphine equivalent over the 7 study days (median 24mg vs 73mg, p =0.03). (Figure 1 and 2). There was no difference between arms for depression, vigor, anger, tension, confusion, or fatigue. In conclusion, despite having similar pain scores between both groups, the patients who received MT required significantly less narcotic pain medication use. Future study will focus on impact of music therapy on pain. Table 1 Patient characteristics Figure 1 Pain assessment Figure 1. Pain assessment Figure 2 Narcotic medication use Figure 2. Narcotic medication use Disclosures: Duong: Celgene: Honoraria, Research Funding. Off Label Use: Approved in the US but not in Europe. Hill:Celgene: Honoraria, Research Funding.

Description: Allogeneic hematopoietic cell transplantation (alloHCT) is a curative therapy for high-risk acute lymphoblastic leukemia (ALL). However, long-term outcomes after alloHCT for adult ALL have not been well described. We conducted a retrospective cohort study of 72 consecutive adult ALL patients who underwent a first myeloablative alloHCT at our institution from January 2000-December 2013. Median age at HCT was 38 yrs (range, 18-62), 40 (56%) were male, 18 (38%) had high HCT CI score, 14 (19%) had prior CNS leukemia and 35 (49%) had BCR-ABL+ disease. Donor source was HLA-matched related donor for 50% patients and 90% received PBSC as graft source. All patients were transplanted in CR (72% were in 1st or 2nd CR) and 92% received T-cell replete grafts. Median time from diagnosis to alloHCT was 5 months (range, 2-90). The incidences of grade II-IV and III-IV acute GvHD, chronic GvHD and extensive chronic GvHD were 43%, 13%, 51% and 36%, respectively. The median follow-up for our cohort is 76 months. At 6 years after HCT, probability of overall survival (OS) was 33% (95% CI, 21-44%) and relapse-free survival (RFS) was 30% (95% CI, 19-42%), and the cumulative incidence of relapse was 36% (95% CI, 25-48%) and non-relapse mortality (NRM) was 37% (95% CI, 26-49%). The most common causes of death were relapse (43%) and infection (21%); majority of relapses occurred within the first 2-years post-transplantation. There were no second cancer related deaths. In multivariable analyses, factors significantly associated with OS were HCT CI score (HR 2.69 for high vs. low/int., P=0.002) and CMV status (HR 2.62 for donor+ vs. others, P=0.05). HCT CI score was the only predictive factor for RFS (HR 2.26 for high, P=0.007). We also compared outcomes by BCR-ABL status. BCR-ABL+ patients were older (median age 42 vs. 36 yrs, p=0.02), had low HCT CI score (34% vs 22%, p=0.01), were more likely to be in CR1 (74% vs. 32%, p=0.002), and as a result, proceeded to HCT sooner after diagnosis (median 4 vs 7 months, p=

Description: Background Adolescents and young adults (AYA) with cancer have been designated as a vulnerable population by the National Cancer Institute. This group, defined by the ages of 16-39 years, has not enjoyed the same survival improvements over the past several decades as older and younger cohorts. Most of the AYA patients with lymphoma are curable, even in advanced stage. After first-line therapy, 15% to 20% do not respond to treatment and relapse. Busulfan based preparative regimens have been effective in ASCT for a Hodgkin lymphoma (HL) and non- Hodgkin lymphoma (NHL). This study aims to determine the long term outcomes among AYA patients with lymphoma who received Busulfan based regimen for ASCT. Study and patient characteristics This was a retrospective study for AYA patients (age 16-39) undergoing ASCT for lymphoma consolidation between Jan/2000 and Dec/2010 at Taussig’s Cancer Center. Patients were identified from our Bone Marrow Transplantation database. Most of the patients (98.6%) had received Bu-Cy-VP16. Briefly, Busufan (Bu) total dose was 14 mg/kg, Etoposide 60mg/kg and cyclophosphamide dose 120mg/kg. Busulfan was not targeted and it was administered orally or IV. Pre-transplant patient and transplant characteristics are presented in table-1 and table-2 respectively. Outcomes and results There were total 146 patients who received Bu-Cy-VP16 (80 HL, 66 NHL). The median age was 32 years (range, 16-39 years). Only 37 patients (25.3%) were in CR, 89 patients (61.0%) were PR and 20 patients (13.7%) had refractory disease. Most patients had at least 2 regimens of chemotherapy prior to ASCT. The regimen was well tolerated, with day 100 mortality 4.1% and non-relapse mortality 2.7%. With a median follow up of 6.2years, 5-year relapse-free survival (RFS) and overall survival (OS) were 46.6 % and 61.2%; 10-year RFS and OS were 44.6% and 55.7% (figures 1). Four patients developed secondary malignancy (2.7%); the secondary malignancy were: ALL at 1.7 yrs after transplant, AML at 2.3 yrs, MDS at 2.5 yrs. One patient developed lung carcinoma. Cumulative incidence of secondary malignancy at 10 years is 3% which is considerably less than 9% that we reported in our whole patient population who gets this regimen which could be attributed to age and also due to previous chemotherapy regimens. Prognostic factors for OS and RFS Worse ECOG performance status (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.13-2.28, P=0.009) and HL diagnosis (HR 1.78, CI 1.01-3.14, P=0.048) were the only significant risk factors for mortality in multivariable Cox analysis. Worse ECOG performance status (HR 1.53, CI 1.11-2.10, P=0.010 was the only prognostic factor for relapse/mortality (RFS). Conclusion The study confirms that Bu-Cy-VP16 is very well tolerated in AYA population with low 100-day NRM and very low incidence of secondary malignancy. Disclosures: Duong: Celgene: Honoraria, Research Funding. Hill:Celgene: Honoraria, Research Funding.

Description: Purpose: The lived experience of patients undergoing myeloablative (allos) compared to non-myeloablative (mini allos) allogeneic BMT is unclear due to a lack of empirical psychosocial studies. This study compares patient characteristics, psychosocial profiles, and outcomes of patients undergoing allos and mini allos. Methods: From 3/2003 to 12/2005, 125 patients (99 allos and 26 mini allos), completed three psychometric instruments: FACT-BMT (QOL), Brief COPE (coping), and POMS short form (mood states). Patients completed these instruments post discharge for allos and post infusion for mini allos, day 100, 6 months, and 1 year post transplant. P

Description: Background: The role of autologous stem cell transplantation (ASCT) in follicular lymphoma (FL) in the rituximab era remains undefined. Although ASCT has demonstrated to improve outcomes in relapsed/refractory (R/R) FL, there are very few studies addressing this issue in patients who had prior exposure to rituximab. Our aim was thus to assess the outcome of ASCT in FL patients in the modern era. Methods and Patients: We conducted a single center retrospective analysis of patients who underwent ASCT for follicular lymphoma at the Cleveland Clinic. Patient and disease characteristics were examined and prognostic factors for survival were determined using univariate and multivariate Cox analysis. Results: Total of 127 patients with a confirmed diagnosis of FL underwent ASCT at our institution between March 2000 and October 2013. Study population was predominantly male (61%) and Caucasian (92%). Median age at transplant was 55 years. Majority of the patients had FL grade of 1-2 (88%), International Prognostic Index (IPI) 0-2 (81%), and stage IV disease (60%) at the time of diagnosis. All, but 9 patients (93%) received rituximab as part of their prior treatment and 53% had received ³3 prior therapies. Disease status prior to transplant was 1st partial response (PR1) (9%), 2nd complete remission (CR2) (24%), 2nd PR (PR2) (60%), and R/R (8%); no patients received transplant in the 1st CR (CR1). An uniform preparative regimen consisting of Busulfan, Cyclophosphamide and Etoposide (Bu/Cy/VP16) was used in all patients. Median CD34+ cell dose was 7.49 x 106/kg. Median days to neutrophil engraftment were 10 days and platelet engraftment was 14 days. In our cohort, 10-year progression free survival (PFS) and overall survival (OS) were 33.2% and 52.4% respectively. Disease relapsed in 58/127 (46%) of the patients and 67% were alive at the time of last follow up. Age at transplant (Figure 1) and number of prior therapies, 〉3 vs 1-3 (Figure 2) were significant prognostic factors for OS, in both univariate and multivariate analyses. Higher age (HR 1.76, 95% CI 1.23-2.52, p=0.002) and 〉3 prior therapies (HR 2.58, 95% CI 1.31-5.12, p=0.006) were predictive for inferior OS. Disease status at transplant, IPI, and stage had no impact on survival. Disease relapse (67%) and secondary malignancies (7.1%) were the leading causes of death. Conclusions: In our analysis, a durable PFS, median of 49 months, was observed in patients with R/R FL who underwent an ASCT in the rituximab era. Age at transplant and number of prior therapies were identified as poor prognostic factors for OS. These data suggest that ASCT should be considered in young patients with R/R FL early in their disease course. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Hill: Millenium: Research Funding; Novartis: Research Funding.

Description: Consolidative autologous stem cell transplantation (ASCT) is a commonly utilized treatment modality for peripheral T cell lymphomas (PTCL) and has been shown to improve progression free survival. The optimal timing of ASCT for PTCL is not well defined and studies have included upfront ASCT or ASCT at the time of relapse. However, long-term outcomes of ASCT, especially when used as upfront consolidation, have not been well described. Previously published data, including the one from our institution, (Smith S et al BMT. 2007;40:239-243) revealed inferior outcomes following ASCT in relapsed PTCL. We performed a retrospective study to describe our institutional experience in a relatively large cohort of patients with PTCL who were treated with ASCT (N=78) between 1996 and 2013 and had a median follow up of 55 months. Among these, 62% were male, 89% Caucasian and 84% had a Karnofsky performance score ³90. The subtypes included 26 peripheral T cell lymphomas (PTCL) (33%), 19 anaplastic large cell lymphoma (ALCL) alk- (24%), 13 ALCL alk+ (17%) 16 angioimmunoblastic T cell lymphoma (AITL) (21%) and 4 extranodal NK/T cell nasal type (5%). Prominent disease characteristics at diagnosis included stage III-IV in 80%, and IPI score of 0-3 in 73%. Only 26% had bone marrow (BM) involvement. Majority of the patients (76%) received 2 or more prior therapy. 99% of the transplants was performed using Busulfan, Cyclophosphamide, and Etoposide (Bu/Cy/VP16) preparative regimen. While 27 (35%) patients received ASCT as part of their initial treatment, 51 (65%) patients were transplanted after their disease had relapsed. About one third of our cohort (31%) attained a complete response (CR) post ASCT. The 5-year relapse rate (RR) for CR1, CR2 and PR1 were 22%, 53% and 66% (Figure 1) implying that both the disease status and response prior to transplant are key determinant factors for long-term outcome. The RR curve plateaued after 8 years indicating that a proportion of patients had attained a durable remission. At the time of analysis, 42% were alive. Disease relapse was the cause of death in 76% of the cases. Our 10-year RR, relapse free survival (RFS) and overall survival were 64%, 25% and 31% respectively. On univariate analysis disease status, BM involvement and stage were prognostic for RFS and OS, but only disease status (RFS: HR 2.27, p=0.023; OS: HR 4.75, p=0.006) and BM involvement (RFS: HR 3.10, p=0.019; OS: HR 2.94, p=0.018) retained significance on multivariate analysis. Moreover, disease status was also predictive for relapse in both univariate and multivariate analyses (HR 2.12, 95% CI 1.05-4.27, p=0.035). Conclusions: In a relatively large cohort of PTCL patients with long-term follow up after ASCT, upfront consolidative autologous stem cell transplantation in chemo sensitive patients resulted in lower RR and improved RFS and OS. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Hill: Millenium: Research Funding; Novartis: Research Funding.