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BackgroundRelugolix is the newest form of androgen deprivation therapy (ADT) approved for prostate cancer. However, as an oral drug, several real-world concerns exist, particularly medication compliance, safety with other androgen receptor-targeted agents, and financial burden to patients.MethodsA single institution retrospective chart review was conducted evaluating all patients who were prescribed relugolix for any prostate cancer indication from January 1, 2021 to January 31, 2022. Demographic data, cardiac risk factors, concomitant therapy usage, and PSA/testosterone levels, were abstracted from the chart review. Adverse effects were obtained by examining progress notes. Compliance was assessed by clinic notes as well as prescription fills by specialty pharmacy records. The reasons patients did not fill or discontinued the medication were noted.ResultsHundred and one patients were prescribed relugolix, and 91 patients consented to research. Seventy-one (78%) patients filled the prescription to relugolix, with a median follow-up of 5 months. Prescription fill data were available for 45 (63%) patients, with 94% of days covered. The most commonly reported reason not to fill was cost at 50%. Sixty-six (93%) patients reported never missing a dose. PSA levels were available in 71 (100%) patients with 69 (97%) showing stable or improved PSA. Testosterone levels were available in 61 (86%) of patients, which showed 61 (100%) stable or successful castration. Twenty-four (34%) patients used relugolix in combination. No new major safety signals were seen in combination therapy. Nineteen (27%) patients had switched to another form of ADT. Fifteen of these (79%) felt similar or better on relugolix therapy.ConclusionsCompliance with relugolix seemed acceptable. No major new safety signals were seen, even in combination. Among patients who switched therapy, most tolerated relugolix similarly or better than the previous form of ADT. The cost was a major reason for patients not initiating and for discontinuing therapy.

High-risk relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) is associated with poor outcomes after conventional salvage therapy and autologous hematopoietic cell transplantation (AHCT). Post-AHCT consolidation with brentuximab vedotin (BV) improves progression-free survival (PFS), but with increasing use of BV early in the treatment course, the utility of consolidation is unclear. CD25 is often expressed on Reed-Sternberg cells and in the tumor microenvironment in HL, and we hypothesized that the addition of 90Y-antiCD25 (aTac) to carmustine, etoposide, cytarabine, melphalan (BEAM) AHCT would be safe and result in a transplantation platform that is agnostic to prior HL-directed therapy. Twenty-five patients with high-risk R/R HL were enrolled in this phase 1 dose-escalation trial of aTac-BEAM. Following an imaging dose of 111In-antiCD25, 2 patients had altered biodistribution, and a third developed an unrelated catheter-associated bacteremia; therefore, 22 patients ultimately received therapeutic 90Y-aTac-BEAM AHCT. No dose-limiting toxicities were observed, and 0.6 mCi/kg was deemed the recommended phase 2 dose, the dose at which the heart wall would not receive >2500 cGy. Toxicities and time to engraftment were similar to those observed with standard AHCT, though 95% of patients developed stomatitis (all grade 1-2 per Bearman toxicity scale). Seven relapses (32%) were observed, most commonly in patients with ≥3 risk factors. The estimated 5-year PFS and overall survival probabilities among 22 evaluable patients were 68% and 95%, respectively, and non-relapse mortality was 0%. aTac-BEAM AHCT was tolerable in patients with high-risk R/R HL, and we are further evaluating the efficacy of this approach in a phase 2 trial. This trial was registered at www.clinicaltrials.gov as #NCT01476839.

The inexpensive, well-tolerated, immunomodulatory agent leflunomide, used extensively for the treatment of rheumatoid arthritis, has been shown to produce significant activity against multiple myeloma (MM) in pre-clinical studies. We conducted a phase 1 study (clinicaltrials.gov: NCT02509052) of single-agent leflunomide in patients with relapsed/refractory MM (≥3 prior therapies). At dose levels 1 and 2 (20 mg, 40 mg), no dose-limiting toxicities (DLTs) were observed. At dose level 3 (60 mg), one patient experienced elevated alanine aminotransferase; an additional three patients were enrolled at this dose level without further DLTs. Overall, toxicities were infrequent and manageable. Nine out of 11 patients achieved stable disease (SD), two subjects experiencing SD for nearly one year or longer. The tolerable safety profile of leflunomide, combined with a potential disease stabilization, is motivating future studies of leflunomide, in combination with other MM drugs, or as an approach to delay progression of smoldering MM.

Acute lymphoblastic leukemia (ALL) is associated with poor survival in older adults, and allogeneic hematopoietic cell transplant (HCT) with reduced-intensity conditioning (RIC) has been an increasingly used strategy in this population. At City of Hope we conducted a retrospective analysis of 72 patients who underwent allogeneic HCT with fludarabine and melphalan (FluMel) as the conditioning regimen between 2005 and 2018, from either a matched sibling or fully matched unrelated donor while in complete remission. Tacrolimus and sirolimus (T/S) were used as graft-versus-host disease (GVHD) prophylaxis. Overall survival and progression-free survival at 4 years post-HCT were 58% and 44%, respectively. The cumulative incidences of relapse/progression and nonrelapse mortality at 4 years were 34% and 22%, respectively. Patients with Philadelphia chromosome–positive (Ph+) ALL had a significantly lower cumulative incidence of relapse/progression (20% versus 48% for patients with Ph-negative status, P = .007). In conclusion, RIC HCT with FluMel conditioning and T/S GVHD prophylaxis was associated with favorable outcomes in patients with Ph+ ALL and should be considered as a viable consolidative therapy for adult patients with ALL.

Therapy-related acute lymphoblastic leukemia remains poorly defined due to a lack of large data sets recognizing the defining characteristics of this entity. We reviewed all consecutive cases of adult acute lymphoblastic leukemia treated at our institution between 2000 and 2017 and identified therapy-related cases - defined as acute lymphoblastic leukemia preceded by prior exposure to cytotoxic chemotherapy and/or radiation. Of 1022 patients with acute lymphoblastic leukemia, 93 (9.1%) were classified as therapy-related. The median latency for therapy-related acute lymphoblastic leukemia onset was 6.8 years from original diagnosis, and this was shorter for patients carrying the MLL gene rearrangement compared to those with other cytogenetics. When compared to de novo acute lymphoblastic leukemia, therapy-related patients were older (P

In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose-limiting. Per 3 + 3 phase I design, an additional three patients were enrolled to DL1, with no further dose-limiting toxicity (DLT). At dose level 2 (DL2, 4 mg Ixa), 1/3 patients had dose-limiting febrile neutropenia, neutropenia, and thrombocytopenia (grade 4 each). DL2 was expanded to enroll three additional patients with no further DLT, establishing the recommended phase II dose (RP2D). In phase II, 19 additional patients were treated at RP2D. With a median follow-up of 11.9 months, 48% achieved ≥ partial response (PR), with 5 patients (20%) achieving very good partial response (VGPR) and 76% experiencing ≥ stable disease. The most common adverse events (≥grade 2) were anemia, neutropenia, thrombocytopenia, and infections. Peripheral neuropathy was infrequent. In summary, Ixa/Pom/Dex is a well-tolerated and effective oral combination therapy for patients with relapsed/refractory MM.

Background: Blinatumomab, a bispecific anti-CD19/CD3 antibody, demonstrated single-agent efficacy with 42% CR/CRh in R/R B-ALL. Upregulation of immune inhibitory molecules has been shown to confer resistance to blinatumomab. Here, we set out to test the combination of pembrolizumab and blinatumomab in a phase 1/2 trial (NCT03512405). Methods: Pts [≥18 years old (yo); ECOG Results: As of February 1, 2021, 7 pts were enrolled to phase 1, with one unevaluable. Six treated and evaluable pts received a median of 2 (1–5) cycles of treatment. At baseline, the median age was 51 yo (29–74) with median 2 (2–4) prior lines of regimens and median 29% (0–83) BM blasts. Two pts had extramedullary disease. In cycle 1, all 6 pts experienced grade (gr) 1–2 cytokine release syndrome. Neurologic toxicities were all reversible with only 1 ≥ gr3 AE. All-non-hematologic gr3 toxicities, were reversible. No dose-limiting toxicity, ≥ gr4 non-hematologic toxicity, or treatment-related deaths were seen. Five of 6 evaluable pts (83%) achieved MRD-negative CR after a median of 1 (1–2) cycle. Three pts in CR received alloHCT, all engrafted. With a median follow-up of 2.8 (1.1–9.6) months, 4 CRs are ongoing (1 post-transplant), and 5 of 6 pts are still alive at the data cut-off. Conclusions: The combination of pembrolizumab and blinatumomab in phase 1 of this study in pts with B-ALL was deemed safe with a manageable side effect profile and encouraging anti-leukemic activity. The study is now open for phase 2 with the primary objective of overall response rate.

Standard-dose 90yttrium-ibritumomab tiuxetan (.4 mci/kg) together with high-dose BEAM (BCNU, etoposide, cytarabine, and melphalan) (Z-BEAM) has been shown to be a well-tolerated autologous hematopoietic stem cell transplantation preparative regimen for non-Hodgkin lymphoma. We report the outcomes of a single-center, single-arm phase II trial of Z-BEAM conditioning in high-risk CD20+ non-Hodgkin lymphoma histologic strata: diffuse large B cell (DLBCL), mantle cell, follicular, and transformed. Robust overall survival and notably low nonrelapse mortality rates (.9% at day +100 for the entire cohort), with few short- and long-term toxicities, confirm the safety and tolerability of the regimen. In addition, despite a high proportion of induction failure patients (46%), the promising response and progression-free survival (PFS) rates seen in DLBCL (3-year PFS: 71%; 95% confidence interval, 55 to 82%), support the premise that the Z-BEAM regimen is particularly effective in this histologic subtype. The role of Z-BEAM in other strata is less clear in the context of the emergence of novel agents.

Background: Peripheral T cell lymphomas (PTCL) have a poor prognosis with current treatment regimens. High-dose chemotherapy followed by autologous stem cell transplant (ASCT) has been used as a consolidation strategy in remission states (CR1 or above) endorsed by the NCCN guidelines in appropriate patients. 5-year DFS is reported at 70% for alk -ve anaplastic large cell lymphoma (ALCL) and 30-40% for most other histologies (D'Amore et al, 2012, JCO). It is also performed in the relapsed settings if no previous ASCT performed and allogeneic transplant is not an option. CD25 is a targetable protein expressed differentially in PTCL and antibody based anti-CD25 therapies are efficacious in PTCL i.e denileukin diftitox (Foss et al Blood 2006, Dang et al, BJH 2006) , monoclonal antibody dacluzimab (Waldman et al 1995 Blood). Yttrium-90 (90Y) labeled chimeric antiCD25 antibody basiliximab emits beta particles and has been shown to inhibit the growth of human ALCL tumors and increase survival in SUDHL-1 xenograft mice (Zhang et al 2009 Cancer Biother Radiopharm). Previous investigations at COH by Raubitschek, Colcher et al established a safe does of Yttrium-90 (90Y) labeled basiliximab at 0.4mCi/kg in combination with BEAM. This is a phase 1 clinical trial of a novel conditioning regimen that includes the use of Yttrium-90 (90Y) labeled basiliximab with BEAM chemotherapy for PTCL patients eligible for ASCT. The trial utilizes a modified version of the rolling 6 design (Skolnik et al) to test 3 dose levels of Yttrium-90 (90Y) Basiliximab i.e 0.4mCi/kg, 0.5miC/kg and 0.6mCi/kg with the primary objective of evaluating the safety and tolerability of this combination and to establish the MTD. Secondary objectives include estimating incidence of relapse, OS, PFS, NRM at day 100, 1 year and 2 years post-transplant. Patients and Methods: Dose limiting toxicity (DLT) is defined according to the Bearman and CTCAE 4.03 scales, the latter for hematologic toxicity. The study/treatment schema is shown in Figure 1. Results: From 07/29/2015 to 06/10/2020, 20 patients underwent ASCT on this trial; n=4 at 0.4mCi/kg n=4 at 0.5mCi/kg and n=12 at 0.6mCi/kg. Median age at ASCT was 51 years (range: 18-76), and histologies included; PTCL-nos (n=10); alk-ve ALCL (n=5); angioimmunoblastic T-cell lymphoma (n=3); and intestinal T-cell lymphoma (n=2). Disease status at ASCT were CR1 in18, CR2 in 2 patients. Median number of prior therapies was 1 (range: 1-4). At a median follow-up of 17.1 months (range: 0.9-26.2), 12 patients remain in remission, 8 have relapsed out of which 5 have died of progressive lymphoma. OS was 100% (95% CI: N/A) at 100-days, and 83% (95% CI: 57-94) at 1 year. Non-relapse Mortality was 0% at both 100-days and 1-year. All patients successfully engrafted with the median days to ANC >= 500/ul was 10 (range: 10 - 21), and days to PLT >= 20,000/ul: 13 (12 - 92). Overall, no dose limiting toxicities were experienced. The most common/highest grade toxicity experienced (per Bearman Scale) was grade 2 stomatitis, which was seen in 3 patients at 0.4mCi/kg; 4 patients at 0.5 mCi/kg, and 7 at0.6mCi/kg. The only other toxicities seen were grade 2 GI in 2 patients at 0.4mCi/kg, and grade 2 bladder in one patient at 0.6mCi/kg dose.. Toxicities >grade 2 were not seen. Conclusion: aTac- BEAM appears to be safe as an ASCT conditioning regimen for PTCL with no increased toxicity as compared to the historical toxicities seen with BEAM alone in this patient population (D'Amore 2012 J of Clin Onc). The dose level 0.6mCi/kg will likely be the recommended phase II dose. An expanded phase is planned to evaluate the efficacy of this regimen followed by a randomized trial of BEAM alone plus a combination of aTac- BEAM. Figure 1 Disclosures Zain: Mundi Pharma: Research Funding; Seattle Genetics: Research Funding; Kyowa Kirin: Research Funding. Herrera:Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Karyopharm: Consultancy; Pharmacyclics: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Merck: Consultancy, Research Funding. Salhotra:Kadmon: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Nakamura:NapaJen Pharma: Consultancy; Celgene: Other: Support on seminar; Magenta Therapeutics: Other: Advisory board meeting; Viracor: Consultancy; Merck: Other: advisory board meeting; Alexion: Other: Support on a meeting presentation; Kyowa-Kirin: Other: Support on a meeting presentation; Kadmon Corporation: Other: Advisory board meeting. OffLabel Disclosure: Yittrium labelled Basiliximab

Background: Allogeneic hematopoietic cell transplantation (alloHCT) is the approach that offers the highest curative rate for acute myelogenous leukemia (AML) with intermediate or high-risk cytogenetics. Graft versus host disease (GvHD) has remained the main cause of post-transplantation mortality and morbidity, despite advances in prophylaxis and therapy, adding significant economic burden and affecting quality of life. It would be desirable to reduce the rate of GvHD among patients in complete remission (CR) without increasing the risk of relapse. In this study, we have developed a novel conditioning regimen of total marrow and lymphoid irradiation (TMLI) at 2000 cGy, together with post-transplant cyclophosphamide (PTCy), to 1) reduce the possibly increased risk of relapse from PTCy, by using escalated radiation doses of TMLI, as increasing radiation doses has the potential to decrease the post-transplantation relapse rate (Blood, vol 76, pp. 1867-1871, 1990); and 2) reduce the risk of chronic GvHD by using PTCy. The major goal of this pilot study of TMLI and PTCy (clinicaltrials.gov: NCT03467386), was to thus improve GvHD-free/relapse-free survival (GRFS), reported to be 45% from total body irradiation (TBI) and tacrolimus/sirolimus prophylaxis (BBMT, vol 26(2), pp. 292-299, 2020), in patients with AML in remission. Patients and Methods: A total of 18 patients were enrolled and treated (see Table) between March 2018 and December 2019. Key criteria were ages 18 to 60, first or second CR, minimal residual disease negative by multi-color flow cytometry, and normal organ function. TMLI was administered on days -4 to 0 without addition of chemotherapy. The radiation dose for all patients (n=18) was 2000 cGy, delivered in 200 cGy fractions twice daily. The radiation dose delivered to the liver and brain was kept at 1200 cGy. Remaining organs were considered non-targeted. All patients received peripheral blood stem cells on day 0. Cyclophosphamide was given on days +3 and +4, 50 mg/kg each day for GVHD prevention. Tacrolimus, 1 mg continuous infusion adjusted to maintain levels from 5 to 10 ng/mL was given from day +5 to day +90, and G-CSF 5 µg/kg daily was administered at day +5 until recovery of neutrophil counts. Endpoints included toxicity, GRFS at 1 year, engraftment, overall survival (OS), and non-relapse mortality (NRM). Toxicities were defined according to the Bearman and CTCAE 4.03 scales, the latter for hematologic toxicity. A patient safety lead-in segment (n=6) was conducted to ensure that there were no unexpected toxicities, allowing for a dose de-escalation to 1800 cGy. GRFS was defined as grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurred first. Results: Bearman toxicity data are available for all patients. Among these patients, grade 2 toxicities were bladder toxicity and stomatitis. No grade 3-4 toxicities or toxicity-related deaths were observed. Acute GVHD (aGVHD) developed in 2 of patients (100-day Grade II-IV aGVHD: 11.1%, 95%CI: 1.7-30.4); of those, only 1 patient developed Grades III-IV (100-day Grade III-IV aGVHD: 5.6%, 95%CI: 0.3-23.1). Five patients developed mild chronic GVHD (1-year cGVHD rate: 28.6%, 95%CI: 7.5%-54.7%). The GRFS rate at 1 year was 59.3% (95% CI: 28.8-80.3) (Figure). The median follow up was 11.3 months (range 4.7 to 25.4) for surviving patients (n=17). All patients engrafted. Time to neutrophil and platelet recovery were 14 days (range 13-32 days) and 20 days (range 11-49 days), respectively. One-year estimates of OS and relapse-free survival were 100% and 80.8% (95% CI: 50.5-93.6), respectively (Figure). Disease relapse at 1 year was 19.2% (95% CI: 4.1-42.6). The estimates of NRM at 100 days and 1 year were both 0%. Relapsed disease after transplant occurred in 3 patients (16.7%). One patient died after relapse. Conclusions: 1) This chemotherapy-free conditioning regimen, together with PTCy and tacrolimus, is safe and feasible, with no NRM. 2) All patients achieved engraftment. 3) Participants with ≥1 year follow-up have discontinued immunosuppressive therapy, reducing financial burden and leading to improved quality of life. The preliminary results suggest an improved GRFS rate. A larger phase 2 trial is in preparation to corroborate these data. Disclosures Stein: Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Al Malki:Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Rigel Pharma: Consultancy. Ali:Incyte Corporation: Consultancy. Aribi:Seattle Genetics: Consultancy. Marcucci:Novartis: Speakers Bureau; Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Pfizer: Other: Research Support (Investigation Initiated Clinical Trial); Abbvie: Speakers Bureau; Merck: Other: Research Support (Investigation Initiated Clinical Trial); Iaso Bio: Membership on an entity's Board of Directors or advisory committees. Nakamura:Alexion: Other: Support on a meeting presentation; Kyowa-Kirin: Other: Support on a meeting presentation; Merck: Other: advisory board meeting; Celgene: Other: Support on seminar; Magenta Therapeutics: Other: Advisory board meeting; Viracor: Consultancy; Kadmon Corporation: Other: Advisory board meeting; NapaJen Pharma: Consultancy. Pullarkat:AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Salhotra:Celgene: Research Funding; Kadmon: Membership on an entity's Board of Directors or advisory committees.

The prognostic relevance of cytogenetics at diagnosis on the outcome of allogeneic hematopoietic stem cell transplantation (alloHCT) for adult acute lymphoblastic leukemia (ALL) remains unclear. We retrospectively analyzed outcomes of 333 adult ALL patients who underwent alloHCT at our institution over a 10-year period. Patients were classified according to disease status at transplantation (complete response [CR] 1 [n = 202] or > CR1) and according to cytogenetic risk, defined as good (2%), intermediate (42%), poor (46%), or unknown (10%) based on available outcome data for each of the cytogenetic abnormalities. Three-year overall survival (OS), leukemia-free survival (LFS), and relapse incidence (RI) were 55.7%, 47.9% and 27.5%, respectively; 1-year nonrelapse mortality (NRM) was 17.3%. For patients undergoing alloHCT in CR1, 3-year OS, LFS, and RI were 69.8%, 62.3%, and 17.1%, respectively. In multivariable analysis, cytogenetic risk did not impact OS or LFS for the whole cohort or for patients who underwent transplantation in CR1. Disease status at alloHCT was an independent predictor for LFS (CR1 versus others: hazard ratio [HR], 3.17; P

Plerixafor has been used to improve peripheral blood stem cell (PBSC) mobilization in multiple myeloma, non-Hodgkin lymphoma, and very recently in Hodgkin lymphoma (HL) patients. Because prior studies have suggested that mobilization with plerixafor affects the composition of mobilized cells, there are concerns that this may in turn adversely impact the immune reconstitution and longer term outcomes of transplanted patients. However, data on the engraftment characteristics and long-term post-transplant outcomes in patients transplanted with plerixafor-mobilized PBSCs are lacking. This retrospective study examined the post-transplant outcomes of 105 consecutive adult HL patients, and compared the post-transplant outcomes of 21 patients who received plerixafor in addition to G-CSF ± chemotherapy because of poor mobilization with those of 84 patients who mobilized well without plerixafor. Despite collecting significantly lower CD34+ cell doses (median of 3.41 vs. 6.05 × 106 /kg, p

Pegylated asparaginase (PEG-Asp), a key component in the treatment of acute lymphoblastic leukemia (ALL), is associated with coagulopathy and an increased risk of venous thromboembolism (VTE). PEG-Asp also lowers antithrombin (AT) levels. Between April 2014 and October 2017, 75 adult ALL patients were identified to have received at least one dose of PEG-Asp. Patients were assigned to the AT group if a physician monitored AT levels with an intention to correct low AT levels (60%). Incidence of VTE was not significantly different, with 17% (8/47) of the AT patients and 11% (3/28) of the control patients experiencing a VTE event (p = .52). The occurrence of coagulopathies was not significantly different. Within the AT group, 37 patients (78%) received AT, and median AT% prior to supplementation was 49%. The median number of AT doses received was 2 (range 0-12) and the mean cost of AT per patient was $11,847.

Mantle cell lymphoma (MCL) is an aggressive and incurable lymphoma. Standard of care for younger patients with MCL is induction chemotherapy followed by autologous stem cell transplantation (auto-HCT). Rituximab maintenance after auto-HCT has been shown to improve progression-free survival (PFS) and overall survival (OS) in MCL. Bortezomib maintenance therapy has also been shown to be tolerable and feasible in this setting. However, the combination of bortezomib and rituximab as maintenance therapy post-auto-HCT has not been studied. We conducted a multicenter, phase II trial of bortezomib given in combination with rituximab as maintenance in MCL patients after consolidative auto-HCT. Enrolled patients (n = 23) received bortezomib 1.3 mg/m2 subcutaneously weekly for 4 weeks every 3 months (up to 24 months) and rituximab 375 mg/m2 intravenously weekly for 4 weeks every 6 months (up to 24 months) for a total duration of 2 years. The primary study endpoint was disease-free survival (DFS). With a median follow-up of 35.9 months, the 2-year DFS probability was 90.2% (95% CI 66–97), and 2-year OS was 94.7% (95% CI 68–99). The most frequent grade 3/4 toxic events were neutropenia (in 74% of patients) and lymphopenia (in 35%). The incidence of peripheral neuropathy was 48% for grade 1, 9% for grade 2, and 0% for grade 3/4. We also examined the role of quantitative cyclin D1 (CCND1) mRNA in monitoring minimal residual disease. Combined bortezomib and rituximab as maintenance therapy in MCL patients following auto-HCT is an active and well-tolerated regimen. ClinicalTrials.gov NCT01267812 , registered Dec 29, 2010.

Transformation from indolent non-Hodgkin lymphoma (NHL) to diffuse large B cell lymphoma (DLBCL) has historically been associated with a poor prognosis. A small series of autologous stem cell transplantation (ASCT) studies using conventional conditioning regimens has demonstrated durable progression-free survival (PFS) rates ranging from 25% to 47%, but data in the rituximab era are lacking. Here we report the results of a multicenter retrospective trial evaluating ASCT in patients with transformed lymphoma using the Z-BEAM conditioning regimen, which combines yttrium-90–labeled ibritumomab tiuxetan (Zevalin) with high-dose BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy. Sixty-three patients from 4 institutions were treated between 2003 and 2011. Histological confirmation of transformation was required and defined as a diagnosis of DLBCL in patients with either a prior history or concomitant diagnosis of low-grade B cell NHL. Median patient age at ASCT was 59.5 years, median number of prior regimens was 2, and all patients were exposed to rituximab. Disease status at ASCT was as follows: first complete remission (CR) (n = 30), first partial remission (n = 11), first relapse (n = 14), and at least second CR (n = 8). The median time from diagnosis of histological transformation to ASCT was 7.5 months (range, 2.8 to 116). Two-year nonrelapse mortality was 0%. Median follow-up for living patients was 28 months (range, 5 to 103). Two-year PFS was 68% (95% confidence interval, 58% to 75%), and overall survival was 90% (95% confidence interval, 80% to 95%). In conclusion, the Z-BEAM conditioning regimen for ASCT is well tolerated by patients with transformed lymphoma and demonstrates encouraging clinical outcomes.

We previously reported that brentuximab vedotin (BV) enabled successful reduced-intensity allogeneic hematopoietic cell transplantation (RIC-alloHCT) in patients with relapsed Hodgkin lymphoma, after a median follow-up of 14.4 months. We now provide an updated report on 21 patients who were treated from 2009 to 2012 with BV before RIC-alloHCT with a uniform fludarabine/melphalan conditioning regimen and donor source after a median follow-up of 29.9 months. We have also retrospectively compared the patient characteristics and outcomes of these BV-pretreated patients to 23 patients who received fludarabine/melphalan RIC-alloHCT without prior BV, in the time period before the drug was available (2003 to 2009). Patients who were treated with BV before RIC-alloHCT had a lower median hematopoietic cell transplantation–specific comorbidity index and a reduced number of peri-transplantation toxicities. There were also improvements in 2-year progression-free survival (59.3% versus 26.1%) and cumulative incidence of relapse/progression (23.8% versus 56.5%).

Background: Mature T cell and NK cell neoplasms collectively known as peripheral T-cell lymphomas (PTCL) comprise 15-20% of Non-Hodgkin lymphomas in adults and have a poor prognosis with a 5-year survival of less than 30% for the most aggressive subtypes. Allogeneic HCT (allo-HCT) is offered to eligible patients as a potentially curative modality in the salvage setting or in high risk patients to consolidate an initial response to frontline therapy. There are few studies that report clinical outcomes derived from large sample size and long-term follow up data. Methods: We retrospectively reviewed medical records of 87 consecutive patients with PTCL including transformed mycosis fungoides and NK/T-cell lymphoma without prior autologous transplant who underwent allo-HCT at City of Hope from January 2000 to June 2018 after IRB approval was obtained. Descriptive statistics were used to summarize baseline patient demographic, treatment, and disease characteristics. Kaplan-Meier curves and the log-rank test were used to evaluate the overall survival (OS) and progression-free survival (PFS). Cumulative incidences of time to relapse and time to non-relapse mortality (NRM) were calculated with relapse and NRM as competing risks. Cumulative incidences of acute and chronic GVHD were calculated as time to onset of GVHD with relapse and death as competing events for GVHD. Results: 87 patients were included for the analysis. Median age at the time of allo-HCT was 49 years (range 2-70 years). Histologies were PTCL-NOS (n=21); transformed CTCL (n=19); NK T-cell lymphoma (n=17); AITL (n=15), ALCL (n=7); gamma delta T-cell lymphoma (n=6) and other rare subtypes (n=2). None of the patients had a prior auto transplant. 42 patients (48%) received myeloablative conditioning, with the majority of patients receiving FTBI based conditioning (n=39) and three patients received BEAM regimen for conditioning. 45 patients (52%) received reduced intensity conditioning; fludarabine/melphalan based-conditioning was the most common regimen used (n=39). Sibling HCT was performed in 47 patients (54%), while MUD HCT was performed in 36 patients (41%) with fully matched HLA unrelated donor in 15 (17%) and HLA mismatched in 21 (24%) patients; 4 (5%) received haploidentical HCT. GVHD prophylaxis consisted of tacrolimus/sirolimus (n=54), tacrolimus/sirolimus/MTX (n=11), tacrolimus or cyclosporine/MTX (n=7), tacrolimus or cyclosporine/MMF (n=7), post-transplant cyclophosphamide/tacrolimus/MMF (n=5) and other (n=3). Source of stem cells was PBSC in 77 (88%), bone marrow in 5 (6%), and cord blood in 5 (6%) patients. At the time of allo-HCT, there were a total of 25 (29%) patients in complete remission (CR1 n=15, CR2+ n=10), 25 (29%) patients in partial remission 22 (25%) with induction failure and 14 (16%) with relapsed disease. The median follow-up among survivors was 6.9 years (range 1.1-15.5). The 5- and 10-year PFS was 47% (95% CI: 36%-58%) and 38% (95% CI: 26%-50%), respectively. The 5- and 10-year OS was 53% (95% CI: 41%-63%) and 42% (95% CI: 29%-54%), respectively (Fig.1). Relapses at 5 and 10 years were both 24% (95% CI: 16%-34%), while NRM at 5 and 10 years was 28% (95% CI: 19%-39%) and 37% (95% CI: 25%-50%), respectively. At day 100 after allo-HCT, the rates of acute GVHD grade II-IV were 41% (95% CI: 30%-51%) and grade III-IV of 16% (95%CI: 9%-25%). Chronic GVHD rates at 3 years were 62% (95% CI: 51%-72%), with extensive GVHD of 55% (95% CI: 44%-65%). On univariate analysis, age (> 60 or not), sex, TBI-based conditioning, donor type (MSD vs MUD), stem cell source or remission status prior to allo-HCT did not predict for overall survival in our study. Conclusions: Our results constitute the largest reported single-institution series with a long-term follow-up on allo-HCT outcomes in patients with aggressive T-cell NHL. The 5-year PFS and OS of 47 and 53%, respectively, are encouraging for the high-risk T-cell NHL patients with limited treatment options. Disclosures Salhotra: Celgene: Other: Research Support; Kadmon Corporation: Other: Non paid consultant. Popplewell:City of Hope: Employment. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Mei:Seattle Genetics, Inc.: Research Funding. Zain:spectrum: Honoraria; Seattle Genetics: Honoraria, Speakers Bureau.

Introduction: Nivolumab (nivo) is an anti-PD-1 antibody that restores effective anti-tumor immune responses and is tolerable and effective in patients (pts) with relapsed/refractory (RR) Hodgkin lymphoma (HL). Nivo combined with brentuximab vedotin (BV) as first salvage therapy (tx) yields high response rates and favorable progression-free survival (PFS) as a bridge to autologous stem cell transplantation (ASCT) in pts with RR HL. With the frontline approval of BV, it is necessary to evaluate the role of nivo as salvage tx separate from BV. We report interim results of a phase 2 trial evaluating PET-adapted nivo or nivo + ICE (NICE) chemotherapy as first salvage tx in RR HL. Methods: In this prospective, multicenter trial, pts with biopsy-proven RR HL after frontline tx received 3 mg/kg nivo every 2 weeks for up to 6 cycles (C). PET-CT was performed after C3 and C6. After C6, pts in CR proceeded to ASCT while pts not in CR received NICE for 2 cycles. The primary endpoint was complete response rate according to 2014 Lugano classification. PFS and overall survival (OS) were calculated using the Kaplan Meier method. Results: 39 pts were evaluable for toxicity; 37 were evaluable for response. Baseline characteristics are shown in Table 1. 32 pts received nivo alone and 7 pts received nivo/NICE. 32 pts completed study tx, 2 pts continue on protocol tx, 1 pt discontinued early in CR to undergo ASCT, 2 pts discontinued nivo early due to nivo-related adverse events (AE, 1 pt = Gr 4 altered mental status, 1 pt = Gr 2 pneumonitis), 1 pt discontinued due to unrelated death during nivo (Gr 5 sepsis due to untreated dental abscess), 1 pt withdrew due to refusal to receive NICE following nivo. After C3 of nivo, the overall response rate (ORR) was 89% (33/37), with a CR rate of 59% (22/37), partial response (PR) rate of 30% (11/37), and 2 pts each had stable disease (SD) and PD. After C6 of nivo (n=31), the ORR was 90%, with 24 CR (77%), 4 PR (13%), and 3 PD. Thus, including pts who stopped nivo early (due to toxicity or insufficient response and switch to NICE), at the end of nivo (n=37, not including 2 pts with ongoing tx) the ORR was 78%, with 26 CR (70%), 3 PR (8%), 1 pt with SD and 5 with PD. 7 pts were treated with NICE and all responded (100% ORR) with 6 CR (86%) and 1 PR (14%). At the end of protocol tx (nivo or nivo/NICE) including all pts (n=37) except the 2 who remain on ongoing tx, the ORR was 89% with 32 CR (86%) and 1 PR (3%). Among 35 evaluable pts, the ORR was 94% and CR rate was 91% (Figure). 27 pts proceeded to ASCT directly after protocol tx, 1 pt is awaiting ASCT, and 4 pts in CR refused ASCT. One pt with PR after NICE responded to subsequent salvage tx and underwent ASCT. In pts who had ASCT, a median of 2 (range 1-4) stem cell collections were required, a median of 4.7x106 CD34+ cells/kg (range 3.12 - 16.23) were collected, and the median time to neutrophil and platelet engraftment were 11 and 12 days, respectively. The median follow-up time in all pts (n=39) was 10.5 months (range 1.6-24.5 mo). The 1-year PFS was 79% (95 CI, 63-98%) and 1-year OS was 97% (95 CI, 92-100%). Two PD events occurred in pts who had CR but refused ASCT. There were 2 PD events in pts who completed therapy and proceeded to ASCT - both were in pts who required NICE. The most common AEs related to nivo alone (n=39) were fatigue (28%), rash (18%), fever (15%), thrombocytopenia (10%), and dyspnea (10%), and all were grade (gr) 1-2. Only 2 pts had gr 3-4 nivo-related AE, 1 pt had gr 3 thrombocytopenia and another pt had gr 4 altered mental status and gr 3 tumor lysis syndrome. Among 7 pts who received NICE, the most common AEs were nausea (71%), vomiting (57%), anemia (43%), fatigue (43%), hypertension (43%), and hyponatremia (29%) - all were gr 1-2. The only Gr 3-4 NICE-related AE was gr 4 neutropenia in 1 pt. Conclusion: PET-adapted nivo followed by NICE in patients without CR is a well-tolerated and effective first salvage approach in pts with RR HL. In our cohort, nivo alone was an effective bridge to ASCT in a majority of pts, sparing them the toxicity of traditional salvage chemotherapy. Pts who did not achieve CR with nivo were effectively salvaged by NIVO+ICE Disclosures Herrera: Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Chen:Autolus Therapeutics: Employment. Palmer:Gilead Sciences: Consultancy. Mei:Seattle Genetics, Inc.: Research Funding. Popplewell:City of Hope: Employment. Kwak:Pepromene Bio: Consultancy, Equity Ownership, Research Funding; InnoLifes: Consultancy, Equity Ownership; Xeme BioPharma, Inc: Consultancy, Equity Ownership; Enzychem LifeSciences: Consultancy; Celltrion, Inc.: Consultancy; Celltrion Healthcare: Consultancy. Lee:Seattle Genetics, Inc.: Research Funding.

Extramedullary relapse following allogeneic hematopoietic transplant (alloHCT) for acute leukemia was first highlighted as a problem by a survey of European Group for Blood and Marrow Transplantati...

We conducted a matched-cohort analysis of autologous transplant conditioning regimens for diffuse large cell lymphoma in 92 patients treated with either radioimmunotherapy (RIT) or total body irradiation (TBI)–based conditioning regimens. The RIT regimen consisted of 0.4 mCi/kg of 90Y-ibritumomab tiuxetan plus BEAM (BCNU, etoposide, cytarabine, melphalan). The TBI-based regimen combined fractionated TBI at 1200 cGy, with etoposide and cyclophosphamide. Five factors were matched between 46 patient pairs: age at transplant ±5 years, disease status at salvage, number of prior regimens, year of diagnosis ±5 years, and year of transplantation ±5 years. Patients in the TBI group had higher rates of cardiac toxicity and mucositis, whereas Z-BEAM patients had a higher incidence of pulmonary toxicity. Overall survival at 4 years was 81.0% for the Z-BEAM and 52.7% for the TBI group (P = .01). The 4-year cumulative incidence of relapse/progression was 40.4% and 42.1% for Z-BEAM and TBI, respectively (P = .63). Nonrelapse mortality was superior in the Z-BEAM group: 0% compared with 15.8% for TBI at 4 years (P < .01). Our data demonstrate that RIT-based conditioning had a similar relapse incidence to TBI, with lower toxicity, resulting in improved overall survival, particularly in patients with ≥2 prior regimens.

Randomized trials comparing autologous stem cell transplant (ASCT) to conventional chemotherapy have demonstrated superior survival among HIV-negative ASCT patients with relapsed non-Hodgkin lymphoma (NHL). Recent trials explored the feasibility of ASCT in the HIV setting. Although these studies have shown that ASCT in HIV-positive NHL patients (HIVpos-NHL) is well tolerated, the impact of HIV infection on long-term transplant outcome is not well characterized. Ongoing comparison of long-term survival following ASCT in HIVpos-NHL patients and HIVneg-NHL patients will allow investigators to explore whether there should be inclusion of HIVpos-NHL patients in ASCT trials. To study long-term outcome we conducted a single-institution matched case-controlled study in HIVpos-NHL patients (cases) and HIVneg-NHL patients (controls). Twenty-nine patients with HIVpos-NHL were matched with HIVneg-NHL controls on sex, time to ASCT, year of transplant, histology, age, disease status, number prior regimens, and conditioning regimen. Nonrelapse mortality (NRM) was similar: 11% (95% confidence interval [CI]: 4%-28%) in HIVpos-NHL patients and 4% (95% CI: 1%-25%) in HIVneg-NHL controls (P = .18). Two-year disease-free survival (DFS) for the HIVpos-NHL patients was 76% (95% CI: 62%-85%) and 56% (95% CI: 45%-66%) for the HIVneg-NHL controls (P = .33). Overall survival was also similar; the 2-year point estimates were 75% (95% CI: 61%-85%) and 75% (95% CI: 60%-85%), respectively (P = .93), despite inclusion of more poor risk HIVpos-NHL patients. These results provide further evidence that HIV status does not affect the long-term outcome of ASCT for NHL, and therefore HIV status alone should no longer exclude these patients from transplant clinical trials.

Plerixafor is a reversible antagonist of the CXC chemokine receptor 4 (CXCR4), preventing binding of the chemokine stromal-cell-derived factor-1 α (SDF-1 α ) [1]. Phase III trials comparing stem cell mobilization for autologous transplant with plerixafor plus granulocyte colony stimulating factor (G-CSF) versus placebo plus G-CSF demonstrate increased effi cacy of the plerixafor arm [2,3]. Over twice as many patients achieve the target CD34 collection endpoint within two apheresis attempts with the plerixafor/G-CSF combination compared to placebo/G-CSF [2,3]. Plerixafor is approved by the Food and Drug Administration (FDA) for subcutaneous administration in conjunction with G-CSF, for hematopoietic stem cell mobilization in patients with multiple myeloma and non-Hodgkin lymphoma. For stem cell mobilization in patients with multiple myeloma, there is growing concern over suboptimal mobilization with G-CSF alone in older patients with myeloma, or in those with extensive lenalidomide exposure [4]. For these compromised patients, cyclophosphamide (CY) priming prior to mobilization is often used, although this may still be insuffi cient, since the goal is frequently adequate stem cell collection for two transplants. Two retrospective studies have reported on the feasibility of using rescue plerixafor following chemotherapy combined with G-CSF-based priming [5,6]. Traditionally this has been achieved using subcutaneous plerixafor, given 9 – 11 h prior to apheresis. Intravenous (IV) plerixafor may result in a faster and higher peak in peripheral CD34 cells, allowing same-day administration. We report here a phase I trial using planned IV plerixafor plus CY priming for mobilization in patients with multiple myeloma. Th is study was approved by the City of Hope Institutional Review Board and all patients were consented. Th e trial was registered with ClinicalTrials.gov (NCT01074060). Patients aged 18 – 70 years with multiple myeloma who were approved for autologous hematopoietic cell transplant (HCT) were eligible to receive plerixafor. Patients who had received prior autologous or allogeneic HCT were excluded from plerixafor treatment.

Triplet regimens combining an immunomodulatory agent, a proteasome inhibitor (PI), and a steroid are used to treat newly diagnosed and relapsed multiple myeloma (MM). Although ixazomib (Ix), an oral PI with single agent activity, can be combined with lenalidomide (LEN), patients (pts) with relapsed/refractory (R/R) MM are often LEN-refractory. Pomalidomide (POM) has single agent activity in LEN-refractory disease, and both POM and Ix also show activity in poor cytogenetic risk pts. Methods: Primary objectives: 1) determine the maximum tolerated dose (MTD) of Ix in combination with standard dose POM and dexamethasone (DEX), and 2) evaluate the anti-tumor activity of the triplet. The treatment regimen included two dose levels (3 mg and 4 mg) of Ix on days 1, 8, 15; POM 4 mg days 1-21; and DEX 40 mg days 1, 8, 15, 22, of a 28 day cycle. Eligibility: R/R MM after >1 prior therapy, LEN-refractory, and ≤ grade(gr) 1 peripheral neuropathy (PN). Pts were treated until progression or unacceptable toxicity. Design: Phase I study utilizing a standard 3+3 design; dose limiting toxicities (DLTs) defined during cycle 1. Results: 32 pts treated, 31 evaluable for toxicity and response. Pts received a median 4 cycles (range 1-13); median follow-up is 5.5 months (range 1.8-21.1). Six pts treated on DL1, 25 treated on DL2, the MTD/Phase II dose (P2D). Median age: 62 years (range 38-84); median time from diagnosis: 3.7 years (range 1.0-8.9); median number prior therapies: 3 (range 1-5); prior transplant: n = 23 (74%); double (LEN/Bortezomib[BOR]) or triple (LEN/BOR/Carfilzomib[CFZ]) refractory: 19 (61%). Phase I: DL1 expanded to n=6 after 1/3 pts experienced DLT (gr3 lung infection); no further DLT seen on DL 1 or 2. Adverse events (AEs) related to POM and/or Ix: ANC decrease Gr1/2 n=11 (35%), Gr3/4 n=10 (32%), platelet decrease Gr1/2 n=9 (29%), lymphocyte decrease Gr1/2 n=8 (26%), Gr3/4 n=11 (35%), PN Gr1/2 n=9 (29%), no Gr3/4. Response: Phase I and II, n=31 pts treated. ORR: 45% (6 VGPR, 8 PR); Clinical Benefit Rate (CBR): 81% (6 VGPR, 8 PR, 3 MR, 8 SD). In the pts with high risk cytogenetics (7[23%] 1q, 3[10%] 17p, 2[6%] t(4;14)) an ORR of 58% (3 VGPR, 4 PR) was seen, and the CBR was 83%. In the double or triple refractory pts, an ORR of 26% and CBR of 79% (1 VGPR, 4 PR, 3 MR, 7 SD) were observed. Conclusions: Ix/POM/DEX is a well-tolerated oral combination therapy, and responses were seen even at DL1 and in high risk patients, including those with poor-risk cytogenetics or advanced refractory disease. Disclosures Kapoor: Celgene: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Kumar:Millennium: Consultancy, Research Funding; AbbVie: Research Funding; Glycomimetics: Consultancy; Sanofi: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy; Kesios: Consultancy; Onyx: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding. Lonial:Novartis: Consultancy; BMS: Consultancy; Janssen: Consultancy; Merck: Consultancy; Celgene: Consultancy; Onyx: Consultancy; Novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy; Millenium: Consultancy; Janssen: Consultancy; Onyx: Consultancy. Nathwani:Carevive Systems, Inc.: Research Funding. Forman:Mustang Therpapeutics: Other: Construct licensed by City of Hope. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding.

The study analyzed outcomes of a consecutive case series of 37 patients with peripheral T-cell non-Hodgkin lymphoma, from related and unrelated donors, using allogeneic hematopoietic cell transplant (allo-HCT), between the years 2000 and 2007. All patients were pretreated; the majority had either relapsed or progressive disease (n = 25, 68%), 13 had cutaneous histologies (CTCL), and all were ineligible for autologous transplant. Fully ablative conditioning regimens were used in 13 patients while 24 patients underwent reduced intensity conditioning (RIC). At 5 years the overall survival (OS) and progression-free survival (PFS) probabilities were 52.2% and 46.5%, respectively. At the time of analysis, nine (24.3%) patients had either relapsed (n = 6) or progressed (n = 3) post allo-HCT. The cumulative incidences of relapse/progression and non-relapse mortality at 5 years were 24.3% and 28.9%. No statistically significant variables for survival or relapse were discovered by univariate Cox regression analysis of disease and patient characteristics; differences between CTCL and other histologies were not significant. The median follow-up of 64.0 months (range: 16.4-100.4) indicates a mature data-set with probable cure in the survivors. The relapse/progression curves reached and maintained plateaus after 1 year post-transplant, demonstrating that long-term disease control is possible after allo-HCT in patients with peripheral T-cell lymphoma with advanced disease.

Background: Hodgkin lymphoma (HL) patients who are relapsed/refractory to induction chemotherapy are salvaged with multiagent chemotherapy such as ICE followed by autologous hematopoietic cell transplantation (AHCT). This strategy yields a 2 year EFS of ~65%. Brentuximab vedotin (BV), an antibody drug conjugate, selectively induces apoptosis of CD30+ HL. We previously reported the response rates and toxicities of a multicenter phase II trial evaluating BV as first line salvage therapy in relapsed/refractory HL prior to AHCT. We now report the transplant outcome results of BV as first line salvage therapy in relapsed/refractory HL followed by AHCT. Patients and Methods: This is a prospective, multicenter (City of Hope, Cornell Weill Medical College), phase II trial in patients with relapsed/refractory HL prior to AHCT. All patients had biopsy proven relapsed/refractory HL post induction therapy with ABVD, BEACOPP or a combination +/- consolidative XRT. Patients were treated with 1.8 mg/kg of BV intravenously every 3 weeks for a maximum of 4 cycles. Patients who do not achieve CR after BV are allowed to receive multiagent salvage chemotherapy prior to AHCT. The primary endpoint was the best response rate according to revised Cheson criteria. Secondary endpoints were toxicities, stem cell mobilizations, engraftment analysis, and 2 year PFS/OS post AHCT Results: 37 patients were accrued (Table 1). The overall best response (CR+PR) rate was 69% and CR rate was 35%. 33/37 (89%) patients successfully proceeded to AHCT (1went to alloHCT, 3 could not be salvaged). Among the 13 CR patients, all proceeded to AHCT without additional chemotherapy. Among the 12 PR patients, 4 proceeded to AHCT without additional chemotherapy while 8 received additional chemotherapy (ICE/DICE/IGEV/GND). All patients with SD/PD received additional chemotherapy with exception of 1 patient who received XRT. 24/33 patients were in CR at with 8/33 in PR and 1/33 in SD at time of AHCT. All patients were primed with cyclophosphamide/G-CSF and 9 patients received plerixafor per institutional guidelines. The median time to collect was 2 days and median cells collected was 5.9 x 10^6 CD34 cells. As AHCT conditioning regimens, 22 patients received BEAM, 9 patients received CBV, and 2 patients received BEAM plus yttrium-90 labeled anti-CD25. The median time to reach ANC engraftment was 11 days and platelet engraftment was 14 days. The response rate post AHCT was 100% in all evaluable patients. Peritransplant toxicities are not evaluated on all patients but will be updated by ASH to include all 33 patients. With a median follow up of 17.6 months, the 18 month PFS is 73%, OS is 97%, and NRM is 3%. When stratified by disease status at time of AHCT, the 18 month PFS is 78% for CR and 50% for non CR patients. The 18 month OS is 89% for CR and 88% for non CR patients. When stratified by patients who received BV only vs. BV followed by combination chemotherapy, the 18 month PFS is 80% for BV only vs. 65% for BV followed by combination chemotherapy (Fig 1). The 2 year PFS and OS will be updated by ASH presentation. Conclusion: BV as first line salvage therapy results in 89% of patient successfully going to AHCT. The overall 18 month PFS of patients who underwent AHCT is 73%, which compares favorably with historical control. Patients who received BV as the only salvage therapy prior to AHCT without combination chemotherapy had an 18 month PFS of 80%, which also compares favorably with historical control. BV prior to AHCT did not negative impact stem cell collection, engraftment, 18 month NRM, PFS or OS. Given the excellent post transplant outcome, BV as first line salvage is a viable option for relapsed/refractory HL patients undergoing AHCT. Table 1. Characteristics N (%) or Median (Range) Age 34 (11-67) Institution City of Hope Weill Cornell 31 (84%) 6 (16%) Stage at Diagnosis I-II III-IV 19 (51%) 18 (49%) B symptoms 23 (62%) Bulky Disease (> 5 cm) 32 (86%) Induction Chemotherapy ABVD ABVD/BEACOPP ABVE-PC 34 (92%) 2 (5%) 1 (3%) Prior XRT 9 (24%) Best Response to Induction Primary Refractory Relapsed (within 7 months) 24 (65%) 13 (35%) Figure 1. Figure 1. Disclosures Chen: Seattle Genetics, Inc.: Consultancy, Other: Travel expenses, Research Funding, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau. Off Label Use: 90-Y ibritumomab tiuxetan is a radiotherapeutic antibody targeting CD20. It is part of a regimen indicated for treating patients with relapsed/refractory, low-grade or follicular B cell non-Hodgkin lymphoma (NHL), or patients with previously untreated follicular NHL who achieved a complete or partial response to first-line chemotherapy. Martin:Genentech, Inc.: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES, Speakers Bureau; Janssen: Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES; Celgene: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES; Gilead: Consultancy. Siddiqi:Seattle Genetics: Speakers Bureau; Kite pharma: Other: attended advisory board meeting; Pharmacyclics/Jannsen: Speakers Bureau. Nademanee:Spectrum: Research Funding; Gilead: Consultancy; Celgene: Consultancy; Seattle Genetics Inc.: Research Funding. Forman:Mustang: Research Funding; Amgen: Consultancy.

Background: MCL patients deemed fit for high dose regimens undergo induction therapy with rituximab and chemotherapy (HyperCVAD/CHOP/bendamustine) followed by consolidation with ASCT (autologous stem cell transplantation). R-HyperCVAD is a dose intense regimen with high response rates for MCL when used in the upfront setting (ORR 97%; CR 38%; Romaquera JE, JCO 2005). R-bendamustine and R-CHOP are contemporary regimens with similar efficacy (ORR 85-93%; Rummel MJ, Lancet 2013). In a recent randomized phase II trial (SWOG 1106) accrual to the HyperCVAD arm was stopped due to higher than expected rates of peripheral blood stem cell (PBSC) mobilization failure. Methods: To assess the impact of these regimens on PBSC collection, we performed a retrospective analysis of newly diagnosed MCL patients undergoing induction chemotherapy with R-HyperCVAD versus R-CHOP/R-bendamustine and referred to transfusion medicine for PBSC collection prior to ASCT from 01/2009 to 12/2013. Patients were not allowed any salvage chemotherapy. The primary end point was successful stem cell collection defined as ability to collect ≥2.1 million CD34 cells/Kg. Secondary endpoints were number of days of apheresis, use of pleraxifor as mobilization salvage and total number of CD34+ cells collected. Results: A total of 91 MCL patients were eligible for analysis (Table 1). Patients who received HyperCVAD were younger at the time of collection (median: 56 vs 62 years; p Ultimately, 81/91 (89%) patients proceeded to high dose chemotherapy and ASCT [82% in HyperCVAD versus 96% in non-HyperCVAD (p=0.06)]. Four of the remaining 10 patients with mobilization failure (all from HyperCVAD arm) proceeded to Allogeneic HCT, the remaining 6 patients did not receive any further treatment. Conclusion: Patients with MCL receiving R-HyperCVAD chemotherapy in the frontline setting have a significantly higher rate of PBSC mobilization failure and collect significantly fewer CD34+ PBSCs when compared to patients treated with comparable regimens. R-HyperCVAD should be used with caution in patients with newly diagnosed MCL who are eligible for ASCT. Some patients failing mobilization may be salvaged with use of plerixafor. Table 1: Patient, Transplant Characteristics Variable Hyper-CVAD, n=45Median (Range)N (%) Other, n=46Median (Range)N (%) Patient Gender Female Male 9 (20) 36 (80) 12 (26) 34 (74) Age at Collection Completion (years) 56 (40 – 68) 62 (36 – 74) Time from Diagnosis to Start of Collection (months) 4.5 (2.3 – 65.3) 6.4 (3.9 – 69.4) Stage at Diagnosis I II III IV 1 (2) 3 (7) 2 (4) 39 (87) 2 (4) 1 (2) 6 (13) 37 (81) Bone Marrow Involvement at Diagnosis No Yes Not Done 9 (20) 35 (78) 1 (2) 13 (28) 32 (70) 1 (2) Treatment after Chemotherapy Auto Transplant Allo Transplant No Transplant 37 (82) 4 (9) 4 (9) 44 (96) 0 (0) 2 (4) Mozobil Era (08/16/2009) Pre Post 8 (18) 37 (82) 3 (7) 43 (93) Mozobil Usage No Yes 29 (64) 16 (36) 30 (65) 16 (35) Number of Collections 4 (1 – 9) 3 (2 – 8) Total CD34 4.5 (0.3 – 100.5) 5.3 (0.7 – 76.6) Total CD34 (Failure Rate) < 2.1 >/= 2.1 8 (18) 37 (82) 2 (4) 44 (96) Disclosures Chen: Seattle Genetics: Honoraria, Research Funding, Speakers Bureau.

Abstract 4553 High dose (HD) therapy followed by autologous hematopoietic stem cell transplantation (AHCT) has been the mainstay of treatment in patients diagnosed with advanced neuroblastoma (NBL). Busulfan and Melphalan (Bu/Mel) was demonstrated to be superior to other HD regimens and is widely considered as standard treatment. (Ladenstein, Bone Marrow Transplant. 2008 Jun;41 Suppl 2:S118-27), Topotecan (Topo) with or without cyclophosphamide has demonstrated efficacy in treatment of advanced NBL (Kushner, Cancer 116: 3054, 2010). We hypothesize that adding Topo to Bu/Mel as HD therapy followed by AHCT is well tolerated and will result in favorable outcomes. Patients and Methods: Patients with NBL, stage III or IV were eligible and consented to participate in the study. Seven patients were enrolled, the median age was 2.65 yrs (range 2.3 – 4.x yrs), and there were 4 males (57%). All patients were initially treated on COG protocols and in all cases a complete response was documented prior to proceeding with AHCT. Autologous hematopoietic cells were collected, following mobilization with G-CSF, after 2 (n=6) or 3 (n=1) cycles of chemotherapy. All patients were given post transplant radiation therapy to the primary tumor bed and cis-retinoic acid, 3 patients were also given monoclonal antibodies. Data on engraftment, toxicities, event free survival (EFS) and overall survival (OS) were analyzed. Results: The median cell dose was 6.62 × 106 CD34+/kg (5.57×106−7.33 × 107). Engraftment occurred promptly in all patients. Myeloid and platelet recovery occurred at a median of 12 (8–17 days) and 22 (17–41 days), respectively. The treatment was well tolerated with no grade 4 or higher toxicities. Grade 3 toxicities included; mucositis (n=7, 100%), electrolyte imbalance (n=3), diarrhea (n=3), autoimmune hemolysis (n=1) and epistaxis (n=1). Three patients suffered disease recurrence, 156, 821 and 899 days post AHCT. One patient is dead and two continue salvage therapy 55 and 52 months, post transplant, respectively. The 4-year OS and EFS were 87% to 57%, respectively. Conclusion: This novel regimen of Topo/Bu/Mel appears to be well tolerated with low TRM and promising EFS and OS. Further and larger studies are required to establish its role as HD therapy prior to AHCT in patients with advanced NBL. Disclosures: No relevant conflicts of interest to declare.

6545 Background: RIC allo-HCT has reduced transplant-related mortality (TRM) in patients with relapsed NHL. However, relapses do occur despite potential graft vs. lymphoma (GVL) effect. We hypothesized that adding Zevalin to Flu/Mel may improve disease control and reduce relapse post allo-HCT. Methods: Patients received In- Zevalin on day -21 followed by 90Y- Zevalin 0.4mCi/kg on day -14, flu 25 mg/m2 daily on days -9 to -5 and mel 140 mg/m2 on day -4. Rituximab (R) level was measured on Day -22 and -15 and if the level was ≥ 10 μg/ml, R was not given prior to In-Zevalin or 90Y- Zevalin to enhance biodistribution. Tacrolimus and sirolimus was used for GVHD prophylaxis. Between 10/2007 and 11/2011, 31 were treated. Median age 55 (range 27-67), median regimen =3 (range 2-8). Median time from diagnosis to HCT was 20 mo (range 5-105). Histology: DLBCL (including transformed lymphoma)=14 (45%), MCL=7 (23%), FL=5 (16%) and SLL/CLL=5 (16%). Disease status at HCT: 1CR=7, Relapse=9, ≥2CR=5, primary refractory =10. Fifteen had chemoresistant and 19 had FDG PET+ at HCT. Donors: sib=13, URD=18. Results: All patients engrafted with the median time to ANC ≥500 and platelet ≥ 20,000 was 14 (range 10-28) and 13.5 days (range 11-28), respectively. There were 10 deaths from disease progression (2) infection (5) GVHD (1) and multi-organ failure (2). TRM at day +100 and at 1 yr was 6.5% and 17%, Five with DLBCL relapsed between 3-7 mos. Grade II-IV acute GVHD was 65%, Grade III-IV was 16%, chronic GVHD was 65%. Fifteen became PET- at day +100 while 4 remained PET+ and relapsed. Twenty-one are alive at a median followup of 24 mos (range 2-46). The 2 yrs OS and PFS was 65% (95% CI, 51-75%) and 57% (95% CI, 46-67%), respectively. Univariate analysis identified disease status predict for OS and PFS while histology predict for PFS. Conclusions: This study demonstrates the feasibility of adding Zevalin to flu/mel in the allo-HCT setting for B-cell NHL and suggest that this approach could be used to provide early disease control before GVL effect takes place. Innovative approaches should be explored in DLBCL.

6547 Background: Gene expression profiling has improved risk stratification of diffuse large B-cell lymphoma (DLBCL) in the first line setting as shown by DNA microarray analysis and immunohistochemistry (IHC). 5-year overall survival (OS) for germinal center B-cell-like (GCB) DLBCL is significantly better than that for non-GCB DLBCL in newly diagnosed patients. However, in the relapsed/refractory setting, autologous stem cell transplant (ASCT) appeared to overcome the poor prognosis of cell of origin as defined by IHC using CD10, Bcl6 and MUM1 and there was no difference in survival between GCB and non-GCB groups. Ibritumomab tiuxetan (Z)-BEAM conditioning regimen for ASCT in DLBCL has produced promising response rates and progression free survival (PFS). The role of poor risk molecular markers in predicting outcome with the novel conditioning regimen Z-BEAM is unknown. Methods: We evaluated cell of origin (GCB, non-GCB) using IHC in 36 patients undergoing ASCT with Z-BEAM conditioning from 2002 to 2010. Median age of the patients was 54.5 years. There were 12 females and 24 males. 6 patients were in 1st CR/PR ( 17%), 12 had induction failure disease (33%), 9 were in 1st relapse (25%), 1 in 2nd relapse (3%) and 8 were in ≥2nd CR (22%). 27 patients had chemosensitive disease (75%) and all had prior rituximab exposure. Median number of prior treatments was 2. IPI at transplant was mainly low risk (78%). 22 patients had GCB (61%) and 14 (39%) had non-GCB DLBCL. Results: Median follow up is 25.6 months. 12 patients relapsed (33%) and 9 died (25%). The major cause of death is relapse/disease progression. At 2 years, median OS is 79% and median PFS is 64%. No significant difference in 2 year OS and PFS is noted between the GCB and non-GCB groups (p=0.07 and 0.06 respectively). Conclusions: Z-BEAM conditioning for ASCT may overcome the poor prognostic effect of non-GCB DLBCL in relapsed/refractory disease. Further evaluation of cell of origin using new markers like GCET1, LMO2 and FOXP1 could confirm these results as there seems to be better concordance of these markers with DNA microarray analysis.

Abstract 664 Background: The prognosis of patients with Hodgkin lymphoma (HL) who relapse following autologous hematopoietic cell transplantation is poor. Although reduced intensity allogeneic hematopoietic cell transplantation (RIC allo-HCT) can induce durable remissions in some patients with relapsed/refractory HL, its use is limited by a lack of disease control prior to transplantation. Brentuximab vedotin (b-vedotin, SGN-35), a novel antibody-drug conjugate, has a 75% objective response rate in patients with relapsed/refractory HL (Chen 2011). To examine the impact of b-vedotin on RIC allo-HCT, we performed a retrospective analysis of relapsed/refractory HL patients who received b-vedotin at City of Hope National Medical Center (COH) and Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) and then went on to receive RIC allo-HCT. Methods: Between October 2008 and July 2011, 46 patients with relapsed/refractory HL received b-vedotin at COH and SCCA through Seattle Genetics trials (SGN-35-03, 06, 07, and 08). 16/46 (34.8%) patients subsequently underwent RIC allo-HCT, including 12 at COH (2/12 were transplanted at University of Utah and Wellington Hospital) and 4 at the SCCA. The baseline characteristics are listed in Table 1 . All 12 COH patients received fludarabine/melphalan as the conditioning regimen, 5/12 used matched related donors and 7/12 used matched unrelated donors. 10/12 received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis and 2 patients received mycophenolate mofetil (MMF) and cyclosporine (CSP). In contrast, 3/4 patients transplanted at the SCCA received haploidentical donors transplantation using fludarabine/cytoxan/2Gy TBI conditioning and cytoxan/tacrolimus/MMF as GVHD prophylaxis while 1/4 underwent conditioning using 2Gy TBI followed by CSP/MMF prophylaxis. Patients were monitored for engraftment, aGVHD, cGVHD, chimerism, and infectious complications per institutional standards. Each institutional review board approved the retrospective analysis of individual center data and we plan to present combined analysis of COH/SCCA data at ASH. Results: At COH, the 1 year PFS was 90% (95% CI: 54.0, 98.2) and the 1 year OS was 100% with a median follow-up of 13.2 months (range: 2, 20), In addition, the 1 year relapse rate was 10% (95% CI: 1.7, 46) and the non-relapse mortality at 1 year was 0%. Likewise, all 4 of the SCCA patients are alive and progression-free with a median follow up of 7.2 months (range: 2.9, 19). For the entire cohort the rates of aGVHD and cGVHD were 25% and 63%, respectively. There was no grade III-IV aGVHD and only 1/16 (6.3%) with extensive cGVHD. There was no delay of engraftment or increased incidence of CMV/EBV infections ( Table 1 ). The only patient who relapsed after RIC allo-HCT had progressive disease at the time of transplantation, and 276 days had elapsed between the last dose of b-vedotin to RIC allo-HCT. Table 1 . COH (n=12) FHCRC/SCCA (n=4) Median age (range) 32 (23, 55) 28.5 (25, 32) Median number of prior regimens (range) 3.4 (2, 6) 5 (2, 6) Prior Auto-HCT 11/12 3/4 Previous XRT 7/12 2/4 Best response to b-vedotin 5 CR, 7 PR 2 CR, 2 SD Median number of cycles of b-vedotin (range) 9.5 (2, 14) 7 (4, 16) Intermittent therapy between b-vedotin and allo-HCT 3/12, GVD 2/4, 1 RICE/ASCT, 1 DHAP Disease status at end of b-vedotin 4 CR, 4 PR, 4 PD 2 CR, 1 SD, 1 PD (no bulky disease) Disease status at transplantation 5 CR, 5 PR, 2 PD (no bulky disease) 2 CR, 1 PR, 1 SD Median time from last dose b-vedotin to allo-HCT (range) 41 days (30, 276) 82.5 days (40, 162) Type of transplant 5 MRD, 7 MUD 3 haplo, 1 MRD Conditioning regimen 12/12 fludarabine/melphalan 3 Flu/Cy/2Gy TBI, 1 2Gy TBI GVHD prophylaxis 10/12 Tacro/Siro 2/12 CSP/MTX 3 Cy/TAC/MMF, 1 CSP/MMF WBC engraftment (range) 14 days (12, 20) 12 (0, 17) Plt engraftment (range) 11 days (9, 16) 8 (0, 14) Chimerism 100% 100% aGVHD II-IV, III-IV 25%, 0% 25%, 0% cGVHD extensive 75%, 8.3% 25%, 0% EBV/CMV (PCR reactivation only) EBV 2/12, CMV 2/12 EBV 0/4, CMV 1/4 Conclusion: These data suggest that b-vedotin prior to RIC allo-HCT in HL can yield prolonged disease control without a delay in engraftment, increase in non-relapse mortality, aGVHD, cGVHD, and post transplant infectious complications. Such a strategy may allow more patients with relapsed or refractory HL to gain sufficient pre-transplant disease control to undergo this potentially curative procedure. Disclosures: Chen: Seattle Genetics: Consultancy, Research Funding. Off Label Use: SGN-35, a novel antibody drug conjugate, is used as salvage therapy for relapsed hodgkin lymphoma prior to allogeneic hematopoietic cell transplantation. Grove: seattle genetics: Employment. Gopal: Bio Marin: Research Funding; SBio: Research Funding; Pfizer: Research Funding; Abbott: Research Funding; Millenium: Honoraria, Speakers Bureau; Cephalon: Research Funding; Piramal: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Spectrum: Research Funding; GSK: Research Funding; Biogen-Idec: Research Funding.

Abstract 3423 Poster Board III-311 Long term survival for patients with chemo-refractory non-Hodgkin lymphoma (NHL) is poor even with high dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Strategies such as novel transplant conditioning regimens and post transplant maintenance therapy are being evaluated to improve outcomes. Herein we report on the results of a phase II study designed to assess the impact of a novel radioimmunotherapy (RIT) based conditioning regimen of Y90 ibritumomab tiuxetan in conjunction with high dose BEAM (BCNU, Etoposide, Ara–C, Melphalan) in patients with poor risk NHL. Between May 2002 and Jan 2009, 31 patients who were either primary induction failure (n=18) or in partial remission (n=13) underwent HDC with Y90 plus BEAM. Patients received an imaging dose of Indium 111 on day -21 followed by a treatment dose of Y90 (0.4mCi/kg) on day-14. HDC with BEAM was started on day -7. The median age at ASCT was 57 (range: 19–70). The majority of patients were male (n=23, 74%) and had advanced stage disease (III or IV) at the time of diagnosis, (n=23, 74%). The histologies included Follicular n=6, Diffuse Large B-cell n=13, Mantle cell n=8, and Transformed n=4. The median number of prior regimens was 2 (range: 1-5). All patients engrafted at a median of 11 days. At the time of analysis, 23 (74%) patients were alive, and eight had expired (seven due to relapse/progressive disease, one due to COPD). The non-relapse mortality was 3.2%. The median length of follow-up for surviving patients is 46.9 months (range: 3.3-75.0). The two-year overall survival and disease-free survival was 77.9% (95%CI: 62.7-87.6%) and 50.9% (95%CI: 40.5-60.3%) respectively for the entire cohort. However, the relapse rate in the subset of MCL pts was strikingly high and approached 80% at 4 yrs. The other subgroups had a stable DFS (figure 1). In conclusion in this poor risk group of patients Y90 plus high dose BEAM can induce responses and long term remissions, however, for patients with chemorefractory MCL other treatment approaches may be warranted. Disclosures Off Label Use: yttrium 90 in combination with high dose BEAM chemotherapy.

Abstract 1225 Poster Board I-247 Background High dose chemotherapy and AHCT can effectively salvage 50-60% of relapsed HL patients with chemosensitive disease and about 25-40% of patients with chemorefractory disease. Patients with chemosensitive disease at time of AHCT will have improved progression free survival and decreased relapse rate. Traditionally, standard response criteria use conventional computed tomography (CT) scans as the radiographic assessment tool. However, CT scans often can not distinguish between residual disease and scar tissue in malignant lymphomas status post chemotherapy. Functional imaging with FDG-PET is more sensitive and specific than CT scans for characterization of residual mass after chemotherapy, and may offer more prognostic information. The predictive value of FDG-PET on clinical outcomes among HL patients who undergo AHCT has been reported by relatively few centers. We conducted a retrospective analysis of 41 consecutive HL patients who had FDG-PET scan after at least two cycles of salvage chemotherapy and before undergoing AHCT at City of Hope National Medical Center. Aim To determine the prognostic impact of pre-transplant functional FDG-PET in predicting the outcome of AHCT in relapsed HL. Methods A total of 41 consecutive HL patients who had FDG-PET scan after at least two cycles of salvage chemotherapy and before undergoing AHCT at City of Hope National Medical Center between January 2004 and December 2008 were included in this analysis. Results Patient characteristics show median age is 36. 34 patients were chemosensitive at time of AHCT. 31 patients received BCNU/VP-16/CTX, 9 patients received BCNU/VP-16/MEL/Ara-C, and 1 patient received fTBI/VP-16/CTX. Median number of prior regimen is 2. 11 patients received radiation at induction. The patients were then categorized into FDG-PET positive (N=21) and negative (N=20) groups. The median follow-up for all patients after AHCT was 24.1 months (1.3, 54.2). The disease free survival (DFS) at 2 years for FDG-PET positive group was 51.3% (CI 39.7% - 61.8%) compared to 77.9% (CI 58.3% - 89.0%) for the FDG-PET negative (p=0.24). The 2-years overall survival (OS) for FDG-PET positive was 73.9% (CI 55.8% - 85.4%) versus 83.5% (CI 62.7% - 93.3%) for FDG-PET negative (p=0.63). There was a trend for lower relapse rate in the FDG-PET negative patients. The probability of relapse at 1 year for FDG-PET positive was 33.3% (CI 21.9% - 48.7%) compared to 11.5% (CI 3.5% - 34.0%) for FDG-PET negative (p= 0.15). There was no significant difference between the FDG-PET positive group versus FDG-PET negative group in terms of gender, time from diagnosis to transplant, conditioning regimen, number of prior regimens, radiation at induction, KPS at AHCT, or stage at diagnosis. Conclusion Pre-transplant functional FDG-PET is useful in predicting the outcomes AHCT in relapsed HL. Our data suggests that a positive FDG-PET prior to AHCT predicts for relapses and decreased DFS. Disclosures No relevant conflicts of interest to declare.

Abstract 2323 Poster Board II-300 Introduction: High dose chemotherapy with ASCT can increase overall survival (OS) in patients with poor risk or relapsed Non- Hodgkin lymphoma (NHL). Novel conditioning regimens combining radioimmunotherapy (RIT) with high dose chemotherapy have demonstrated favorable toxicity profiles and potentially improved response rates. Herein we report on 84 patients who underwent conditioning with Y90 Ibritumomab plus high dose BEAM (BCNU VP16 AraC Melphalan) and the effects of pretreatment rituximab levels on relapse. On day-23 and day-16 of conditioning pts had a blood draw for rituximab levels. If levels were &10ug/ml, pts received rituximab 250mg/m2. This was followed by pretherapy imaging with Indium 111 on day -21 and Y90 treatment on day -14. High dose BEAM chemotherapy started on day-7and all pts received rituximab 250mg/m2 at day+8. Results: The median age at ASCT was 58.5 years (range 19-78). Histologies included DLC n=36, Mantle Cell n=27, Follicular n=11, Transformed NHL n=10. Disease status at ASCT was 1st or 2nd CR n=35, 1stPR n=13, 1st or 2nd rel n=18, induction failure (IF) n=18. Median length of f/u for living pts was 34 months. All patients engrafted at a median of 11 days (anc>500) Transplant related mortality was 2.3 %. Two year OS/PFS for the entire cohort was 85.62% (77-91) and 66% (58-73). There was no significant difference in either DFS or OS based on histology (figure 1)Rituximab levels were available in a subset of 18 pts. and of note there was a trend towards higher relapse rates in patients with higher day-23 rituximab levels (35% vs. 0) (see figure 2). Conclusions. Y90 BEAM conditioning is well tolerated. Short term outcome is similar among different histologic types of NHL. The true effects of rituximab levels may not yet be fully appreciated due to small patient numbers. However, the trend towards higher relapse rates in the cohort with high circulating pre RIT rituximab levels suggests that titration of rituximab dosing pre RIT may be another strategy in which to improve transplant outcomes by optimizing targeting of the RIT. Disclosures: Off Label Use: yttrium 90 in combination with high dose BEAM chemotherapy.

Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT); however, it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine (Flu)/melphalan (Mel) prior to allogeneic peripheral blood stem cell transplantation (PBSCT) between 6/14/02 and 6/15/07 at the City of Hope. Indications for the RIC regimen were: (1) aged 50 years or older (42%), (2) compromised organ function (54%), or (3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 months for living patients. Both overall survival (OS) and disease-free survival (DFS) at 2 years was 61.5%. Relapse incidence was 21.1% and nonrelapse mortality (NRM) was 21.5% at 2 years. Chronic graft-versus-host (cGVHD) developed in 86% of evaluable patients. In this series, no significant correlations were made between outcomes and patient age, presence of Philadelphia chromosome, relatedness of donor source, or prior HCT. These high survival rates for high-risk ALL patients following RIC HCT may offer a promising option for patients not eligible for a standard myeloablative transplant.

Patients with peripheral T cell lymphoma (PTCL) have a poor prognosis with current treatment approaches. We examined the outcomes of high-dose therapy (HDT) and autologous hematopoietic cell transplant (AHCT) on the treatment of PTCL and the impact of patient/disease features on long-term outcome. Sixty-seven patients with PTCL–not otherwise specified (n = 30), anaplastic large cell lymphoma (n = 30), and angioimmunoblastic T cell lymphoma (n = 7) underwent HDT/AHCT at the City of Hope. The median age was 48 years (range: 5-78). Twelve were transplanted in first complete remission (1CR)/partial remission (PR) and 55 with relapsed or induction failure disease (RL/IF). With a median follow-up for surviving patients of 65.8 months (range: 24.5-216.0) the 5-year overall survival (OS) and progression-free survival (PFS) were 54% and 40%, respectively. The 5-year PFS was 75% for 1CR/PR compared to 32% for RL/IF patients (P = .01). When the Prognostic Index for PTCL unspecified (PIT) was applied at the time of transplant, patients in the PIT 3-4 group had 5-year PFS of only 8%. These results show that HDT/AHCT can improve long-term disease control in relapsed/refractory PTCL and that HDT/AHCT should ideally be applied either during 1CR/PR, or as part of upfront treatment. More effective and novel therapies are needed for patients with high-risk disease (PIT 3-4 factors) and allogeneic HCT should be explored in these patients.