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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.

Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P < .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA > 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA < 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.

Background: Primary mediastinal large B-cell lymphoma (PMBCL) is a subset of aggressive B-cell non-Hodgkin lymphoma (B-NHL) with distinct biological and clinical features. Although most patients are cured with frontline chemoimmunotherapy with or without radiation therapy (RT), relapsed or refractory (rel/ref) PMBCL is much harder to control. Standard treatment of rel/ref PMBCL is similar to other aggressive B-NHLs, including salvage therapy and autologous (auto) stem cell transplantation (SCT) in chemosensitive patients. Recently, immunotherapy with PD-1 blockade and chimeric antigen receptor modified T-cells has proven to be effective in rel/ref PMBCL. Despite this, allogeneic (allo) SCT retains an important potential role as it has curative potential for patients with advanced aggressive B-NHLs. However, there are scant modern data on alloSCT outcomes in patients with PMBCL, limited to case reports or small series. We therefore performed a multicenter retrospective study to evaluate alloSCT outcomes in patients with rel/ref PMBCL. Methods: We retrospectively studied consecutive patients with rel/ref PMBCL who underwent alloSCT at Fred Hutchinson Cancer Center, Dana-Farber Cancer Institute, Massachusetts General Hospital, or City of Hope between 1/2000 and 5/2014. Baseline and transplant characteristics are reported descriptively. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Incidence of relapse and non-relapse mortality were calculated using competing risks methods. Results: 28 patients with rel/ref PMBCL underwent alloSCT at participating institutions during the study period. Among these patients, median age at SCT was 36 years, 54% were female, median number of prior therapies was 4 (range, 2-7), 57% were refractory to frontline therapy, 86% received prior RT, and 71% had prior autoSCT. At alloSCT, 1 (4%) patient was in complete response (CR), 21 (75%) were in partial response (PR), and 6 (21%) were refractory to pre-alloSCT therapy (18 patients were assessed with PET). Most patients (86%) received reduced intensity conditioning, most commonly fludarabine/melphalan +/- ATG or Zevalin (25%), fludarabine/TBI200 (21%), or fludarabine/busulfan (14%). GVHD prophylaxis most frequently consisted of a calcineurin inhibitor (CNI) with mycophenolate mofetil (12, 43%), CNI with sirolimus +/- methotrexate (8, 29%), or CNI with MTX (4, 14%). 15 (54%) patients had a matched (8/8) related donor, 8 (29%) had a matched unrelated donor, 2 had a mismatched unrelated donor (7/8), and 3 had umbilical cord donors. All patients received peripheral blood stem cell grafts except for the 3 cord recipients. The median follow-up time in survivors was 5.0 (range 0.5-14.0) years. The 2 year PFS and OS in the cohort were 39% and 45%, respectively, while non-relapse mortality (NRM) and cumulative incidence of relapse (CIR) were 32% and 29%, respectively. The 5-year PFS, OS, NRM, and CIR were 34%, 45%, 32%, and 33%, respectively. The cumulative incidence of grade II-IV and III-IV acute GVHD were 39% and 4% at day 100, while the incidence of chronic GVHD at 1 year was 21% (18% extensive). Among patients in CR/PR at the time of alloSCT, the 2-year PFS and OS were 50% and 58%, respectively, as compared to a 2-year PFS and OS of 0% in patients who were refractory at the time of alloSCT (p=0.046 for PFS, p=0.014 for OS). One patient received post-alloSCT lenalidomide as maintenance therapy and remained in ongoing CR. Of the 9 patients who relapsed after alloSCT, 3 out of 4 patients exhibited a response to immunosuppression taper, while 4 out of 5 patients responded to subsequent systemic therapy. 2 patients underwent a donor lymphocyte infusion (DLI) and both developed subsequent GVHD - 1 patient had a CR documented 64 days after DLI while the other had continued disease progression. In the 9 patients who relapsed after alloSCT, the 2-year OS was 33%. Conclusions: AlloSCT can produce durable remissions in a subset of patients with heavily treated, rel/ref PMBCL. Patients with refractory disease at alloSCT had dismal outcomes. Despite the expanding treatment options available for these patients, alloSCT should be considered in the management of patients with rel/ref PMBCL who are sensitive to salvage therapy. Figure 1A PFS and OS After AlloSCT in Patients with Rel/Ref PMBCL Figure 1B PFS in Patients with Sensitive versus Refractory PMBCL at AlloSCT Disclosures Herrera: Merck, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; AstraZeneca: Research Funding; Gilead Sciences: Research Funding; KiTE Pharma: Consultancy, Research Funding; Immune Design: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Consultancy, Research Funding. Maloney:Roche/Genentech: Honoraria; GlaxoSmithKline: Research Funding; Juno Therapeutics: Research Funding; Seattle Genetics: Honoraria; Janssen Scientific Affairs: Honoraria. Ho:Jazz Pharmaceuticals: Consultancy. Soiffer:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Antin:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding. Chen:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; REGiMMUNE: Consultancy; Magenta Therapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy. Armand:Otsuka: Research Funding; Affimed: Consultancy, Research Funding; Pfizer: Consultancy; Infinity: Consultancy; Merck: Consultancy, Research Funding; Adaptive: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding. Shadman:Acerta Pharma: Research Funding; AbbVie: Consultancy; Genentech: Research Funding; Beigene: Research Funding; Verastem: Consultancy; Qilu Puget Sound Biotherapeutics: Consultancy; Mustang Biopharma: Research Funding; Gilead Sciences: Research Funding; AstraZeneca: Consultancy; TG Therapeutics: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Genentech: Consultancy.

A mismatch at HLA-DPB1 locus is associated with higher acute GVHD and lower relapse rate after myeloablative (MAC) allogeneic hematopoietic cell transplantation (alloHCT). Also, in MAC setting, mismatch permissiveness and expression level impact alloHCT outcomes. However, in reduced intensity conditioning (RIC), DP mismatch effect on transplant outcomes is unknown. We retrospectively evaluated DP mismatch influence (number, permissiveness, and expression) on HCT outcomes in 310 patients with high-resolution typing (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1), who underwent RIC HCT. By multivariable analysis, 11/12 had better overall survival (OS) and relapse vs. 12/12 (HR = 1.61 and 2.02; p = 0.04 and 0.01, respectively) and better OS vs. 10/12 (HR = 1.68; p = 0.02). Within the 11/12, nonpermissive (NoPR) mismatch was associated with higher risk of grade II-IV acute GVHD (HR = 1.97; p = 0.005) and nonrelapse mortality (HR = 2.13; p = 0.02) vs. permissive (PR). Grouping 11/12 based on the DP expression conferred higher mortality (HR = 3.78; p = 0.003) when low expressers received a graft from high expressers (AG) vs. low expressers (AA). Better OS was achieved in PR 11/12, when expression was low in patient and donor (AA) vs. all other combinations. Therefore, in RIC HCT, a single-DP mismatch has a protective role, especially in permissive setting, when donor and recipient are low expressers.

The phase 3 AETHERA trial established brentuximab vedotin (BV) as a consolidative treatment option for adult patients with classical Hodgkin lymphoma (cHL) at high risk of relapse or progression after autologous hematopoietic stem-cell transplantation (auto-HSCT). Results showed that BV significantly improved progression-free survival (PFS) vs placebo plus best supportive care alone. At 5-year follow-up, BV continued to provide patients with sustained PFS benefit; 5-year PFS was 59% (95% confidence interval [CI], 51-66) with BV vs 41% (95% CI, 33-49) with placebo (hazard ratio [HR], 0.521; 95% CI, 0.379-0.717). Similarly, patients with ≥2 risk factors in the BV arm experienced significantly higher PFS at 5 years than patients in the placebo arm (HR, 0.424; 95% CI, 0.302-0.596). Upfront consolidation with BV significantly delayed time to second subsequent therapy, an indicator of ongoing disease control, vs placebo. Peripheral neuropathy, the most common adverse event in patients receiving BV, continued to improve and/or resolve in 90% of patients. In summary, consolidation with BV in adult patients with cHL at high risk of relapse or progression after auto-HSCT confers a sustained PFS benefit and is safe and well tolerated. Physicians should consider each patient's HL risk factor profile when making treatment decisions. This trial was registered at www.clinicaltrials.gov as #NCT01100502.

The negative impact of iron overload (IO) on outcomes of allogeneic hematopoietic cell transplantation (HCT) is well recognized, but its impact on umbilical cord blood (UCB) transplant outcome is unknown. We retrospectively analyzed outcomes of 150 patients who received UCB-HCT at our institution, stratified by pre-HCT serum ferritin (SF) level of 2000 ng/mL. Two-year overall survival rate among patients with SF >2000 and ≤2000 ng/mL was 26.1% (95% CI, 10.6% to 44.7%) and 52.1% (95% CI, 40.1% to 62.8%), respectively; hazard ratio (HR) = 2.26 (95% CI, 1.28 to 4.00, P = .005). Two-year nonrelapse mortality rate was higher among patients with SF >2000 ng/mL (56.5%; 95% CI, 33.3% to 74.4%) compared to SF ≤2000 ng/mL (30.1%; 95% CI, 20.0% to 40.9%); HR = 2.18 (95% CI, 1.10 to 4.31, P = .025). Neutrophil engraftment at 42 days was 78.3% (95% CI, 53.5% to 90.8%) in patients with SF >2000 ng/mL versus 91.8% (95% CI, 82.1% to 96.4%) in patients with SF ≤2000 ng/mL; HR = 0.58 (95% CI, 0.35 to 0.96, P = .034). A significant difference in platelet engraftment at 3 months was also observed: 52.2% (95% CI, 29.4% to 70.8%) for SF >2000 ng/mL versus 80.8% (95% CI, 69.5% to 88.3%) for SF ≤2000 ng/mL; HR = 0.48 (95% CI, 0.23 to 0.98, P = .044). In conclusion, IO defined by SF of 2000 ng/mL is a strong adverse prognostic factor for UCB-HCT and should be considered when UCB is chosen as the graft source for patients without a fully matched donor.

Allogeneic hematopoietic stem cell transplantation (alloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those who are 70 years or older are limited, and no standard conditioning regimen has been established for this population. In this retrospective study we evaluated the outcome of 53 consecutive patients aged 70 years and older who underwent alloHCT with melphalan-based reduced-intensity conditioning (RIC) at City of Hope. Engraftment was prompt, with median time to neutrophil engraftment of 15 days. More than 95% of patients achieved complete donor chimerism within 6 weeks from HCT, consistent with the "semiablative" nature of this regimen. With a median follow-up of 31.1 months, the 2-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) were 68.9%, 63.8%, and 17.0%, respectively. Cumulative incidence of relapse at 1 and 2 years was 17.0% and 19.3%, respectively. One hundred–day cumulative incidence of grades II to IV acute graft-versus-host disease was 37.7% (grades III to IV, 18.9%), and 2-year cumulative incidence of chronic graft-versus-host disease was 61.9% (extensive, 45.9%). The only significant predictor for poor OS was high/very high disease risk index. Transplant-related complications and morbidities observed here did not differ from the commonly expected in younger patients treated with RIC. In conclusion, alloHCT with a melphalan-based conditioning regimen is associated with acceptable toxicities and NRM, lower incidence of relapse, and favorable OS and PFS in patients aged 70 years or older.

The purpose of this report is to analyze long-term clinical outcomes of patients exposed to plerixafor plus granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization. This was a study of patients with non-Hodgkin lymphoma (NHL; n = 167) and multiple myeloma (MM; n = 163) who were enrolled in the long-term follow-up of 2 pivotal phase III studies (NCT00741325 and NCT00741780) of 240 µg/kg plerixafor plus 10 µg/kg G-CSF, or placebo plus 10 µg/kg G-CSF to mobilize and collect CD34+ cells for autologous hematopoietic stem cell transplantation. Overall survival (OS) and progression-free survival (PFS) were evaluated over a 5-year period following the first dose of plerixafor or placebo. The probability of OS was not significantly different in patients with NHL or MM treated with plerixafor or placebo (NHL: 64%; 95% confidence interval [CI], 56% to 71% versus 56%; 95% CI, 44% to 67%, respectively; MM: 64%; 95% CI, 54% to 72% versus 64%; 95% CI, 53% to 73%, respectively). In addition, there was no statistically significant difference in the probability of PFS over 5 years between treatment groups in patients with NHL (50%; 95% CI, 44% to 67% for plerixafor versus 43%; 95% CI, 31% to 54% for placebo) or those with MM (17%; 95% CI, 10% to 24% for plerixafor versus 30%; 95% CI, 21% to 40% for placebo). In this long-term follow-up study, the addition of plerixafor to G-CSF for stem cell mobilization did not affect 5-year survival in patients with NHL or patients with MM.

Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are associated with resistance to frontline and salvage immunochemotherapy, as well as autologous stem cell transplantation (SCT). We hypothesized that allogeneic SCT (alloSCT) could overcome the chemoresistance associated with DEL/DHL. We retrospectively studied the impact of DEL/DHL status in a multicenter cohort of patients who underwent alloSCT for relapsed/refractory (rel/ref) aggressive B cell non-Hodgkin lymphoma (B-NHL). Seventy-eight patients transplanted at 3 centers in whom tumor tissue was available for immunohistochemistry and fluorescence in situ hybridization were enrolled; 47% had DEL and 13% had DHL. There were no significant differences in 4-year progression-free (PFS) or overall survival (OS) between patients with DEL compared with patients without DEL (PFS 30% versus 39%, P = .24; OS 31% versus 49%, P = .17) or between patients with DHL compared with patients without DHL (PFS 40% versus 34%, P = .62; OS 50% versus 38%, P = .46). The lack of association between DEL or DHL and outcome was confirmed in multivariable models, although inadequate sample size may have limited our ability to detect significant differences. In our cohort alloSCT produced durable remissions in patients with rel/ref aggressive B-NHL irrespective of DEL and DHL status, justifying its consideration in the treatment of patients with rel/ref DEL/DHL.

Recognizing the significant biological and clinical heterogeneity of mature T cell and natural killer (NK)/T cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of autologous hematopoietic cell transplantation (auto-HCT) and allogeneic HCT (allo-HCT) for specific histological subtypes. We used the GRADE methodology to aid in moving from evidence to decision making and ultimately to generating final recommendations. Auto-HCT in front-line consolidation is recommended in peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma–anaplastic lymphoma kinase (ALCL-ALK)-negative, NK/T cell (disseminated), enteropathy-associated T cell lymphoma (EATL), and hepatosplenic lymphomas. Auto-HCT in relapsed-sensitive disease is recommended for NK/T cell (localized and disseminated), EATL, subcutaneous panniculitis-like T cell, and ALCL-ALK–positive lymphomas. Auto-HCT is also recommended for PTCL-NOS, AITL, and ALCL-ALK–negative lymphomas if not performed as front-line therapy. Auto-HCT in refractory (primary or relapsed) disease is not recommended for any of the histological subtypes discussed. Allo-HCT in front-line consolidation is recommended for NK/T cell (disseminated), adult T cell leukemia/lymphoma (ATLL; acute and lymphoma type), and hepatosplenic lymphomas. Allo-HCT for relapsed-sensitive disease is recommended for PTCL-NOS, AITL, ALCL-ALK–negative, ALCL-ALK–positive, NK/T cell (localized and disseminated), ATLL (acute, lymphoma type, smoldering/chronic), mycosis fungoides/Sezary syndrome (advanced stage IIB-IVB or tumor stage/extracutaneous), EATL, subcutaneous panniculitis-like T cell, and hepatosplenic lymphoma. Allo-HCT in refractory (primary or relapsed refractory) disease is recommended for any aforementioned histological subtypes. Emerging novel therapies will likely be incorporated into the pretransplantation, peritransplantation, and post-transplantation algorithms (auto-HCT or allo-HCT) with the goals of optimizing efficacy and improving outcomes. We acknowledge that there are unique clinical scenarios not covered by these recommendations that may require individualized decisions.

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.

Daclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25+FOXP3+ regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0.3 mg/kg (n = 69) or 1.2 mg/kg (n = 76) or placebo (n = 65) after unrelated marrow transplantation for treatment of hematologic malignancies or severe aplastic anemia. The risk of acute GVHD did not differ among the groups (P = .68). Long-term follow-up of clinical outcomes and correlative analysis of peripheral blood T cell phenotype suggested that the patients treated with daclizumab had an increased risk of chronic GVHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.0 to 2.3; P = .08) and a decreased risk of relapse (HR, 0.57; 95% CI, 0.3 to 1.0; P = .05), but similar survival (HR, 0.89; 95% CI, 0.6 to 1.3; P = .53). T cells from a subset of patients (n = 107) were analyzed by flow cytometry. Compared with placebo, treatment with daclizumab decreased the proportion of Tregs among CD4 T cells at days 11-35 and increased the proportion of central memory cells among CD4 T cells at 1 year. Prophylactic administration of daclizumab does not prevent acute GVHD, but may increase the risk of chronic GVHD and decrease the risk of relapse. By delaying Treg reconstitution and promoting immunologic memory, anti-CD25 therapy may augment alloreactivity and antitumor immunity.

Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)–based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months. Thirty-two patients were in first complete remission (CR1), while the rest were beyond CR1. Neutrophil engraftment occurred in 95% of the patients. The cumulative incidences of grades II to IV and III and IV acute GVHD at day 100 after transplantation were 32% and 11%, respectively, whereas chronic GVHD, nonrelapse mortality, relapse rate, and disease-free survival (DFS) at 1 year after transplantation were 32%, 21%, 27%, and 51%, respectively. Patients in CR1 had 52% DFS at 3 years. These results suggest that haploidentical transplants performed with PTCy-based GVHD prophylaxis provide a very suitable alternative to HLA-matched transplantations for patients with ALL.

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

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 While tacrolimus and sirolimus (T/S)-based graft-versus-host disease (GvHD) prophylaxis has been effective in preventing acute GvHD post hematopoietic cell transplantation (HCT), its efficacy and long-term outcome in matched (MUD) and mismatched unrelated donor (mMUD) setting is not well defined. METHODS Herein, we evaluated a consecutive case-series of 482 patients who underwent unrelated donor HCT (2005-2013) with T/S-based GvHD prophylaxis. RESULTS With a median follow-up of 6.2 years (range = 2.4-11.3), the 5-year overall survival (OS) and relapse/progression-free survival were 47.5% (95% confidence interval [CI]: 43.0-52.0) and 43.6% (95% CI: 39.1-48.1), respectively; and the 5-year cumulative incidence of nonrelapse mortality (NRM) and relapse were 24.9%, and 31.5%, respectively. In this cohort, mMUD was associated with worse OS (39.0% versus 50.7% at 5 y; P = 0.034), primarily due to greater risk of NRM (33.5% versus 21.7%; P = 0.038). While rates of relapse, acute (II-IV or III-IV) or chronic GvHD (limited or extensive) were not different, death caused by chronic GvHD (20.8% versus 12.8%; P = 0.022) and infection (33.0% versus 18.1%; P < 0.01) were significantly greater in mMUD. In multivariable analysis, high-risk disease (hazard ratio [HR] = 2.21, 95% CI: 1.16-4.23; P < 0.01) and mMUD (HR = 1.55, 95% CI: 1.15-2.08; P = 0.004) were independent predictive factors for OS. CONCLUSIONS T/S-based GvHD prophylaxis is an effective and acceptable GvHD prophylactic regimen. However, survival after mMUD remained poor, possibly related to the severity of chronic GvHD.

Introduction Peripheral T-cell lymphomas (PTCL) comprise 15-20% of adult non-Hodgkin lymphoma and have a poor prognosis; 5-year survival is 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. Objective To 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 who underwent allo-HCT at City of Hope from January 2000 to June 2018. Baseline patient demographic, treatment, and disease characteristics were summarized by descriptive statistics. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier curves and the log-rank test. 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 Median age at allo-HCT was 49 (range 2-70) years. Histologies were PTCL-NOS (n=21); transformed CTCL (n=19); NK TCL (n=17); AITL (n=15), ALCL (n=7); γδTCL (n=6) and other rare subtypes (n=2). No patients had a prior auto transplant. 42 patients (48%) had myeloablative conditioning; FTBI-based (n=39), or BEAM regimen (n=3). 45 patients (52%) had reduced intensity conditioning with a fludarabine/melphalan based regimen in 39. Sibling HCT was done in 47 (54%) patients. MUD HCT was done in 36 (41%); donors were fully HLA matched for 15 (17%) patients and mismatched in 21 (24%); 4 (5%) got haploidentical HCT. The most common GVHD prophylaxis was tacrolimus/sirolimus (n=54). Stem cell source was PBSC in 77 (88%), bone marrow in 5 (6%), and cord blood in 5 (6%) patients. At allo-HCT 25 (29%) patients were in complete remission, 25 (29%) 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). At day 100 after allo-HCT, the rate of acute GVHD grade II-IV was 41% (95% CI: 30%-51). 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, stem cell source or remission status prior to allo-HCT did not predict for OS. Conclusions This large single-institution series with a long-term follow-up on allo-HCT outcomes in patients with high-risk, aggressive T-cell NHL shows encouraging survival outcomes for these patients with limited treatment options.

Despite of the continuous increase in the number of volunteer donors available through the registry, many patients who require an allogeneic hematopoietic cell transplantation (HCT) cannot find a fully-matched donor. While a mismatched unrelated donor (MMUD) is frequently available, it is associated with inferior outcomes and increased risk of graft-versus-host disease (GvHD). Post-transplant cyclophosphamide (PTCy) has been effective in haploidentical HCT, and increasingly used in matched donor HCTs. However, limited data exist in MMUD setting. We conducted a prospective single center trial (NCT 03128359) of PTCy for MMUD HCT with the primary objective of estimating 1-year GvHD-free relapse/progression-free survival (GRFS). As of October 2019, all planned 39 patients have been enrolled with a median follow up of 11 months (range: 1-23). Here we present the preliminary estimate of 1-year GRFS and other HCT outcomes in two strata; myeloablative conditioning (n=19) using Fludarabine (90 mg/m2) and FTBI (1200 cGy) or reduced intensity conditioning (n=19) using Fludarabine (100 mg/m2) and Melphalan (140 mg/m2 or 100 mg/m2 if >60 years old). Patients between 0 to 75 years of age and KPS of ≥70% with hematologic malignancies undergoing HCT from a 7/8 HLA-matched (A-, B-, C-, and DR-) donor were eligible. Patients with donor specific antibodies to the mismatched HLA-locus were excluded. All patient received PBMCs (3-5 × 106/kg) followed by GVHD prophylaxis consisting of PTCy (50 mg/kg for 2 days), Tacrolimus (1 mg), and mycophenolate mofetil (1 gr 3 × a day). Median age at the time of HCT was 53 years (range: 21-72), and 50% of patients were male. Disease risk was low in 47% (n=18), intermediate in 37% (n=14), and high in 16% of the patients (n=6). At transplant, 29 patients were in complete remission, and 9 had active disease. HCT-CI was 0 in six (16%) and 1-2 in 15 (39%) and >2 in 17 (45%) patients. Donors' median age was 32 years (range: 19-53) and donors were mismatched at HLA-A (n=14), -B (n=12), -C (n=8), or DR-loci (n=5). Median number of mismatches was 2 of 12 (range: 1-4). Female to male donor HCT was in 11% of recipients. Neutrophil engraftment occurred in all patients (median time to engraft: 16 days; range 13-35). One-year overall survival (OS) and GRFS were 92% (95% CI: 70-98) and 70% (95% CI: 51-83), respectively. Non-relapse mortality and relapse rate at 1 year were at 8% (95% CI: 2-29) and 13% (95% CI: 5-34), respectively. Cumulative incidence of day 100 acute GvHD grade 2-4 was 50% (95% CI: 35-71) and 1-year chronic GvHD was 56% (95% CI: 39-81). No severe chronic GvHD by the NIH criteria was observed. In conclusion, the data from our phase II trial of PTCy showed highly promising OS/GRFS in patients receiving 7/8 MMUD HCT, and that PTCy in MMUD setting offers an alternative and effective HCT approach for patients who do not have an available matched donor.

The current standard of care for patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is high-dose conditioning followed by autologous stem cell transplantation (ASCT). For some patients (ie, those with highest-risk disease, insufficient stem cell numbers after mobilization, or bone marrow involvement) allogeneic hematopoietic cell transplantation (alloHCT) offers the potential for cure. However, the majority of patients undergoing alloHCT receive reduced-intensity conditioning as a preparative regimen, and studies assessing outcomes of patients after alloHCT with myeloablative conditioning are limited. In this retrospective study, we reviewed outcomes of 22 patients with recurrent and refractory NHL who underwent alloHCT with myeloablative BEAM conditioning and received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis at City of Hope between 2005 and 2018. With a median follow-up of 2.6 years (range, 1.0 to 11.2 years), the probabilities of 2-year overall survival and event-free survival were 58.3% (95% confidence interval [CI], 35.0% to 75.8%) and 45.5% (95% CI, 24.4% to 64.3%), respectively. The cumulative incidence of grade II to IV acute GVHD was 45.5% (95% CI, 23.8% to 64.9%), with only 1 patient developing grade IV acute GVHD. However, chronic GVHD was seen in 55% of the patients (n = 12). Of the 22 eligible patients, 2 had undergone previous ASCT and 2 had undergone previous alloHCT. Both patients with previous ASCT developed severe regimen-related toxicity. Patients who underwent alloHCT with chemorefractory disease had lower survival rates, with 1-year OS and EFS of 44.4% and 33.0%, respectively. In conclusion, alloHCT with a BEAM preparative regimen and tacrolimus/sirolimus-based GVHD should be considered as an alternative option for patients with highest-risk lymphoma whose outcomes are expectedly poor after ASCT.

The phase III AETHERA trial demonstrated the efficacy of brentuximab vedotin (BV) as consolidation therapy in patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression after autologous hematopoietic stem cell transplantation (auto-HSCT; hazard ratio, .57; P .001). The objective of this analysis is to provide further detail on the most common and clinically important treatment-emergent adverse events (AEs) in the AETHERA BV arm including their occurrence and management. AEs of clinical importance occurring in patients who participated in AETHERA (BV + best supportive care [BSC], n = 165; placebo + BSC, n = 164) were evaluated for time to onset, manageability through dose modification, and resolution. As previously reported, peripheral neuropathy (PN; 67%), infections (60%), and neutropenia (35%) were the most common BV-associated treatment-emergent AEs. Neutropenia was managed with dose delays and granulocyte colony-stimulating factor; no dose reductions or discontinuations were required. Most PN cases (57%) were managed with dose delays and reductions. The median time to PN onset was 13.7 weeks (range, .1 to 47.4). After the end of treatment, PN continued to resolve; symptom resolution was similar to that in the placebo arm at 3 years, demonstrating reversibility. BV had no significant impact on pre-existing PN. Patients with PN-related dose modifications had progression-free survival (PFS) comparable with patients without. Other less common but serious AEs, including pulmonary toxicities, hepatotoxicity, and cardiotoxicity, were rare in both arms and were managed with BV dose modifications or discontinuations. Secondary malignancies were rare and reported in patients with comorbidities or other risk factors. Consolidation therapy with BV for patients with HL at high risk of relapse after auto-HSCT is associated with sustained PFS. The most common AEs in the BV arm were manageable and reversible. Awareness of these AEs and management approaches will enable healthcare providers and patients to plan the safest and most effective treatment plan.

High-dose therapy followed by autologous stem-cell transplantation is standard of care for patients with relapsed or primary refractory Hodgkin's lymphoma. Roughly 50% of patients might be cured after autologous stem-cell transplantation; however, most patients with unfavourable risk factors progress after transplantation. We aimed to assess whether brentuximab vedotin improves progression-free survival when given as early consolidation after autologous stem-cell transplantation.We did this randomised, double-blind, placebo-controlled, phase 3 trial at 78 sites in North America and Europe. Patients with unfavourable-risk relapsed or primary refractory classic Hodgkin's lymphoma who had undergone autologous stem-cell transplantation were randomly assigned, by fixed-block randomisation with a computer-generated random number sequence, to receive 16 cycles of 1·8 mg/kg brentuximab vedotin or placebo intravenously every 3 weeks, starting 30-45 days after transplantation. Randomisation was stratified by best clinical response after completion of salvage chemotherapy (complete response vs partial response vs stable disease) and primary refractory Hodgkin's lymphoma versus relapsed disease less than 12 months after completion of frontline therapy versus relapse 12 months or more after treatment completion. Patients and study investigators were masked to treatment assignment. The primary endpoint was progression-free survival by independent review, defined as the time from randomisation to the first documentation of tumour progression or death. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01100502.Between April 6, 2010, and Sept 21, 2012, we randomly assigned 329 patients to the brentuximab vedotin group (n=165) or the placebo group (n=164). Progression-free survival by independent review was significantly improved in patients in the brentuximab vedotin group compared with those in the placebo group (hazard ratio [HR] 0·57, 95% CI 0·40-0·81; p=0·0013). Median progression-free survival by independent review was 42·9 months (95% CI 30·4-42·9) for patients in the brentuximab vedotin group compared with 24·1 months (11·5-not estimable) for those in the placebo group. We recorded consistent benefit (HR1) of brentuximab vedotin consolidation across subgroups. The most frequent adverse events in the brentuximab vedotin group were peripheral sensory neuropathy (94 [56%] of 167 patients vs 25 [16%] of 160 patients in the placebo group) and neutropenia (58 [35%] vs 19 [12%] patients). At time of analysis, 28 (17%) of 167 patients had died in the brentuximab vedotin group compared with 25 (16%) of 160 patients in the placebo group.Early consolidation with brentuximab vedotin after autologous stem-cell transplantation improved progression-free survival in patients with Hodgkin's lymphoma with risk factors for relapse or progression after transplantation. This treatment provides an important therapeutic option for patients undergoing autologous stem-cell transplantation.Seattle Genetics and Takeda Pharmaceuticals International.

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: T-lymphoblastic lymphoma (T-LBL) is a highly aggressive non-Hodgkin lymphoma seen in young adults that usually presents with a mediastinal mass and less than 20% bone marrow involvement with neoplastic cells. T-LBL and T-cell ALL are morphologically and immmunophenoytpically similar and are thus frequently grouped together. However there are differences in clinical presentation, cytogenetic features and molecular pathogenesis indicating biologic differences. Patients with relapsed refractory T-LBL have poor prognosis and there is a paucity of data on allogeneic HCT (allo-HCT) outcomes in this setting. Methods: We retrospectively reviewed medical records of 25 consecutive patients with T lymphoblastic lymphoma without prior auto-HCT 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: 25 patients were included for the analysis. Median age at the time of allo-HCT was 25 years (range 7-70 years). 21 patients (80%) received myeloablative conditioning: FTBI containing regimens (n=20) with FTBI/VP-16 being most commonly used(n=16) and one patient received Bu/Cy based conditioning; 4 patients received reduced intensity conditioning with Flu/Mel. Sibling HCT was performed in 12 patients (48%), while MUD HCT was performed in 13 patients (52%) with fully matched HLA unrelated donor in 9 (36%) and HLA mismatched in 4 (16%) patients. GVHD prophylaxis consisted of tacrolimus/sirolimus (n=10), tacrolimus or cyclosporine/MTX (n=7), tacrolimus/sirolimus/MTX (n=4) and others (n=4) Source of stem cells was PBSC in 19 (76%), bone marrow in 5 (20%), and cord blood in 1 (4%) patients. At the time of allo-HCT, there were a total of 11 (44%) patients in complete remission (CR1 n=4, CR2+ n=7), 9 (36%) patients in partial remission and unknown remission status (n=5). The median follow-up among survivors was 8.9 years (range 2.3-12.1). The 5- and 10-year PFS was 31% (95% CI: 14%-50%). The 5- and 10-year OS was 31% (95% CI: 14%-49%) (Fig.1). Cumulative incidence of relapses at 5 and 10 years were both 36% (95% CI: 18%-55%) while NRM at 5 and 10 years was 33% (95% CI: 15%-52%). At day 100 after allo-HCT, the rates of acute GVHD grade II-IV were 63% (95% CI: 39%-79%) and grade III-IV of 25% (95%CI: 10%-44%). Chronic GVHD rates at 3 years were 60% (95% CI: 37%-77%). In univariate analysis, preHCT remission status did not improve PFS on long term follow up. Conclusions: Our results in patients with T-LBL shows 5-year PFS and OS of 31%, respectively, indicating that a subset of patients can be cured with allo-HCT in the high-risk setting. Disclosures Salhotra: Celgene: Other: Research Support; Kadmon Corporation: Other: Non paid consultant. Popplewell:City of Hope: Employment. Herrera:Kite Pharma: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Research Funding; Immune Design: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Mei:Seattle Genetics, Inc.: Research Funding. Aldoss:AUTO1: Consultancy; Helocyte: Consultancy, Honoraria, Other: travel/accommodation/expenses; Jazz Pharmaceuticals: Honoraria, Other: travel/accommodation/expenses, Speakers Bureau; Agios: Consultancy, Honoraria. Zain:Seattle Genetics: Honoraria, Speakers Bureau; spectrum: Honoraria.

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.

CMVi leads to significant morbidity in R+ HCT and preemptive therapy (PET) has been the standard of care. LTV was FDA-approved in Nov. 2017 for CMVi prevention in R+ HCT. Besides the clinical trials, there is are real world data on LTV. Upon IRB approval, we retrospectively studied consecutive R+ HCT pts with their first HCT between 1/1/2017 and 6/30/2018. LTV group included pts with HCT between 2/20/18 and 6/30/2018, who had LTV Px started within 28 days of HCT (n=59), and R+ HCT between 1/1/2017 and 2/19/2018 (n=307) served as control (ctrl). We compared CMVi rates in first 100 days of HCT, and time to engraftment between the 2 groups. Risk stratification: high risk - haplo/cord HCT & ATG use, low risk - all others. CMVi was defined as viral load (VL) of 625 IU/ml to 1250 IU/ml or higher (CMV assay conversion factor of 1 genomic copy/ml = 2.5 IU/ml). CMV VL less than 625 IU/ml is reported negative, VL between 625 and 1250 IU/ml is qualitative positive but numeric value is provided only for VL ≥ 1250 IU/ml. PET was recommended for VL >1250 IU/ml (500 copies/ml) in high risk and > 3750 IU/ml (1500 copies/ml) in low risk HCT (including those on LTV requiring PET). Descriptive statistics was done for baseline characteristics. Cumulative incidence curves were generated for CMVi within 100 days post-HCT and Gray's test was used to compare the difference between the 2 groups. In both groups, median age was 54 years and HCT indications were similar. Donor type in LTV/ Ctrl groups: MRD (27 vs 36%), MUD (44 vs 47%), haplo (27 vs 15%), cord (1.7 vs 1.6%). PBMC was graft source in 90% of both groups. Myeloablative conditioning: 40.7% in LTV and 35% in Ctrl. GVHD Px: Cellcept (32 vs 25%), methotrexate (7 vs 9%), tacro/siro (58 vs 65), and others (3.4 vs 0.3%) in LTV & Ctrl respectively. A majority (n=36) received both intravenous & oral LTV formulation while 23 received oral only. Median time from HCT to LTV start was 13 days (range: 4-26). LTV group had significant reduction in CMVi rate (22.4% [95%CI: 12.7-34.0]) compared with ctrl group (41.1% [95%CI: 35.4-46.7], p=0.008, Fig 1). In a subgroup of high-risk HCT LTV was significantly reduced CMVi rate (22.2%) compared with ctrl (62.8%, p=0.004, Fig 2) while statistical difference was not reached in low-risk HCT pts (22.8% vs. 35.6%, p=0.11). In the LTV Px, clinically significant (CS)-CMVi requiring PET occurred in 8.4% (n=5) and on excluding 2 pts who were not on LTV at the time of CMVi, the rate was 5% (Fig 1). CMVi cleared without PET in 8/13 LTV pts and LTV was continued; all pts had VL LTV use in a real world setting is associated with significant reduction of CMVi and CS-CMVi without any discernible myelosuppression. The low level CMVi resolved spontaneously in majority with continued LTV Px and PET was not necessary. The high-risk HCT had most benefit with LTV Px.

Histological transformation (HT) is a major cause of morbidity and mortality in patients with indolent non-Hodgkin lymphoma (NHL). The multicentre National Cancer Comprehensive Network database for NHL provides a unique opportunity to investigate the natural history of HT in the rituximab era. 118 patients with biopsy-confirmed indolent lymphoma and subsequent biopsy-confirmed HT were identified. Treatments for HT included autologous stem-cell transplant (auto-SCT) (n = 50), allogeneic SCT (allo-SCT) (n = 18), and treatment without transplant (n = 50). The 2-year overall survival (OS) for the entire cohort was 68%. For auto-SCT patients aged ≤ 60 years (n = 24), the 2-year OS was 74%. For non-transplanted patients aged ≤ 60 years (n = 19), the 2-year OS was 59%. The 2-year OS of patients naïve to chemotherapy prior to HT was superior to patients who were exposed to chemotherapy prior to HT (100% vs. 35%, P = 0.03). In this largest prospective cohort of patients of strictly defined HT in the rituximab era, the natural history of HT appears more favourable than historical studies. Younger patients who were not exposed to chemotherapy prior to HT experienced a prolonged survival even without transplantation. This study serves as a benchmark for future trials of novel approaches for HT in the Rituximab era.

Many institutions have adopted algorithms based on preapheresis circulating CD34+ cell counts to optimize the use of plerixafor. However, a circulating peripheral blood CD34+ cell threshold that predicts mobilization failure has not been defined. The superiority of plerixafor + granulocyte colony-stimulating factor (G-CSF) over placebo + G-CSF for hematopoietic stem cell mobilization and collection was shown for patients with non-Hodgkin lymphoma in a phase III, prospective, randomized, controlled study. The question remains as to which patients may benefit most from the use of plerixafor. In this post hoc retrospective analysis, mobilization outcomes were compared between the 2 treatment arms in patients stratified by peripheral blood CD34+ cell count (

Allogeneic (allo) hematopoietic cell transplantation (HCT) can induce long-term remissions in chemosensitive relapsed follicular lymphoma (FL). The Blood and Marrow Transplant Clinical Trials Network conducted a multicenter phase 2 trial to examine the efficacy of alloHCT using reduced-intensity conditioning with rituximab (RTX) in multiply relapsed, chemosensitive FL. The primary endpoint was 2-year progression-free survival (PFS). The conditioning regimen consisted of fludarabine, cyclophosphamide, and high-dose RTX (FCR), in which 3 of the 4 doses of RTX were administered at a dose of 1 gm/m2. Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus and methotrexate. Sixty-five patients were enrolled and 62 were evaluable. Median age was 55 years (range, 29 to 74). This group was heavily pretreated: 77% had received ≥ 3 prior regimens, 32% had received ≥ 5 prior regimens, and 11% had received prior autologous HCT. Donors were HLA-matched siblings (n = 33) or HLA-matched unrelated adults (n = 29). No graft failures occurred. The overall response rate after HCT was 94% with 90% in complete remission (CR), including 24 patients not in CR before alloHCT. With a median follow-up of 47 months (range, 30 to 73), 3-year PFS and overall survival rates were 71% (95% confidence interval, 58% to 81%) and 82% (95% confidence interval, 70% to 90%), respectively. Three-year cumulative incidences of relapse/progression and nonrelapse mortality were 13% and 16%, respectively. Two-year cumulative incidences of grades 2 to 4 and grades 3 or 4 acute GVHD were 27% and 10%, respectively, and extensive chronic GVHD incidence was 55%. Serum RTX concentrations peaked at day +28 and remained detectable as late as 1 year in 59% of patients with available data. In conclusion, alloHCT with FCR conditioning confers high CR rates, a low incidence of relapse/progression, and excellent survival probabilities in heavily pretreated FL patients.

Preapheresis peripheral blood (PB) CD34(+) cell count is a strong predictor of hematopoietic stem cell (HSC) mobilization and is routinely used to optimize the timing, cost, and success of HSC collection in patients with multiple myeloma. However, a uniform PB CD34(+) cell count that predicts mobilization failure has not been defined, resulting in the development of institute-specific algorithms for mobilization, particularly regarding the decision of when to use the novel stem cell mobilization agent plerixafor. In this post hoc analysis, we evaluated the mobilization efficacy of plerixafor plus granulocyte colony-stimulating factor (G-CSF) versus placebo plus G-CSF in patients with multiple myeloma, stratified by preapheresis PB CD34(+) cell count:10,15,20, and ≥20 cells/μL. Regardless of the PB CD34(+) cell count, the total yield of CD34(+) cells from apheresis was significantly higher in the plerixafor group than in the placebo group, and significantly more patients in the plerixafor group collected the minimum (≥2 × 10(6) cells/kg) and optimum (≥6 × 10(6) cells/kg) stem cell yields on each day of apheresis. As a corollary, the greater stem cell collection in plerixafor-treated patients resulted in the need for significantly fewer days of apheresis to reach minimum and optimum cell doses across all cell count groups. For all CD34(+) cell count groups, the proportion of patients proceeding to transplantation and the median time to platelet and neutrophil engraftment were similar in the plerixafor and placebo groups. Our findings demonstrate that in patients with multiple myeloma who might be predicted to fail mobilization based on low PB CD34(+) cell count, the addition of plerixafor to G-CSF allows for collection of the minimal and optimal cell doses in a greater proportion of patients compared with G-CSF alone. In addition, plerixafor plus G-CSF significantly improves the likelihood of optimal HSC collection in patients with higher preapheresis PB CD34(+) cell counts (≥20 cells/μL) compared with placebo plus G-CSF. Collectively, this analysis of predicted poor mobilizers validates the superiority of plerixafor plus G-CSF compared with G-CSF alone, which had been demonstrated previously in the overall patient population.

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.

Clofarabine is a novel purine nucleoside analog with immunosuppressive and antileukemia activity. We performed a phase I study of the combination of clofarabine plus melphalan as a reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with acute myelogenous leukemia. Patients over age 18 in complete remission or with active disease (up to 50% marrow blasts) who had a matched related or unrelated donor were eligible. The conditioning regimen consisted of escalating doses of clofarabine plus melphalan, followed by allogeneic stem cell transplantation. Sixteen patients (median age, 63 years) were treated at 3 dose levels; 4 of these patients had primary induction failure, and 3 were in first relapse. One patient at dose level 2 and 1 patient at dose level 3 died of multiorgan toxicity; no other dose-limiting toxicities were seen. All other patients at both doses of clofarabine studied demonstrated complete engraftment by day 30, with a median time to absolute neutrophil count recovery of 14 days, and 16 days for platelet recovery. With a median follow-up of 17 months, only 2 patients relapsed, and 4 patients died. Clofarabine plus melphalan at dose level 2 is a well-tolerated conditioning regimen with activity in patients with advanced acute myelogenous leukemia.

BACKGROUND: Unrelated cord blood (CB) is an important stem cell source for unrelated hematopoietic cell transplantation (HCT) of patients with nonmalignant disorders. Processing methods to prepare red blood cell–reduced CB units incur significant nucleated cell loss. In contrast, plasma depletion or reduction (PDR) processing of CB units entails the removal of only a portion of the plasma with minimal nucleated cell loss. However, there are relatively limited data regarding outcomes of CB transplants using units processed by PDR. STUDY DESIGN AND METHODS: A Center for International Blood and Marrow Transplant Research (CIBMTR)-audited analysis was performed on 120 pediatric patients with nonmalignant disorders transplanted between November 2001 and January 2008 at 29 US and 17 international centers using PDR CB units from two CB banks. RESULTS: Transplant characteristics were as follows: median age, 3.5 years (range, 0.1-14 years); median patient weight, 15 kg (range, 4-61 kg); 58% male; HLA matches (intermediate-resolution HLA-A and HLA-B and high-resolution HLA-DRB1) of the units used in these patients six of six in 26, five of six in 48, four of six in 47, and three of six or two of six in 6; median prefreeze total nucleated cell dose, 10.5 × 107/kg; median prefreeze CD34+ dose, 3.7 × 105/kg; and nonmyeloablative regimen in 24%. The median times to myeloid and platelet engraftment were 21 and 49 days, respectively. The cumulative incidence of reported Grade II to IV acute graft-versus-host disease (aGVHD) was 38 ± 5%, and 19 ± 4% had Grade III to IV aGVHD. The Kaplan-Meier estimates of 3-year transplant-related mortality, overall survival, and disease-free survival were 20 ± 4, 79 ± 4, and 70 ± 6%, respectively. CONCLUSION: These data demonstrate the effectiveness of PDR CB units for HCT.

Autologous hematopoietic stem cell transplantation (ASCT) is an established treatment for patients with hematologic malignancies, yet the impact of transplanted CD34(+) cell dose on clinical outcomes is unresolved. We conducted post hoc analyses of transplanted CD34(+) cell dose and hematopoietic recovery following ASCT in 438 patients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), using data from 2 multicenter phase 3 clinical studies that compared plerixafor plus granulocyte-colony stimulating factor (G-CSF) versus placebo plus G-CSF as stem cell mobilization regimens. Days to engraftment and the proportion of patients who reached predetermined blood count thresholds were compared across 3 CD34(+) cell dose levels: 2-4 × 10(6) cells/kg, 4-6 × 10(6) cells/kg, and6 × 10(6) cells/kg, regardless of mobilization treatment. Short-term neutrophil and platelet engraftment times were similar regardless of cell dose. A significant linear trend was observed between transplanted CD34(+) cell dose and the proportion of patients with platelet count150 × 10(9)/L at 100 days (P.001), 6 months (P = .026), and 12 months (P = .020) in patients with NHL, and at 100 days in patients with MM (P = .004). A linear trend was also observed between transplanted cell dose and the proportion of patients with platelet count100 × 10(9)/L at 100 days (P.001) and 6 months (P = .023) in patients with NHL. A higher cell dose was associated with a lower percentage of NHL patients requiring red blood cell transfusions (P = .006). Our analyses confirm previous findings that transplanted CD34(+) cell dose may be associated with better long-term platelet recovery after ASCT.

Hodgkin lymphoma (HL) can be aggressive and intractable in some cases. Patients who relapse after autologous HCT (auto-HCT) have limited treatment options. City of Hope reports our experience in the use of reduced intensity allogeneic hematopoietic cell transplantation (allo-HCT) in 24 heavily pretreated patients with relapsed HL, between January 2003 and December 2008. The median number of prior therapies was 5; 20/24 patients had prior auto-HCT. The conditioning regimen for all patients was fludarabine and melphalan. With a median follow-up for living patients of 39.0 months, at 2 years the overall survival (OS) was 60% (95% CI 42, 72) and the progression-free survival was 27% (95% CI 22, 32). Non-relapse mortality was 13.1% (95% CI 5.1, 31.4) at 2 years. The incidence of grade II-IV aGVHD was 45.8% and 8.3% for grade III-IV. Allo-HCT in heavily pretreated relapsed Hodgkin lymphoma is feasible, tolerable, and can induce durable clinical remissions.

Haploidentical hematopoietic cell transplantation (HaploHCT) using high-dose post-transplant cyclophosphamide (PTCy) has been increasingly used in patients with hematologic disorders with promising results. However, limited data are available on the incidence, pattern, and risk factors including donor/recipient KIR genotypes for cytomegalovirus (CMV) reactivation after HaploHCT with PTCy. Furthermore, the impact of CMV reactivation on HaploHCT outcomes is not yet well-described. In this retrospective study, we evaluated a series of 119 consecutive patients who underwent HaploHCT with PTCy at City of Hope for hematological diseases, between January 2009 and December 2016. CMV reactivation was monitored by our institutional PCR assay (quantitative detection limit: 500 gc/ml, qualitative limit: 250 gc/ml) at least once a week for 100 days post-transplant, with preemptive anti-CMV therapy for positive PCR according to our institutional guidelines. The median age of the cohort was 43 years (range: 2 to 71 years); with 47 female and 72 male patients. CMV serostatus of donor/recipient was Donor−/Recipient− (D−/R−) in 7, D+/R− in 6, D−/R+ in 23, and D+R+ in 82 patients. Patients received fully ablative (n=46) or reduced intensity/non-myeloablative conditioning (n=73) followed by peripheral blood stem cell (n=81) or bone marrow (n=38) graft from sibling (n=42) or non-sibling haploidentical donors (n=77). Graft-versus-host disease (GVHD) prophylaxis was PTCy plus tacrolimus/mycophenolate mofetil. Diagnoses of these patients were acute leukemia (n=80), bone marrow failure (n=15), lymphoma (n=11), chronic leukemia (n=6), hemoglobinopathies (n=5), and multiple myeloma (n=2), and the HCT-comorbidity index was more than 2 in 42% (n=50) of patients. Cumulative incidence (CI) of CMV reactivation for the entire cohort was 68.1% (95%CI: 58.8-75.7%) at 100-days, with the median time to reactivation at 35 days (95%CI: 33-40); 76.2% in seropositive recipients and 7.7% in seronegative recipients (p17days of CMV viremia) was seen in 47 patients. In univariate analysis; recipient CMV serostatus, recipient sex, and stem cell source were statistical significant factors, affecting CI of CMV reactivation, but only recipient CMV serostatus stood as an independent factor on multivariable analysis (HR=15.5, 95%CI: 2.3-106.3 for R+ compared to R−, p=0.005) (Figure 1). We also evaluated the effect of KIR status on the CI of CMV reactivation. Multivariable analysis indicated a trend towards decreased incidence of CMV reactivation in donors with 2DS5 and 3DS1 (HR= 0.71 for both donors; p value= 0.1). Donor-recipient KIR mismatch was also associated with a trend towards increased incidence of CMV reactivation (p=0.1) and statistically significant prolonged CMV reactivation (OR=2.48, 95%CI: 1.12-5.47, p=.025). With median follow up duration of 24.3 months (range: 10.3 to 99.2) and in univariate analysis, CMV reactivation, higher peak CMV PCR, time to CMV reactivation, or prolonged exposure to CMV were not associated with worse overall survival (OS), relapse-free survival (RFS), relapse incidence, or non-relapse mortality (NRM). Interestingly, the risk of extensive chronic GVHD was greater in patients who had no CMV reactivation than those who developed prolonged/recurrent CMV reactivations (41.9% vs. 26.2%, p= 0.046) In conclusion, recipient and not donor serostatus is predictive of CMV reactivation in HaploHCT with PTCy. With the current pre-emptive therapy approach, CMV reactivation did not translate into higher rate of CMV disease or worse survival outcome. Donor-recipient KIR match (KIR licensing) and donor activating KIR genes (2DS5 and 3DS1) may be involved with CMV control after HaploHCT. Figure 1. Figure 1. Disclosures Dadwal: MERK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Research Funding; AiCuris: Research Funding; Gilead: Research Funding. Ali:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Salhotra:Kadmon Corporation, LLC: Consultancy. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

Allogeneic hematopoietic stem cell transplant (alloHCT) remains the only potentially curative treatment for patients with myelodysplastic syndrome (MDS). However, this treatment is associated with significant risk of transplant-related mortality/morbidity such as graft-versus-host disease, infections, and regimen-related toxicities. Since there has been no "randomized" trial comparing between patients undergoing or not undergoing transplantation, the relative benefit of this treatment, particularly in elderly patients, is largely unknown. Retrospective comparative studies are significantly limited by the inherent selection bias of healthier/well-supported patients in the alloHCT group. Therefore, a critical knowledge gap exists regarding the survival outcome of MDS patients who are transplant eligible yet did not undergo alloHCT due to lack of suitable donors or other reasons. Herein, we retrospectively identified a consecutive case-series of 73 patients with MDS (excluding CMML), who were considered alloHCT candidates, based on initiation of an official donor search from 2005 to 2015, yet did not proceed with alloHCT. Median age at time of donor search was 60 years (range: 20-79) with the majority (63%) being male. Classifications of MDS were single or multi-lineage dysplasia (n=20), excess blast (n=39), MDS unclassified (n=6) or other/unknown classification (n=8). The cohort included 51 de novo MDS and 14 therapy-related MDS (t-MDS). Per International Prognostic Scoring System (IPSS) 29 patients (39.7%) were Intermediate (Int)-1, 14 (19.2%) were Int-2, and 23 (31.5%) were high risk at the time of donor search (Table 1). Reasons for no alloHCT were lack of donor (n=29), persistent/progressive disease (n=9), patient choice (n=13), or infections/complications after initiating the donor search (n=18). Treatments of these patients included chemotherapy (n=14), hypomethylating agents (n=61) and supportive care (n=23). Of the 73 patients, 15 (20.5%) had disease progression to acute leukemia at 1 year. There were 38 deaths with the median OS of 26.2 months (95%CI: 17.3-48.3 months). The 2-year probability of OS was 51% (95%CI: 36.7-62.9%). We next compared outcomes of these MDS patients who had a donor search without subsequent HCT to a consecutive case-series of MDS patients who underwent alloHCT from matched related and unrelated donors (cord blood and haploidentical transplants were excluded) during the same time period (n=276) at our center (Aldoss et al. Haematologica 2017). Patient demographics and MDS disease characteristics were similar between the two groups (Table 1). Median number of days from HLA typing to HCT were 168. By Kaplan-Meier method, OS (from the time of donor search) was significantly better for the alloHCT group (74% at 2-years) compared with non-HCT group (51% at 2-years), log-rank P In conclusion, using a unique cohort of patients who were referred for a donor search, our study in real-world practice demonstrates that transplant eligible MDS patients (at the time of donor search) who do not undergo alloHCT have worse survival outcomes compared to those undergoing transplantation. A prospective biologic assignment study is currently underway by the BMT CTN (#1102) to more definitively determine the impact and relative benefits of alloHCT in patients (≥50 years old) with Int2/high-risk de novo MDS. Disclosures Khaled: Alexion: Consultancy, Speakers Bureau; Daiichi: Consultancy; Juno: Other: Travel Funding. Salhotra:Kadmon Corporation, LLC: Consultancy. Ali:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding. Stein:Celgene: Speakers Bureau; Amgen Inc.: Speakers Bureau.

The prevalence of vancomycin-resistance Enterococci colonization (VRE-C) in patients undergoing allogeneic hematopoietic cell transplantation (aHCT) is between 23-40%. Pre-HCT VRE-C is shown to be associated with high risks of VRE bloodstream infection (VRE-BSI), non-relapse mortality (NRM) and lower overall survival. Recent studies investigating the association between VRE-C and risk of acute graft-versus-host disease (aGVHD) after aHCT has demonstrated conflicting results, possibly due to the heterogeneous transplant conditioning and GVHD prophylactic regimens. Here, we sought to examine the VRE-C prevalence and determine its impact on aHCT outcomes, in patients receiving tacrolimus and sirolimus (T/S) as aGVHD prophylaxis. To explore the association between pre-HCT VRE-C and transplant outcomes, we retrospectively reviewed medical records of a cohort of 1074 consecutive patients who underwent aHCT at City of Hope from 2014 to 2017. Patients with stool culture screening within 30 days pre-aHCT (n=862) were identified from the microbiology database and were grouped as VRE-C and non-colonized (VRE-NC). Data was not available on VRE-C in 185 patients and they were not included in analysis. Overall survival (OS) and progression-free survival (PFS) were examined by Kaplan-Meier curves and log-rank tests. Non-relapse mortality (NRM), VRE-BSI, and GVHD rates of the 2 groups were compared by cumulative incidence rates and Gray's test. Multivariate analyses were performed when adjusting for prognostic factors. Two-sided P value of ≤0.05 was considered significant. Of the 862 evaluated patients, 68 had VRE-C (7.9% prevalence). Median age of patients in VRE-C and VRE-NC groups were 53 and 55 years, respectively. Gender distribution, transplant indications, stem cell source, proportion of unrelated donors, GVHD prophylaxis with T/S and other clinical variables including intensity of conditioning regimen and HCT-CI were similar between the two groups (Table 1) . Karnofsky performance status (KPS) of 90-100 and 70-80 were seen in 40% and 53% of patients with VRE-C compared to 47% and 48% of VRE-NC patients (p=0.12). Overall, VRE-BSI episodes were rare (n=7) with 4 patients in VRE-C (6.1%) and 3 patients in VRE-NC (0.4 %); p At a median follow-up duration of 19.4 months (range: 2.7-48.4), similar 1-year OS was achieved in both groups (67.4% in VRE-C and 76.5% in VRE-NC; p=0.11) but 1 year PFS was significantly lower in the VRE-C cohort (55.6% Vs. 69.4%; p=0.038). Higher NRM was achieved in the VRE-C cohorts on days +100 and +365 (11.8% Vs. 7.2% and 25.1% Vs. 14.4%, respectively, p=0.041). (Figure 1) There were no differences in rates of day 100 aGVHD (grades II-IV) (Figure 2) and relapse rates at 12 months between the two groups. Conditioning regimen intensity, donor type, KPS, and primary diagnosis were significantly associated with NRM. When these variables were included in the multivariate model, VRE-C was found to be independently associated with higher NRM (HR=1.82, 95%CI: 1.12-2.93; p=0.015). In conclusion, in our cohort of patients receiving predominantly T/S-based aGVHD prophylaxis, no association was detected between VRE-C and aGVHD incidence. Higher rate of VRE-BSI in the VRE-C group is in accordance with published data, albeit lower rates of VRE-BSI was seen in our cohort. VRE-C contributed to higher NRM at days 100 and 365 post-aHCT and was an independent risk factor for poor HCT outcomes Since VRE-C is a potentially modifiable risk factor, our data supports continued efforts for specific interventional strategies (i.e. antimicrobial stewardship) to reduce drug resistant bacterial colonization, and for clinical research to reverse the impact of VRE-C, such as the use of agents, which may modulate gut microbiome. Disclosures Salhotra: Kadmon Corporation, LLC: Consultancy. Ali:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Stein:Amgen Inc.: Speakers Bureau; Celgene: Speakers Bureau. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding. Dadwal:AiCuris: Research Funding; Gilead: Research Funding; MERK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Research Funding.

Purpose This study evaluates the safety and efficacy of plerixafor (AMD3100), a CXCR4 antagonist, in mobilizing hematopoietic stem cells for autologous stem-cell transplantation in non-Hodgkin's lymphoma (NHL) patients. Patients and Methods This is a phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study. Patients with non-Hodgkin's lymphoma requiring an autologous hematopoietic stem-cell transplantation in first or second complete or partial remission were eligible. Patients received granulocyte colony-stimulating factor (G-CSF; 10 μg/kg) subcutaneously daily for up to 8 days. Beginning on evening of day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 μg/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until ≥ 5 × 106 CD34+ cells/kg were collected. The primary end point was the percentage of patients who collected ≥ 5 × 106 CD34+ cells/kg in 4 or fewer apheresis days. Results This report presents all data for all patients (n = 298) through 12 months follow-up. Eighty-nine (59%) of 150 patients in the plerixafor group and 29 (20%) of 148 patients in the placebo group met the primary end point (P < .001). One hundred thirty-five patients (90%) in plerixafor group and 82 patients (55%) in placebo group underwent transplantation after initial mobilization. Median time to engraftment was similar in both groups. The most common plerixafor-associated adverse events were GI disorders and injection site reactions. Conclusion Plerixafor and G-CSF were well tolerated and resulted in a significantly higher proportion of patients with non-Hodgkin's lymphoma achieving the optimal CD34+ cell target for transplantation in fewer apheresis days, compared with G-CSF alone.

High-dose therapy followed by autologous hematopoietic stem cell transplantation (auto-HCT) has become the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, relapse remains the most common cause of treatment failure after auto-HCT. More intensive regimens incorporating radioimmunotherapy into high-dose regimens have been developed to prevent relapse. The role of auto-HCT for follicular lymphoma and mantle cell lymphoma remain inconclusive. Since prognosis of patients with peripheral T-cell lymphoma, not otherwise specified are very poor with conventional chemotherapy, auto-HCT during first remission is being explored in peripheral T-cell lymphoma. Given the lower risk of relapse after allogeneic HCT (allo-HCT) in NHL, allo-HCT has been performed in patients with refractory or relapsed NHL, especially after auto-HCT failure. However, the transplant-related mortality remains high after myeloablative allo-HCT. Reduced-intensity conditioning followed by allo-HCT has been shown to reduce transplant-related mortality but graft-versus-host disease continues to be the major problem, thus the role of allo-HCT in NHL remains an investigational approach for NHL. The outcomes of auto-HCT and allo-HCT for various lymphomas are reviewed.

Purpose Transplantation of hematopoietic stem cells from an unrelated donor (URD) is an option for many patients who do not have an HLA-identical sibling donor (MSD). Current criteria for the selection of URDs include consideration for HLA alleles determined by high resolution typing methods, with preference for allele-matched donors. However, the utility and outcome associated with transplants from URDs compared with those from MSDs remains undefined. Patients and Methods We examined clinical outcome after patients received bone marrow transplants (BMTs) from MSDs; HLA-A, -B, -C, and DRB1 allele-matched URDs (8/8); and HLA-mismatched URDs in a homogeneous population of patients with chronic myeloid leukemia (CML) in first chronic phase (CP1) where a strong allogeneic effect and hence a lower risk of relapse is anticipated. Transplantation outcomes were compared between 1,052 URD and 3,514 MSD BMT recipients with CML in CP1. Results Five-year overall survival and leukemia-free survival (LFS) after receipt of BMTs from 8/8 matched URDs were worse than those after receipt of BMTs from MSDs (5-year survival, 55% v 63%; RR, 1.35; 95% CI, 1.17 to 1.56; P < .001; LFS, 50% v 55%; RR, 1.21; 95% CI, 1.06 to 1.40; P = .006). Survival was progressively worse with greater degrees of mismatch. Similar and low risk of relapse were observed after receipt of transplant from either MSD or URD. Conclusion In this homogeneous cohort of good risk patients with CML in CP1, 5-year overall survival and LFS after receipt of transplant from 8/8 allele-matched donors were modestly though significantly worse than those after receipt of transplant from MSDs. Additive adverse effects of multilocus mismatching are not well tolerated and should be avoided if possible.

Purpose This phase II trial evaluated the safety and efficacy of combining yttrium-90 (90Y) ibritumomab tiuxetan with high-dose carmustine, cytarabine, etoposide, and melphalan (BEAM) and autologous stem-cell transplantation in patients with non-Hodgkin's lymphoma who were considered ineligible for total-body irradiation because of older age or prior radiotherapy. Patients and Methods Between May 2002 and January 2006, 14 days before autologous stem-cell transplantation, 41 patients with non-Hodgkin's lymphoma received standard-dose 90Y ibritumomab tiuxetan (14.8 MBq/kg [0.4 mCi/kg]) followed by high-dose BEAM. Results The median age was 60 years (range, 19 to 78 years), and the median number of previous therapies was two (range, one to six). Disease histologies were diffuse large B-cell (n = 20), mantle cell (n = 13), follicular (n = 4), and transformed lymphoma (n = 4). With a median follow-up of 18.4 months (range, 5.5 to 53.3 months) the estimated 2-year overall and progression-free survival were 88.9% (95% CI, 75.3% to 95.2%) and 69.8% (95% CI, 56.4% to 79.7%). The median time to WBC engraftment was 11 days (range, 9 to 26 days) and time to platelet engraftment was 12 days (range, 3 to 107 days). Adverse events were similar to those seen historically with high-dose BEAM alone, and included grade 3 or 4 pulmonary toxicity in 10 patients. Conclusion Adding 90Y ibritumomab tiuxetan to high-dose BEAM with autologous stem-cell transplantation is feasible and has a toxicity and tolerability profile similar to that observed with BEAM alone. Rates of progression-free survival seen in these patients are promising and warrant additional study.

We assessed late mortality in 1479 individuals who had survived 2 or more years after allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 25.9 years and median length of follow-up was 9.5 years. The conditional survival probability at 15 years from HCT was 80.2% (SE = 1.9%) for those who were disease-free at entry into the cohort, and the relative mortality was 9.9 (95% confidence interval, 8.7-11.2). Relative mortality decreased with time from HCT, but remained significantly elevated at 15 years after HCT (standardized mortality ratio = 2.2). Relapse of primary disease (29%) and chronic graft-versus-host disease (cGVHD: 22%) were the leading causes of premature death. Nonrelapse-related mortality was increased among patients older than 18 years at HCT (18-45 years: relative risk [RR] = 1.7; 46+ years: RR = 3.7) and among those with cGVHD (RR = 2.7), and was lower among patients who received methotrexate for GVHD prophylaxis (RR = 0.5). HCT survivors were more likely to report difficulty in holding jobs (odds ratio [OR] = 13.9), and in obtaining health (OR = 7.1) or life (OR = 9.9) insurance compared with siblings. This study demonstrates that mortality rates remain twice as high as that of the general population among 15-year survivors of HCT, and that the survivors face challenges affecting their health and well-being.

Limited cell dose hampers wider use of cord blood transplantation (CBT). By depleting plasma but not RBC during processing, nucleated cell (NC) loss is reduced to0.1% which increases significantly the proportion of high cell dose products-3-fold for products with NCor=200 x 10(7). Clinical outcome for plasma depleted (PD) CBT was previously unavailable. A retrospective audited analysis was performed on 118 PD CBT, with mean and median NC doses of 7.6 x 10(7)/kg and 5.6 x 10(7)/kg, respectively, for this mostly pediatric population. The median times to engraftment and engraftment rates for ANC 500 and platelet 20K were 22 and 50 days, respectively, and 90% +/- 3% and 77% +/- 5%, respectively. The incidences of grade III-IV acute graft-versus-host disease (aGVHD) and extensive chronic GVHD (cGVHD) were 13% +/- 4% and 17% +/- 6%, respectively. Relapse rate for malignancies was 25% +/- 6% and 100-day treatment-related mortality (TRM) was 16% +/- 3%. With a median follow-up of 557 days, the 1-year overall survival and relapse-free survival are 65% +/- 5% and 51% +/- 6%, respectively. These results demonstrate that PD CBT is safe and effective, and that eliminating RBC reduction or depletion improves cell recovery during CB processing, resulting in a larger proportion of the inventory with high NC number.

Although autologous stem cell transplantation (ASCT) for patients with relapsed/refractory Hodgkin lymphoma (HL) appears to offer a survival advantage over conventional therapy, only approximately 25% to 35% of patients with primary progressive or poor-risk recurrent HL can achieve durable remission after ASCT, with disease progressive after transplant accounting for most of the treatment failures. We conducted a pilot study to evaluate the toxicities and efficacy of a tandem transplant approach in this subgroup of patients. Between April 1998 and March 2000, 46 patients were enrolled in the study. Eligibility criteria: primary progressive (n = 28) or recurrent HL (n = 18) with at least 1 of the following poor prognostic factors: first complete remission (CR)

This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status after brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes, and association of CD68+ with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events, including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete remission at time of AHCT. Thirteen patients in complete remission, 4 in partial remission, and 1 with stable disease (49%) received AHCT without salvage combination chemotherapy. CD68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 106 (range, 2.6 to 34), and median number of days to obtain minimum collection (2 × 106) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease after induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT.

Allogeneic hematopoietic cell transplant (alloHCT) has emerged as a potential curative treatment for advanced non-Hodgkin’s lymphoma (NHL), especially for patients with chemorefractory disease, relapsed after prior autologous HCT and those with relapsed lymphoma who failed to collect adequate stem cells for autologous HCT. There are several phase II studies supported the role of alloHCT in low-grade lymphomas, but the data is scarce on the other subtypes of lymphomas. However, retrospective registries studies highlighted the inferior outcomes of alloHCT in aggressive lymphomas, with unacceptable higher relapse rate and non-relapse mortality when compared to low-grade lymphomas. Patients with chemorefractory disease and those with active disease at alloHCT had poor outcome. Therefore, incorporation of new target therapies to induce remission prior to transplant or as a bridge to alloHCT may lead to better outcome of alloHCT in NHL. Furthermore, well design prospective studies of alloHCT in NHL and employment of novel transplant approaches tailored toward specific histological subtype are urgently needed.