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Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.

Background: The chronic lymphocytic leukemia (CLL) tumor microenvironment (TME) is laden with hyporesponsive T-cells that permit disease persistence. Yet, redundant TME immunosuppressive mechanisms and epigenetic maintenance of T-cell exhaustion limit the efficacy of T-cell targeted therapies in CLL. Bromodomain and extra-terminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T-cell function and differentiation. We hypothesize that blocking BET protein function can reverse T-cell exhaustion to yield durable tumor elimination in CLL. Methods: WT C57BL/6 mice were engrafted with Eμ-TCL1 spleen-derived lymphocytes, then treated daily with the novel pan-BET inhibitor, OPN-51107 (OPN5; 20mg/kg PO) for up to 4 weeks. Splenic gene expression was evaluated with the NanoString PanCancer iO360 panel. T-cell differentiation status, immune inhibitory receptor (IR) expression, proliferation (72 h ex vivo α-CD3/α-CD28 stimulation), and cytokine production (6 h ex vivo PMA/ionomycin stimulation) was measured via flow cytometry. CLL patient and healthy donor PBMCs were used for validation studies and to assess T-cell transcription factor (TF) expression via flow cytometry. Evaluation of BRD4 occupancy at select T-cell TFs via ChIP qPCR is ongoing. Results: OPN5 significantly increased cytotoxic cell signatures and reduced exhaustion-associated cell signatures in leukemic mice through inhibition of T-cell exhaustion signaling, as well as activation of Th1, natural killer cell, and IL-7 signaling pathways. Correspondingly, T-cells from OPN5-treated mice demonstrated greater ex vivo proliferative capacity and effector response to stimuli. A greater proportion of CD8+ T-cells from OPN5-treated mice were classified as naïve, and OPN5 significantly reduced KLRG1 expression on antigen-experienced CD8+ T-cells. Importantly, OPN5 curtailed IR co-expression (PD-1, PD-L1, VISTA, CD244, CD160, and LAG3) on splenic T-cells. These findings were confirmed with primary CLL cells ex vivo. OPN5 also impaired expression of terminal differentiation-associated TFs in CLL patient-derived T-cells, enriching for a TCF1+ progenitor T-cell population. While BTK inhibitors are known to similarly improve T-cell function in CLL, ibrutinib treatment was inadequate to revert CLL T-cell terminal differentiation. Future ATAC-sequencing analysis will inform how BET inhibition alleviates exhaustion-associated chromatin organization in CLL T-cells. Conclusion: BET inhibition dismantles immunosuppressive mechanisms in the CLL TME, alleviating CLL-induced T-cell dysfunction and terminal differentiation. These findings suggest that BET inhibition may be a useful component of combination strategies for the treatment of CLL to yield lasting anti-cancer immune memory and prevent relapsed/refractory disease. Citation Format: Audrey L. Smith, Alexandria P. Eiken, Sydney A. Skupa, Christopher R. D'Angelo, Avyakta Kallam, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Ben Powell, Gideon Bollag, Dalia El-Gamal. BET inhibition alleviates T-cell dysfunction in chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6396.

Background: We used the Therapy Preference Scale, a 30-item questionnaire, to determine cancer treatment preferences of adults with cancer. Methods: We used Wilcoxon’s rank sum test and Fisher’s exact test to compare the preferences of younger (

Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m

Non-Hodgkin lymphoma (NHL) is one of the most prevalent cancers in the Western world with an increasing incidence in US (Zelenetz, et al 2010) This group of lymphomas encompasses a heterogeneous group of diseases with a wide range of histology, pathogenesis and clinical course ranging from indolent to aggressive diseases. The most common indolent subtype of B-cell lineage is follicular lymphoma (FL), and that of the T-cell lineage is cutaneous T-cell lymphoma (CTCL), whereas aggressive subtypes include diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL), representing approximately 80% of all NHL diagnoses in adults (Swerdlow et al 2016). There is often patient-to-patient variability in clinical course, with a significant proportion of patients relapsing or refractory to first line therapies. While many treatment difficulties exist in NHL, relapsed/refractory disease represents a major challenge and is currently under intense investigation, especially in the rituximab era for B-cell lineage lymphomas. The use of the monoclonal antibody rituximab, as a single agent or in combination with cytotoxic chemotherapy, is currently the standard of care in the first line setting for B-cell NHLs and has significantly improved the prognosis of affected patients. However, rituximab resistance has been reported in multiple NHL subtypes, including relapsed FL or low-grade NHL, and is associated with poor prognosis (Davis, et al 2000, Hagberg and Gisselbrecht 2006, Martin, et al 2008). Patients with PTCL generally have a poor prognosis with current standard-of-care therapy, and no progress in their outcome has been achieved in the past two decades (Xu and Liu 2014). The prognosis of relapsed PTCL is very poor and novel effective treatments are urgently needed. Autologous haematopoietic stem cell transplantation has been associated with extended survival in relapsed/refractory NHL, however the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) demonstrated that, in the post-rituximab era, patients with DLBCL, the most common type of NHL in the US, derive less benefit from autologous transplant, with a dismal progression-free survival (PFS) of 20% at 3 years (Gisselbrecht, et al 2010). As patients relapse after autologous transplant, progress through multiple lines of treatment, the subsequent responses achieved are incrementally shorter, with eventual exhaustion of meaningful options. This clearly highlights the need for additional safe, effective and targeted agents for this high-risk population. Several novel classes of drugs, such as next generation monoclonal antibodies, antibody–drug or radioactive isotope conjugates and specific small-molecule inhibitors of oncogenic pathways, are emerging as therapeutic options in NHL. However, despite the recent array of drug approvals, long-term remission remains elusive for a significant proportion of NHL patients, particularly those with relapsed/refractory disease (Crump, et al 2017). In this context, we studied the safety and efficacy of single agent dasatinib in patients with relapsed/refractory NHL. Dasatinib, originally developed as a pan-Src kinase inhibitor, is a potent and broad-spectrum multi-kinase inhibitor with proven safety and efficacy in chronic myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) (Cortes, et al 2016, Lilly, et al 2010). Dasatinib has selective 100-fold higher affinity for ABL1 than imatinib mesylate (Shah, et al 2004), and targets several tyrosine kinase families that are implicated in cell survival in NHLs (Brave, et al 2008, Sprangers, et al 2006). The half-life of the drug is approximately 5 h, shown to be well tolerated in CML patients (Talpaz et al. 2004), and achieves sustained inhibition of Lyn kinase, which is critical for B-cell survival. Given that Lyn could be inhibited by dasatinib at tolerable doses, we initiated this phase 1/2 trial in patients with relapsed NHLs.

Purpose To improve the curability of older patients with newly diagnosed Hodgkin lymphoma. Patients and Methods We conducted a multicenter phase II study that administered brentuximab vedotin (Bv) sequentially before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) for untreated patients with Hodgkin lymphoma age 60 years or older. After two lead-in doses of single-agent Bv (1.8 mg/kg once every 3 weeks), patients received six cycles of AVD chemotherapy followed by four consolidative doses of Bv in responding patients. Results Patient characteristics included median age of 69 years (range, 60 to 88 years), 63% male, median Eastern Cooperative Oncology Group performance status 1, 81% stage III to IV disease, 60% International Prognostic Score 3 to 7, median Cumulative Illness Rating Scale-Geriatric comorbidity score of 7 (52% grade 3 to 4); and 12% had loss of instrumental activities of daily living at diagnosis. Thirty-seven (77%) of 48 patients completed six cycles of AVD, and 35 patients (73%) received at least one Bv consolidation. Overall response and complete remission rates after initial Bv lead-in dose were 18 (82%) of 22 and 8 (36%) of 22, respectively, and 40 (95%) of 42 and 34 (90%) of 42, respectively, after six cycles of AVD among 42 response-evaluable patients. Twenty (42%) of 48 patients experienced a grade 3 to 4 adverse event, most commonly neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%); 33% had grade 2 peripheral neuropathy, which was reversible in a majority of patients. By intent-to-treat, the 2-year event-free survival, progression-free survival, and overall survival rates were 80%, 84%, and 93%, respectively. Furthermore, 2-year progression-free survival rates for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of ≥ 10 versus < 10 were 45% versus 100%, respectively ( P < .001), and with baseline loss versus no loss of instrumental activities of daily living were 25% versus 94% ( P < .001), respectively, the latter persisting on multivariable analyses. Conclusion Altogether, sequential Bv-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival.

High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, "double-hit" or "triple-hit" lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique "pseudo-double-hit" BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed. All new cases displayed aggressive morphologic features, and most previously published cases were classified as aggressive lymphomas. Collectively, all t(3;8)(q27;q24) cases had a germinal center (GC) phenotype, and most had complex karyotypes (22/24, 92%), including frequent concomitant BCL2 rearrangements (17/24, 71%). When compared to two large published DTHL cohorts, t(3;8)(q27;q24) lymphomas less often expressed BCL2 (P < .01), had a greater likelihood of extranodal involvement (P < .01), and more frequently appeared triple-hit by FISH analysis (P < .01). Despite presenting with aggressive clinicopathologic features, 100% (6/6) of t(3;8;)(q27;q24) patients achieved complete remission after intensive induction regimens, and 2- and 3-year overall survival rates were 63% (10/16) and 57% (8/14), respectively. These findings suggest that lymphomas with t(3;8)(q27;q24) may represent a subset of GC B-cell lymphomas distinct from conventional DTHL. Our results further highlight the value of routine karyotype assessment in aggressive B-cell lymphomas, and the importance of recognizing the t(3;8)(q27;q24) so that its clinical significance can be more fully explored.

Introduction : Chronic Lymphocytic Leukemia (CLL) is characterized by the clonal expansion of mature CD19+/CD5+ lymphocytes in the peripheral blood and secondary lymphoid organs. The accumulation of B-CLL cells yields profound immune defects in the CLL tumor microenvironment (TME), promoting evasion of immune surveillance that contributes to tumor persistence and thus relapsed/refractory disease. The bromodomain and extra-terminal domain (BET) family of proteins are epigenetic readers that bind acetylated histone residues to regulate transcription of numerous genes involved in critical CLL protumor pathways. Of the BET family proteins, BRD4 is overexpressed in CLL and highly enriched at super-enhancers of genes that regulate CLL-TME interactions such as B cell receptor pathway components, chemokine/cytokine receptors, and immune checkpoint molecules. Pan BET inhibitors (BET-i), such as PLX51107 (Plexxikon Inc.) significantly improve survival in aggressive CLL murine models. Here we demonstrate that blocking BRD4 function with PLX51107 (PLX5) can alleviate the inherent immune defects observed in CLL, hence reducing B-CLL induced T cell dysfunction and allowing for robust B-CLL cell elimination. This therapeutic strategy may be vital in overcoming frequent drug resistance and/or bolstering the anti-tumor effect of current CLL therapies. Methods : Primary leukemic B cells were isolated from the peripheral blood of CLL patients and co-cultured with healthy donor T cells to evaluate the effect of PLX5 (0.1-0.5μM) on CLL-induced T cell immunosuppression ex vivo via an array of flow cytometry assays. T cell proliferation was assessed using CFSE after 96 h co-culture with α-CD3/α-CD28 stimulation. Effector cytokine production was evaluated after 48 h co-culture in the presence of PMA/ionomycin (final 6 h) and brefeldin A (final 5 h). Immune inhibitory molecule surface expression was measured following 48 h co-culture with α-CD3/α-CD28 stimulation. To further validate our ex vivo findings, the E μ-TCL1 adoptive transfer model was used. Once disease onset was confirmed in recipient WT B6 mice (>10% CD45+/CD19+/CD5+ peripheral blood lymphocytes), mice were randomized to receive either PLX5 (20 mg/kg) or vehicle (VEH) equivalent daily by oral gavage for 4 weeks. Following treatment, mouse spleens were processed to evaluate exhaustion marker expression, T cell proliferation (CellTrace™ Violet, 72 h a-CD3/α-CD28 stimulation ex-vivo), and T-cell effector function (ex-vivo mitogenic stimulation, 6 h). Results : T cell proliferation indices were reduced following ex vivo co-culture with primary B-CLL cells (mean ± SEM for T cells vs. co-culture, 2.0 ± 0.13 vs. 1.57 ± 0.05; P Conclusion : Epigenetic-targeted therapies such as BET-i have the potential to alleviate CLL-induced T cell dysfunction while eliminating B-CLL cells and preventing tumor expansion. Future profiling studies are pending to further illuminate how BET proteins regulate immune function in CLL. Figure 1 Figure 1. Disclosures Lunning: AstraZeneca: Consultancy; Legend: Consultancy; Acrotech: Consultancy; ADC Therapeutics: Consultancy; Kyowa Kirin: Consultancy; Myeloid Therapeutics: Consultancy; Beigene: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; Verastem: Consultancy; Janssen: Consultancy; Daiichi-Sankyo: Consultancy; Morphosys: Consultancy; TG Therapeutics: Consultancy; Novartis: Consultancy; Karyopharm: Consultancy; AbbVie: Consultancy; Spectrum: Consultancy; Kite, a Gilead Company: Consultancy. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Powell: Plexxikon Inc.: Current Employment.

Background: Acute Lymphoblastic Leukemia (ALL) outcomes have significantly improved over time with multi-agent chemotherapy, and the addition of asparaginase (ASP) has demonstrated the ability to prolong overall survival. ASP has multiple toxicities, and it remains a challenge to manage them safely, particularly coagulopathy and thrombosis (30-40% based on historical studies). The best prophylactic anticoagulation strategy in patients with acute leukemias, particularly ALL with asparaginase use, remains unclear due to severe coexisting thrombocytopenia and coagulopathy. Though the current guidelines recommend using Antithrombin (AT) replacement or low molecular weight heparin (LMWH) for thrombosis prophylaxis, the evidence is weak with concerns of thrombosis (Blood (2020) 136 (3): 328-338) with the use of fibrinogen concentrates(cryoprecipitate) and limited efficacy data with AT replacement and unfractionated heparin (UFH) for thrombosis prophylaxis. Due to potential "resistance" to LMWH and UFH from acquired AT deficiency with ASP use, our institution in 2017 has adopted the use of the direct Xa inhibitor, Apixaban for thrombosis prophyalxis. We report the safety and effectiveness of Apixaban for thrombosis prophylaxis with ASP. Methods: In this retrospective study, we reviewed the data on 20 patients treated with ASP between 2017-2020. Thrombosis prophylaxis was instituted with Apixaban 2.5 mg PO Q 12 hourly for three weeks along with cryoprecipitate as needed for bleeding or fibrinogen levels Results: Among the 20 patients treated during this period, 18 (90%) had ALL, and 2(10%) had NK/T cell lymphoma. Of the patients with ALL, 67% had high risk and 33% with standard-risk ALL. The median age of this cohort was 29.5 years (range: 19-63 years), 80% were males, 70% white, 30% were Latino or Hispanic, median body mass index-BMI of 30.2 kg/m 2(19.4-40.7 kg/m 2) and 65% were non-smokers. The median baseline AT activity was 107% (79-221%), 95% used concurrent corticosteroids (65%- Prednisone, and 30% used Dexamethasone). The most common induction treatment was CALGB 10403 (55%). Of the total, 95% received pegylated ASP, and only one patient received Erwinia ASP due to prior history of anaphylaxis. The major toxicities attributed to ASP included 5% grade II and 15% grade III-IV aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, 20% had bilirubin elevation, 10% developed grade III-IV acute pancreatitis, and 5% developed severe hypertriglyceridemia needing aphaeresis. Two patients (10%) developed thrombosis [catheter associated deep venous thrombosis (DVT) and one patient with lower extremity proximal DVT] within 4 weeks of use of ASP, with one of the two patients (5%) developing (lower extremity proximal DVT) while on being off anticoagulation due to bleeding. Major bleeding or CRNMB developed in 5% (spontaneous splenic rupture from ALL leading to hemorrhagic shock). The median number of cryoprecipitate units used per patient during weeks 1,2,3, and 4 was 5(0-35), 5(0-40), 5(0-15), 7.5(0-15), respectively; No patients received fresh frozen plasma or AT concentrates. Conclusions: With the use of Apixaban prophylaxis, the incidence of thrombosis was 10% within four weeks from ASP and 5% while on anticoagulation. The incidence of major bleeding or CRNMB was 5%. Hypofibrinogenemia, acquired AT deficiency due to ASP, was seen between days 7-21 after using ASP (figure 1 & 2) and recovered subsequently. This study demonstrates initial evidence of the safety and efficacy of Apixaban for thrombosis prophylaxis and cryoprecipitate infusions in patients treated with ASP. Figure 1 Figure 1. Disclosures Gundabolu: Samus Therapeutics: Research Funding; Pfizer: Research Funding; BioMarin Pharmaceuticals: Consultancy; Bristol-Myers Squibb Company: Consultancy; Blueprint Medicines: Consultancy. Bhatt: Jazz: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Partnership for health analytic research, LLC: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Lunning: Myeloid Therapeutics: Consultancy; Janssen: Consultancy; Kyowa Kirin: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; Novartis: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; AbbVie: Consultancy; TG Therapeutics: Consultancy; Daiichi-Sankyo: Consultancy; Legend: Consultancy; Kite, a Gilead Company: Consultancy; Verastem: Consultancy; Acrotech: Consultancy; Karyopharm: Consultancy; Spectrum: Consultancy; Beigene: Consultancy; Morphosys: Consultancy. Baljevic: BMS/Celgene: Consultancy; Oncopeptides: Other: Advisory Board; Janssen Research: Other: Advisory Board; Karyopharm: Other: Advisory Board; BMS/Celgene: Other: Advisory Board; Amgen: Research Funding; Exelixis: Research Funding. Ganti: Merck: Research Funding; Apexigen: Research Funding; Nektar: Research Funding; Top Alliance Biosceinces: Research Funding; Lovance: Research Funding; Novartis: Research Funding; WindMil Therapeitucs: Research Funding; Takeda: Research Funding; Flagship Biosciences: Consultancy; AstraZeneca: Consultancy, Other: Advisory Board; Mirati Therapeutics: Consultancy, Other: Advisory Board; G1 Therapeutics: Consultancy, Other: Advisory Board; Blueprint Medicines: Consultancy, Other: Advisory Board; Cardinal Health: Consultancy, Other: Advisory Board; Roche: Consultancy, Other: Advisory Board; YMabS Therapeutics: Other: DSMC Chair.

PURPOSE/OBJECTIVE(S) The role of radiotherapy following high dose chemotherapy and autologous stem cell transplantation (ASCT) for relapsed or refractory Hodgkin lymphoma (HL) has not been addressed in a prospective randomized trial. While the benefit of consolidative radiotherapy has been demonstrated in other clinical settings for HL, concern of late radiotherapy associated toxicity and uncertain treatment efficacy remain as deterrents in the peritransplant setting. MATERIALS/METHODS We retrospectively reviewed patients with relapsed or refractory HL who underwent high dose chemotherapy and an ASCT from 2000-2019 at our institution. The association of clinicopathologic factors with the delivery of consolidative radiotherapy was assessed by Chi squared analysis. Kaplan Meier and a cox regression analysis were used to estimate factors independently associated with progression-free survival (PFS) and overall survival (OS). RESULTS From 2000-2019, 179 consecutive patients underwent salvage chemotherapy (most commonly ICE: ifofsamide, carboplatin, and etoposide) followed by high dose chemotherapy (most commonly BEAM: BCNU, Etoposide, Ara-C and Melphalan) and an autologous stem cell transplant for relapsed (63.4%) or refractory (36.6%) HL with a median follow up of 59.4 months. Post-transplant consolidative radiotherapy was delivered to a median dose of 3600 cGy in 20 fractions to 72 patients (40.2%). Consolidative radiotherapy was associated with younger age (median age 32 vs. 42 years, P < 0.001), stage I-II disease at the time of salvage chemotherapy (76.4% vs 52.3%, P = 0.001), and no prior radiotherapy (76.4% vs 45.8%, P < 0.001). On univariate analysis, consolidative radiotherapy was associated with an improved two-year PFS (84.1% vs 64.1%, P = 0.005) and OS rates (95.7% vs 80.8%, P = 0.017). In the Cox regression analysis, consolidative radiotherapy was significantly associated with improved PFS (HR: 0.492, 95% CI: 0.288-0.84, P = 0.009) along with ECOG performance status < 2 (HR: 0.188, 95% CI: 0.045-0.79, P = 0.022), achieving a complete response to salvage chemotherapy (HR: 0.463, 95% CI: 0.233-0.92, P = 0.028), and stage I-II disease (HR: 0.546, 95% CI: 0.325-0.918, P = 0.022). Similarly, consolidative radiotherapy was associated with significantly improved OS (HR: 0.398, 95% CI: 0.205-0.771, P = 0.006) along with ECOG performance status < 2 (HR: 0.073, 95% CI: 0.016-0.333, P = 0.001). Following transplantation, grade ≥2 pneumonitis was identified in 10 patients (5.6%) of which only 7 patients underwent consolidative radiotherapy which was delivered to mediastinal (50.0%), supraclavicular (10.0%), or abdominal (10.0%) fields. No patient deaths were associated with pneumonitis. CONCLUSION Our findings suggest that consolidative radiotherapy in the salvage management of HL is associated with improved PFS and OS with low rates of treatment associated complications. Further investigation in the role of consolidative radiotherapy in this setting is warranted.

Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p= When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived > 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

The optimal management of hematologic malignancy-associated venous thromboembolism (VTE) in patients with moderate-to-severe thrombocytopenia is unclear. This is a retrospective study of 128 adult patients with hematologic malignancies who were diagnosed with VTE. The outcome of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Forty-seven patients (36.7%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation. The median nadir platelet count in those with significant thrombocytopenia was 10,000/µL (range 2,000-45,000/µL) versus 165,000/µL (50,000-429,000/µL) in those without (P < 0.001). The median duration of significant thrombocytopenia in the first group was 10 days (1-35 days). Therapy during the period of significant thrombocytopenia included prophylactic-dose low-molecular-weight heparin (LMWH) (47%), therapeutic-dose LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%), and observation (17%). Patients without thrombocytopenia were managed with the standard of care therapy. At a median follow-up of more than 2 years, the risk of clinically significant bleeding (11% vs 6%, P = 0.22) including major bleeding (6% vs 2%) and clot progression or recurrence (21% vs 22%, P = 1.00) were similar in patients with or without significant thrombocytopenia. In a multivariate analysis, the risk of recurrence/progression (hazard ratio, HR 0.59, 95% CI 0.21-1.66, P = 0.31) and hemorrhage rate (HR 0.29, 95% CI 0.05-1.56, P = 0.15) did not differ based on the presence of significant thrombocytopenia. Within the limits of this retrospective study, cautious use of prophylactic-dose LMWH may be safe in thrombocytopenic patients with hematologic malignancy-associated VTE. Am. J. Hematol. 91:E468-E472, 2016. © 2016 Wiley Periodicals, Inc.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare entity with no previous population-based study.We used the Surveillance, Epidemiology, and End Results 18 database to identify adult patients with SPTCL and peripheral T-cell lymphoma not otherwise specified (PTCL NOS) diagnosed between 1973 and 2011. The actuarial survival of SPTCL was compared with a propensity-matched cohort of PTCL NOS. Multivariate analysis was conducted using weighted Cox proportional hazard regression model.Patients with SPTCL (n = 118), compared with PTCL NOS (n = 3296), were more likely to be younger (median age of 47 vs. 62 years; P .01), women (67% vs. 40%, P .01), and diagnosed with stage I/II disease (46% vs. 36%; P = .01). The 5-year actuarial, relative, and cause-specific survival for SPTCL was 40%, 57%, and 64%, respectively. After propensity-matching, the 5-year overall survival (OS) of SPTCL was better than that of PTCL NOS (57% vs. 40%; P .01). In a multivariate analysis, mortality was significantly lower among SPTCL versus PTCL NOS (hazard ratio, 0.54; 95% confidence interval, 0.39-0.75; P .01). Among patients with SPTCL, advanced age (P .01) and diagnosis before the year 2008 (P = .02) were predictors of worse OS.Our study provides characteristics and OS of a large cohort of SPTCL. Compared with PTCL NOS, SPTCL patients were more likely to be younger, female, and diagnosed at an early stage. The OS of SPTCL was better than PTCL NOS.

56 Background: Burnout is a syndrome whose manifestations include pervasive emotional and physical exhaustion, depersonalization, a lack of motivation and an inability to complete tasks efficiently. We sought to use quality improvement (QI) methodology to approach problems contributing to burnout and workplace stress in our oncology care team. Methods: Through a broad survey of cancer center team members, we identified the coordination of same-day outpatient visits for acutely ill oncology patients as a source of excessive stress for team members across various disciplines including case managers, infusion clinic nurses, advanced practice providers, and physicians. We used the Plan-Do-Study-Act (PDSA) framework to identify a feasible, appropriate intervention to reduce the time required to coordinate visits with the specific aim of reducing the time to schedule an ill patients by 25%. We generated a cause and effect diagram to map the elements involved in the ill call scheduling process, and used a priority/payoff matrix to evaluate possible countermeasures that could streamline the process by re-designing/improving the efficiency of the workflow for scheduling ill calls. Our initial workflow involved paging individual practitioners at three locations. The process led us to the creation of a HIPPA-compliant group text to simultaneously coordinate scheduling of an ill call among/between three campuses in a more collaborative/efficient manner. We tracked time from patient call to time of scheduled appointment pre- and post-test of change (Voalte group text). We also tracked quantity of phone calls required to arrange a visit and perceived frustration with the process. Results: After one PDSA cycle, we found case manager time required to arrange a visit had decreased by 21%, number of calls required by 59% and frustration with the process by 41%. Conclusions: While we did not meet our specific aim of decreasing scheduling time by 25%, we feel use of a QI approach led to an easily implemented, yet effective modification to streamline a previously inefficient and disruptive workflow. The use of QI methodology ensured we understood the baseline process and involved all stakeholders before implementing a change and also ensured we followed data to understand the impact of our intervention on team members. Viewing sources of burnout and workplace frustration through the lens of QI may lead to more consistently high-yield interventions than traditional wellness-based, administrative approaches.

e24186 Background: Patients’ (pts) preferences, crucial in selecting an appropriate treatment (tx), are understudied in cancer pts. We developed a novel self-reported questionnaire “Therapy Preference Scale” (TPS) (J Geriatr Oncol. 2019:677-679, J Clin Oncol 2019 37: e23179-e23179). Our single-center prospective observational study utilized TPS to gain in-depth understanding of pts’ preferences of various aspects of cancer tx. Methods: Eligible pts were adults aged ≥19 y with a diagnosis of cancer. Pts were asked to complete TPS; this 30-item scale captures pts’ rating of the importance of safety, efficacy and other characteristics of cancer tx (on a scale of 0-10), and importance of one over the other aspects of tx (using a 4-item Likert scale). Demographics, cancer-specific and therapy-related data were collected. Descriptive statistics were used for analysis. Results: Total 100 pts were enrolled- 52% were receiving cancer tx; 40% had completed tx; 8% were newly diagnosed and had not yet started tx. Pts were willing to accept short term SE for increased life expectancy but valued maintenance of cognition, functional ability and QoL. 70% valued maintaining cognition, functional ability and quality of life (QoL) than increased life expectancy; 75% would accept cancer tx if it improved QoL but 88% would reject a harsh tx for improved life expectancy of ≤6 months. Conclusions: Avoiding long term side effects (SE), life threatening infections, tx burden and financial toxicity were most important to pts. Harsh tx with ≤6 months improvement of life was unacceptable. These findings will help physicians understand pt preferences and guide selection of tx that will meet pts’ goals of care, and may also have implications for insurance policies and drug approval. [Table: see text]

e20024 Background: Richter's transformation (RT) from Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) to a Diffuse Large B-Cell Lymphoma (DLBCL) is a rare complication with an estimated incidence of less than 5% and a poor prognosis based on small retrospective studies. Large studies investigating the natural history and patient outcomes with this entity of DLBCL are lacking, and prospective data on the best treatment option are scarce and limited by rarity of this condition. Methods: We queried the US Surveillance, Epidemiology, and End Results (SEER) 18 database for patients sequentially diagnosed with CLL/SLL followed by DLBCL from January 2000 to December 2016 with a cutoff latency of 2 months. Data obtained included patient demographics, history of treatment for CLL/SLL, overall survival (OS) after DLBCL diagnosis and latency period between CLL/SLL and DLBCL diagnoses. For comparison, SEER data was obtained for patients with de novo DLBCL and for CLL/SLL patients without RT in the same date range. Survival was estimated by Kaplan Meier method and log rank test was used to compare outcomes. Results: 471 patients who developed RT to DLBCL and 98425 patients with de novo DLBCL were identified. The median time for developing RT to DLBCL was 54 months. Median OS was worse for DLBCL arising from RT compared to de novo DLBCL (64 months versus 10 months, p < 0.0001). In patients with RT to DLBCL, no statistically significant difference in median OS was seen in patients who received treatment for CLL/SLL versus those assigned as No/Unknown treatment status (p = 0.51). In patients with CLL/SLL in the specified time period; median OS was significantly lower for those who developed RT to DLBCL compared to those who did not (91 months versus 100 months, p = 0.0012). Conclusions: DLBCL arising from RT in CLL/SLL patients is not necessarily a late complication. Prognosis is dismal with a trend towards a poor OS in the subset of patients with pretreated CLL/SLL. This large population study correlates with prior reports and highlights the need for prospective data to inform prognosis and treatment decisions.

e19204 Background: Methotrexate (MTX) is used in high doses for the treatment of ALL, lymphoma, and metastatic breast cancer with CNS involvement. To avoid drug accumulation and mitigate toxicities caused by delayed clearance, patients (pts) are usually admitted to the hospital and standard supportive care with IV hydration, urinary alkalization, and leucovorin is provided and adjusted based on daily levels. Historically, a serum methotrexate level ≤ 0.05 µmol/L has been used to declare clearance and an ideal level for discharge based on studies conducted in the 1970s. We conducted a retrospective review in 2018 to identify frequency of supportive dose escalations required with MTX levels > 0.05 µmol/L. In 69 pts, 4 patients demonstrated delayed renal clearance and required supportive care escalations but all occurred at MTX levels > 0.3 µmol/L. This led to a proposed pilot discharge process once MTX was < 0.3 µmol/L to confirm the safety of earlier discharge. Methods: A retrospective chart review of pts with baseline CrCl ≥60 who received HD MTX between 07/2018 – 08/2019. Data collection included diagnosis, MTX discharge level, supportive care at discharge including PO Leucovorin and PO sodium bicarbonate and number of days supply, post-discharge complications (AKI, mucositis, fever, others). Primary outcome was the number of patients who required inpatient or outpatient supportive care for acute complications after being discharged with a methotrexate level ≥ 0.1 µmol/L. Descriptive statistics were used. Results: A total of 41 pts were included. Median age was 55 yrs (32-78), 25% were male. 73% were treated for DLBCL, median dose of MTX was 3500 mg/m2. Median MTX level at the time of discharge was 0.16 µmol/L (0.1-0.3 µmol/L). 12 pts were discharged with PO Leucovorin and 15 pts were discharged with both Leucovorin and PO Sodium bicarbonate with an average of 2 day’s supply. 1 acute complication of neutropenic fever requiring admission for inpatient antibiotics occurred which was felt to be unrelated to MTX level at discharge. Conclusions: This pilot suggests that pts can be safely discharged with MTX levels upto 0.3 µmol/L without acute complications. Results of this study will be used to a develop a standardized protocol outlining criteria for early discharge in select pts with MTX levels < 0.3 µmol/L to reduce length of stay, cost of hospitalization and improve patient satisfaction. [Table: see text]

Introduction Chimeric Antigen Receptor (CAR) T-cell therapy has been approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Long-term follow-up of the ZUMA-1 trial demonstrated that 39% of patients who received axicaptogene ciloleucel were progression free at two-years. Objectives CAR-T cell therapy, as a treatment option, has likely been hindered by logistical barriers, including patients' insurance approval/single case agreement (SCA) process and the distance to the CAR-T treatment center from their home. Methods Patient (Pt) information was retrospectively reviewed from our commercial CAR-T cell therapy experience between 1/2018 and 7/2019. Standard patient demographics and disease characteristics were collected. Progression free survival (PFS) and overall survival (OS) time points started with the treating physician's documentation of intent to CAR-T (iCAR-T). Pts were further assessed based on public (Medicare/Medicaid) or private insurance and distance from CAR-T center to home (> or ≤ than 120 miles). Statistical analysis was then completed on the data. Fischer's Exact tests and Mann-Whitney tests were used to compare the patients, while log-rank tests were used to compare Kaplan-Meier Curves. Results A total of 25 pts were reviewed. Four pts had intended to be apheresed for CAR-T but did not reach the apheresis time point. In the entire cohort, the median PFS and OS have not been reached. The median follow-up was 5.5 months (range: 1.5 to 15 months) for those infused with CAR-T. Pts with public insurance (N=7) received CAR-T infusion more quickly (p = 0.0080) than those with private insurance (N=14). However, this did not influence PFS (p = 0.2856) or OS (p = 0.5073) with balanced disease and demographic characteristics other than age 120 miles; N=10 or ≤ 120 miles; N=11) from a patient's home to the CAR-T center did not affect PFS (p = 0.8914) or OS (p = 0.9078). Neither analysis for PFS or OS was significantly altered with the addition of the iCAR-T population. Conclusion In this experience, pts with public insurance appear to proceed from agreement to CAR-T with subsequent CAR-T infusion (Brain to Vein) more quickly, but the time to apheresis does not appear to affect outcome. Also, the distance from the CAR-T cell center does not appear to be a predictor for worse outcomes. Both logistical barriers occurring pre-apheresis warrant further assessment in a larger multicenter experience.

Autologous stem cell transplantation (ASCT) is standard of care for patients with Hodgkin lymphoma (HL) who have relapsed/refractory disease after frontline chemotherapy. Achievement of complete remission (CR) with pre-ASCT salvage chemotherapy predicts favorable outcomes post-ASCT. This phase 1/2 study evaluated the combination of brentuximab vedotin (BV) plus bendamustine as a first salvage regimen in relapsed/refractory HL. A total of 55 patients (28 primary refractory and 27 relapsed) were enrolled. Patients received BV (1.8 mg/kg) on day 1 and bendamustine (90 mg/m 2 ) on days 1 and 2 of a 21-day cycle for up to 6 cycles. Patients could undergo ASCT any time after cycle 2. Following ASCT or completion of combination therapy if not proceeding to ASCT, patients could receive BV monotherapy for up to 16 cycles of total therapy. After a median of 2 cycles of combination therapy (range, 1-6), the objective response rate among 53 efficacy-evaluable patients was 92.5%, with 39 patients (73.6%) achieving CR. Forty patients underwent ASCT. Thirty-one patients (25 of whom underwent ASCT) received BV monotherapy (median, 10 cycles; range, 1-14). After a median of 20.9 months of follow-up, the estimated 2-year progression-free survival was 69.8% and 62.6% for patients who received ASCT and all patients, respectively. Thirty-one patients (56.4%) experienced infusion-related reactions (IRRs), with a majority occurring during cycle 2 of combination therapy. A protocol amendment requiring premedication reduced IRR severity. BV plus bendamustine as first salvage therapy in relapsed/refractory HL is highly active with a manageable toxicity profile. This trial was registered at www.clinicaltrials.gov as #NCT01874054.

Introduction Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) is a validated scoring system that assesses the risks of patients (pts) undergoing allogenic stem cell transplant. [Sorror et al. 2005] There has been emerging evidence of its value in risk discussion for pts undergoing autologous stem cell transplantation (ASCT). In a recent large (N=1730) retrospective study in pts with multiple myeloma (MM) or lymphoma, a high-risk HCT-CI was associated with higher rates of orotracheal intubation (OTI), 100-day non-relapsed mortality (NRM), and 1-year mortality. [Berro et al. 2017] Not well studied was disposition of a pt at the time of discharge post-transplant as it relates to HCT-CI risk. This could be an additional useful variable in pts/caregiver discussions pre-ASCT. Herein, we report a retrospective single institution review of our experience as it relates to HCT-CI to post-ASCT outcomes including level of care requirements at time of discharge. Methods We performed a retrospective review of pts with MM or lymphoma who received consolidative ASCT between May 2013 and March 2018. Pt demographic were collected. Pts HCT-CI were collected per defined variables by Sorror et al. Each pt was divided into three cohorts: low risk (HCT-CI score of 0), intermediate risk (HCT-CI score of 1-2), and high risk (HCT-CI ≥ 3). Discharge location was categorized into five dispositions: home with caregiver, home with supplemental care, skilled nursing facility, acute rehab facility, and died during transplant. Results Four hundred sixty-one charts were reviewed. Males were 62.0% of the population with a median age of 58.5. Disease populations were balanced with MM/lymphoma at 48.4%/51.6% respectively. MM pts received melphalan (140 or 200 mm/m2) and lymphomas received BEAM based conditioning. We found no statistical correlation of high-risk HCT-CI patients requiring higher rates of OTI during ASCT (p=0.1066) nor requiring a higher level of care post-ASCT transplant (p=0.2998). Furthermore we were unable to statistically correlate high-risk HCT-CI score with an increased rates of 100-day NRM (p=0.0681) or 1-year mortality (p=0.0656). We further investigated the breakdown of HCT-CI scoring of high-risk pts (n=177). The dominant comorbid conditions that appeared to be driving points towards a high-risk designation was cardiopulmonary (70.5%) and psychiatric (34.5%). Conclusion In our single center experience the categorization of high-risk HCT-CI prior to ASCT did not portend a higher risk with regards to OTI, 100-day NRM, or 1-year NRM when compared to pts categorized as low and intermediate risk in ASCT. A high risk HCT-CI score did not predict for a statistically significant increase in need for higher level of care post ASCT beyond caregiver support.

The objective of this retrospective study (N = 169) was to compare the overall survival (OS) of different subtypes of mantle cell lymphoma (MCL) treated by the Nebraska Lymphoma Study Group between 1984 and 2012. The overall response rate to various therapies including stem cell transplant (SCT) was similar (p = 0.44) between blastoid, diffuse and nodular subtypes. At 5 years, blastoid and diffuse subtypes had worse OS (overall p = 0.005) compared to nodular subtype. In multivariate analysis, the blastoid and diffuse subtypes had similar risk of death (p = 0.14) whereas the nodular subtype had a lower risk compared to blastoid (HR 0.48, 95% CI 0.27-0.87, p = 0.01). The use of SCT was associated with lower risk of death. In univariate analysis, blastoid subtype had better OS with intensive upfront therapy. In conclusion, the OS of blastoid subtype is worse than nodular MCL but may improve with the use of SCT and probably intensive induction therapy.

Background Central nervous system complications (CNSC) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to determine the incidence of CNSC and its impact on survival. Patients and Methods This retrospective cohort study included patients with hematologic disorders who received allo-HSCT between 2002 and 2011 at the University of Nebraska Medical Center. Results Of the 351 patients identified, 45 developed CNSC (12.8%). The 100-day cumulative incidence of CNSC was 8% (95% confidence interval, 8-15). The most common CNSC included posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSC (14% vs. 44%, P = .0004). In multivariate analysis, the risk of mortality for patients with versus without CNSC was significantly higher (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36; P = .04). Conclusion The occurrence of CNSC after allo-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of CNSC after allo-HSCT are needed to improve outcomes.

Essential thrombocythemia is well-known to transform to other myeloid disorders, such as leukemia; however, the risk for development of lymphoma is not as well studied. This case report discusses a 76-year-old man with a history of prefibrotic post-essential thrombocythemia myelofibrosis on ruxolitinib, who developed anemia, thrombocytopenia, and leukocytosis with peripheral blasts. Results of a bone marrow biopsy and PET and CT scans revealed stage IV leukemic diffuse large B-cell lymphoma. Several days after cessation of ruxolitinib, the patient developed fevers, hypotension, and low-grade disseminated intravascular coagulation, and subsequently developed spontaneous tumor lysis syndrome, which resulted in death. This case is unique in several aspects: it highlights the rare possibility of lymphomatous transformation of myeloproliferative disorders, an unusual presentation of lymphoma masquerading as leukemia, and the possibility of ruxolitinib withdrawal syndrome. Additionally, this case serves as a reminder that the use of novel therapies should be adopted after a thorough assessment of long-term risks, including those associated with abrupt withdrawal.

Positron emission tomographic (PET) scanning with a near-simultaneous computedtomography(CT)scan(ie, integrated PET-CT scan) is the preferred imaging modality for staging lymphomas. PET scanning detects Hodgkin lymphoma as well as the aggressive and most indolent non-Hodgkin lymphomas. PET-CT has become the standardof care for assessment of remission in patients with [F]fluorodeoxyglucose (FDG)-avid lymphomas, including Hodgkin lymphoma. The use of PET-CT scans for restaging is not without pitfalls. Although the sensitivity of a PET scan is nearly 100%, the positive predictive value is lower. We report the case of a woman with a history of Hodgkin lymphoma who was noted to have new lymphadenopathy in a restaging scan, implying progression of the disease. However, on further workup, it was determined that this was not the case.

Background With the improving outcomes of patients with follicular lymphoma (FL), it is imperative to focus on survivorship issues, including the development of second primary malignancies (SPMs). We used a large US database to measure the risk of SPMs among FL survivors. Materials and Methods We used the Surveillance, Epidemiology, and End Results-13 registry to identify FL patients from 1992 to 2011. We calculated the risk of SPMs, developing ≥ 6 months after diagnosis, using the standardized incidence ratio (SIR) and absolute excess risk. We calculated the cumulative incidence of SPMs using the competing risk method and risk factors for SPMs using univariate and multivariate methods. Results Of a total of 15,517 patients with FL followed up for a median of 71 months, 1540 (9.9%) developed SPMs, with a SIR of 1.08 and absolute excess risk of 11.3 per 10,000 person-years. A significantly increased risk was noted for Hodgkin lymphoma (SIR, 5.85), acute myeloid leukemia (SIR, 4.88), and the following sites: oral cavity and pharynx (SIR, 1.43), stomach (SIR, 1.43), lung and bronchus (SIR, 1.35), melanoma of skin (SIR, 1.38), other nonepithelial cancers of the skin (SIR, 2.88), urinary bladder (SIR, 1.24), and kidney/renal pelvis (SIR, 1.43). The cumulative incidence of SPMs was 11.06% at 10 years. Multivariate regression showed that age > 65 years (SIR, 1.57; P P P = .001) predicted a higher rate of SPMs. Conclusion Patients with FL have increased risk of both hematologic and solid malignancies. Risk factors for SPMs include advanced age, male gender, and receipt of radiation therapy.

e19063 Background: Constitutive activation of the JAK-STAT pathway has been reported in lymphomas, suggesting that targeting this pathway could show clinical benefit. Ruxolitinib phosphate, an oral JAK inhibitor represents a potential therapeutic agent for high grade lymphomas. This study is designed to investigate benefits of ruxolitinib in patients with relapsed or refractory PTCL and DLBCL Methods: Patients with relapsed/refractory DLBCL and aggressive T cell lymphomas who were ineligible for, or relapsed after, stem cell transplantation were eligible. Patients received ruxolitinib, at a dose of 10mg or 5mg BID, with gradual escalation to 25mg BID. Weekly hematological assessments were done during the first cycle, CT scans were done after every two cycles. Descriptive statistics for response to therapy were collected. Progression free survival (PFS), Overall survival (OS) curves were plotted using Kaplan-Meier method, comparisons between groups were made using the log rank test. Primary outcome of the study was to assess the overall response rate (ORR). Secondary objectives were to determine PFS, OS, duration of response and safety. Relationship between responses to oral ruxolitnib and gene expression profiling was explored. Results: Of the 60 patients enrolled, 25 patients had PTCL, 32 DLBCL, 3 pending path review. Median age was 62 yrs., 56.6% had stage IV disease. Median number of cycles received was 2 (min 1, max 60). At the time of evaluation, 76% patients had progressed on therapy. The median follow-up of patients was 3.7 months (min 0.9; max 61.4). Data for 41 patients was available for evaluation of response. Complete response (CR) was noted in 1 patient with PTCL. Partial response (PR) was noted in 1, stable disease (SD) in 4 patients. Among the responders, a PTCL patient with SD had a sustained response for 60 months, a patient with PR had a response duration of 31 months. The median OS and PFS were 5.9 and 1.8 months. PFS was 2.2 months in patients with PTCL and 1.8 months in DLBCL. Median OS was 5 months in patients with DLBCL, 6.9 months in PTCL. The estimated 6 month PFS and OS were 17% (95%CI: 9%, 28%) , 49% (95%CI: 35%, 62%). There was no difference in PFS or OS between PTCL and DLBCL (p = 0.42, p = 0.94). Grade 3 or higher adverse events were seen in 62%. Anemia was seen in 20%, thrombocytopenia in 8%, infections in 6%. Conclusions: Ruxolitinib can produce responses in some patients with relapsed/refractory NHL, particularly in patients with PTCL. It may play a role in combination therapies in future. Clinical trial information: NCT01431209.

The use of radiation (RT) in primary mediastinal large B-cell lymphoma (PMBCL) may predispose young patients to the risk of cardiopulmonary toxicities and secondary malignancies. We used Surveillance, Epidemiology and End Results (SEER) 18 database to compare the overall survival (OS) differences among adult patients treated with and without RT after rituximab approval in the US. Multivariate analyses were performed using Cox proportional hazards regression to compare OS based on the use of RT while adjusting for age, year of diagnosis, race, stage and gender. PMBCL patients (n = 258), who received RT (48%), were similar in terms of age, gender, race, and stage at diagnosis to patients who did not receive RT. The five year OS was similar between patients treated with versus without RT (82.5% vs. 78.6%, P = 0.47). In a multivariate analysis, the use of RT did not influence OS in the rituximab era (HR 0.83; 95% CI 0.43-1.59; P = 0.56). Rituximab may reduce the benefit of RT in select patients such as those who achieve a metabolic complete remission at the end of chemotherapy.

Background Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is often associated with concurrent or subsequent development of T-cell/histiocyte-rich large B-cell lymphoma (THR-LBCL). Distinguishing the two is important because their therapies are different. Functional imaging with PET/CT is used to stage both Hodgkin and non-Hodgkin lymphomas. Aggressive lymphomas are usually more PET avid than the indolent subtypes. Therefore, it is possible that PET/CT may help distinguish NLPHL from THR-LBCL. Patients and Methods Herein, we retrospectively describe the clinical and PET/CT findings of 12 patients with NLPHL or THR-LBCL seen from 2004-2010. Results and Conclusions Six patients each were identified and the average SUV max was 6.9 (range, 5.7-7.3) in NLPHL and 16.6 (range, 4-29) in THR-LBCL (p = 0.055). Bone and extranodal involvement was found in one patient with NLPHL compared to four patients with THR-LBCL. This patient failed to respond to ABVD and was subsequently found to have THR-LBCL. We suggest that patients with NLPHL and THR-LBCL have different clinical and PET/CT characteristics. NLPHL patients had lower SUV max on PET/CT compared to those with THR-LBCL. The presence of bone or extranodal involvement is more common in patients with THR-LBCL. Patients with NLPHL and an uncharacteristically higher SUVmax on PET/CT, or those with bone or extranodal involvement, should alert the clinician to consider the presence of THR-LBCL.

Classical Hodgkin lymphoma treatment is evolving rapidly with high response rates from antibody-drug conjugates targeting CD30 and immune checkpoint antibodies. However, most patients do not achieve a complete response, therefore development of novel therapies is warranted to improve patient outcomes. In this phase II study, patients with relapsed or refractory Hodgkin lymphoma were treated with entinostat, an isoform selective histone deacetylase inhibitor. Forty-nine patients were enrolled: 33 patients on Schedule A (10 or 15 mg oral entinostat once every other week); 16 patients on Schedule B (15 mg oral entinostat once weekly in 3 of 4 weeks). Patients received a median of 3 prior treatments (range 1-10), with 80% of the patients receiving a prior stem cell transplant and 8% of patients receiving prior brentuximab vedotin. In the intention-to-treat analysis, the overall response rate was 12% while the disease control rate (complete response, partial response, and stable disease beyond 6 months) was 24%. Seven patients did not complete the first cycle due to progression of disease. Tumor reduction was observed in 24 of 38 (58%) evaluable patients. Median progression-free survival and overall survival was 5.5 and 25.1 months, respectively. The most frequent grade 3 or 4 adverse events were thrombocytopenia (63%), anemia (47%), neutropenia (41%), leukopenia (10%), hypokalemia (8%), and hypophosphatemia (6%). Twenty-five (51%) patients required dose reductions or delays. Pericarditis/pericardial effusion occurred in one patient after 12 cycles of therapy. Future studies are warranted to identify predictive biomarkers for treatment response and to develop mechanism-based combination strategies. (clinicaltrials.gov identifier: 00866333).

Background: This large population-based study determined the epidemiology and outcomes of secondary acute myeloid leukemia (sAML) developing in Hodgkin lymphoma survivors. Methods: We utilized the Surveillance Epidemiology and End Results (SEER) 9 database to identify 104 cases of sAML. Results: Patients with sAML (median age: 47 years; 82%

The optimal management of hematologic malignancy-associated venous thromboembolism (VTE) in patients with moderate-to-severe thrombocytopenia is unclear. This is a retrospective study of 128 adult patients with hematologic malignancies who were diagnosed with VTE. The outcome of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Forty-seven patients (36.7%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation. The median nadir platelet count in those with significant thrombocytopenia was 10,000/µL (range 2,000-45,000/µL) versus 165,000/µL (50,000-429,000/µL) in those without (P 0.001). The median duration of significant thrombocytopenia in the first group was 10 days (1-35 days). Therapy during the period of significant thrombocytopenia included prophylactic-dose low-molecular-weight heparin (LMWH) (47%), therapeutic-dose LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%), and observation (17%). Patients without thrombocytopenia were managed with the standard of care therapy. At a median follow-up of more than 2 years, the risk of clinically significant bleeding (11% vs 6%, P = 0.22) including major bleeding (6% vs 2%) and clot progression or recurrence (21% vs 22%, P = 1.00) were similar in patients with or without significant thrombocytopenia. In a multivariate analysis, the risk of recurrence/progression (hazard ratio, HR 0.59, 95% CI 0.21-1.66, P = 0.31) and hemorrhage rate (HR 0.29, 95% CI 0.05-1.56, P = 0.15) did not differ based on the presence of significant thrombocytopenia. Within the limits of this retrospective study, cautious use of prophylactic-dose LMWH may be safe in thrombocytopenic patients with hematologic malignancy-associated VTE. Am. J. Hematol. 91:E468-E472, 2016. © 2016 Wiley Periodicals, Inc.

These case studies illustrate infections encountered in hospitals among patients with compromised immune systems. As a result of immunocompromise, the patients are vulnerable to common and uncommon infections. These cases are carefully chosen to reflect the most frequently encountered infections in the patient population, with an emphasis on illustrations and lucid presentations to explain state-of-the-art approaches in diagnosis and treatment. Common and uncommon presentations of infections are presented while the rare ones are not emphasized. The cases are written and edited by clinicians and experts in the field. Each of these cases highlights the immune dysfunction that uniquely predisposed the patient to the specific infection, and the cases deal with infections in the cancer patient, infections in the solid organ transplant recipient, infections in the stem cell recipient, infections in patients receiving immunosuppressive drugs, and infections in patients with immunocompromise that is caused by miscellaneous conditions.

Diffuse large B-cell lymphoma (DLBCL) includes two prognostically important subtypes, the germinal center B-cell (GCB) and the non-GCB types. The aim of this study was to evaluate immunohistochemical approaches for predicting the survival of patients with DLBCL following autologous hematopoietic stem cell transplantation (AHSCT). We identified 62 patients with DLBCL who either had an initial complete remission (17 patients) or received salvage chemotherapy for relapsed or refractory disease (45 patients), followed by AHSCT. Tissue microarrays were immunostained with monoclonal antibodies against GCET1, CD10, BCL6, MUM1, FOXP1 and LMO2. Using the Hans algorithm, we classified 50% of the cases as GCB type, whereas the Choi algorithm classified 58% as GCB type and LMO2 was positive in 69%. However, no significant differences were found in the 5-year overall or event-free survivals using any of these approaches. In conclusion, cell of origin fails to predict survival of DLBCL patients treated with AHSCT.