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Glofitamab is a CD3xCD20 bi-specific antibody with two fragments directed to the CD20 antigen and a single CD3-binding fragment. Encouraging response and survival rates were recently reported in a pivotal phase II expansion trial conducted in patients with relapsed/refractory (R/R) B-cell lymphoma. However, the real-world data of patients of all ages with no strict selection criteria are still lacking. Herein, this retrospective study aimed to evaluate the outcomes of diffuse large B-cell lymphoma (DLBCL) patients who received glofitamab via compassionate use in Turkey. Forty-three patients from 20 centers who received at least one dose of the treatment were included in this study. The median age was 54 years. The median number of previous therapies was 4, and 23 patients were refractory to first-line treatment. Twenty patients had previously undergone autologous stem cell transplantation. The median follow-up time was 5.7 months. In efficacy-evaluable patients, 21% and 16% of them achieved complete response and partial response, respectively. The median response duration was 6.3 months. The median progression-free survival (PFS) and overall survival (OS) was 3.3 and 8.8 months, respectively. None of the treatment-responsive patients progressed during the study period, and their estimated 1-year PFS and OS rate was 83%. The most frequently reported toxicity was hematological toxicity. Sixteen patients survived, while 27 died at the time of the analysis. The most common cause of death was disease progression. One patient died of cytokine release syndrome during the first cycle after receiving the first dose of glofitamab. Meanwhile, two patients died due to glofitamab-related febrile neutropenia. This is the largest real-world study on the effectiveness and toxicity of glofitamab treatment in R/R DLBCL patients. The median OS of 9 months seems promising in this heavily pretreated group. The toxicity related mortality rates were the primary concerns in this study.

© 2021 Edizioni Scientifi che per l'Informazione su Farmaci e Terapia.The prognosis is poor for relapsed or refractory (R/R) classical Hodgkin Lymphoma (cHL) patients. The brentuximab vedotin (Bv) and bendamustine (B) combination has been used as a preferable salvage regimen in R/R cHL patient trials. We retrospectively evaluated response rates, toxicities, and the survival in R/R cHL patients treated with the BvB combination. In a multi-centre real-life study, 61 R/R HL patients received intravenous doses of 1.8 mg/kg Bv on the first day plus 90 mg/m2 B on the first and second days of a 21-day cycle as a second-line or beyond-salvage regimen. Patients’ median age at BvB initiation was 33 (range: 18–76 years). BvB was given as median third-line treatment for a median of four cycles (range: 2–11). The overall and complete response rates were 82% and 68.9%, respectively. After BvB initiation, the median follow-up was 14 months, and one- and two-year overall survival rates were 85% and 72%, respectively. Grade 3/4 toxicities included neutropenia (24.6%), lymphopenia (40%), thrombocytopenia (13%), anaemia (13%), infusion reactions (8.2%), neuropathy (6.5%), and others. The BvB combination could be given as salvage regimen aiming a bridge to autologous stem cell transplant (ASCT), in patients relapse after ASCT or to transplant-ineligible patients with manageable toxicity profiles.

Here we report a challenging case of a 52-year-old man presenting with subacute constipation, urinary retention, impotence, absent Achilles reflexes, and hypoesthesia in S2-S5 dermatomes. We review the clinical decision-making as the symptoms evolved and diagnostic testing changed over time. Once the diagnosis is settled, we discuss the sign and symptoms, additional diagnostic tools, treatment options and prognosis.

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB-IV classical HL receiving frontline treatment (

Introduction: we aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey. Material and methods: in this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity. Results: ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B- cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% (= 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%). Conclusions: objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy., NA

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease.We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response.A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy.Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).

INTRODUCT ̇ION Glofitamab is a T-cell-engaging bispecific antibody connecting CD20 on B cells and CD3 on T cells. Although, most of the patients with B-cell non-Hodgkin lymphoma (BNHL) achieve complete response (CR) following firstline treatment with rituximab and chemotherapy, about 40% of patients with diffuse large B-cell lymphoma (DLBCL) is refractory or relapse (R/R). Autologous stem-cell transplantation (ASCT) can cure some of these patients but many patients cannot undergo this procedure. CAR-T therapies are a significant advance but not available in many countries like Turkey. In Phase II expansion study, the overall response rate (ORR) was 51.6% and complete remission (CR) rate was 39.4% in R/R DLBCL patients (Dickinson er al. JCO 2022). In this retrospective study, we aimed to report the outcomes of patients who used glofitamab via compessionate use in Turkey.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4-84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05-0.22) and 26% (95% CI, 0.16-0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13-0.54) and 60% (95% CI, 0.33-0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.

ObjectiveChimeric antigen receptor T (CAR-T) cell therapies already made an impact on the treatment of B cell malignancies. Although CAR-T cell therapies are promising, there are concerns with commercial products regarding their affordability and sustainability. In this preliminary study, results of the first productional and clinical data of academic CAR-T cell (ISIKOK-19) from Turkey are presented.Materials and MethodsA pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy in patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. Production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusion is presented in this study.ResultsNine patients were enrolled for the trial (ALL n=5 and NHL n=4) but only 7 patients could receive the treatment. Two out of three ALL patients and three out of four NHL patients had complete/partial response (ORR 72%). Four patients (57%) had CAR-T-related toxicities (CRS, CRES, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up.ConclusionProduction efficacy and fulfilling the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles are acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19 positive tumors. The findings of this study need to be supported by the currently ongoing clinical trial of ISIKOK-19.

The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real-world patients. Seventy-five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease

Background: Despite therapeutic advances in classical Hodgkin lymphoma (cHL), only half of patients with relapsed/refractory (R/R) cHL are cured with salvage chemotherapy followed by stem cell transplantation (SCT). Most studies to date have been undertaken in Europe or North America and data on treatment patterns and clinical outcomes from other regions are limited. We present the results from the B-CD30+ HOdgkin Lymphoma International Multi-center Retrospective Study of Treatment PractIces and OutComes (B-HOLISTIC), which assessed cHL treatment pathways, clinical outcomes and healthcare resource utilization across East Asia, Latin America, Middle East, South Africa, Australia and Russia (data as of 04 March 2020). Methods: Data were collected retrospectively for patients (≥18 years) diagnosed with stage IIB-IV cHL or R/R cHL between 01 January 2010 and 31 December 2013, until death or last follow-up (whichever occurred first) across 13 countries. Patients with initial diagnosis of cHL and subsequent progression to R/R cHL were included in both groups, provided R/R cHL was diagnosed within the study period. The primary endpoint was progression-free survival (PFS) in patients with R/R cHL. Secondary endpoints included overall survival (OS), best clinical response, and adverse events (AEs). Results: In total, 1703 patients were enrolled from East Asia (n=426), Latin America (n=366), Middle East and South Africa (n=694), Australia (n=56) and Russia (n=161): 1598 and 426 patients were eligible for the cHL and R/R cHL groups (321 patients in the cHL group progressed to R/R cHL and were included in both groups). Median study follow-up was 65.2 and 53.2 months for the cHL and R/R cHL groups. Baseline patient characteristics are shown in Table 1. All patients in the cHL group received first-line chemotherapy: the most common regimens were ABVD (1363/1598; 85.3%) and BEACOPP (104/1598; 6.5%). First-line radiotherapy was given to 357/1598 (22.3%) patients in the cHL group. For R/R cHL, intensive chemotherapy was used as first-line salvage in 372/426 (87.3%) patients: the most common regimens were ESHAP (98/372; 26.3%) and DHAP (65/372; 17.5%), with an overall response rate of 62.0% (complete remission in 30.8% and partial remission in 31.2%). Of the 426 patients with R/R cHL, 292 (68.5%) were eligible for SCT at relapse/refractory diagnosis; 10 patients who were initially ineligible for SCT subsequently became eligible. In total, 222/302 (73.5%) eligible patients underwent SCT; 63/222 (28.4%) patients relapsed after SCT. Median PFS (95% CI) for the R/R cHL group was 13.2 (9.9-20.2) months following initial therapy (Figure 1), with estimated 1-, 3- and 5-year PFS rates of 51.2%, 38.7%, and 33.9%, respectively (Table 2). Median PFS was not reached for the first-line cHL group. Factors for PFS in the R/R cHL group are shown in Table 3. Median OS was not reached for both groups. All-cause, any grade AEs were reported by 783/1598 (49.0%) patients with cHL and by 233/426 (54.7%) patients with R/R cHL. Serious AEs were reported by 303/1598 (19.0%) patients with cHL and by 103/426 (24.2%) patients with R/R cHL: the most common (≥2.0%) were febrile neutropenia, pneumonia and pyrexia for cHL, and febrile neutropenia and pyrexia for R/R cHL. Conclusion: Results from B-HOLISTIC show that PFS rates remain low in patients with R/R cHL receiving salvage therapy; the greatest risk was among patients with inadequate response to salvage chemotherapy. The low PFS rates highlight the importance of considering novel targeted therapies to address unmet medical needs. PFS rates in patients with cHL were comparable with previous studies from Italy, Spain, and Israel (Avigdor A et al. EHA 2020) and the ECHELON-1 study (Bartlett NL et al. ASH 2019). The higher OS rates compared to PFS rates may be related to the effect of modern salvage regimens. Approximately half of patients with R/R cHL underwent SCT which may support the use of targeted therapies. Overall, these results from 2010-2013 show that despite the differences in healthcare systems, ethnicities and treatment patterns in B-HOLISTIC, clinical outcomes remain consistent. The authors note that given that the management of high-risk cHL has changed dramatically since 2013, further investigation in diagnostic criteria, response assessment and treatment patterns is needed. Study support: Data analysis (IQVIA) and medical writing (Synergy Vision) funded by Takeda Pharmaceuticals. Disclosures Ferhanoglu: Takeda: Other: Advisory Board; Abbvie: Other: Advisory Board; Roche: Other: Advisory Board; Janssen: Other: Advisory Board. Kim:Novartis: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; Sanofi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Voronoi: Consultancy; Boryung: Consultancy; AstraZeneca: Consultancy; Takeda: Consultancy. Karduss:Takeda: Honoraria. Rivas-Vera:Takeda: Current Employment, Other: Steering Committee in Clinical Research; Roche: Consultancy. Lim:National Cancer Centre Singapore: Current Employment. Yeh:AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees. Abdillah:Takeda: Current Employment. Huang:Takeda: Current Employment. Dalal:Takeda: Current Employment, Current equity holder in publicly-traded company. Wan:Takeda: Current Employment. Hertzberg:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support; Gilead: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; BMS: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction Bleomycin pulmonary toxicity (BPT) is a potentially life-threatening consequence of bleomycin usage in patients. An overproduction of epithelium-derived cytokines, habitually linked to allergic inflammation, has been recently revealed in experimental models of BPT. Methods We assessed retrospectively our cohort of patients with Hodgkin Lymphoma treated with bleomycin between 2014 and 2016 for their demographic, clinical features, including BPT development, atopy status and risk factors for BPT. Then they were invited for allergy testing and blood sample collection. The samples were stimulated with different stimuli (Bleomycin, IL-33, TSLP) for 24 h on cell culture. The culture supernatants were analysed for TGF-β, Galectin3, Arginin, Amphiregulin, Eotaxin, IFNγ, TNFα, IL1β, 4, 5, 6, 10, 13, 17, MIP-1α, and bleomycin hydrolase (BLH) levels. Results The cohort consisted of 51 patients showed that atopy was the only significant risk factor for BPT occurrence (OR: 7.2, p = 0.007). Fourteen subjects were included for blood analysis. The analysis of supernatants at the unstimulated condition revealed that BLH and Amphiregulin were significantly lower in patients who had BPT than controls. The BLH cut-off that best identified a history of BPT was 175.31 (Sensitivity: 62.5%, specificity: 100%). Following the stimulation, BLH reduced compared to the unstimulated condition and the difference between groups remained significant (p Conclusion Our study is the first to report that low levels of bleomycin hydrolase in allergic individuals may be predisposing to a possible pathway of fibrosis.

Coronavirus disease 2019 (COVID-19) has led to a global pandemic that has also challenged the management of various other life-threatening conditions, such as malignant disorders. In this study, we present the clinical features and treatment outcomes of twenty-seven COVID-19 positive patients with leukemia across seven different centers in Istanbul. From March 1st to December 31st 2020, 116 patients were diagnosed with acute leukemia. Thirty-two cases with acute lymphocytic leukemia (ALL), 82 cases with acute myeloid leukemia (AML), and 2 cases with mixed phenotype acute leukemia (MPAL) were identified. Of the 27 patients with the COVID-19 infection, seven patients had ALL, 19 patients had AML and one patient had MPAL. The mortality rate was 37% among the patients with AML, whereas there were no deaths in the ALL group. The mortality rate of AML patients with the COVID-19 infection was higher compared to cases without the infection (P

Context The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Objective To determine the impact and safety of BV as maintenance after ASCT in real-world patients. Design Patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were retrospectively analyzed. Setting All patients were followed by the bone marrow transplantation team of their hospital. Patients or Other Participants Seventy-five patients were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease Interventions BV consolidation was initiated within 6 months of ASCT and administered at a dose of 1.8 mg/kg intravenous infusion over 30 min every 3 weeks for up to 16 cycles in an outpatient setting. Main Outcome Features The primary endpoint of the study was PFS; secondary endpoints were safety and overall survival (OS). Results At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in six, and SD in three patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-years PFS and OS rates were 67.75% (95% CI:0.55–0.77) and 87.61% (95% CI:0.76–0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV naive and BV exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to AE in 12 patients. Conclusions Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55–0.75) with an acceptable toxicity profile.

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age +/- standard deviation: 64.6 +/- 10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p, Janssen Pharmaceutica Turkey, This study was supported by Janssen Pharmaceutica Turkey. The authors would like to thank Prof. Sule Oktay, MD, PhD, and Cala Ayhan, MD, from KAPPA Consultancy Training Research Ltd. (stanbul, Turkey) , who provided editorial support.

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We aimed to describe the effectiveness of our standardized protocol for febrile neutropenia (FN), which was targeted to minimize unintended outcomes and reduce antimicrobial consumption.The study was performed in a private hospital with 300 beds. We included all adult hematologic and oncologic cancer inpatients admitted between January 1, 2015-December 31, 2015, and January 1, 2016-May 31, 2017. The outcomes of the study were fatality, infections, and adherence to the antimicrobial stewardship program (ASP).We included 152 FN attacks of 95 adult inpatients from hematology and oncology wards; of these, 43% were women, and the median age was 57 years. The case fatality rate was 30% in the pre-ASP period and decreased to 11% in the post-ASP period (P = .024). The appropriate adding or changing (P = .006) and appropriate continuation or de-escalation or discontinuation of antimicrobials improved (P .001). In the post-ASP period, Staphylococcus spp infections (from 22% to 8%, P = .02) and gram-negative infections decreased (from 43% to 20%, P = .003). In the multivariate analysis, appropriate continuation or de-escalation or discontinuation was increased in the post-ASP period (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.82-10.41; P = .001), and gram-positive infections were decreased (OR, 0.32; 95% CI, 0.11-0.95, P = .041). Vancomycin and fluoroquinolone use decreased significantly.After implementation of the ASP, the case fatality rate among the patients with FN decreased. Appropriate antimicrobial use increased and overall antimicrobial consumption was reduced. Bacterial infections and Candida infections decreased.

Background The biosimilar rituximab (Redditux) was approved in Turkey for all indications of the reference molecule (MabThera) in March 2018. Large clinical trials and real-life experiences are lacking in hematological malignancies. Aims We aimed to evaluate the efficacy and safety of Redditux in de-novo diffuse large B-cell lymphoma (DLBCL). Methods Our institution decided to provide Redditux for hematological indications since February 2019. We retrospectively analyzed medical records of 51 consecutive de-novo DLBCL patients (pts) diagnosed between February 2019 and September 2019 in the hematology department of Istanbul University Istanbul Medical Faculty. We compared the response rates with historical controls treated with MabThera-CHOP at Cerrahpaşa Medical Faculty. Our study was approved by I.U. Istanbul Medical Faculty Ethical Committee (2019/1454). Results A total of 51 pts without CNS involvement received Redditux-CHOP. Median follow-up was 24 months (range: 8-31). A median of 6 cycles of biosimilar (range: 4-8) was administered. Four pts with high CNS-IPI score received four intrathecal methotrexate injections and 13 pts had additional radiotherapy for their initial bulky disease. The patient characteristics and response rates of the Redditux and historical MabThera cohorts are summarized in Table 1. Apart from 6 cases who were refractory to Redditux-CHOP, 8 pts had progressive disease (6 with CR, 1 with PR and 1with SD) in the follow-up. The median time to relapse was 11.5 months for 6 cases who had CR following first-line treatment. Five of 8 cases with PD experienced CNS relapse. Their CNS-IPI score (Schmitz et al. J Clin Oncol 2016) were low in 2 pts, intermediate in 2 pts and high in 1 patient. Of 11 pts with bone involvement at the time of diagnosis, three cases had CNS relapse (p=0.028). Two pts with CNS relapse were treated with intrathecal chemotherapy only due to their poor performance status. Eight pts received salvage combination chemotherapy [R-ICE (n=3); R-benda (n=3); R-DHAP (n=1); MATRix (n=1)] and two of them responded. One of these 2 cases underwent auto-SCT and the other proceeded to allo-SCT; however, he died during conditioning treatment. Ten pts died in the follow-up. Causes of death were progressive disease (n=7, two cases with CNS involvement), infection during allo-conditioning (n=1), post-COVID herpes zoster infection (n=1) and unknown (n=1). The 24 month PFS and OS rates were 75.8% (95% CI: 0.61-0.85) and 80.3% (95% CI: 0.67-0.89) for Redditux cohort, respectively. In the historical MabThera group, the 24 month PFS and OS rates were 85.2 (95% CI: 0.79-0.90) and 81.4% (95% CI: 0.75-0.86), respectively. For pts with high R-IPI score in the Redditux cohort (3-5); the 24-month PFS and OS rates were 54.2% (95% CI: 0.29-0.74) and 55.6% (95% CI: 0.31-0.75), respectively. In the historical Mabthera group, the 24-month PFS and OS rates were 68.7% (95% CI: 0.53-0.80) and 59.4% (95% CI: 0.47-0.70), respectively. Although the PFS rates seems to be worse in high R-IPI cases receiving Redditux, the difference was not significant (p=0.18; Figure 1). AEs were reported in 51% (n=26) of patients. Most common AE was grade 2 infusion reactions (shivering, nausea, fever) requiring medical intervention in 20% of pts, accompanied with rash in half of them. Grade 3&4 AEs were leucopenia (n=2; 4%), neutropenia (n=20; 39%) febrile in 2 cases, anemia (n=6; 12%), thrombocytopenia (n=3; 6%). Grade 2 pneumonia (n=2) and urinary tract infections (n=2) were other infectious complications. Conclusion Although the PFS rate at 24 months in high-IPI group treated with Redditux seems to be lower compared to MabThera treated historical control group, survival rates were not significantly different. Our results should be cautiously evaluated due to small sample size. Compared to the original trial of MabThera added to CHOP based regimen, (Coiffier et al N Eng J Med. 2002), our CR rates in stage 2-4 pts seem to be slightly lower (70.7% vs 76%), although the OS rates are quite similar (86.3% vs 82%). Grade 3&4 neutropenia requiring empirical administration of G-CSF was 39% in our cohort. Infusion reactions were observed in 20% of pts, which was reported to be around 30% with original molecule (Patel et al. Clin Lymphoma Myeloma Leuk 2019). The CNS relapse rate was relatively high (9.8%) in our cohort. Prospective randomized clinical trials are needed to determine the efficacy and safety profile of Redditux. Figure 1 Figure 1. Disclosures Ferhanoglu: Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

Background: Positron emission tomography-computed tomography (PET-CT) is used for staging and response assessment in classical Hodgkin lymphoma (cHL) and for evaluation and management of refractory/relapsed Hodgkin lymphoma (RRHL). According to the World Health Organization's Global Atlas of Medical Devices 2017 report, 92-95% of lower-middle and low-income countries have no PET/CT unit, and only 3% of upper-middle income countries have 1 PET scanner/million people, versus 29% of high-income countries. Real-world data on PET scan use in cHL and RRHL outside Europe and North America are limited. The B-CD30+ HOdgkin Lymphoma International Multi-center Retrospective Study of Treatment Pract Ices and Out Comes (B-HOLISTIC) study assessed real-world treatment practices and clinical outcomes in patients with stage IIB-IV cHL and RRHL in countries outside Europe and North America and imaging results are presented here. Methods: The B-HOLISTIC study retrospectively reviewed patients (≥18 years) with stage IIB-IV cHL or RRHL between 2010 and 2013. Patients initially diagnosed with cHL who progressed to RRHL during the study were included in both groups. Details of PET and CT scans at baseline and during/end of frontline/salvage treatment, were reported in both groups. Results: Overall, 1703 patients (cHL: 1598, RRHL: 426, both: 321) were enrolled (East Asia: 426, Latin America: 366, Middle East and South Africa: 694, Australia: 56, Russia: 161). Median follow-up was 5.4 and 4.4 years in the cHL and RRHL groups, respectively. PET and CT results for cHL and RRHL groups are shown in Tables 1 and 2, respectively. The proportion of patients with PET scan was 73.2% in the cHL group with a median (interquartile range [IQR]) frequency of 2.0 (2.0-4.0) and 72.3% in the RRHL group with a median (IQR) frequency of 3.0 (2.0-5.0). In both groups, the proportion of PET scans at baseline was lower (cHL: 54.4%; RRHL: 32.8%) than during/ end of frontline treatment (cHL: 85.8%; RRHL: 58.8%) and at relapse/refractory diagnosis (54.5%). In contrast, the proportion of CT scans was higher (cHL: 76.4%; RRHL: 79.1%), particularly at baseline (cHL: 66%; RRHL: 51.6%). The highest proportion of PET scans was reported in Australia and lowest in Russia. The highest proportion of CT scans was in Russia in the cHL group and in Australia and East Asia in the RRHL group, while the lowest was in Middle East and South Africa in both groups. The frequency of interim PET scans was low in both cHL and RRHL groups, and were rarely used in cHL surveillance. In the RRHL group, interim PET scans during the frontline therapy were higher after cycles 3-4 and 5-6 than after cycles 1-2. Deauville 5-point scale (5-PS) was used for PET assessment at interim treatment cycles, end of frontline/salvage treatment, relapse, and surveillance in both groups with increased scans reporting a 5-PS rating towards the end of treatment and surveillance. However, its overall use was suboptimal with a minority ( Discussion and Conclusion: This study provides real-world evidence on PET use in cHL and RRHL outside Europe and North America, which is suboptimal. Although PET is part of standard care for cHL now, during 2010-2013 it was more commonly used only in RRHL, as reflected in the higher PET use in RRHL than cHL in this study. Lower overall PET use than CT and the regional differences may reflect the comparatively limited access and availability of PET, especially in low-income countries. Lower PET use at baseline may have been due to low accessibility of PET at the beginning of the study, which improved over time. Higher PET use at the end of frontline treatment in cHL is in line with the literature, and suggestive of its recognized benefits in guiding further treatment if used early in treatment. Lack of data on Deauville ratings could be because its use was uncommon during the time of the study. However, the increased Deauville score reporting towards the end of the study suggests a trend for its use. Overall, the low interim PET use, regional differences, and lack of data on use of Deauville rating in this study, suggest an existing gap in real-world practice and highlight the global inequities in access to PET. These findings suggest the need for upscaling numbers and access to PET scanners outside Europe and North America through careful planning and in-depth assessment of socioeconomic, demographic, and epidemiological circumstances of each country. Figure 1 Figure 1. Disclosures Ferhanoglu: Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Zerga: Takeda: Honoraria; Sandoz: Honoraria; Bristol Myers Squib: Honoraria; Jansen: Honoraria; Roche: Honoraria. Kim: Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeyondBIO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Boryung: Consultancy, Membership on an entity's Board of Directors or advisory committees; Hanmi: Consultancy, Membership on an entity's Board of Directors or advisory committees; GI CELL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca-KHIDI: Research Funding; AstraZeneca/MedImmune: Consultancy, Membership on an entity's Board of Directors or advisory committees. Karduss: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees. Kwong: Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Wu: Takeda: Current Employment, Current equity holder in publicly-traded company. Huang: Takeda: Current Employment, Current equity holder in publicly-traded company. Hertzberg: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background:Waldenström Macroglobulinemia (WM) remains an incurable disease with a heterogeneous course, relapse following initial treatment happens in virtually all patients. Ibrutinib, a Bruton Tyrosine Kinase inhibitor, is a promising drug used in WM, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and chronic graft versus host disease. Ibrutinib first received FDA approval in WM as a monotherapy in January 2015 and expanded the approved use of ibrutinib with rituximab in August 2018.Ibrutinib-related prior data in Waldenström Macroglobulinemia (WM) remain sparse, particularly outside of clinical trials. Herein, we share a real-life experience using off-label ibrutinib in the treatment of heavily pretreated WM. Methods:This multicenter retrospective study conducted in eight different sites included 13 adult patients diagnosed with WM and used off-label ibrutinib monotherapy or with rituximab from April 2016 to November 2019. Disease-refractoriness to prior therapy was defined as progression on therapy or within 2 months of treatment interruption. The response rates were assessed by the modified Third International Workshop on WM Response Criteria. Results:TwelveRRWM patients received ibrutinib monotherapy for active/symptomatic WM during the study period; median follow up of the entire cohort was 29 months for the subset that received ibrutinib as salvage therapy. The median time on therapy for the entire cohort was 12.5 months. WM IPSS score was calculated intermediate in three patients and high in nine patients. MYD88 mutation status was assessed in five patients and detected positive at the time of WM diagnose. Before therapy, six of the 12 (50%) had a serum level of 3000 mg per deciliter or higher; after treatment, at the time of best response, two of the 12 patients (16.6%) had a serum IgM level of 3000 mg per deciliter or higher. ECOG performance score was 1 in 75% of our cohort. The median lines of prior therapy for the RRWM were 3 (range: 2-8). Only two patients had received autologous stem cell transplantation (ASCT) prior to ibrutinib monotherapy. Responses included a complete response in three patients, a very good response in 1 patient and a partial response in six patients, representing overall response of 83.3%. The remaining two patients discontinued ibrutinib due to progressive disease. No several adverse events due to ibrutinib were observed in our cohort. At the time of data collection, one patient had deceased. Conclusion:Ibrutinib is an effective drug, associated with durable responses, and safety for both previously-treated and newly diagnosed WM. Our study has several limitations that should be considered when reviewing the results, including the retrospective design and inclusion of a small number of patients. Nevertheless, because of the rarity of the diseases, our data provide useful information on the use of ibrutinib in patients with heavily pretreated WM. Disclosures Ferhanoglu: Janssen: Other: Advisory Board; Roche: Other: Advisory Board; Abbvie: Other: Advisory Board; Takeda: Other: Advisory Board. Beksac:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen&janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Deva: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: ibrutinib were used off-label

Key Clinical Message New PET‐positive lesions in previously treated patients with lymphomatous malignancies need further investigations. Relapse, sarcoidosis and secondary malignancies are the most important differential diagnosis. Inflammatory myofibroblastic tumors (IMT) is a rare complication after treatment of Hodgkin's disease and every PET‐positive lesion should be biopsied to prevent unnecessary intervention.

Summary Background Preclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed or refractory B-cell malignant diseases. Methods We did a two-part, open-label, phase 1/2a study at 21 hospitals in Australia, Israel, Poland, Spain, Turkey, and the USA. The primary objective of part A (dose escalation) was to assess the safety of daily oral ibrutinib (420 mg or 560 mg) in combination with intravenous nivolumab (3 mg/kg every 2 weeks) to ascertain a recommended phase 2 dose in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma (del17p or del11q), follicular lymphoma, or diffuse large B-cell lymphoma. Dose optimisation was investigated using a modified toxicity probability interval design. The primary objective of the part B expansion phase was to establish the preliminary activity (the proportion of patients who achieved an overall response) of the combination of ibrutinib and nivolumab in four cohorts: relapsed or refractory high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma (del17p or del11q), follicular lymphoma, diffuse large B-cell lymphoma, and Richter's transformation. All participants who received at least one dose of treatment were included in the primary analysis and analyses were done by disease cohort. This trial is registered with ClinicalTrials.gov, number NCT02329847. The trial is ongoing. Findings Between March 12, 2015, and April 11, 2017, 144 patients were enrolled in the study. Three patients died before receiving study treatment; thus, 141 patients were included in the analysis, 14 in part A and 127 in part B. One dose-limiting toxicity (grade 3 hyperbilirubinaemia) was reported at the 420 mg dose in the diffuse large B-cell lymphoma cohort, which resolved after 5 days. The combination of ibrutinib and nivolumab led to overall responses in 22 (61%) of 36 patients with high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma, 13 (33%) of 40 patients with follicular lymphoma, 16 (36%) of 45 patients with diffuse large B-cell lymphoma, and 13 (65%) of 20 patients with Richter's transformation. The most common all-grade adverse events were diarrhoea (47 [33%] of 141 patients), neutropenia (44 [31%]), and fatigue (37 [26%]). 11 (8%) of 141 patients had adverse events leading to death; none were reported as drug-related. The most common grade 3–4 adverse events were neutropenia (40 [28%] of 141 patients) and anaemia (32 [23%]). The incidence of grade 3–4 neutropenia ranged from eight (18%) of 45 patients with diffuse large B-cell lymphoma to 19 (53%) of 36 patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma; incidence of grade 3–4 anaemia ranged from five (13%) of 40 patients with follicular lymphoma to seven (35%) of 20 patients with Richter's transformation. The most common serious adverse events included anaemia (six [4%] of 141 patients) and pneumonia (five [4%]). The most common grade 3–4 immune-related adverse events were rash (11 [8%] of 141 patients) and increased alanine aminotransferase (three [2%]). Interpretation The combination of ibrutinib and nivolumab had an acceptable safety profile and preliminary activity was similar to that reported with single-agent ibrutinib in chronic lymphocytic leukaemia or small lymphocytic lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma. The clinical response in patients with Richter's transformation was promising and supports further clinical assessment. Funding Janssen R&D.

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Patients receiving hematopoietic stem cell transplantation (HSCT) are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs) are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively.The epidemiological properties of 312 patients with HSCT were retrospectively evaluated.A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62%) and allogeneic (38%) HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28%) and Hodgkin lymphoma (21.5%). A total of 142 (45%) patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011), and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2%) and Acinetobacter baumannii (8.8%) were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively.A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.Amaç: Hematopoetik kök hücre transplantasyonu (HKHT) yapılan hastaların bağışıklık sistemi ciddi şekilde baskılanmıştır ve kan akımı enfeksiyonları (KAE) bu süre içinde karşılaşılan majör komplikasyonlardan biridir. Bu çalışmada amacımız, geriye dönük olarak bu hastalarda KAE’lerinin epidemiyolojisini değerlendirmektir. Gereç ve Yöntemler: HKHT yapılan 312 hastanın epidemiyolojik özellikleri retrospektif olarak değerlendirildi. Bulgular: 2000 ve 2011 yılları arasında otolog (%62) ve allojeneik (%38) HKHT yapılan 312 hasta, çalışmaya dahil edildi. Çalışmaya dahil edilen hasta grupları en sık multipl miyelom (%28) ve Hodgkin lenfoma (%21,5) tanılı hastalar idi. Yüz kırk iki hastada (%45) en az bir kez KAE gelişmiş ve kan kültürlerinden 193 ayrı patojen elde edilmiştir. KAE’lerde 2005-2008 yılları arası bir artışın yanında, 2009-20011 yılları arasında da gram pozitiflerde göreceli bir artış da saptanmış ve en sık KAE kaynağı santral venöz kataterler olarak tespit edilmiştir. Koagülaz negatif staphylococi (%49,2) ve Acinetobacter baumannii (%8,8), kan kültürlerinden en sık elde edilen patojenlerdir. Genişlemiş spektrumlu beta laktamaz üretimi Escherichia coli ve Klebsiella spp. suşları arasında sırası ile %23 ve %22 idi. Kinolon dirençli Enterobacteriaceae oranı %10 olarak tespit edilmiştir. Pseudomonas ve Acinetobacter suşlarında karbapenem direni sırasıyla, %11,1 ve %23,5 iken, Enterobacteriaceae grubunda karbapenemlere hiç direnç saptanmamıştır. Sonuç: Yıllar içinde, gram negatif bakterilerden gram pozitiflere doğru bir kayma gözlenirken, en sık KAE kaynağı santral kataterler olarak saptanmıştır.

61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) -- DEC 07-10, 2019 -- Orlando, FL, BERBER, Ilhami/0000-0003-3312-8476, WOS:000577164606194, [No Abstract Available], Amer Soc Hematol

This phase 2 study evaluated whether substituting bortezomib for vincristine in frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy could improve efficacy in non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL), centrally confirmed by immunohistochemistry (Hans method). In total, 164 patients were randomized 1:1 to receive six 21-day cycles of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), all IV day 1, prednisone 100 mg/m(2) orally days 1-5, plus either bortezomib 1.3 mg/m(2) IV days 1, 4, 8, 11 (rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib [VR-CAP]; n = 84) or vincristine 1.4 mg/m(2) (maximum 2 mg) IV day 1 (R-CHOP; n = 80). There were no significant differences between VR-CAP and R-CHOP in complete response rate (64.5%, 66.2%; odds ratio [OR], 0.91; P = .80), overall response rate (93.4%, 98.6%; OR, 0.21; P = .11), progression-free survival (hazard ratio [HR], 1.12; P = .76), or overall survival (HR, 0.89; P = .75). Rates of grade ≥3 adverse events (AEs; 88%, 89%), serious AEs (38%, 34%), discontinuations due to AEs (7%, 3%), and deaths due to AEs (2%, 5%) were similar with VR-CAP and R-CHOP. Grade ≥3 peripheral neuropathy rates were 6% and 3%, respectively. VR-CAP did not improve efficacy vs R-CHOP in non-GCB DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT01040871.

This study aimed to investigate the impact of the different therapy regimens used in multiple myeloma (MM) on bone-specific alkaline phosphatase (BALP) levels.One hundred and thirteen patients with MM were included in the study. Patients were grouped according to the regimens they received, as follows: group 1, melphalan and prednisolone (MP); group 2, vincristine, adriablastin, and dexamethasone (VAD); group 3, thalidomide plus dexamethasone; and group 4, bortezomib plus dexamethasone. BALP levels were measured before treatment and at the third and sixth months of treatment. A fifth group consisted of patients in the post-treatment remission period at study entry (no-treatment group).The BALP levels at the third and sixth months of the treatment were significantly higher than the pre-treatment levels in the bortezomib and the no-treatment groups, whereas no significant difference was observed in the MP, VAD, and thalidomide groups.Considering that BALP is a surrogate marker of bone formation, our study suggests that bortezomib more efficiently leads to the improvement of bone disease in myeloma than other treatment options.Amaç: Bu çalışmanın amacı; multipl myelomda (MM) kullanılan farklı tedavi rejimlerinin kemik-spesifik alkalen fosfataz (BALP) düzeyleri üzerine etkisini incelemektir. Gereç ve Yöntemler: Çalışmaya 113 MM hastası dahil edildi. Hastalar aldıkları tedavi rejimlerine göre; 1. grup, melfalan ve prednizolon (MP); 2. grup, vinkristin, adriablastin ve deksametazon (VAD); 3. grup talidomid artı deksametazon; 4. grup, bortezomib artı deksametazon olarak gruplara ayrıldı. BALP düzeyleri tedaviden önce, tedavinin üçüncü ve altıncı aylarında ölçüldü. Çalışmanın başında, tedavi sonrası remisyon dönemindeki hastalardan beşinci bir grup oluşturuldu (tedavi almayan grup). Bulgular: Bortezomib grubu ve tedavi almayan grupta tedavinin üçüncü ve altıncı aylarında bakılan BALP düzeyleri, tedavi öncesine göre anlamlı olarak yüksek bulunurken; MP, VAD, ve talidomid gruplarında anlamlı fark saptanmadı. Sonuç: BALP’nin kemik formasyonunun bir belirteci olduğu göz önünde tutulduğunda, bu çalışma ile diğer tedavi seçeneklerine göre bortezomib tedavisinin miyelomda kemik hastalığının iyileşmesine daha etkin bir şekilde yol açtığı gösterilmiştir.

Bleomycin is an antineoplastic agent causing fatal pulmonary toxicity. Early diagnosis of bleomycin-induced pneumonitis is crucial to prevent irreversible damage. Pulmonary function tests are unreliable for identifying risk of bleomycin toxicity. Fluorodeoxyglucose PET/CT scanning can reveal inflammation secondary to pneumonitis but is not sufficiently specific for diagnosis. We retrospectively analyzed scans from 77 patients with Hodgkin lymphoma (median age 41 years, mean bleomycin dose 134 mg) to evaluate bleomycin-induced pneumonitis. We identified 13 patients with abnormal lung uptake of fluorodeoxyglucose. Tracer activity was predominantly diffuse, bilateral, in the lower lobes and subpleural areas. Interim scanning during treatment revealed pneumonitis in eight of 13 patients (asymptomatic in six). One asymptomatic patient died of bleomycin toxicity. For remaining 12 patients, bleomycin was discontinued and methylprednisolone given, all showed resolution of the pneumonitis. These findings suggest that routine interim or end-of-treatment FDG-PET/CT scanning could be beneficial for alerting clinicians to asymptomatic bleomycin-induced toxicity.

e19027 Background: Bendamustine is an old conventional agent which is used in the treatment of hodgkin's lymphoma (HL), non-hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL) patients despite they are relapsed or refractory cases. In our study we wanted to reveal retrospectively the efficacy and side effects of bendamustine in relapse/refractory patients from Turkey. Methods: We included in the study relapse/refractory HL and NHL patients who underwent multiple line chemotherapy. Bendamustine was administered at 90 mg/m² on days 1 and 2, every 3 weeks by 60 minutes infusion. The primary endpoint of the study was to determine the objective response and toxicity. Results: Seventy-five patients (31 female) with a median age of 62.8 years (range 16-89 years) were included in the study. 58 of the patients were NHL (follicular lymphoma:8, diffuse large B-cell lymphoma: 17, mantle cell lymphoma: 11, marginal zone lymphoma: 4, Small lymphocytic lymphoma:11, Others:7) and 17 of them were HL patients. The patients were underwent median three lines chemotherapy (range 1-8) accept autologous stem cell transplantation, 20 patients (HL: 12, NHL:8) were underwent autologous stem cell transplantation. Bendamustine was performed an average of 6 cycles (range 1-38). The objective response rate was 73.3%, complete response rate was 44% (n = 33), partial response rate was 29.3% (n = 22), respectively. The response rate was 65% (11/17) in HL cases, 79% (30/38) in indolent NHL cases and 70% (14/20) in aggressive NHL cases. For median follow-up of 20.7 months, the median overall survival (OS) was 64.9 months, OS rate was 75.5% for 1 year, 67.6% for 2 years and 63.1% for 3 years. The most common side effects associated with treatment were lymphopenia, neutropenia, thrombocytopenia, abdominal pain, fatigue and diarrhea. Side effects which were seen as grade 3 and higher levels: 9.6% lymphopenia, thrombocytopenia 8% and 12% fatigue. Conclusions: Objective response rate of bendamustine with tolerable side effect profile was found to be 73.3% in relapsed / refractory HL and NHL patients as a rescue agent. It appears to be an ideal agent for rescue treatment which had previously received intensive treatment.

Dasatinib is a potent second generation TKI, and it is widely used in patients with CML, both in the up-front setting and failure after imatinib. Lymphocytosis in cases receiving dasatinib therapy has been shown to be associated with pleural effusion (PE) and better outcome. Although patients who gather lymphocytosis during dasatinib have superior responses, there is only little data about the correlation between PE, response rates, and survival. In order to answer this question, the aim of our study was to determine the frequency of PE and lymphocytosis among our CML patients receiving second-line dasatinib, and to compare the responses and outcomes between patients with or without PE. There were 18 patients (44%) who developed PE, in a total of 41 patients, with a median time of 15 months. Lymphocytosis was observed in nine patients (9/41, 22%) with a median duration of 6.5 months of dasatinib treatment. There were fourteen patients with at least one comorbidity that may play a role in the generation of PE. The cumulative MMR and CCyR rates were greater in PE+ patients (p

Summary Objectives Fever of unknown origin (FUO) remains one of the most compelling diagnostic issues in medicine. We aimed to evaluate the potential clinical contribution of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) in the identification of the underlying cause of FUO. Methods Fifty consecutive patients (27 men and 23 women; age range 16–88 years) with FUO based on the revised definition criteria were included in the study. A diagnostic protocol including biochemistry, histopathology, and microbiological tests was performed and the patients were followed up. FDG-PET was performed in 25 of the 50 patients (12 males and 13 females; age range 16–88 years) in order to determine the etiology of the patient's fever. PET-CT images were obtained with the Gemini Philips TF 18 F-FDG-PET/CT camera after a 60-min ‘standard uptake' period following an injection of a mean 330 MBq (range 290–370 MBq) intravenous 18 F-FDG. Results A total of 21 patients were available for analysis of the diagnostic contribution of PET/CT (two patients were undiagnosed and two had non-contributory PET/CT findings). 18 F-FDG-PET/CT was able to precisely detect the cause of fever in 60% of the cases ( n =15). The accuracy, sensitivity, and specificity of this imaging modality were 90.5%, 93.8%, and 80%, respectively. Among the cases with a true-positive 18 F-FDG-PET/CT finding (i.e., 15 cases), the identified underlying causes of FUO included localized infection ( n =7), non-infective inflammatory process ( n =5), and malignancy ( n =3). Conclusions Further studies to confirm the high diagnostic yield of 18 F-FDG-PET/CT observed in the present study would lend support to the inclusion of this imaging modality in the initial diagnostic work-up of patients with suspected FUO.

Background: The cure rate for advanced classical Hodgkin lymphoma (cHL) is approximately 70%, which is calculated based on data from clinical trials performed in North American and/or European countries (Canellos GP, et al. N Engl J Med. 1992;327:1478-84; Carde P, et al. J Clin Oncol. 2016;34:2028-36; Gordon LI, et al. J Clin Oncol. 2013;31:684-91). However, there are limited outcome data available in other countries, apart from some small hospital-based studies (Ramirez P, et al. Rev Bras Hematol E Hemoter. 2015;37:184-9; Law MF, et al. Arch Med Sci. 2014;10:498-504; Jaime-Pérez JC, et al. Oncologist. 2015;20:386-92; Omer Al-Sayes FM, Sawan A. J Taibah Univ Med Sci. 2006;1:48-56). The B-HOLISTIC retrospective chart review study seeks to address the paucity of data on cHL treatment patterns, clinical outcomes, and healthcare resource utilization in 13 countries across Latin America, Africa, Middle East, and the Asia-Pacific region. Methods: The study will collect data from approximately 2,600 patients aged ≥18 years and newly diagnosed with stage IIB-IV cHL or relapsed/refractory cHL (RRHL) between 01 January 2010 and 31 December 2013, and will follow them until death or chart review, whichever occurs first. The primary objective is to describe progression-free survival (PFS) in patients with RRHL. Secondary objectives include describing demographic and clinical characteristics, clinical outcomes (overall survival, best clinical response after completion of treatment, response duration), key adverse events associated with each line of therapy, and cHL-related healthcare resource use. Results: As of 14 May 2018, a total of 165 patients from 12 sites have been included in the interim analysis, predominantly from Turkey and South Korea. At this time, 150 patients had cHL and 24 patients had RRHL, including 9 patients who were enrolled in the cHL group and had a documented relapse/progression during the study period. Here, we report the results of the newly diagnosed cHL group; data from the RRHL group will be reported in subsequent publications. At diagnosis, 64.7% of the cHL group were male, with a median age of 36.5 years (range, 18-89 years); 22.7% had stage IV disease, 30% had extranodal disease, 59.3% had 'B' symptoms, and 34.9% had an International Prognostic Score (IPS) of ≥4. Patients were classified as 13.3% in stage I-IIA; 24% in stage IIB; 53.3% in stage IIIA-IVB; and 9.3% as unknown. Patients classified as stage I-IIA are a deviation from the clinical study protocol and will be removed from the final study analysis. The proportion of patients alive was 94%, with the cause of death reported as either HL-related (44.4%), due to an adverse event (11.1%), or other (44.4%). Positron emission tomography (PET) or PET-computed tomography (CT) imaging was performed in 58.5% of patients at baseline, 48% of patients at interim, and 36.6% at end-of-treatment; CT imaging was performed in 68.7% of patients at baseline, 83.6% of patients at interim, and 59.7% of patients at end-of-treatment. At frontline treatment, 95.3% of patients received chemotherapy (mostly doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD], 92.3% [median number of cycles, 6; range, 2-8]), 22.7% of patients received radiotherapy, with 22% of patients receiving radiotherapy and chemotherapy (median total dose, 34.5 Gy; range, 24-45 Gy). The majority of patients received involved-field radiotherapy (53.1%), with other modalities including involved-node (21.9%), involved-site (18.8%), whole body (3.1%), or other (3.1%). The proportion of patients who achieved a complete or partial response to frontline treatment was 52.1% and 21.1%, respectively. The PFS for treatment in frontline cHL in the overall patient population at 48 months was 81% (95% CI, 73.1-86.7; Figure 1), with a median duration of follow-up of 58.9 months (range, 2.6-128.3 months). The PFS for treatment in frontline cHL excluding ineligible patients classified as stage I-IIA (13.3%) at 48 months was 78.9% (95% CI 69.7-85.6). Due to the retrospective nature of this study, adverse events were under-reported and will be presented once the data are mature. Conclusion: The B-HOLISTIC study is ongoing, with final patient enrolment anticipated in December 2018. These interim data provide real-world information on the incidence, treatment, and outcomes of cHL in countries where little is known about this patient population. Disclosures Ferhanoglu: Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Yeh:GNT Biotech & Medicals Crop.: Research Funding. Brittain:Takeda: Membership on an entity's Board of Directors or advisory committees. Karduss:Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Kwong:Bayer: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Song:Peking University Cancer Hospital (Beijing Cancer Hospital): Employment. Zerga:Bristol Myers Squibb: Other: Conference fees; Roche: Other: Conference fees; Janssen: Other: Conference fees; Takeda: Other: Conference fees. Blair:Takeda Pharmaceuticals International Co.: Employment. Dalal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Employment, Equity Ownership. Wan:Takeda Pharmaceuticals International Co.: Employment. Hertzberg:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees.

The aim of this single-center, retrospective study was to investigate the impact of rituximab, reconsider the validity of International Prognostic Index (IPI), and evaluate the prognostic role of the cell of origin (CoO) in a relatively young cohort. Three hundred twelve diffuse large B cell lymphoma patients (median age: 52) were included. Rituximab significantly improved the 3- and 5-year progression free survival (PFS) (70% versus 65% and 41% versus 36%, resp.; P<0.001) but led only to a slight, insignificant increase in 3- and 5-year overall survival (OS) (71% versus 77.3% and %67 versus 74.5%, resp.; P=0.264). In the young, low risk patient subgroup (aaIPI = 0&1; n=129), rituximab improved 3- and 5-year PFS and OS rates (P<0.001 and P=0.048, resp.). The efficacy of rituximab in young high risk patients was comparable to the literature. CoO data were available in 190 patients. The OS at 3 years was 79% for GC and 64% for non-GC subgroups (P=0.014). To the best of our knowledge, this is the first study which investigated the impact of R-CHOP in the context of CoO and IPI in a relatively young cohort. CoO was not an independent risk factor for prognosis in the multivariate analysis although patients with GC showed a significant survival advantage in the univariate analysis. CoO was also found to be a significant determinant of response in refractory/relapsed patients. Our results confirm the efficacy of rituximab in low and high risk, young patients outside of a randomized clinical trial setting.

Background Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, neurologic disturbances, and renal failure. Plasma therapy has dramatically improved prognosis of TTP, whereas recurrent acute episodes still occur in approximately 40% of patients. Moreover, patients with acquired ADAMTS13 deficiency, which is a significant factor for relapse, may require additional immunosuppressive treatment to get a durable remission. Study Design and Methods We hereby report two patients with a history of relapsed idiopathic TTP, who both received cyclosporin A (CSA) as a prophylactic manner after the remission was achieved. We also discuss the efficacy of CSA in patients with relapsed idiopathic TTP with a review of the published literature. Results Under CSA therapy, both patients maintained their clinical remission state, and the ADAMTS13 levels were normalized. Conclusion To conclude, CSA therapy may be useful for the prevention of relapsed idiopathic TTP in patients with a history of frequent relapses.

Hematopoietic cell transplantation is an established treatment option with curative potential for a variety of clinical conditions. The last decade especially witnessed a remarkable increase in HCT activity in Turkey. In 2014, 696 pediatric and 2631 adult (total 3327) HCT were performed in Turkey. Corresponding transplant rates per 10 million inhabitants for autologous-HCT and allogeneic-HCT were 226 and 202, respectively. Total HCT procedures in Turkey increased 177% in the last 5 years and 791% in the last 14 years. This report focuses mainly on HCT activity of Turkey in 2014 based on the national HCT registry and presents a general picture of national HCT activity. (c) 2016 Elsevier Ltd. All rights reserved.