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In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 15, No. S1 ( 2017-5)

Type of Medium: Online Resource

ISSN: 1546-0096

URL: Article

DOI: 10.1186/s12969-017-0142-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2279468-2

In: Leukemia & Lymphoma, Informa UK Limited, Vol. 61, No. 5 ( 2020-04-15), p. 1220-1225

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.1080/10428194.2020.1728753

Language: English

Publisher: Informa UK Limited

Publication Date: 2020

detail.hit.zdb_id: 2030637-4

In: Leukemia, Springer Science and Business Media LLC, Vol. 34, No. 12 ( 2020-12), p. 3149-3160

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-020-0783-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

detail.hit.zdb_id: 2008023-2

In: Blood Advances, American Society of Hematology, Vol. 5, No. 14 ( 2021-07-27), p. 2852-2862

Abstract: Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P & lt; .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase & gt;5 upper limit of normal (HR 2.09; P & lt; .001); and & gt;1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2021004458

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 2876449-3

In: Cell Death & Differentiation, Springer Science and Business Media LLC, Vol. 30, No. 5 ( 2023-05), p. 1097-1154

Type of Medium: Online Resource

ISSN: 1350-9047 , 1476-5403

URL: Article

DOI: 10.1038/s41418-023-01153-w

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 1496681-5

SSG: 12

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 397-397

Abstract: Introduction: Historically, outcomes for BL have improved in adults using dose intensive chemotherapy regimens and early CNS prophylaxis. More recent data using a less intensive regimen, DA-EPOCH, have been reported. We analyzed detailed patient (pt) & disease characteristics and treatment patterns across 26 US CCs over a recent 9 year (yr) period and also determined survival rates & prognostication. Methods: We conducted a large multicenter retrospective study of newly diagnosed (dx) adult BL pts (6/2009 - 6/2018). Dx was established by institutional expert pathology review; all cases were verified for BL based on 2016 WHO criteria (high grade B cell lymphoma, BL like, etc were excluded). Survival rates were estimated by Kaplan-Meier with differences assessed by log rank test. Univariate (UVA) associations were derived via Cox model with variables P ≤0.05 entered stepwise into a multivariate (MVA) model. Using significant factors from the MVA, a prognostic survival model was constructed. Results: Among N=557 verified BL cases, clinical features included: median age 47 yrs (17-88 yrs; 24% ≥60 yrs); male 76%; HIV+ 22%; ECOG PS 0/1 76%; B symptoms 51%; elevated LDH 78% (3, 5, & 10x elevation: 44%, 29% & 15%, respectively); hemoglobin & lt;10.5 gm/dL 32%; albumin & lt;3.5 30%; bone marrow (BM) involved 35%; non-BM extranodal (EN) in 80%; & gt;1 EN 43%; and 76% stage 3-4 disease (10% stage 1). Additionally, 16% and 3% of pts had baseline leptomeningeal (CSF or cranial nerve palsy) or parenchymal CNS involvement, respectively (see Zayac A et al. ASH 2019 for details). For MYC partner, 68% had t(8;14), 4% light chain, 5% negative FISH (otherwise classic BL) and 23% + break apart probe. HIV+ pts had several clinical differences: CSF+ 23% vs 12% P=0.003; CNS 19% vs 8% P & lt;0.001; ECOG PS 2-4 32% vs 21% P=0.002; BM 64% vs 34% P=0.03; and & gt;1 EN 60% vs 38% P & lt;0.001. For all pts, 87% had Tx at an academic CC (13% at community CC). Tx regimens were: CODOX-M/IVAC (Magrath) 31%, HyperCVAD/MA 29%, DA-EPOCH 28%, other 10% (mostly CHOP-based & CALGB Tx) & 1% were never treated. 90% of pts received rituximab as part of Tx (69% inpatient (inpt) & 31% outpatient) & 2% had consolidative autologous SCT. Response among all pts were CR 72%, PR 6%, SD 1%, PD 14%, 7% not evaluable. The treatment related mortality (TRM) rate across all pts was 8.9% (HIV+ vs not: 13% vs 8% P=0.09); most common: sepsis 48%, GI bleed/perforation 14% & respiratory failure 12%. TRM by Tx: hyperCVAD/MA 11.5%, EPOCH 6.4%, Magrath 6.3% & other 18.9%. With 39 month median follow-up, 3 year progression-free survival (PFS) and overall survival (OS) were 65% and 72%, respectively (Fig 1A). Among all pts who experienced disease progression, 90% occurred & lt;12 months from dx (4% after 2 yrs). There were 20 cases (4%) of 2nd cancers seen including 7 secondary MDS/AML (median 26 months) & 6 cases of Hodgkin or other NHL (median 54 months). For prognostication, outcomes were inferior for pts ages ≥40 yrs & LDH & gt;3x normal (Fig 1B/C). Notably, survival rates were not different based on HIV status (Fig 1D) or by the 3 most common Tx regimens (Fig 1E). However, there were important Tx differences based on presence of CNS involvement (see Zayac A et al. ASH 2019). Additionally, use of rituximab was associated with improved PFS & OS (Fig 1F), while outcomes were similar whether rituximab was given inpt vs outpatient (inpt PFS HR 1.25, P=0.19). Furthermore, Tx at an academic CC was associated with improved outcomes, which persisted on MVA (PFS HR 0.54, 95%CI 0.33-0.88 P=0.01; OS HR 0.50, 95%CI 0.29-0.87 P=0.01) & achievement of initial CR was strongly prognostic (Fig 1G). Baseline factors significant on UVA for PFS & OS were: age ≥40 yrs; PS 2-4; LDH & gt;3x; anemia, low albumin; BM involvement; Stage 3-4; CSF+; & & gt;1 EN. On MVA, factors associated with inferior survival were: age ≥40 yrs (PFS HR 1.57, P & lt;0.001; OS HR 1.89, P=0.001); PS 2-4 (PFS HR 1.57, P=0.002; OS HR 2.16, P & lt;0.001); & LDH & gt;3x (PFS HR 2.28, P & lt;0.0001; OS HR 1.96, P & lt;0.0001). Collectively, these factors yielded a BL survival model (Fig 1H/I). Conclusions: Outcomes for adult BL in this contemporary, large, multicenter RW analysis appear inferior to smaller published series. Interestingly, despite increased adverse prognostic factors, survival rates appeared similar in HIV+ pts. In addition, use of rituximab, achievement of initial CR, and Tx at an academic CC were associated with improved survival. Finally, a novel BL-specific survival model identified pts with markedly divergent outcomes. Disclosures Evens: Seattle Genetics: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Tesaro: Research Funding; Verastem: Consultancy, Honoraria. Danilov:Janssen: Consultancy; Seattle Genetics: Consultancy; MEI: Research Funding; Abbvie: Consultancy; Pharmacyclics: Consultancy; Takeda Oncology: Research Funding; Janssen: Consultancy; TG Therapeutics: Consultancy; Curis: Consultancy; Pharmacyclics: Consultancy; Aptose Biosciences: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Meyers Squibb: Research Funding; MEI: Research Funding; Gilead Sciences: Consultancy, Research Funding; Abbvie: Consultancy; Bristol-Meyers Squibb: Research Funding. Reddy:KITE Pharma: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy; Genentech: Research Funding; Abbvie: Consultancy. Farooq:Celgene: Honoraria; Kite Pharma: Research Funding. Khan:Janssen: Other: Educational Content/Symposium; Abbvie: Membership on an entity's Board of Directors or advisory committees; Bristol Myers: Other: Research Funds; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Yazdy:Genentech: Research Funding; Bayer: Honoraria; Abbvie: Consultancy; Octapharma: Consultancy. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Astrazeneca: Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution. Martin:Janssen: Consultancy; Teneobio: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy. Diefenbach:LAM Therapeutics: Research Funding; Incyte: Research Funding; Genentech: Consultancy, Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; MEI: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Feldman:Eisai: Research Funding; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding; Trillium: Research Funding; Viracta: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Roche: Research Funding. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Naik:Celgene: Other: Advisory board. Kamdar:Celgene: Consultancy; AstraZeneca: Consultancy; Seattle Genetics: Speakers Bureau; University of Colorado: Employment; Pharmacyclics: Consultancy. Portell:AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Amgen: Consultancy. Olszewski:Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Genentech: Research Funding; Adaptive Biotechnologies: Research Funding. Alderuccio:Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; Foundation Medicine: Other: Immediate family member; Targeted Oncology: Honoraria; Inovio Pharmaceuticals: Other: Immediate family member; OncLive: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-122971

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4040-4040

Abstract: Introduction: Pts with AML often present with hyperleukocytosis, defined with a white blood cell count (WBC) of 〉 50 or 〉 100 × 109/L. Hyperleukocytosis is associated with higher rates of complications and death especially when associated with clinical leukostasis. There are no clear guidelines outlining the best cytoreductive strategy and the use of leukapheresis is based on institutional practice. Limited data is available regarding characteristics of AML pts with hyperleukocytosis, treatment patterns, short and long-term clinical outcomes. Methods: Data were collected retrospectively from 12 centers in the United States and Europe. Eligible pts had newly diagnosed AML, WBC 〉 50 × 109/L, and had received intensive chemotherapy (IC). Pts with hyperleukocytosis who did not receive IC are described in a separate abstract. Kaplan-Meier methods estimated overall survival (OS) from time of presentation till death or end of follow-up. Clinical evidence of leukostasis was defined as new onset hypoxia, chest pain, headache, focal neurological symptoms, priapism, intestinal ischemia and acute renal failure attributed to hyperleukocytosis by the primary provider of the pt. Results: Among 1050 pts with AML and hyperleukocytosis whose data were collected, 787 were reported to have received intensive chemotherapy and were included in this analysis. The median age was 55 years (range [R], 15-86), and 51% were male (Table 1). Median WBC at presentation was 109 × 109/L (R, 47-561) and 57% had WBC 〉 100 × 109/L. Median hemoglobin was 9.2 g/dL (R, 3.6-126) and median platelet count was 31 x 109/L (R, 3-1268). A good, intermediate and poor risk karyotype were present in 31%, 51% and 18% of pts, respectively. Clinical leukostasis, tumor lysis syndrome (TLS) and disseminated intravascular coagulation (DIC) were present in 27%, 28% and 18% of pts at time of presentation, respectively (Table 1). Organs affected by leukostasis were the lung, CNS, retina, heart, kidney and GI tract in 44%, 36%, 6%, 6%, 5% and 4%, respectively. Leukapheresis was administered in 117 pts (15%) (Figure 1). Four centers did not use leukapheresis. 31% of pts with clinical leukostasis underwent leukapheresis and 10% of pts without clinical leukostasis received leukapheresis (p 〈 0.001). Pts, who underwent leukapheresis, had statistically significant higher WBC and higher % of FLT3 mutations compared to pts, who did not undergo leukapheresis (Table 1). In pts who did not receive leukapheresis, hyperleukocytosis was managed either by immediate initiation of intensive chemotherapy (n=342, 53%) or by the administration of hydroxyurea followed by intensive chemotherapy (n=302, 47%). Pts managed with leukapheresis, received either immediate (within 24h) induction of intense chemotherapy (n=71, 61%) or delayed (after 24h) induction of intensive chemotherapy (n=42, 36%) after completion of leukapheresis. The 30-day mortality was 16.6% (95%CI, 13.9-19.3%); 20%, 11% and 14% of pts were admitted to the ICU, underwent hemodialysis, or required mechanical ventilation, respectively (Table 2). After initiation of chemotherapy, 51% (95%CI, 46.9%-54.1%) had a complete remission (CR), 14% (95%CI, 11.4%- 16.4%) had a complete remission with incomplete count recovery (CRi) and 4% (95%CI, 2.5%-5.4%) achieved a partial remission (PR) whereas 32% (95%CI, 28.7%-35.4%) had no response to therapy (Table 2). Response to chemotherapy lasted a median of 202 days (R,14-3575) and 43% of pts experienced a relapse of their disease; 31% of pts underwent a hematopoietic stem cell transplant (HSCT). Median OS for all pts was 12.6 months (95%CI, 11.5-14.9) (Figure 1A). Median OS was 14.1 months (95%CI, 12.3-18.7) for pts with a WBC 〈 100 × 109/L versus 11.5 months (95%CI, 9.3-14.1) for pts with a WBC 〉 100 × 109/L (p=0.11) (Figure 1B). Median OS was 15.2 months (95%CI, 13.4-17.5) for pts without clinical leukostasis, significantly longer than the median OS of 7.4 months (95%CI, 3.9-9.8) for pts with symptoms of leukostasis (p 〈 0.0001) (Figure 1C). Conclusions: To our knowledge, this is largest reported cohort of pts with AML and hyperleukocytosis treated with intensive chemotherapy. Clinical leukostasis was present in about a quarter of pts and was associated with worse OS. Most pts were managed with chemotherapy alone, and leukapheresis was only used in a small subgroup of pts (15%). The impact of leukapheresis and other variables on outcomes are presented in a separate abstract. Disclosures Montesinos: Novartis: Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Speakers Bureau. Bhatt:Pfizer: Consultancy; CSL Behring: Consultancy; Incyte: Research Funding. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Fathi:Boston Biomedical: Consultancy, Honoraria; Jazz: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Astellas: Honoraria; Agios: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria. Khan:Teva: Speakers Bureau. Roboz:Janssen Pharmaceuticals: Consultancy; Aphivena Therapeutics: Consultancy; Roche/Genentech: Consultancy; Argenx: Consultancy; Aphivena Therapeutics: Consultancy; Jazz Pharmaceuticals: Consultancy; Sandoz: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy; Cellectis: Research Funding; Orsenix: Consultancy; Bayer: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Cellectis: Research Funding; Sandoz: Consultancy; Otsuka: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; AbbVie: Consultancy; AbbVie: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Janssen Pharmaceuticals: Consultancy; Eisai: Consultancy; Otsuka: Consultancy; Daiichi Sankyo: Consultancy; Orsenix: Consultancy; Celltrion: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Eisai: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy. Cluzeau:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Speakers Bureau; Pfizer: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Consultancy; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Germing:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria. Mukherjee:Pfizer: Honoraria; Projects in Knowledge: Honoraria; BioPharm Communications: Consultancy; LEK Consulting: Consultancy, Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squib: Honoraria, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Aplastic Anemia & MDS International Foundation in Joint Partnership with Cleveland Clinic Taussig Cancer Institute: Honoraria. Brunner:Celgene: Consultancy, Research Funding; Takeda: Research Funding; Novartis: Research Funding. Ritchie:Incyte: Consultancy, Speakers Bureau; NS Pharma: Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; ARIAD Pharmaceuticals: Speakers Bureau; Astellas Pharma: Research Funding; Bristol-Myers Squibb: Research Funding. Podoltsev:Pfizer: Research Funding; Sunesis Pharmaceuticals: Research Funding; LAM Therapeutics: Research Funding; Genentech: Research Funding; Boehringer Ingelheim: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; Celgene: Research Funding; Astellas Pharma: Research Funding; Celator: Research Funding; Daiichi Snakyo: Research Funding. Gore:Celgene: Consultancy, Research Funding. Zeidan:Otsuka: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-112974

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1122-1122

Abstract: Background: Venous thromboembolism (VTE) is a leading cause of mortality, morbidity, and hospitalization in cancer patients. Despite convincing evidence that treatment with low molecular weight heparin (LMWH) offers the best outcomes for patients with acute VTE, there exists a great variation in care, with up to 60% of patients in the United States not receiving LMWH. We instituted a centralized service for care of cancer patients with suspected deep venous thrombosis (DVT) and/or pulmonary embolism (PE) at Taussig Cancer Institute of the Cleveland Clinic in August 2014. We hypothesized that a cancer-associated thrombosis (CAT) clinical service that provides standardized management would reduce variation in care, and lower rates of recurrence, bleeding, and hospitalization in this patient population. Methods: We conducted a prospective cohort study of patients seen by the CAT clinical service. We collected data regarding demographics, cancer types, VTE characteristics, treatment recommendations, and outcomes in these patients. Outcome data included VTE recurrence, major or clinically relevant nonmajor bleeding according to International Society on Thrombosis and Haemostasis definitions, hospitalization, and mortality. Results: The study population comprised 221 patients with suspected VTE seen by the CAT clinical service between August 2014 and July 2015. Patients were 51% female, with a median age of 62±13 years. Hematologic malignancies (23%, N=50 of 221), breast cancer (10%, N=22 of 221), brain cancer (10%, N=22 of 221), pancreatic cancer (10%, N=21 of 221), and lung cancer (10%, N=21 of 221) were among the most commonly observed cancer types. VTE was diagnosed in 51 patients (23%, N=51 of 221). Of these, 39 patients (76%) had DVT, 5 (10%) had PE, and 7 (14%) had both. Hospitalization for VTE was necessary in only 24% (N=13 of 51) of cases. The mean and median costs of hospitalization for VTE (all costs) were US$7,656 and US$2,842, respectively, whereas the mean and median costs of outpatient treatment of VTE were US$1,160 and US$824 respectively. Initial treatment for 94% (N=48 of 51) of patients was with enoxaparin. Other treatments included warfarin (2%, N=1 of 51), heparin (2%, N=1 of 51), and apixaban (2%, N=1 of 51). Of patients started on enoxaparin, 71% (N=34 of 48) remained on enoxaparin for the duration of their care, while 16% (N=8 of 48) were bridged to warfarin after a median of 9 days and 10% (N=5 of 48) were taken off anticoagulants due to bleeding or other considerations. Common causes for transitioning to warfarin were financial considerations (50%, N=4 of 8), patient preference (38%, N=3 of 8), and poor renal function (13%, N=1 of 8). VTE recurred in 14% (N=7 of 51) of patients with a median follow-up of 3.5 months. Recurrences occurred in 9% (N=3 of 34) of patients on enoxaparin monotherapy, in 22 % (N=2 of 9) of patients started on or bridged to warfarin and 33% (N=2 of 6) of patients taken off anticoagulation. A total of 10 recurrent VTE events occurred in 7 patients. Of these, 4 required hospitalization. The mean and median costs of hospitalization for recurrence (all costs) were US$19,528 and US$18,627, respectively. The mean and median costs of initial outpatient care (excluding drug costs) for recurrent VTE were US$998 and US$728, respectively. Major or clinically relevant bleeding was seen in 14% (N=7 of 51) of patients on anticoagulants, with 86% (N=6 of 7) requiring hospitalization. The risk of bleeding in patients on enoxaparin (15%, N=5 of 34) was similar to that seen in patients who bridged to warfarin (14%, N=1 of 8). The mean and median costs of hospitalization for bleeding (all costs) were US$11,754 and US$8,806 respectively. Conclusions: Centralizing care of CAT reduces treatment variation and appears to improve patient related outcomes including the need for VTE-related hospitalizations and recurrent VTE. Substantial cost savings can be achieved by avoiding unnecessary hospitalization for appropriate patients and by reducing recurrence and bleeding rates with appropriate therapy. Disclosures McCrae: Halozyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Syntimmune: Consultancy; Momenta: Consultancy. Bartholomew:Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy. Khorana:Pfizer: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; sanofi: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.1122.1122

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 458-458

Abstract: 458 Background: FOLFIRINOX is an active regimen for metastatic pancreatic cancer demonstrating a median overall survival of 11.1 months at the expense of significant treatment-related toxicity. Dose modifications are routinely used in clinical practice however there is little data regarding impact on outcomes and use of second line therapy. In this study we report on the treatment course and outcomes of 92 patients treated at two academic centers. Methods: We conducted an IRB-approved retrospective cohort study of patients with metastatic pancreatic adenocarcinoma treated with first line FOLFIRINOX between 2011 and 2015. Hazard ratios were calculated by Cox proportional hazard models and median survival was estimated using Kaplan-Meier method. Results: 92 patients were identified with a median follow-up of 13.2 months (range 1.2-47.3 mo); 57 males (62%), ECOG 0/1 = 75 (82%). Fifty-four percent required dose reductions of 〉 25% in at least one of three component drugs within the first 6 cycles [95% CI 0.44, 0.65]. Irinotecan was dose reduced in 43% of patients (n=39) while 64% required modification or discontinuation of 5FU. Ten patients (11%) received the full dose of FOLFIRINOX as originally published and 17 patients (25%) discontinued FOLFIRINOX due to toxicity. 60% of patients demonstrated disease control at first imaging assessment after 4-6 cycles of treatment. Median PFS was 7.11 months (95% CI: 5.06-8.51) and OS 13.01 months (95% CI: 9.17-16.95). There was a decrease in PFS and OS associated with a dose reduction of two or more drugs with a HR of 1.68 (95% CI 1.01-2.82, p=0.048) and 1.98 (95% CI 1.08-3.65, p=0.027) respectively. Sixty-seven patients [73%] went on to receive 2 nd line therapy [n=67] with 55% receiving gemcitabine-based regimens, the majority with nab-paclitaxel [82%] . Forty-two patients demonstrated progressive disease [63%]. Conclusions: Modest FOLFIRINOX dose modifications are prevalent in clinical practice and are not associated with a reduction in efficacy. A median survival of 13 months with dose modified FOLFIRINOX is compelling. Dose reduction of 2 or more agents was associated with diminished survival. Second line therapy following FOLFIRINOX was associated with modest activity.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2017.35.4_suppl.458

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2017

detail.hit.zdb_id: 2005181-5

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 49-50

Abstract: Introduction: There are few data about prognostication and outcomes in patients (pts) with HIV-BL treated in the cART era. Optimal treatment strategies to minimize treatment-related mortality (TRM) remain unclear and current recommendations are based on small studies. We conducted a multicenter international analysis to identify prognostic factors and outcomes in pts with HIV-BL treated in the cART era. Methods: This retrospective analysis included a subcohort from a recent study across 30 US sites (Evens et al. Blood 2020) augmented by data from 5 UK centers treated 2009-2018. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier & differences assessed by log-rank test. Univariate (UVA) associations were derived via Cox model and multivariable (MVA) models were constructed by forward selection of significant variables with P & lt;0.05. Results: 249 (US: 140 & UK: 109) pts with newly diagnosed HIV-BL were included. Clinical features included median age 43 (IQR 35-50 years [yrs]); male sex: 84%; ECOG PS: 2-4: 48%; elevated LDH: 85% ( & gt; 3x upper limit of normal (ULN) 49% & & gt;5xULN 39%); & gt;1 extranodal (EN) site: 60%; any CNS involvement (CNSinv) 25%; and +bone marrow (BM) 46%. MYC rearrangement was reported in 93% of pts with t(8;14) in 49%, break-apart probe in 41% and MYC-light chain in 3%; the rest had classical BL with negative MYC testing (4%) or missing result (3%) (otherwise classical BL). Median CD4 count was 217 (IQR 90-392 cells/µL) with 68% pts having CD4 & gt;100 cells/µL. At BL diagnosis, HIV viral load was detectable in 55%; 39% of pts were on cART. Baseline features were similar between the US & UK cohorts with significant differences only in ECOG PS 2-4 (32% vs 65%; P & lt;0.001) & baseline CNSinv (30% vs 17%, respectively; P=0.02). Tx regimens included: CODOX-M/IVAC (Magrath) 60%, DA-EPOCH 25%, HyperCVAD/MA 13%, & other 1%; most pts (87%) received rituximab (R). Similar regimens were used in pts with baseline CNSinv: Magrath 64%, DA-EPOCH 24% & HyperCVAD 12%. In the US, pts most frequently received DA-EPOCH (42%) followed by Magrath (32%) & HyperCVAD/MA (24%), whereas in the UK, 96% received Magrath. R was more frequently given in the US (94% vs 79%, P & lt;0.001). Similar baseline features were seen in US pts selected for DA-EPOCH as those selected for Magrath or HyperCVAD/MA except for lower median CD4 count (144 vs 260 cells/µL; P=0.04). Overall response to Tx was: CR 70%, PR 9%, PD 14%, not evaluable 7%. TRM was 18% following HyperCVAD/MA, 13% after DA-EPOCH & 7% in patients treated with Magrath. Overall, 33% of pts had a relapse of HIV-BL with 23% systemic only & 10% CNS. With median follow-up of 4.5 yrs, 3-yr PFS & OS were 61% & 66%, respectively, and nearly identical in both countries (Fig A). Pts with CD4 & gt;100 cells/µL had better 3-yr PFS (Fig B) & OS (68% vs 57% P=0.03). We observed significantly worse outcomes in pts with baseline CNSinv (3-yr PFS 36% vs 69%, P & lt;0.001; OS 41% vs 73%, P & lt;0.001; Fig C). Magrath was associated with the highest 3-yr PFS (66%) compared with 63% after HyperCVAD/MA & 51% after DA-EPOCH, but the difference was not significant (P=0.13; Fig D). Pts receiving R had numerically higher PFS, but also not statistically significant (63% vs 53% P=0.16). We observed poor outcomes in pts with baseline CNSinv regardless of frontline Tx (3-yr PFS HyperCVAD/MA 40%, Magrath 39%, DA-EPOCH 32%; P=0.93; Fig E). The incidence of CNS recurrence at 3 yr across all Tx was 11%. Higher incidence was observed with DA-EPOCH (P=0.032 vs other regimens; Fig F) with no difference according to CD4 count. Variables associated with PFS & OS on UVA included: ECOG PS 2-4, & gt;1 EN, +BM, baseline CNSinv, LDH & gt;ULN, CD4 & lt;100 cells/µL. On MVA, the variables independently associated with inferior PFS were ECOG PS 2-4 (HR 1.87 P=0.007); baseline CNSinv (HR 1.70, P=0.023); LDH & gt;5xULN (HR 2.09, P & lt;0.001); and & gt;1 EN sites (HR 1.58 P=0.043). The same variables were significant on MVA for OS. Adjusting for all of the prognostic variables, Tx with Magrath was associated with longer PFS (adjusted HR, 0.45, P=0.005). Conclusions: These data represent the largest analysis of HIV-BL to date. There were favorable tolerance and outcomes with intensive R-containing regimens with Magrath being associated with lower TRM and the highest PFS. In addition, prognostic factors for pt outcomes were associated with lymphoma characteristics rather than with HIV-related features. Pts with baseline CNSinv represent a high-risk group with unmet therapeutic needs. Disclosures Alderuccio: Oncinfo: Honoraria; Puma Biotechnology: Other: Family member; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; OncLive: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member. Olszewski:Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding. Evens:Epizyme: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Mylteni: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Collins:Gilead: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding; Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau; BeiGene: Consultancy; Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses , Speakers Bureau; Celleron: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Celgene: Research Funding; Amgen: Research Funding; Pfizer: Honoraria. Danilov:Astra Zeneca: Consultancy, Research Funding; Verastem Oncology: Consultancy, Research Funding; Takeda Oncology: Research Funding; Gilead Sciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Nurix: Consultancy; Celgene: Consultancy; Aptose Biosciences: Research Funding; Bristol-Myers Squibb: Research Funding; Rigel Pharmaceuticals: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Consultancy; BeiGene: Consultancy; Abbvie: Consultancy. Jagadeesh:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Debiopharm Group: Research Funding; MEI Pharma: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding. Reddy:Genentech: Research Funding; Abbvie: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy. Farooq:Kite, a Gilead Company: Honoraria. Bond:Seattle Genetics: Honoraria. Khan:Celgene: Research Funding; Janssen: Honoraria; Pharmacyclics: Honoraria; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding. Yazdy:Bayer: Honoraria; Genentech: Research Funding; Octapharma: Consultancy; Abbvie: Consultancy. Karmali:Karyopharm: Honoraria; Takeda: Research Funding; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Martin:Janssen: Consultancy; Regeneron: Consultancy; Bayer: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Beigene: Consultancy; Cellectar: Consultancy; Incyte: Consultancy; Kite: Consultancy; Morphosys: Consultancy; Celgene: Consultancy; Teneobio: Consultancy; Karyopharm: Consultancy, Research Funding. Diefenbach:Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Trillium: Research Funding. Klein:Takeda: Membership on an entity's Board of Directors or advisory committees. Haverkos:Viracta THerapeutics: Consultancy. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Caimi:Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding; Celgene: Speakers Bureau; Verastem: Other: Advisory Board. Kamdar:Roche: Research Funding. Feldman:Eisai: Research Funding; Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Trillium: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Viracta: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau. Smith:AstraZeneca: Consultancy; Millenium/Takeda: Consultancy; Karyopharm: Consultancy; Beigene: Consultancy; Seattle Genetics: Research Funding; Ayala: Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Acerta Pharma BV: Research Funding; Bristol Meyers Squibb: Research Funding; Portola: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Incyte: Research Funding; Ignyta: Research Funding; Genentech: Research Funding; De Novo Biopharma: Research Funding. Portell:Amgen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; Janssen: Consultancy; TG Therapeutics: Research Funding; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Xencor: Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding. Naik:Celgene: Other: advisory board; Sanofi: Other: advisory board. Lossos:Janssen Biotech: Honoraria; Verastem: Consultancy, Honoraria; Stanford University: Patents & Royalties; NCI: Research Funding; Seattle Genetics: Consultancy, Other; Janssen Scientific: Consultancy, Other. Cwynarski:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Atara: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136989

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7