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In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1554-1554

Abstract: Introduction: The majority of patients with classical Hodgkin lymphoma (cHL) will be cured with anthracycline-containing chemotherapy regimens. However, 10-20% of patients with early-stage disease and 30-40% of patients with advanced-stage cHL will relapse. The standard treatment for patients with relapsed cHL is salvage chemoimmunotherapy followed by high-dose chemotherapy (HDT) and autologous hematopoietic cell transplantation (auto-HCT) in chemotherapy-sensitive patients. Patients with primary treatment failure (PTF), i.e. patients who have progressive disease while on therapy or who fail to achieve complete remission (CR) at the end of initial therapy, or experience early relapse after CR1 are expected to have a worse prognosis than patients with late relapse. Since 2011 newer treatments, namely Brentuximab vedotin and PD1/PDL1 blockers have been introduced for the treatment of relapsed and refractory cHL. It is unknown whether changes in disease monitoring and management, including the availability of new agents, impacted survival of patients with cHL and PTF. Methods: Fifteen US academic medical centers contributed cases to the ECLIPSE study (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs). ECLIPSE retrospectively captured patient, disease and treatment characteristics and treatment response as assessed by treating physicians. Eligible patients were ≥ 15 years diagnosed with cHL on or after 2005, who received treatment with curative intent with anthracycline-containing chemotherapy regimens, and developed one of the 3 patterns of PTF: detection of progressive disease during or within 6 weeks of completion of chemotherapy (PP cohort, primary progression), partial response (PR) or stable disease (SD) by functional imaging at completion of chemotherapy (PR/SD cohort), or disease progression detected within 12 months of completion of chemotherapy after prior documentation of CR (ER cohort, early relapse). Patients were divided into two "eras" based on year of diagnosis, 2005-2010 (era1) and 2011-2018 (era2), with the latter expected to reflect changes in salvage therapy for cHL. Results: Patient characteristics for the 553 cases are summarized in Table. Median follow up of survivors was 58.7 and 31.2 months for patients diagnosed in era1 and era2, respectively. ABVD was the upfront treatment for 97.6% of cases. Nearly all patients (98.5%) received salvage therapy after PTF and 60.9% underwent auto-HCT. Patients who relapsed or progressed post auto-HCT received a median of 1 (range 0 to 3) salvage regimens. Five-year overall survival (OS) from time of PTF was 70.3% (95% CI=63.4-77.2%) for patients diagnosed in era1, and 77.6% (95% CI=70.3-84.8%, p = 0.018) for patients diagnosed in era2 (Figure A). While there was no difference in OS among the PP, PR/SD and ER cohorts in the era1 (Figure B), the PR/SD and ER cohorts had better OS than PP cohort in era2 (Figure C). On comparing the OS for each of the 3 cohorts between era1 and era2, there was an improvement in OS in the PR/SD (Figure E) and ER cohorts (Figure F) but no improvement among the PP cohort (D). Multivariable analysis of patients in era 2 identified only age (HR 1.05, 95% CI=1.03-1.07, P & lt;0.001) and PP pattern of PTF (HR 2.45, 95% CI=1.11-5.40, P=0.03) as predictors of worse survival. Conclusions: Though there has been an improvement in survival among cHL cases with PTF treated in the most recent years, the outcome of patients with PP did not change significantly across eras. Patients with PP disease should be prioritized for clinical trials incorporating newer agents and innovative cellular therapy to current available effective treatments. Disclosures Epperla: Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Costa:Abbvie: Consultancy; Karyopharm: Consultancy; Fujimoto Pharmaceutical Corporation Japan: Other: Advisor; Sanofi: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding. Cashen:Novartis: Other: Speaker's Bureau; Seattle Genetics: Other: Speaker's Bureau; Celgene: Other: Speaker's Bureau. Hamadani:Otsuka: Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Merck: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Celgene: Consultancy; Janssen: Consultancy; Medimmune: Consultancy, Research Funding. Barta:Mundipharma: Honoraria; Celgene: Research Funding; Takeda: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Reddy:Celgene: Consultancy; BMS: Consultancy, Research Funding; Genentech: Research Funding; Abbvie: Consultancy; KITE Pharma: Consultancy. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau. Bello:Celgene: Speakers Bureau. Chavez:Novartis: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Glenn:BMS: Research Funding; Merck: Research Funding; Genentech: Research Funding. Cohen:Lymphoma Research Foundation: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; ASH: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Bristol-Meyers Squibb Company: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-129199

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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detail.hit.zdb_id: 80069-7

In: Journal of Hematopathology, Springer Science and Business Media LLC, Vol. 14, No. 4 ( 2021-12), p. 269-275

Type of Medium: Online Resource

ISSN: 1868-9256 , 1865-5785

URL: Article

DOI: 10.1007/s12308-021-00473-5

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2438687-X

In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 24, No. 17 ( 2018-09-01), p. 4110-4118

Abstract: Purpose: Tumor-associated macrophages (TAMs) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with noninvasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. Experimental Design: In a first-in-patient, Institutional Review Board–approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (two lymphoma and three bone sarcoma) underwent pre- and postcontrast MRI. Subsequently, 20 patients (10 lymphoma and 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24 to 48 hours after i.v. injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68+ and CD163+ TAM quantities on histopathology. Results: Significant ferumoxytol tumor enhancement was noted on postcontrast scans compared with precontrast scans (P = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density (P & lt; 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68+ and CD163+ TAM (P & lt; 0.05). Conclusions: Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies. Clin Cancer Res; 24(17); 4110–8. ©2018 AACR.

Type of Medium: Online Resource

ISSN: 1078-0432 , 1557-3265

URL: Article

DOI: 10.1158/1078-0432.CCR-18-0673

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2018

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detail.hit.zdb_id: 2036787-9

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1841-1841

Abstract: Background: Light chain amyloidosis (AL) is characterized by tissue deposition of misfolded proteins that cause multisystem organ dysfunction. Current treatments, including chemotherapy and autologous hematopoietic cell transplantation (AHCT), target plasma cells producing pathogenic amyloid proteins. The development of amyloid protein targeted monoclonal antibody therapy has led to an increased need for objective measurements of clinical response. The 6-minute walk test (6MWT) has been used for years as the primary outcome measure to monitor disease severity in clinical trials of heart failure (HF). For example, HF trials with cardiac devices MIRACLE (Abraham, 2002) and MUSTIC (Cazeau, 2001) demonstrated important therapeutic effects based on an improved 6MWT distance of 39 meters and a change of 23%, respectively. These findings, in conjunction with improvement in other markers of disease activity, lead to approval of cardiac resynchronization for the management of HF. Our primary objective was to determine the impact of chemotherapy on changes in 6MWT in patients with AL cardiac amyloid and correlate these changes with cardiac biomarkers. Patients and Methods: We retrospectively analyzed outcomes of 22 AL amyloid patients with cardiac involvement. Subjects performed 6MWT at diagnosis and at the end of planned initial chemotherapy. All patients received bortezomib (B)-based chemotherapy. About half received chemotherapy alone (45%) and the others received B-based induction chemotherapy followed by AHCT (55%). To identify factors associated with changes in 6MWT, we analyzed cardiac response and changes in New York Heart Association (NYHA) class, troponin I, brain natriuretic peptide (BNP) and left ventricular ejection fraction (LV EF). Cardiac response was defined as BNP decrease of 30% or NYHA class decrease ≥ 2 in subjects with baseline NYHA class 3 or 4 (adapted from Comenzo, 2012). Results: At baseline, 59% (n=13) of patients were modified AL amyloid cardiac stage I/II and 41% (n=9) stage III. The median percent change in 6MWT was an increase in 26.5% with a median change of 90 meters (range, -120 to 365), p 〈 0.001. Overall, 81% (n=18) had improvement in 6MWT distance, 9% (n=2) declined and 9% (n=2) were unchanged. Patients had reassessment of 6MWT a median of 13.5 months from diagnosis. Hematological responses (HR) included CR (36%), VGPR (36%), PR (23%) and SD (5%). HR was not associated with change in 6MWT. Fifty percent (n=11) experienced a cardiac response. By Wilcoxon rank sum test, variables that were associated with improvement in 6MWT included improved BNP, LV EF, troponin I, NYHA class and cardiac response (all p 〈 0.001). The median follow-up of patients was 2.15 years (range, 1.10 - 7.20). By multivariate analysis, patients with a cardiac response had significantly better improvement in 6MWT disease compared with patients without cardiac response (p=0.02). A cardiac response was associated with a median increase of 170 meters of distance traveled by 6MWT when compared with patients having no cardiac response. All other variables tested were not statistically significant. Conclusion: In AL amyloid patients with cardiac involvement, the 6MWT can be used as an objective marker of functional improvement complementing biochemical and imaging parameters of response. Furthermore, treatment of cardiac amyloidosis with contemporary standard regimens has a major impact on the disease process by a number of objective parameters. Patients experiencing a cardiac response had substantial improvements in 6MWT. The 6MWT should be incorporated in trials of patients with cardiac amyloid. Disclosures Cornell: Prothena: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.1841.1841

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

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detail.hit.zdb_id: 80069-7

In: Current Treatment Options in Oncology, Springer Science and Business Media LLC, Vol. 17, No. 2 ( 2016-2)

Type of Medium: Online Resource

ISSN: 1527-2729 , 1534-6277

URL: Article

DOI: 10.1007/s11864-015-0382-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 2090563-4

In: Current Hematologic Malignancy Reports, Springer Science and Business Media LLC, Vol. 12, No. 3 ( 2017-6), p. 257-267

Type of Medium: Online Resource

ISSN: 1558-8211 , 1558-822X

URL: Article

DOI: 10.1007/s11899-017-0369-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2374151-X

In: The Lancet Oncology, Elsevier BV, Vol. 17, No. 9 ( 2016-09), p. 1176-1177

Type of Medium: Online Resource

ISSN: 1470-2045

URL: Article

DOI: 10.1016/S1470-2045(16)30205-4

Language: English

Publisher: Elsevier BV

Publication Date: 2016

detail.hit.zdb_id: 2049730-1

In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4834-4834

Abstract: Abstract 4834 Multicentric Castleman's Disease(MCD) can have an aggressive course making early diagnosis and treatment important. Although rare, peripancreatic involvement is known in Castleman's disease and an unusual presentation should be considered especially in the setting of HIV. An excisional lymph node biopsy is required for diagnosis. High plasma titers of Human Herpes Virus 8 DNA should also raise this possibility. Coexistence of Castleman disease and body cavity lymphoma has been reported but is rare. Case Presentation: A 42 year old African American gentleman with a history of HIV and CD4 count 271 presented with intractable nausea and vomiting of 1 month duration; associated with epigastric pain and weight loss. Past history was significant for presentation with jaundice 6 months earlier when he was found to have a pancreatic head mass with portocaval and retroperitoneal lymphadenopathy raising the suspicion of pancreatic adenocarcinoma. Endoscopic ultrasound guided fine needle aspiration of the mass had revealed a poorly differentiated malignant neoplasm that could not be further characterized by immunohistochemistry. Considering the HIV status of the patient, there was a strong suspicion of lymphoma. A PET-CT was planned to identify an appropriate site for tissue diagnosis but the patient was lost to follow up. Repeat imaging during the current admission revealed increasing size of the pancreatic mass causing complete obstruction of second part of duodenum. The patient subsequently underwent gastro-jejunostomy to bypass the duodenal obstruction and an excisional biopsy of two mesenteric lymph nodes was performed during the procedure. Pathology revealed HHV-8 positive plasma cell variant of Castleman's disease. Patient also had high plasma titers of HHV-8. Furthermore, the patient was also found to have bilateral pleural effusions and a thoracentesis was performed. Pleural cytology revealed large plasmablastic lymphoid cells that were positive for HHV-8, CD30, CD45, CD138, Ebstein-Barr virus (EBV), epithelial membrane antigen, and multiple myeloma oncogene-1. These findings suggested a diagnosis of body cavity lymphoma. Discussion: Although rare, the association of Multicentric Castleman's disease (MCD) with HIV is well recognized. The incidence is independent of CD4 count and the use of HAART. There are isolated case reports of pancreatic involvement with Castleman's disease and only one involving the duodenum. While most patients with peripancreatic involvement presented with abdominal discomfort, nausea or systemic symptoms, our patient was severely symptomatic from complete duodenal obstruction. Our case also highlights that the diagnosis can be elusive and requires excisional lymph node biopsy. Moreover, HIV MCD is fluorodeoxyglucose avid, and a PET-CT may help identify the gland to biopsy next in difficult to diagnose cases. Body cavity lymphoma is also HHV-8 related and this diagnosis should be considered in any HIV patient with effusions. Pleural fluid cytology and immunohistochemistry usually clinch the diagnosis. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V120.21.4834.4834

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

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detail.hit.zdb_id: 80069-7

In: Oncology & Hematology Review (US), Touch Medical Media, Ltd., Vol. 13, No. 01 ( 2017), p. 34-

Abstract: Until recently, chemoimmunotherapy has been the mainstay of treatment approach in chronic lymphocytic leukemia (CLL) patients requiring intervention. With the emergence of targeted treatments, there has been a shift in CLL therapy. With a better understanding of disease biology and risk stratification, a tailored approach based on patient age and comorbidities has evolved over time. The development of new and potent, next generation CD20 antibodies has refined therapy options especially for elderly unfit patients. Furthermore, agents targeting important pathways involved in proliferation and survival of CLL cells including B-cell receptor (BCR) signaling have provided additional treatment options in traditionally chemo-refractory CLL. Given the rapidly expanding repertoire of drugs, current research is focused on optimizing treatment sequence, duration of treatment and assessing long-term toxicities. Several immune mediated therapies are emerging and new combinations are being tested to re-establish antitumor immune effector response in CLL. While embracing the advances in CLL therapy, a few longstanding lessons remain. There is still little role of treatment of asymptomatic individuals. This review presents an overview of current and emerging drug therapies in the rapidly changing area of CLL treatment.

Type of Medium: Online Resource

ISSN: 2052-3815

URL: Article

DOI: 10.17925/OHR.2017.13.01.34

Language: English

Publisher: Touch Medical Media, Ltd.

Publication Date: 2017

In: International Journal of Hematologic Oncology, Future Medicine Ltd, Vol. 4, No. 4 ( 2015-09), p. 143-150

Abstract: Chronic lymphocytic leukemia is a mature B-cell neoplasm in which the interactions between the malignant B cells and tumor microenvironment play a key role in cell survival and growth. B-cell receptor (BCR) is a key survival pathway in chronic lymphocytic leukemia. Following BCR signal trigger, several kinase pathways are activated that promote signal transduction. Ibrutinib is a first-in-class, potent, orally administered covalently binding inhibitor of Bruton's tyrosine kinase that is US FDA approved. Inhibition of Bruton's tyrosine kinase blocks downstream BCR signaling pathways (AKT, ERK) and thus prevents B-cell proliferation. Ibrutinib impairs microenvironment-induced survival of the malignant B cells. Ibrutinib is currently under investigation for both hematologic and solid tumor malignancies.

Type of Medium: Online Resource

ISSN: 2045-1393 , 2045-1407

URL: Article

DOI: 10.2217/ijh.15.15

Language: English

Publisher: Future Medicine Ltd

Publication Date: 2015

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