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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 7039-7039
    Kurzfassung: 7039 Background: HMAs are an accepted frontline therapy for AML patients (pts) who are unfit for intensive induction therapy (IIT), particularly pts with unfavorable cytogenetics and/or p53 mutations. However, little is known about the response of favorable risk AML to HMAs. We previously reported that NPM1 mutated and/or CD34- AML status were predictors of response to HMAs. Here, we evaluated responses to frontline HMAs in AML. Methods: A total of 117 patients with de novo AML diagnosed between 7/2013 and 9/2016 were evaluated based on pt and disease related variables, overall response rate (ORR = CR + CR with incomplete count recovery + hematologic remission (ANC 〉 1000/µL, Hgb 〉 10g/dL, Plts 〉 100,000/µL, & no circulating blasts)), and overall survival (OS). Categorical variables were compared using Fisher’s exact test. Kaplan Meier methods estimated survival outcomes, and log rank tests compared survival between groups. Multivariable analyses were performed using Cox proportional hazards models. Results: 51 pts, considered unfit for IIT, received frontline HMAs. ORR and OS were highest in the ELN favorable risk AML pts (n = 13; ORR = 92%, p = .009; median OS = 17.5 months, p = .022). Among 41 NPM1 mutated pts, 15 received HMAs; and 26 received intensive induction. ORRs were 73% and 84%, respectively (p = .434). No difference was found in OS distributions between the HMA and IIT groups in univariate and multivariate (adjusted for age and FLT3 status) models (p = .329 and .241, respectively). Interestingly, ORR was 100% among 9 HMA-treated pts with NPM1 mutated, CD34-, FLT3/ITD-, cytogenetically normal AML. Conclusions: HMA therapy is highly effective frontline treatment in favorable risk AML pts considered unfit for IIT. Survival results with HMAs in NPM1 mutated AML are comparable to those of fitter pts treated with IIT. In selected favorable risk pts considered unfit for standard induction, HMAs can be a successful bridge to potentially curative therapy, including more intensive therapy or transplant. Cytogenetically normal AML with an isolated NPM1 mutation and CD34- status appears to be exceptionally responsive to frontline treatment with HMAs. Prospective validation of these findings is necessary.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2017
    ZDB Id: 2005181-5
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  • 2
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 16 ( 2019-08-15), p. 5143-5155
    Kurzfassung: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P & lt; 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P & lt; 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or ≥5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P & lt; 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
    Materialart: Online-Ressource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2019
    ZDB Id: 1225457-5
    ZDB Id: 2036787-9
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    In: Blood, American Society of Hematology, Vol. 130, No. 9 ( 2017-08-31), p. 1156-1164
    Kurzfassung: Over the last decade, allogeneic HCT has been increasingly administered in the United States to adults aged 70 and older with hematologic malignancies. Allogeneic transplant outcomes were reasonable; high comorbidity and ablative conditioning regimens were associated with inferior outcomes.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2017
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 7012-7012
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2018
    ZDB Id: 2005181-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2351-2351
    Kurzfassung: BACKGROUND: Multiple myeloma (MM) is the most common hematologic malignancy in the African American (AA) population with an incidence more than 2-3 times higher than Caucasians [Landgren O et al Blood 2006]. In the pre-novel therapy era, SEER data [1975-2008] indicated better survival outcomes for AA patients with MM. However, with the recent advent of novel drugs for treatment of MM, the survival gap for Caucasian patients with MM has closed [Ailawadhi S et al Br J Haematol 2012]. A recent pooled analysis of diagnostic cytogenetics in 292 AA MM patients [Greenberg et al Blood Cancer J 2015] reported on differences in commonly observed baseline cytogenetic abnormalities (CA) between AA and Caucasian MM patients. The large and diverse population of patients with MM at our institution prompted us to examine diagnostic cytogenetics in our MM patients along with other clinical features. PATIENTS & METHODS: The MM database was interrogated for all patients presenting with MM between January 2012 and February 2016. Baseline clinical and pathology variables were compared between the AA and Caucasian cohorts. Continuous variables were compared using nonparametric rank tests, while incidences and proportions (e.g. CAs including t(11;14), t(4;14), t(14;16), t(14:20), amplification 1q21, monosomy13/del13q and del17p) were compared using Fisher's exact tests. RESULTS: A total of 398 patients were identified for the analysis (African Americans n = 168, Caucasian n = 230). The median age of AA MM patients was significantly younger than Caucasian MM patients (median age 63 years vs. 68 years, p 〈 0.0001), with a similar sex distribution. There was no significant difference in the degree of anemia, renal insufficiency, serum LDH levels, bone marrow flow cytometry, bone marrow cellularity or plasmacytosis in the two cohorts. Although there was a trend toward more ISS I amongst Caucasian MM patients, there was no statistical difference in ISS stages (p = 0.126) and no significant difference in R-ISS stage between the cohorts (p = 0.361). There was 72.7% agreement between the ISS and R-ISS staging (88 of 121 evaluable subjects had the same stage by ISS and R-ISS staging criteria), while 27.3% of the patients were upstaged from Stage I or II by ISS criteria to Stage III by R-ISS criteria. Of those upstaged, 19 patients were in the Caucasian cohort and 14 were in the AA cohort. The magnitude of this upstaging was significant when evaluated with a Generalized McNemar's test (p 〈 0.001). Additionally, there was a similar incidence of common FISH abnormalities in the AA cohort compared to the Caucasian cohort [Table 1]. CONCLUSIONS: This is the largest single institution report of FISH data in AA MM patients. Unlike previous reports, we show similar clinical, pathological, and cytogenetic features between AA and Caucasian patients with MM at presentation. It is possible that molecular abnormalities not detectable by FISH in our patient cohort could account for differences in our data and the published literature. Table 1 FISH Abnormalities Table 1. FISH Abnormalities Disclosures Bhutani: Prothena: Research Funding; Takeda Oncology: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Onyx, an Amgen subsidiary: Speakers Bureau. Symanowski:Eli Lilly & Co: Consultancy; Ra Pharma: Consultancy; Caris Life Sciences: Consultancy; Endocyte: Consultancy. Avalos:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Usmani:Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Pharmacyclics: Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Novartis: Speakers Bureau.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2016
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3580-3580
    Kurzfassung: Introduction Access to appropriate healthcare close to home is a national and global problem with huge geographic variation in availability of subspecialized care and specific therapies, as illustrated by hematopoietic cell transplantation rates [Gratwohl, et al. Lancet Hematol, 2015]. Disease-specific physician specialization appears to improve outcomes in hematologic malignancies [Go, et al. Mayo Clin Proc, 2015] . Charlotte is the 2nd largest city in the Southeastern United States and 17th largest in the US, yet subspecialized care in hematologic malignancies including a leukemia unit and hematopoietic cell transplantation (HCT) program were non-existent 3 years ago. The closest HCT program was a 90-minute drive from Charlotte. Many patients lacked the resources or willingness to travel to a transplant center and died of potentially curable diseases. Establishment of a transplantation program, in particular, requires a substantial upfront investment, broad infrastructure and highly specialized interdisciplinary care. Better transplant outcomes have been associated with higher numbers of procedures [Loberiza, et al. Blood, 2005], but programs established over the last decade have struggled to attract adequate numbers of patients to support the required investment. Methods In 2011 Carolinas HealthCare System (CHS), which serves as a healthcare safety net for the region, decided to develop the Levine Cancer Institute as a primary through quaternary referral and treatment center, integrated through more than 12 sites, with a key focus being a program in HCT. The Department of Hematologic Malignancies and Blood Disorders was established in September 2012. We envisioned that the development of specialized care in leukemia, lymphoma, and plasma cell disorders, as well as more complex non-malignant hematologic disorders, would improve the quality of care for patients with those diseases, attract larger volumes of patients, and serve to identify patients appropriate for HCT in a timely manner. A 16 bed hematologic malignancies unit housed in a protected environment was constructed and completed in January 2014. Results Starting with 4 general hematologists, the department has grown over 4 years to include 23 faculty members, 14 of whom provide subspecialized care in hematologic malignancies and HCT. Patient volumes have grown more than six-fold during this time. The HCT Program performed its first transplant in March 2014, with a total of 60 transplants performed in 2014 and 81 in 2015. The HCT Program is on pace to perform over 100 transplants in 2016. The program received FACT accreditation in 2016, a little more than 2 years after the first HCT was performed. The age range of patients undergoing transplantation is from 22 to 76 (median 58) years. Sixty-nine percent of transplants have been autologous and 31% allogeneic, of which 65% were from haploidentical related donors. The proportion of transplants which are allogeneic is steadily increasing. More than 90% of patients who have undergone transplantation were referred through a disease-specific section. Non-relapse mortality (NRM) at 1 year is 1.8% for autologous transplants and 9.4% for allogeneic transplants, with survival rates at 1 year of 95.6% and 80.8% respectively. Notably, there is no difference in NRM (P=0.86), relapse-free survival (P=0.85), or overall survival (P=0.47) between HLA-identical and haploidentical transplant recipients. Conclusions Three years ago, for patients in Charlotte, access to subspecialized care in hematologic malignancies and HCT required significant travel. The development and growth of a program that provides disease-specific care in hematologic malignancies has overcome this barrier and has provided a base for growth of a newly established program in HCT. These developments have elevated the quality of care in hematologic malignancies in the Charlotte area and permit patients to receive appropriate and complex care close to home. Disclosures Gerber: Janssen: Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Usmani:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Novartis: Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Array: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Grunwald:Amgen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Medtronic: Equity Ownership; Janssen: Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees. Ghosh:Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SGN: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Research Funding; TG Therapeutics: Research Funding. Bhutani:Prothena: Research Funding; Takeda Oncology: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Onyx, an Amgen subsidiary: Speakers Bureau. Symanowski:Endocyte: Consultancy; Eli Lilly & Co: Consultancy; Ra Pharma: Consultancy; Caris Life Sciences: Consultancy. Raghavan:Gerson Lehrman: Consultancy; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees. Avalos:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2016
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
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  • 7
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 7558-7558
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 7558-7558
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2018
    ZDB Id: 2005181-5
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  • 8
    Online-Ressource
    Online-Ressource
    American Society of Hematology ; 2019
    In:  Hematology Vol. 2019, No. 1 ( 2019-12-6), p. 9-16
    In: Hematology, American Society of Hematology, Vol. 2019, No. 1 ( 2019-12-6), p. 9-16
    Kurzfassung: The landscape of acute lymphoblastic leukemia (ALL) has evolved significantly over the last few years. Identification of specific recurrent genetic alterations and of minimal residual disease (MRD) guides prognostic classification and management. Novel agents (eg, blinatumomab) have demonstrated encouraging results in relapsed/refractory (R/R) and MRD+ patients and are currently incorporated into upfront treatment in specific settings. Other new strategies include the incorporation of tyrosine kinase inhibitor-based therapy for patients with Philadelphia chromosome–like ALL and the use of DOT inhibitors and bcl-2/bcl-xl inhibitors in R/R disease. These innovations promise to improve management and outcome in this disease.
    Materialart: Online-Ressource
    ISSN: 1520-4391 , 1520-4383
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2019
    ZDB Id: 2084287-9
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  • 9
    In: Cancer, Wiley, Vol. 124, No. 12 ( 2018-06-15), p. 2541-2551
    Kurzfassung: Early treatment failure is a predictor of poor outcomes for follicular lymphoma patients with a 5‐year survival rate of only 50%. Hematopoietic stem cell transplantation has not been specifically assessed in this population. This Center for International Blood and Marrow Transplant Research analysis has found that hematopoietic stem cell transplantation is associated with a 70% long‐term survival rate for follicular lymphoma patients with early treatment failure, and it supports transplantation as an excellent treatment option. See also pages 2484‐7.
    Materialart: Online-Ressource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2018
    ZDB Id: 1479932-7
    ZDB Id: 2599218-1
    ZDB Id: 2594979-2
    ZDB Id: 1429-1
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 10
    In: American Journal of Hematology, Wiley, Vol. 90, No. 2 ( 2015-02), p. 144-148
    Kurzfassung: Graft‐versus‐host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (HCT) despite current prophylaxis. Methotrexate (MTX) with a calcineurin inhibitor (CNI) is the current standard, however, has several toxicities. Mycophenolate mofetil (MMF) is frequently used in reduced‐intensity HCT, but data in myeloablative transplants is limited. We thus retrospectively identified 241 patients who underwent myeloablative HCT from an HLA‐identical sibling donor; 174 patients received cyclosporine (CSA) + MMF and 67 received CSA+MTX. Patients receiving MMF + CSA had rapid neutrophil (median 11 vs. 19 days with MTX+CSA), and platelet recovery (median 19 vs. 25 days), lower incidence of severe mucositis by OMAS (19% vs. 53%), and shorter length of hospital stay (median 25 vs. 36 days) ( P   〈  0.001 for all comparisons). There were no significant differences in incidence of grade 2–4 (MMF+CSA 37% vs. MTX+CSA 39%) or 3–4 acute GVHD (17% vs. 12%), chronic GVHD (46% vs. 56%), relapse (28% vs. 27%), non‐relapse mortality (20% vs. 27%), or overall survival (47% vs. 44%) ( P  = NS for all). However, in multivariable analysis, the use of MMF+CSA was associated with an increased risk of severe grade 3–4 acute GVHD (HR 2.92, 95% CI 1.2–7.15, P  = 0.019). There were no differences between the two regimens in multivariable analyses for other survival outcomes. This analysis demonstrates that the use of MMF in myeloablative sibling donor transplantation is well tolerated. However, there may be an increased risk of severe GVHD with MMF+CSA compared to MTX+CSA. Further studies evaluating optimal dosing strategies are needed. Am. J. Hematol. 90:144–148, 2015. © 2014 Wiley Periodicals, Inc.
    Materialart: Online-Ressource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2015
    ZDB Id: 1492749-4
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