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  • 1
    Online Resource
    Online Resource
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 5975-5975
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5975-5975
    Abstract: Background: Patients with a single hematological malignancy (SHM) may be unexpectedly diagnosed with a synchronous dual hematological malignancy (SDHM). Management of such patients is challenging and the impact of therapy on the secondary malignancy is often unknown. Methods: We reviewed 3036 patients followed in our center from February 2013 to July 2016. Using WHO 2008 criteria we excluded closely-related diseases (e.g. transformed lymphoma, myeloma arising from monoclonal gammopathy of unknown significance (MGUS), lymphoproliferative disorders with associated paraproteins) and included only clonally unrelated SDHMs. Results: We identified 41 patients with SDHM, a prevalence of 1.35%. Median age was 75 years (range 23-90), with male predominance (26 male, 15 female). All patients were Caucasians except 1 African, and 38/41 were diagnosed locally. Thirteen patients (31.7%) had concomitant solid cancers. Referrals from family practitioners/hospitalists were of two types: 65% with a general diagnosis and 35% with non-specific symptoms requiring work-up. Referrals from specialists (internal medicine or hematology) were more accurate; only asymptomatic secondary diagnoses were missed. SDHMs were diagnosed either incidentally during routine work-up, or because discordant clinical/laboratory findings did not fit a single diagnosis. Three combinations of SDHMs were identified (Table 1). In the Myeloid+Lymphoid group, concomitant MGUS was most frequent. Within the Lymphoid+Lymphoid group, SDHM combinations were random. There were only 3 Myeloid+Myeloid SDHMs. Twenty-nine patients (70.7%) required initiation of therapy for primary malignancy and 12 (29.3%) were on active surveillance. For secondary diagnosis, 29 (70.7%) patients were actively monitored, and 12 (29.3%) needed treatment (9 simultaneously, 3 delayed). At the completion of treatment for primary malignancy, 37 (90.2%) were either in remission or have non-progressing disease, 4 patients progressed. At the time of data cut-off, 34 patients (82.9%) were alive, compared to 87.2% of patients with SHM. Seven patients died, 3 from disease progression, and 4 from unrelated health issues. Our management experience of SDHM is following: - Have low threshold for intensive investigations if there are discordant data - Patients with low-grade/low-acuity SDHM can be managed safely by active surveillance, with early re-evaluation of both diseases if conditions change - If two malignancies require treatment, therapy should be aimed at the more aggressive one - ABVD chemotherapy completely resolved cutaneous T-cell lymphoma lesions - Cladribine, 6 cycles, had no effect on concomitant chronic myelomonocytic leukemia (CMML) - Ruxolitinib either precipitated chronic lymphocytic leukemia from B-cell lymphocytosis or accelerated progression - Hydroxyurea decreased M-spikes in MGUS, regardless of type - Azacitidine given for CMML positively affected mast cell leukemia and was associated with reduction of bone marrow fibrosis, but had no effect on follicular lymphoma - Phlebotomized patients with polycythemia vera may develop profound anemia on chemotherapy. We recommend holding phlebotomies and replacing iron stores intravenously. Temporary therapy with erythropoietin-stimulating agents or red cell transfusions may be needed. Conclusions: SDHMs are not uncommon and require careful investigation if the primary diagnosis is not clear. Myeloid+Lymphoid and Lymphoid+Lymphoid combinations are most common. The high frequency of concomitant solid tumors suggests increased susceptibility to SDHM or impaired immunity. Many second hematological malignancies can be managed by regular monitoring. Active treatment of SDHM requires special considerations. Our recommendations are limited by small patient numbers and a single center. Further studies of SDHM, exploring different cohorts and ethnicities, are needed. Disclosures Nay: Gilead Sciences, Inc.: Honoraria; Janssen: Honoraria, Other: Advisory board; Celgene: Honoraria, Other: Advisory board; Amgen: Other: Advisory board; Lyndbeck: Honoraria; BMS: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1237-1237
    Abstract: Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment option for acute myeloid leukemia (AML) when indicated. Numerous pre-transplant risk scores have been developed to predict post-transplant outcome, utilizing a variety of parameters. The purpose of this single-center study was to retrospectively develop and validate a prognostic score based on known significant pre-transplant variables for outcomes of 747 patients that underwent HCT for AML between 1978 and 2013. Median age of all patients at transplant was 44 years (range 17-71 years), 391 patients (52%) were female. HCT was performed in first complete remission (CR1) for 497 patients (67%) and in second complete remission (CR2) or advanced disease for 250 patients (33%). Donors were related for 538 patients (72%) and unrelated for 209 patients (28%). Peripheral blood stem cells (PBSC) were used as a graft source in 367 patients (49%). Myeloablative conditioning (MAC) was administered to 615 (82%) patients, 132 (18%) received reduced-intensity conditioning (RIC) regimens. HCT was performed over the time periods 1978-1990 (n=139), 1991-1999 (n=192), 2000-2006 (n=183) and 2007-2013 (n=233). Median follow-up of survivors was 90 months. Patients were assigned a combined score based on patient age, disease status and donor status. For disease status CR1, age 〈 45 years and related donors, each parameter received a score 0. For disease status CR2 or advanced stage, age ≥45 and unrelated donors, each parameter received a score 1. Patients demonstrated a cumulative score of 0 (n=197), 1 (n=326), 2 (n=179) or 3 (n=45). All 747 patients were randomized into two groups, a test cohort (n=373) and a validation cohort (n=374). Univariate analysis for the test cohort demonstrated a favorable risk group with score 0 (n=92), an intermediate risk group of score 1-2 (n=255) and an unfavorable risk group with score 3 (n=26) with a 5-year overall survival (OS) of 61%, 35% and 20% respectively (p=0.0001)(Figure). Cumulative incidence of relapse (CIR) demonstrated a marginally significant difference between groups (p=0.05) with 5-year CIR 14%, 28% and 23% respectively. Non-relapse mortality (NRM) was marginally different (p=0.07) with 5-year NRM 27%, 39% and 54% respectively. Multivariable analysis of the test cohort for OS demonstrated that the presented scoring system remained significantly prognostic (p 〈 0.0001) accounting for year of transplant as a continuous variable in the analysis (p=0.001, HR for transplant year 0.97, 95%CI 0.96-0.98). For OS, HR was 2.3 and 4.0 for the intermediate and high risk group respectively compared to favorable risk. For CIR, HR was 2.1 and 1.8 for intermediate and high risk patients respectively (p=0.05). For NRM, HR was 1.5 and 2.8 for intermediate and high risk patients respectively (p=0.01). Analysis of the validation cohort confirmed significant stratification for OS on univariate (p 〈 0.0001, 5-year OS 68%, 36% and 30% for the three risk groups respectively) and multivariable analysis (p 〈 0.0001). For CIR, no significant difference was seen on univariate (p=0.3, 5-year CIR 15%, 23% and 17% respectively) or multivariable analysis (p=0.3). For NRM, the validation cohort confirmed significant stratification between the risk groups on univariate (p 〈 0.0001, 5-year NRM 19%, 42% and 48% respectively) and multivariable analysis (p 〈 0.0001). In the presented study we developed and validated this readily calculable pre-transplant scoring system involving age, CR status and donor type which is highly prognostic for OS and NRM of patients undergoing allogeneic HCT for AML. We also demonstrated that the year transplant was performed over the last three decades had no influence on the prognostic significance of the scoring system. Figure 1 Figure 1. Disclosures Messner: Otsuka Pharmaceuticals Inc: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    American Society for Pharmacology & Experimental Therapeutics (ASPET) ; 2004
    In:  Molecular Pharmacology Vol. 65, No. 3 ( 2004-03), p. 520-527
    In: Molecular Pharmacology, American Society for Pharmacology & Experimental Therapeutics (ASPET), Vol. 65, No. 3 ( 2004-03), p. 520-527
    Type of Medium: Online Resource
    ISSN: 0026-895X , 1521-0111
    Language: English
    Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
    Publication Date: 2004
    detail.hit.zdb_id: 1475030-2
    SSG: 15,3
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  • 4
    In: Molecular and Cellular Biology, Informa UK Limited, Vol. 22, No. 9 ( 2002-05-01), p. 2993-3002
    Type of Medium: Online Resource
    ISSN: 1098-5549
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2002
    detail.hit.zdb_id: 1474919-1
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e19540-e19540
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e19540-e19540
    Abstract: e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m 2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m 2 . A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1179-1179
    Abstract: Late effects occurring post allogeneic hematopoietic cell transplantation (HCT) include the development of secondary malignancies (SM). The purpose of this single-center study was to retrospectively assess the incidence of SM in 2200 patients that consecutively underwent HCT for a variety of hematological conditions between 1970 and 2013, and to investigate parameters associated with occurrence of SM and survival post diagnosis. Median patient age at transplant was 42 years (range 17-71). Graft was bone marrow in 1310 patients (60%), peripheral blood stem cells (PBSC) in 890 patients (40%). Related donors were used in 1624 patients (74%), unrelated in 576 patients (26%). Transplants were performed for acute myeloid leukemia (AML, n=756, 34%), chronic myeloid leukemia (CML, n=486, 22%), acute lymphoblastic leukemia (ALL, n=275, 13%), non-Hodgkin lymphoma (n=174, 8%), myelodysplastic syndrome (n=159, 7%), aplastic anemia (n=128, 6%) and other conditions (n=222, 10%). Conditioning regimen was myeloablative in 1903 patients (87%) and reduced intensity in 297 patients (13%). Concerning total body irradiation (TBI) dose, 556 patients (25%) did not receive TBI, 1060 patients (48%) received 200-500 cGy and 584 patients (27%) received 〉 500 cGy. Median follow-up of survivors was 120 months (range 1-398). SM was observed in 155 patients (7% of total). Of the patients that developed SM, 39 (25% of SM) were with skin malignancy (30 with non-metastatic squamous and basal cell carcinoma), 25 (16%) with gynecological malignancies, 18 (12%) with gastrointestinal, 19 (12%) with hematological, 20 (13%) with oral squamous carcinoma, 14 (9%) with prostate, 6 (4%) with lung, 4 (3%) with thyroid and 10 (6%) with other forms of SM. Excluding patients with non-metastatic squamous and basal cell carcinoma of skin, the remaining 125 patients demonstrated a median time to SM of 99 months (range 1-393). Median time to development of SM was 4, 7 and 12 years for the age groups 〉 55, 41-55 and 〈 41 years of age respectively (p=0.0004). At 5 years post-HCT, 2.5% of patients had developed SM (95%CI 1.9-3.3), at 10 years 3.9% developed SM (95%CI 3.1-4.9) and at 15 years 6.0% of survivors had developed SM (95%CI 4.8-7.3). Analysis was performed for the effect of age at HCT, graft source, donor type, time period transplant was performed, conditioning intensity and TBI dose. In both the univariate and multivariable analysis, none of the aforementioned variables influenced cumulative incidence of SM. Concerning the survival of the 125 patients following diagnosis of SM (excluding non-metastatic squamous and basal cell carcinoma of skin), median follow-up of survivors was 37 months (range 1-344 months), survival at 10 years post-SM was 49% (SE ±6.6%). 25% of patients died of causes related to SM. Univariate analysis demonstrated a significant influence of ECOG score at diagnosis of SM (p 〈 0.0001), while age at SM, coexistence of GvHD at diagnosis, existence of other co-morbidities and time period from HCT to diagnosis of SM did not significantly influence survival. Multivariable analysis demonstrated ECOG score at diagnosis of SM as the only independent predictor of survival post diagnosis, with HR 2.8 for ECOG score 1 and HR 7.0 for ECOG score 2-4 compared to ECOG score 0 (p 〈 0.0001). In conclusion, incidence of SM post-HCT does not seem to be related to dose of TBI or conditioning intensity. Younger patients develop SM significantly later post-HCT, while a higher ECOG score at diagnosis of SM is independently prognostic of poor survival. Disclosures Messner: Otsuka Pharmaceuticals Inc: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    Online Resource
    Online Resource
    SAGE Publications ; 2010
    In:  Clinical Medicine Insights: Cardiology Vol. 4 ( 2010-01), p. CMC.S4755-
    In: Clinical Medicine Insights: Cardiology, SAGE Publications, Vol. 4 ( 2010-01), p. CMC.S4755-
    Abstract: Ventricular tachycardia although not common, can occasionally complicate pregnancy. Its presence may indicate an underlying cardiac structural abnormality, or undiagnosed congenital arrhythmic disease. However, some pregnant patients with ventricular tachycardia have structurally normal hearts. Two cases of ventricular tachycardia in pregnant patients with structurally normal hearts are presented and an approach to diagnosis and management of such patients are discussed.
    Type of Medium: Online Resource
    ISSN: 1179-5468 , 1179-5468
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2575256-X
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  • 8
    Online Resource
    Online Resource
    Dougmar Publishing Group, Inc. ; 2015
    In:  Canadian Journal of General Internal Medicine Vol. 10, No. 3 ( 2015-11-20)
    In: Canadian Journal of General Internal Medicine, Dougmar Publishing Group, Inc., Vol. 10, No. 3 ( 2015-11-20)
    Abstract: Celiac disease (CD) is a common systemic disease, affecting about 1.0% of the population. Classical presentation includes malabsorption syndrome and deficiencies of macro-/micronutrients. Patients with undiagnosed CD may be referred to hematologists with different hematologic issues, including anemia, thrombocytosis, thrombocytopenia, leukopenia, venous thromboembolism, hyposplenism, and IgA deficiency. CD imposes an increased risk of various lymphomas, especially intestinal T- and B-cell lymphomas. Enteropathy-associated T-cell lymphoma (EATL) is a rare and aggressive disease with poor prognosis and often fatal complications. Here we present a case of EATL associated with cavitating mesenteric lymph node syndrome as a first manifestation of undiagnosed CD.
    Type of Medium: Online Resource
    ISSN: 2369-1778 , 1911-1606
    URL: Issue
    Language: Unknown
    Publisher: Dougmar Publishing Group, Inc.
    Publication Date: 2015
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  • 9
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 23, No. 6 ( 2017-06), p. 945-951
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 10
    In: International Journal of Oncology, Spandidos Publications, ( 2005-10-01)
    Type of Medium: Online Resource
    ISSN: 1019-6439 , 1791-2423
    RVK:
    Language: Unknown
    Publisher: Spandidos Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2079608-0
    detail.hit.zdb_id: 1154403-X
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