Vasculitis Associated with Large Granular Lymphocytes Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5109-5109
Author(s):  
Alexandra Audemard ◽  
Thierry Lamy ◽  
Benoit Bareau ◽  
Felipe Suarez ◽  
Margaret Macro ◽  
...  
Keyword(s):  
Nk Cell ◽  
Conflicts Of Interest ◽  
Remission Rate ◽  
Acute Infection ◽  
Response To Therapy ◽  
Laboratory Findings ◽  
Peripheral Neuritis ◽  
The Mean ◽  
Lgl Leukemia

Abstract Abstract 5109 Background: Large granular leukemia (LGL) leukemia is derived from either T-cell or NK-cell lineages. Clinical presentation of LGL leukemia is dominated by recurrent infections associated with neutropenia, anemia, splenomegaly and auto-immune diseases. The association of vasculitis and LGL leukemia has been rarely reported and investigated. Objective: To improve knowledge about this association, we retrospectively describe the clinical and biological characteristics of patients, their response to therapy and their prognosis. Methods: We performed a retrospective study based on 229 patients included in the French national LGL proliferation registry and a national mailing survey to 1350 internists in order to collect medical characteristics of patients displaying both vasculitis and LGL leukemia. We retrospectively collected medical charts from 11 patients between September 1999 and February 2012. Medical history, hematologic laboratory tests and response to therapy were compiled at first presentation of LGL leukemia associated vasculitis (LAV) and at each visit. Results: At the time of diagnosis of LGL leukemia the mean age was 60. 3 years (range, 28–74 years). They were 9 women and two men. The mean of follow up was 45 months (range, 1–108). The main LGL lineage was T-LGL (10 patients, 91%) and only one NK-LGL was identified. Hematological laboratory findings revealed that 5 patients (45%) patients presented hyperlymphocytosis. The mean absolute circulating LGL count for the series was 1. 10 9/L (range, 0. 45–4. 59 x. 10 9/L). Three patient (27%) had neutropenia (<1. 5 x. 109/L), no one had thrombocytopenia. Anemia was detected in 4 patients (36%). The most frequently observed vasculitis was cryoglobulinemia (n=5). Three patients presented cutaneous vasculitis. Two patients had ANCA negative microscopic polyangiitis and one patient presented giant cell arteritis. Clinical features were dominated by skin localization e. g. purpura (91%), arthralgia (37%), peripheral neuritis (27%) and renal glomerulonephritis (18%). Leucocytoclastic vasculitis was histologically demonstrated in 6 cases. Ten vasculitis were treated: the most delivered treatment was the association of cyclophosphamide-corticosteroid (n=3), followed to methotrexate–corticoisteroid (n=2), chlorambucil-corticosteroid (n=2) and corticosteroid alone (n=2). One patient received azathioprine and corticosteroid. The complete remission rate was high 80% and a minority of them presented vasculitis relapse (27%). Three patients (27%) died: one related to LGL leukemia (acute infection) and the 2 others related to heart failure due to vasculitis. Conclusion: Association of LGL leukemia and vasculitis is rare but not fortuitous. Based on this retrospective analysis, it seems that LAV preferentially affect female patients, with a low LGL count. LAV present with frequent cutaneous involvement and have a good response to therapy. Pathophysiological link between LGL leukemia and vasculitis remains to be investigated. Disclosures: No relevant conflicts of interest to declare.

Hodgkin Lymphoma Outcomes: Can We Expect Ethnic Parity in a Hispanic Prevalent Population?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4056-4056
Author(s):  
Michelle Janania Martinez ◽  
Prathibha Surapaneni ◽  
Juan F Garza ◽  
Tyler W Snedden ◽  
Snegha Ananth ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Relative Survival ◽  
Complete Response ◽  
Statistical Testing ◽  
P Value ◽  
Hispanic Population ◽  
Significant Difference ◽  
The Mean

BACKGROUND It is estimated that 8110 persons will be diagnosed with Hodgkin Lymphoma (HL) in the US during 2019, but the advent of new treatment options has increased the cure rate to at least 80%. It has been reported that the rates of HL are lower in the adolescent and young adult (AYA) Hispanic population but significantly higher in the Hispanic population older than 65. The relative survival estimates are stated to be similar between AYA Hispanics (HI) and non-Hispanics (NH) but for ages 65-84, HI have a significantly higher mortality rate. Pediatric studies have suggested that ethnicity plays a role in outcomes in patients with HL but there is limited data in the adult population. There is an unmet need in the field, where dossiers on underrepresented ethnic minorities need to be carefully considered and compared to existing data. Therefore, our study aims to compare survival outcomes in Hispanics vs Non-Hispanics with HL, who were treated at the only NCI designated cancer center of South Texas. To our knowledge this is the largest cohort of HL patients from a single academic institution that serves primarily Hispanics. METHODS We located and retrospectively analyzed a total of 616 patients with diagnosis of Lymphoma (HL and NHL) by International Classification of Diseases (ICD) codes and identified 116 cases of HL; all the patients received care at UT Health San Antonio, between 2008-2018. Key variables for each patient included age, gender, race/ethnicity, comorbidities, insurance status, stage, BM and extranodal involvement, treatment received, outcome at 3 and 5 years and vitality status in 2018. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. The significance of variation in the mean with disease category was assessed with one way ANOVA and the significance of associations between categorical outcomes was assessed with Pearson's Chi Square or Fisher's Exact test as appropriate. Multivariate logistic regression was used to model binary outcomes in terms of covariates and indicators of disease. All statistical testing was two-sided with a significance level of 5%. R1 was used throughout. The study was approved by the local Institutional Review Board. The findings will be available to patients, funders and medical community through traditional publishing and social media. RESULTS We identified 116 patients with HL, of which 73 were HI (63%), 43 NH (36%) and 1 not specified (1%). In regard to race, 92% identified as Caucasian, 4% as African American, 3% other and 1% Asian. The median age at diagnosis was 37.4, (SD 15.13). There were 49 females (42%) and 67 males (58%). The most common funding source was commercial insurance N=54 (47%), followed by a hospital payment plan N=30 (26%), Medicare N=16 (14%), unfunded N=13 (11%) and Medicaid N=3 (2%). Most prevalent co-morbidities were HTN N=28 (24%) and diabetes mellitus N= 23(20%); 50% of patients had no co-morbidities (N=63).At diagnosis ECOG of 0-1 was seen in 108 patients (93%); 8 were Stage I (7%), 39 stage II (33%), 32 stage III (28%), and 37 stage IV (32%). EBV was positive in 26 patients (22%). There were 15 patients that were HIV positive (13%), 54% with CD4 count <200, and 12 (75%) on antiretroviral therapy at diagnosis. Median PFS was 853.85 days (SD 912.92). We excluded patients who were lost to follow up or had not reached 3/5 years. At 3 year follow up there was: complete response in 37 HI (74%) vs 22 NH (92%); disease progression in 8 (16%) vs 0 (0%); death in 5 (10%) vs 2 (8%), respectively (p-value= 0.094). At 5 year follow up there was: complete response in 30 HI (77%) vs 17 NH (90%); progressive disease in 2 (5%) vs 0 (0); death 7 (18%) vs 2 (11%), respectively (p-value = 0.619). At the end of 2018, 41 HI (84%) were alive compared to 22 NH (88%) [p-value 0.74]. CONCLUSION Within the limitations of sample size, our study demonstrates that in the prevalently Hispanic population of our institution, HI patients with HL have no statistically significant difference in outcome when compared to NH patients. Disclosures No relevant conflicts of interest to declare.

Clinical Heterogeneity Of Autoimmune Hemolytic Anemia: A 35-Years Retrospective Study Of 157 Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3428-3428
Author(s):  
Wilma Barcellini ◽  
Bruno Fattizzo ◽  
Tommaso Radice ◽  
Anna Zaninoni ◽  
Nicoletta Revelli ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Acute Infection ◽  
Thermal Characteristics ◽  
Response Rates ◽  
Cytotoxic Drugs ◽  
Clinical Heterogeneity ◽  
Life Threatening

Abstract The clinical presentation of autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening forms. The aim of this study was to correlate the clinical and serological characteristics of the disease, usually classified as warm (WAIHA), cold (CHD), and mixed, based on the thermal and isotype characteristics of the anti-RBC antibody (IgG, IgM or both, respectively). One-hundred fifty seven AIHA patients (61 M and 96 F, median age 57, range 5-95) referred to our institution from 1978 to September 2012 were investigated. They had been followed-up for a median of 26 months (range 12-271), and 50% were still in follow-up. As regards the thermal characteristics 40% of cases were WAIHA, 32% CHD, 19% mixed forms and 9% atypical (12 DAT negative and 1 DAT positive for IgA only). Considering the severity of anemia at onset 33% of cases had Hb levels<6 g/dl, 34% Hb 6-8 g/dL, 18% Hb 8-10 g/dL, and 15% Hb>10 g/dL. The most severe AIHA cases were mainly mixed (18/30, 60% p=0.001) and atypical (6/13, 46%) forms, whereas only a small fraction of CHD was characterized by a severe onset (8/51, 16% p=0.002). Reticulocytopenia (<100.000 mmc) was more frequently observed in cases with severe onset (14/52, 27%), possibly contributing to the clinical picture. Eleven patients experienced an acute event at the onset of hemolysis and the majority of them (7/11, 63% ) were WAIHA; we recorded 4 deep venous thrombosis (with 2 subsequent pulmonary embolisms), 1 disseminated intravascular coagulation, 3 cardiac ischemic events, 2 acute renal failure and 4 acute infection (3 pneumonias and 1 sepsis); 18 patients died because of AIHA during the follow up. As regard therapy, we considered steroids, splenectomy, cytotoxic drugs and rituximab: 45% of cases (mostly WAIHA) were treated with steroids only, 23% with 2 lines, 10% with 3, and 6% with 4 or more lines; splenectomy was performed in 20 cases, mostly mixed and severe forms (p=0.001); 23 patients were treated with various cytotoxic drugs, and 33 with rituximab (the latter was more frequently administered in clinically severe cases, and in mixed and atypical forms, p=0.009). On the whole, the most severe patients were those who underwent 3 or more lines of therapy, compared with the other cases (14/52 versus 11/105, p=0.015). Finally, 16% of cases have never been treated, mostly CHD with mild anemia. Transfusions were performed in 65 cases, plasma-exchange in 3 (all with Hb<6 g/dL), and erythropoietin administered in 6 cases. Of note, the presence of an Hb value lower than 6 g/dL at onset was a risk factor for the requirement of 3 or more lines of therapy (odds ratio 3.148, CI 95% 1.312-7.552). Response rates to steroid therapy were similar in warm, cold, mixed and atypical AIHAs (on average 70%). Responses to rituximab were similar in cold and other AIHA forms (70-80%). Splenectomy, was ineffective in the 2 CHD who underwent surgery, whereas response rates were 63% in WAIHA and 80% in mixed and atypical cases. In conclusion, AIHAs showed a marked clinical heterogeneity, 1/3 of cases with a severe onset and with life threatening complications. These cases are frequently mixed or atypical forms and refractory to different therapies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals the Effects of Deferasirox on Iron in Pituitary, Pancreas and Thyroid Glands: An Observational Case-Control Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4892-4892
Author(s):  
Sule Unal ◽  
Munevver Bas ◽  
Tuncay Hazirolan ◽  
A. Murat Tuncer ◽  
Mualla Cetin ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Iron Accumulation ◽  
Iron Chelators ◽  
Time Interval ◽  
Iron Loading ◽  
Thyroid Glands ◽  
The Mean

Abstract In the absence of adequate chelation therapy, cardiomyopathy caused by iron overload is the leading cause of death in patients with β-thalassemia major (BTM). Additionally, more than half of the adult patients with BTM suffer from hypogonadism (HG), osteoporosis, diabetes mellitus (DM) or hypothyroidism. The use of iron chelators is the mainstay of treatment in patients with BTM to ameliorate these complications. In this study, we aimed to compare the chelation effects of deferasirox (DFX) and other iron chelators on iron in heart, liver, in addition to pituitary, pancreas and thyroid glands. The study included a total of 37 patients with BTM, who were on the same iron chelator for at least 1 year of duration and above 7 years of age. All of the patients were on iron chelation therapies with either monotherapy with DFX (n=29), desferrioxamine (n=4), deferiprone (n=1) or combination therapy of desferrioxamine and deferiprone (n=3). The mean dose of DFX was 30.8 ± 6.3 mg/kg/day (20-40), the mean dose of desferrioxamine 43.1 ± 5.3 mg/kg/day (39-50) and mean dose of deferiprone was 73.26 ± 9.45 mg/kg/day (70-90). All of the patients were compliant to chelation treatment. Cardiac T2*, hepatic T2*, thyroid T2 and R2, pituitary T2 and R2, pancreas T2* and R2* MRI were ordered twice to the patients in order to measure the accumulation of iron. The median time interval between the two MRI was 6 months (range 6-11 months). The effect of DFX (n=29) on iron measurements in different organs were compared to the effects of other chelators group (OCG) (n=8). The mean age of patients participating in the study was 20.8 ± 6.3 years (7.1-36.8). Of the study group, 7.1% of the patients had DM, 8.1% had hypothyroidism and 13.5% had HG at enrollment. According to our previous study for the cut-off value determinations for iron accumulation in BTM with comparison to healthy controls (data unpublished), all of the patients in both groups were found to have pituitary iron accumulation at initial MRI. The changes in iron measures in various organs were summarized in Table 1, indicating a decrease in cardiac, pituitary and pancreas iron loading in both drug groups in follow-up MRI’s (p>0.05). On the other hand δ Liver T2* was negative direction indicating a decrease in hepatic iron loading in DFX group, wheras positive in OCG indicating an increase in follow-up, although insignificant (Table 1, p=0.9). In both groups iron loading in thyroid was found to increase in follow-up and there was no difference between drug groups (Table 1). In conclusion, DFX is as effective as other drugs in chelation of iron from cardiac, hepatic, pituitary, pancreas and thyroid. The increase in iron in thyroid gland during follow-up in both groups may indicate that iron chelation may not be as efficient in thyroid as it is in other organs. Although, all patients had pituitary iron accumulation, only 13.5% were found to have HG, indicating that patients become symptomatic only occur after a threshold of accumulation was achieved. Our study is initiative for the measurements of iron accumulation with MRI in thyroid. Table 1. δT2* and δR2 change values between first and second MRI assessments Chelation type Mean±SD Median Range p δ Liver T2 * a (ms) Deferasirox -0.06 -8.5-7.20 0.90 Other chelators 0.79 -0.98-4.40 δ Cardiac T2 * b (ms) Deferasirox -3.83±9.5 0.88 Other chelators -3.2±8.82 δ Pituitary T2 b (ms) Deferasirox -0.7±11.3 0.09 Other chelators -1.4±6.4 δ Pituitary R2 a (Hz) Deferasirox 0.10 -6,20-3,10 0.25 Other chelators 0.20 -4,60-1,30 δ Thyroid R2 a (Hz) Deferasirox -1.4 -6,1-12,7 0.06 Other chelators -0.1 -3,80-8,1 δ Thyroid T2 a (ms) Deferasirox 4.8 -59,8-14,6 0.08 Other chelators 0.4 -20,6-20,1 δ Pancreas T2* b (ms) Deferasirox -7.46±21.6 0.99 Other chelators -7.52±9.63 δ Pancreas R2 * b (Hz) Deferasirox 9.24±45.23 0.11 Other chelators 56.4±73.3 SD: Standard Deviation; aNon-parametric variable, median values were provided; bParametric variables, mean±SD were provided. Disclosures No relevant conflicts of interest to declare.

Characteristics and Outcomes of Autoimmune Hepatitis from a Tertiary Paediatric Centre, Cape Town, South Africa

2020 ◽  
Vol 66 (4) ◽  
pp. 448-457
Author(s):  
Sawsan Yassin ◽  
Ronalda De Lacy ◽  
Komala Pillay ◽  
Elizabeth Goddard
Keyword(s):  
South Africa ◽  
Autoimmune Hepatitis ◽  
Remission Rate ◽  
Significant Risk ◽  
Red Cross ◽  
Unfavourable Outcome ◽  
Ethical Approval ◽  
Autoimmune Sclerosing Cholangitis ◽  
The Mean

Abstract Objectives To describe the clinical characteristics, biochemical and histological features, outcomes and predictors of prognosis of children with autoimmune hepatitis (AIH) from a paediatric centre in South Africa. Methods Thirty-nine children diagnosed with AIH at Red Cross War Memorial Children’s Hospital between 2005 and 2015 were included. Relevant patient’s data were retrieved from the hospital’s medical records and database. Liver biopsy slides were reviewed. Ethical approval was obtained. Data were analysed using SPSS. Results Females were 29 (74%). Mean age at presentation was 7.27 ± 3.35 years and the mean follow-up was 4.5 ± 2.4 years. Jaundice was present in 97% of patients at presentation. An acute presentation was observed in 26 (67%) even though cirrhosis was detected in 22 (56%). Autoantibody screening was completed in 35 patients, 20 (57%) were AIH-1, 1 (3%) was AIH-2 and 14 (40%) were seronegative AIH. Of the 25 patients who underwent magnetic resonance cholangiography 17 (68%) had associated autoimmune sclerosing cholangitis. The remission rate was 79%. However, 11 children relapsed later. One child required liver transplantation and one demised. Seronegative and seropositive patients have comparable characteristics and outcomes. While a higher alanine transaminase (ALT) level at presentation is a significant predictor of remission, a lower ALT level and cirrhosis are significant risk factors for unfavourable outcome. Overall survival rate was 97%. Conclusion AIH responds well to therapy with excellent survival. Hence, it should be considered in any child presenting with viral screen negative hepatitis and start therapy timeously to prevent disease progression.

The Role of Her2/Neu in ALL: Long Term Clinical Follow-up of Surface-Positive Patients and Induction of NK Cell ADCC by Trastuzumab in Vitro

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1421-1421
Author(s):  
Sebastian P. Haen ◽  
Benjamin J Schmiedel ◽  
Nora Roth ◽  
Christoph Faul ◽  
Robert Möhle ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Additional Risk Factor ◽  
Cytokine Release ◽  
Breast Cancer Patients ◽  
Time To Relapse

Abstract Abstract 1421 In about one third of patients, acute lymphoblastic leukemia (ALL) cells express Her2/neu (p185Her-2). In epithelial malignancies Her2/neu contributes to oncogenic transformation and metastatic potential, and overexpression often is associated with poor prognosis. Previous reports also suggested an inferior prognosis in patients with Her2/neu-positive ALL, but as of now no study has performed survival analyses. In breast cancer patients, targeting of Her2/neu with the monoclonal antibody Trastuzumab results in improved disease outcome, and induction of antibody dependent cellular cytotoxicity (ADCC) and cytokine release of NK cells contributes to the same. Most recently, application of Trastuzumab in patients with relapsed or refractory ALL was shown to yield promising results, but the mechanisms by which Trastuzumab mediates its efficacy have not been studied so far. Here, we studied patient records and flow cytometry data on Her2/neu expression of patients treated for ALL at our hospital between 2000 and 2011 and determined the effect of Trastuzumab and/or Rituximab on NK cell reactivity against ALL blasts in vitro. In 57 patients (37 men, 20 women, median age at diagnosis 42 years, range 17–83 years) data on Her2/neu expression were available. Her2/neu expression was detected in 15/57 patients (26%). Clinical follow up was assessed for all 57 patients. Median follow-up was 44 months (range 0.5–356 months) until death or last follow-up visit. Overall, 60% of the patients had died at the end of follow-up (25 of 42 Her2/neu-negative and 9 of 15 Her2/neu-positive patients, respectively). Median survival times were 43 (Her2/neu-negative, range 0.5–356 months) and 41 months (Her2/neu-positive, range 3.5–138 months; p = 0.81. Kaplan Meyer regression analysis). Also, median time to relapse was comparable in both groups (22.5 months vs. 15.5 months; p = 0.77). In functional analyses with NK cells, incubation of Her2/neu-positive CD20-positive ALL blasts with Trastuzumab or Rituximab comparably induced ADCC and cytokine release of NK cells. Only minor additional effects were observed upon combined application of both antibodies. When blasts from Her2/neu-negative ALL patients were employed (phentotype CD20-positive Her2/neu-negative or CD20-negative Her2/neu-negative), no effect of Trastuzumab was observed, and Rituximab exerted effects solely with blasts from CD20-positive ALL patients. Taken together, in our patient cohort Her2/neu expression on ALL blasts was not associated with time to relapse or overall survival and thus did not appear to be an additional risk factor. Rather, Her2/neu is a promising target for antibody therapy, especially in patients with Her2/neu-positive CD20-negative ALL, as treatment with Trastuzumab is suitable to induce ADCC and cytokine production of NK cells also against Her2/neu-positive CD20-negative ALL blasts. Disclosures: No relevant conflicts of interest to declare.

Association Of Stringed Response and Immunoparesis Normalization After Bortezomib-Based Therapy Is Related To Better Outcomes In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5354-5354
Author(s):  
Marcio M Andrade Sr. ◽  
Ilda Murillo-Florez ◽  
Anel Montes-Limon ◽  
Beatriz de Rueda ◽  
Jose-Maria Grasa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
Retrospective Chart Review ◽  
Standard Of Care ◽  
Complete Response ◽  
Response To Therapy ◽  
First Line ◽  
Female Ratio

Abstract Background Proteasoma inhibitors have proven to be one of the major advances on multiple myeloma (MM) therapy. Their principal effect in growth inhibition of MM cells is achieved not only through the inhibition of proteasomes but also by preventing the adhesion of myeloma cells to stromal cells, induction of cytokines by the microenvironment, decrease angiogenic activity and a direct apoptotic effect on MM cells. Actually it is part of the first-line standard of care therapy for patients with MM. On the other hand, multiple strategies have been developed for trying to predict response or improve the assessment of response and follow-up of MM patients. Currently, the International Myeloma Working Group (IMWG) criteria of response include immunophenotype and immunoparesis analysis. The HevyLiteTM and FreeLiteTM assays (The Binding Site Ltd. Birminghan. UK) permit a separate quantification of the amount of kappa- and lambda-bound to a given immunoglobulin (HLC) and the free light chains kappa or lambda amount quantification (FLC), both being excellent tools for immunoparesis assessment. Aims To analyze the usefulness of immunoparesis analysis by HevyLiteTM and FreeliteTM in patients who receive bortezomib-based therapy in our institution. Patients and Methods A retrospective chart review was performed including the patients diagnosed with secretor IgA or IgG MM who received therapy with bortezomib either at relapse or as first-line therapy. General clinical characteristics, therapy schedules, number of cycles, response to therapy according IMWG criteria and relapse were recorded. For the analysis, only patients with at least 4 cycles of bortezomib based regimen and HLC and/or FLC analysis performed between 4-12 weeks after complete therapy were included. Period of study: June 2004 to April 2013. Results At the end of study a total of 67 MM patients had received bortezomib-based therapy, 63 of them completed 4 or more cycles and were included in the analysis. Male/Female ratio: 31/32, mean age: 66.9 years old (46-81), therapeutic schedules were: bortezomib-prednisone: 3 (4.7%), bortezomib-dexametasone: 33 (51.6%), bortezomib-melfalan-prednisone: 18 (28.1%), bortezomib-dexametasone-lenalidomide: 8 (12.5%) and bortezomib-talidomide-dexametasone: 1 (1.6%). 55% of patients received at least 6 cycles of therapy. Immunoglobulin Myeloma subtype: IgAL: 13 (20.4%) patients, IgAK: 10 (15.6%) patients, IgGK: 32 (50.8%) patients and IgGL: 8 (14.1%) patients. A total of 46 (73%) patients showed an abnormal HLC ratio at diagnosis and 48 (76,2%) had immunoparesis before therapy; a total of 47 (74.6%) registered an abnormal FLC ratio at diagnosis. The response to therapy was: 15 (23.8%) of cases achieved a stringent complete response (SR), 3 (4.8%) a very good partial response (VGPR), 36 (57.1%) obtained a partial response (PR) and 9 (14.3%) patients had not-response/progressive-disease. At the time of post-therapy evaluation, 26 (37%) of patients had normalized FLC-ratio, 15 (23.8%) maintain the SR, 1 (1,6%) patient in VGPR and 5 (11.1%) in PR and 1 (1.6%) of non-responder patients. Normalization of HLC-ratio was only observed in patients with SR and VGPR: 13 (20.6%). Regarding the immunoparesis analysis, only 15 (23.8%) of patients with immunoparesis recovered the immune restitution (IR) at the end of therapy, of which 8 (11.7%) were SR patients, 2 VGPR and 5 PR patients. At the end of the study 47(71.4%) patients relapsed, 5 (11.11%) are on maintenance therapy and 11(17.4%) after a median follow-up of 29 months (9-94) without therapy not-relapsed; the association of SR with IR was related to a less tendency to relapse and need of therapy, 7/8 patients who achieved this status are not-relapsed. Conclusion In our cohort, patients who achieved a SR with a normalization of immunoparesis shows a clear tendency to less incidence of relapse; probably reflecting a better response with not only an undetectable monoclonal protein but also the recovery of the immune function. Even in small cohorts, the immunoparesis recovery analysis through HLC quantifications seems to be an useful tool to determine a new level of response. More investigations on this field are warranted. This work has been partially supported by a grant from Fundación para el Estudio de la Hematología y hemoterapia en Aragón (FEHHA) Disclosures: No relevant conflicts of interest to declare.

VEGF, VEGFR2 and GSTM1 polymorphisms in Outcome of Multiple Myeloma Patients in the Thalidomide Era

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4457-4457
Author(s):  
Leisa Lopes-Aguiar ◽  
Marcia Torresan Delamain ◽  
Angelo Borsarelli Carvalho Brito ◽  
Gustavo Jacob Lourenço ◽  
Ericka Francislaine Dias Costa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Response To Therapy ◽  
Patient Choice ◽  
Antiangiogenic Agents ◽  
Wild Type Allele ◽  
Wild Type ◽  
Pairwise Linkage Disequilibrium ◽  
Type Allele

Abstract Introduction: Angiogenesis (AG) abnormalities are crucial in pathogenesis of multiple myeloma (MM), and give support to treat patients with antiangiogenic agents. However, patients with similar clinicopathological aspects may present distinct outcome under AG inhibitors treatment. Single nucleotide polymorphisms (SNPs) in genes involved in blood vessels formation may constitute a plausible explanation for this finding. The wild-type alleles of VEGF c.-2595C>A (rs699947), c.-1154G>A (rs1570360), c.-634G>C (rs2010963), c.*237C>T (rs3025039), VEGFR2 c.-906T>C (rs2071559) and c.889G>A SNPs (rs2305948) SNPs, and GSTM1 and GSTT1 genes determine higher production, transcriptional activity, binding efficiency or best-characterized regulator of VEGF. This study aimed to investigate the roles of VEGF c.-2595C>A, c.-1154G>A, c.-634G>C, c.*237C>T, VEGFR2 c.-906T>C, c.889G>A SNPs, and GSTM1 and GSTT1 genes in outcome of MM patients treated with thalidomide-based regimens. Patients and methods: The study comprised 102 MM patients diagnosed at the Haematology and Haemotherapy Centre of University of Campinas between June 2005 and June 2013. The tumor was diagnosed by standard criteriaand staged by International Staging System. Therapeutic regimens consisted in thalidomide combined with steroids and chemotherapy, followed or not by autologous steam cell transplantation (ASCT). Response was evaluated at the end of treatment using the International Myeloma Working Group guidelines. The follow-up of patients was performed with hematological, biochemical, and immunological exams. The end of the study was February 2016. Genotypes of VEGF, VEGFR2 SNPs, and GSTM1 and GSTT1 genes were analyzed in genomic DNA by polymerase chain reaction based methods. The pairwise linkage disequilibrium (LD) was performed to ensure that markers were appropriate for inclusion in the VEGF and VEGFR2 haplotype estimates. The chi-square test and logistic regression model were used to identify variables influencing response to treatment. The Kaplan-Meier method, log-rank test and Cox hazards models served to assess the associations between event-free survival (EFS) and overall survival (OS). Results: Near half of patients enrolled in this study were male, and most of them were caucasians and with tumor at stages II or III. ASCT was performed after chemotherapy in near 40% of patients. LDs between VEGF and VEGFR2 SNPs were seen in study, and common haplotypes (frequency >1%) of the genes were included in further analyses. Patients with the wild-type allele of VEGF c.-2595C>A alone or plus the wild-type allele of VEGFR2 c.-906T>C SNPs, and the CGGC haplotype of all respective VEGF SNPs had 3.55, 9.91, and 3.86 more chances of achieving better response to therapy than others. The median follow-up time of 102 MM patients enrolled in the study was 43 months (range: 1-88). The estimated probabilities of 60-months EFS and OS were 24.5% and 48.1%, respectively. At 60 months of follow-up, patients with VEGFR2 c.889GG, VEGF c.-634GG plus VEGFR2 c.889GG, and VEGFR2 c.889GGplus GSTM1 present genotypes had 2.62, 2.64, and 2.80 more chances of presenting disease relapse or progression, and 2.21, 4.88, and 4.23 more chances of evolving to death in multivariate analysis, respectively. Conclusion: Our data present, for the first time, a preliminary evidence that VEGF c.-2595C>A, c.-1154G>A, c.-634G>C, c.*237C>T, VEGFR2 c.-906T>C, c.889G>A SNPs, and GSTM1 gene alter outcome of MM patients treated with thalidomide-based regimens. If these findings could be confirmed in multi-center studies with larger sample size, this might constitute a promise in assisting optimal patient choice for treatment with angiogenic agents. Financial support: São Paulo Research Foundation (FAPESP). Disclosures No relevant conflicts of interest to declare.

scholarly journals Preliminary Outcomes of the Cementless UNITED Hip System for primary Total Hip Arthroplasty at a Minimum Two-year Follow-up

2020 ◽  
Author(s):  
Fernando Diaz Dilernia ◽  
Agustin Garcia-Mansilla ◽  
Agustin Albani-Forneris ◽  
Pablo Slullitel ◽  
Gerardo Zanotti ◽  
...  
Keyword(s):  
Total Hip Arthroplasty ◽  
Hip Arthroplasty ◽  
Acute Infection ◽  
Periprosthetic Femoral Fracture ◽  
Consecutive Series ◽  
Total Hip ◽  
Implant Retention ◽  
The Mean ◽  
Primary Total Hip Arthroplasty

Abstract Introduction: This study aimed to report the initial results of the cementless UNITED hip system in primary total hip arthroplasty (THA) with a minimum follow-up of 2 years. Methods We retrospectively studied a consecutive series of 203 cementless THAs in 180 patients operated between 2015–2017. We included 89 female and 91 male patients with a mean age of 67 (28 to 89) years. The mean follow-up was 40 (29 to 62) months. Clinical outcome scores and radiographs were measured. Survival was calculated defining failure as the need for any further femoral or acetabular revision, irrespective of the reason. Results No femoral component loosening was detected. One patient had a Vancouver-B1 intraoperative periprosthetic femoral fracture treated with implant retention and cerclage wires. Two acetabular components were revised for aseptic loosening. Three patients suffered an acute infection treated with debridement, antibiotics, and implant retention. The mean Merle d'Aubigné et Postel scores improved from 13 (4 to 16) points preoperatively to 17 (12 to 18) points at the latest follow-up (p < 0.001). At a mean time of 40 months of follow-up, the survival was 99% and 100% for the acetabular and the femoral components, respectively. Conclusion This cementless design showed excellent preliminary outcomes in terms of fixation and patient satisfaction, comparable to that of other well-known similar systems.

scholarly journals CPX-351 for Acute Myeloid Leukaemia: Real World Results Are Comparable to Trial Outcomes and Exceeds Them in Non-Adverse Risk Patients- a Multicentre Experience from West Midlands Hospitals on Behalf of West Midlands Research Consortium ( WMRC) UK

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4416-4416
Author(s):  
Vidhya Murthy ◽  
Richard Whitmill ◽  
Clare Lodwick ◽  
Peter Dyer ◽  
Maria Ahmed ◽  
...  
Keyword(s):  
Median Survival ◽  
Real World ◽  
Remission Rate ◽  
Wild Type ◽  
Neutrophil Recovery ◽  
Secondary Aml ◽  
Original Trial ◽  
West Midlands ◽  
The Mean

Abstract Patients with secondary AML or MDS derived AML have poor outcomes compared to de-novo AML. The benefits of intensive chemotherapy without anticipated transplant consolidation have been previously doubted. Outcomes in USA trial centres have not often been closely replicable in real world settings. From November 2018 CPX-351 has been available in the UK for secondary AML, therapy related AML, AML with MDS related Karyotype (AML-MRC) and licensed but not funded for AML with myelodysplastic related changes. Objectives Here we report our experience specifically on patient outcomes and toxicity across 5 Hospitals in West Midlands, UK Methods Patients receiving CPX 351 outcomes were evaluated retrospectively from 2018 to 2021. Baseline genetics, CPX 351 indications, patient's comorbidities, overall survival, remission status, number of cycles delivered, early mortality, reasons for early discontinuation, intensive care admission and time for neutrophil recovery (&gt;0.5) was recorded. Time-to-event outcomes reported here are from a data cut on 01-06-21 Results In a total cohort of 57 patients baseline characteristics are shown on table 1 and compared with the original trial CPX-351 group. Median follow up was 376 days (range 21 to 1248 days). The mean age was 63, 17 patients were under 60, 31 males and 26 females. The most common indication for CPX-351 was AML with antecedent MDS/MPN 51% (N=29), therapy related 14% (N=8), MDS related karyotype (AML-MRC) 19% (N=11) and 16% (N=9) other patients. Mean Charleston co-morbidity score was 2.7 (range 0-6), 10.5% (N=6) had previous non myeloid malignancies, 8.7% (N=5) had prior ischaemic heart disease, only 3.5% (N=2) had ejection fractions under 50%. The most common mutations were TP53 21% (N=12), ASXL1 15.7% (N=9), TET2 15.7% (N=9), IDH2 10.5% (N=6), RUNX1 10.5% (N=6), SRSF2 7% (N=4), JAK2 3.5% (N=2), FLT3 5% (N=3), NPM1 5%(N=3) and IDH1 5% (N=3). MRC cytogenetic risk was adverse in 19 patients (33%), intermediate in 35 patients (61%) and favourable in 3 patients (5%). 30 patients (53%) had adverse European Leukaemia Network classification, 17 (30%) had intermediate and 10 (17%) had favourable. 30-day mortality was 3/57 (5%), 60-day mortality was 6 (10.5%) comparable to the 5.9% and 10.6% rates for the original trial. 9% or 5/57 patients were admitted to ITU with 2 survivors beyond 60 days. Neutropenic fever requiring antibiotics was 100% whereas only 5/57 (9%) had radiological evidence of fungal infection. Only one patient died from COVID 19. The mean time to neutrophil recovery was 35 days with a range of 12 to 84 days. 29 patients completed 1 cycle, 25 completed 2 cycles, only 3 completed 3 cycles. The reasons for stopping were death, refractory disease, drop in performance status, alternative chemotherapy chosen or moving to transplantation (39%). Composite remission rate including CRi was 61% 36/57, adverse ELN group demonstrated 50% 15/30, intermediate 76% 13/17 and favourable 80% 8/10. Mutated P53 was associated with a 50% 6/12 rate whereas in wild type P53 the remission rate was 60% 30/45. Overall median survival from diagnosis was 429 days [95% CI 274 to 788 days]. To compare with the original trial, we removed the under 60s and those with less than 1 year follow up, in this cohort of 30 patients the median survival was 289 days (9.5 months) with 95% CI of 255 to 476 days. P53 mutated patients had an estimated median survival of 257 days versus wild type p53 with 524 days hazard ratio of 2.418 (CI 1.077 to 5.248) with p value of 0.032. Median survival for ELN groups was 373 days (adverse), 413 days (intermediate) and not reached for favourable. Of the 36 patients who achieved a remission, 22 went on to receive an allogenic transplant with follow from 254 to 1248 days, median survival estimated 706 days (95% CI 429-not reached). Patients in remission who haven't received a transplant have a similar estimated survival of 788 days (305-not reached) pending longer follow up. Conclusion This is the first UK multicentre analysis to show comparable results to the landmark trial (median survival 9.5 months in equivalent cases). The improved overall remission rate 61% versus the 47% in the trial and the longer median survival 14 months versus 9.5 months in the trial is expected given the younger age and increase in favourable risk genetics. This study therefore supplies further data of CPX-351 efficacy in younger patients not included in the original studies and may now be used as a standard comparator arm. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Importance of Eculizumab in Paroxysmal Nocturnal Hemoglobinuria: A Cohort Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4876-4876
Author(s):  
Mustafa Nuri Yenerel ◽  
Simge Erdem ◽  
Metban Mastanzade ◽  
Meliha Nalcaci
Keyword(s):  
Cohort Study ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Response To Therapy ◽  
Intravascular Hemolysis ◽  
Management Options ◽  
Laboratory Findings ◽  
Main Indication ◽  
Life Threatening ◽  
Thrombotic Complications

Abstract Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, often progressively debilitating and life-threatening acquired disease characterized by chronic, complement-mediated intravascular hemolysis. PNH is characterized by the deficiency of the endogenous glycosyl phosphatidylinositol-anchored complement regulatory proteins CD55 and CD59 and other proteins on the surface of blood cells, which results in chronic uncontrolled activation of the complement system at the site of the PNH cells and intravascular hemolysis and thrombosis. PNH may present in the absence of an underlying bone marrow disorder (BMD), as a condition secondary to BMDs, such as aplastic anemia (AA) or myelodysplastic syndrome, or as sub-clinical PNH. In this cohort study we will report clinical findings, management options and eculizumab response of 38 PNH cases in our clinic. Materials and Metod We followed 38 PNH cases in this cohort study. We used flow cytometric PNH clone detection test since 1993 but HAM's test and sucrose lysis test were the only tests for the PNH diagnosis in older cases. We used eculizumab in 20 of our patients who had transfusion dependent chronic intravascular hemolysis and/or thrombosis. All of of the patients were vaccinated for Neisseria meningitides, Pneumococcus and Hemophilus influenza type B prior to 2 weeks of initiation of Eculizumab. Eculizumab was administered 600 mg/day for 4 weeks and dosage was elevated to 900 mg/day at week 5, then 900 mg/day every other week as maintenance therapy. The response to therapy was evaluated by LDH, blood cell counts and haptoglobin levels. Clinical and laboratory findings, management options and treatment effect on survival curves were evaluated. Findings Thirty-eight PNH patients who were followed in our clinic since 1985 were enrolled in this study. Twenty of 38 were female and the median age was 35 years (ranging from 18 - 62). The oldest one has been followed for 32 years. Chronic hemolytic anemia and at least one lineage of cytopenia were seen in each patient during diagnosis. Fifteen patients were diagnosed as AA and were treated with immunosuppressive therapy before PNH diagnosis. Following AA diagnosis, PNH was diagnosed on average 35 months (three to 192 months) . One of the patients was diagnosed as MDS and followed-up for five years with this diagnosis. Twenty-two of the cases were de-novo PNH disease. Thrombotic complications were seen at the diagnosis in two patients. Unfortunately, we also have seen thrombotic complications in 10 more patients during follow-up period before eculizumab availability. Five of our patients were lost on eight, 14, 60, 86 and 260 months after their diagnosis. We lost two of them with infection and two of them with thrombotic complications. Fifth patient that we lost at 260 months of her follow-up had complete response with eculizumab and was deceased following a fall from height. Two of our patients went to abroad for treatment. Six of them were lost to follow-up. We currently follow 25 of 38 patients. We still use eculizumab in 20 of our patients. We used eculizumab in median 8 months after PNH diagnosis (One to 360 months). In 15 patients, transfusion dependent chronic intravascular hemolysis was the main indication and for the remaining 5 patients thrombosis was the main indication. Quality of life parameters changed significantly in all of the patients and we didn't observe any new thrombotic episodes. We used eculizumab as an important treatment option for a median 63 months (eight to 98 months) and we didn't encounter any side effects other than mild headache and flu-like symptoms in 5 of the cases. Discussion and conclusion PNH is a life-threatening disease and four of the patients in our cohort died in median 37 months of their diagnosis. Although thrombosis was the main mortality and morbidity reason in our cohort, we didn't see any thrombotic episodes under eculizumab treatment. Even in induction period of the therapy, both clinical and laboratory findings improved significantly with Eculizumab. None of our patients needed transfusion on eculizumab treatment. The survival of our PNH patients on eculizumab is excellent and we didn't lose any of our patients since induction of eculizumab therapy. In conclusion, eculizumab is the first disease-modifying, targeted therapy for PNH and its availability has radically changed the management of patients with this rare disease. Disclosures Yenerel: Alexion: Honoraria, Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document