scholarly journals BNT162b2 mRNA COVID-19 Vaccination (BNTCV) in Patients (Pts) Having Hematological Malignancies (HM): Early tolerance with telemedicine application connecting and antibody anti-Spike IgG response (AcAS)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1879-1879
Author(s):  
Jean-Francois Rossi ◽  
Emmanuel Bonnet ◽  
Marion Velensek ◽  
Emma Wisniewski ◽  
Sophie Heraud ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Vaccination Strategy ◽  
Normal Subjects ◽  
Lymphocytic Leukemia ◽  
Vaccine Strategy ◽  
Telemedicine System ◽  
Telemedicine Application ◽  
Non Hodgkin Lymphoma ◽  
Roche Diagnostics

Abstract Pts with HM and particularly those under therapy or with secondary immune deficiency have been reported to have a low or delayed specific immune response. In addition, pts receiving rituximab for either HM or auto-immune disease presented a low specific antibody response. Daratumumab, an anti-CD38 moAb was demonstrated to lower normal plasma cells and to reduce polyclonal IgA, M and E in pts with multiple myeloma (MM). It is fundamental to evaluate the early post-vaccination tolerance and the level of seroconversion for such pts. Patients' population. 194 pts having HM and followed at the Institute (IC), received at least 2 doses of BNTCV (BioNTech Pfizer, Paris, France) by IM route with 3 weeks between the 2 doses. Currently, analysis was performed on 147 pts, including 63 pts with non-Hodgkin lymphoma (NHL), 18 with B-chronic lymphocytic leukemia (CLL), 34 with MM, 14 with monoclonal gammopathy of undetermined significance (MGUS) and 18 with myeloproliferative disorder (MPD). Mean age was 69 years-old (range 27-92). Follow-up of early tolerance in pts using a telemedicine application. 43 pts vaccinated at the IC received Thess®, a telemedicine system connecting the patient to the IC, developed by La Valeriane Inc. (Montpellier, France, www.thess-corp.fr) 24/24h, 7days. Local pain (<1 day) was common and transient, particularly reported after the 2nd dose. Only 4/43 patients reported significant adverse events through telemedicine and followed by a medical call, including mainly severe asthenia for 2 days or more, fever (>38°C) for at least 2 days, headache, or general pain. The satisfaction survey of monitoring system was good. In addition, adherence to vaccination was excellent with only one refusal out of the 194 pts. AcAS follow-up IgG AcAS and IgG+M AcAS were analyzed in the serum 3 to 4 weeks after the 1st dose and 4-8 weeks after the 2 nd dose and every 2 months, respectively by SARS-CoV-2 IgG II Quant ® Assay with a threshold of positivity at 50 AU/mL (Abbott, Rungis, France) and Elecsys ® Anti-SARS-CoV-2 S (Roche Diagnostics, Meylan, France) with a threshold of positivity at 0.8 U/mL. 270 samples were analyzed in duplicate with the 2 assays, by 2 independent labs. Data were reported and statistically analyzed by the clinical research team. 17 results were discordant including 12 with Abbott IgG test undetectable and Roche IgG+M detectable, and 5 with Abbott test detectable and Roche undetectable. After the first dose of BNTCV, 72/147 (49%) pts were seroconverted, including 7/18 (39%) with CLL, 27/63 (43%) with NHL, 10/14 (71%) with MGUS, 17/34 (50%) with MM and 11/18 (61%) with SMD. The median levels of the AcAS response for pts were 0 (range 0-40 000 AU/mL) for the AdviseDX test as compared to 12 normal subjects (mean 257 AU/mL, range 226-283), and 0 U/mL (range 0-2500) for the Elecsys test. 49/75 (65%) of untreated pts were seroconverted after the 1 st dose as compared to 26/72 (36%) of treated patients (p<0.001), with rituximab or ibrutinib as negative factors in addition to low gammaglobulin level (<5g/L, p=0.019), similarly to the IgG level. Analysis of CRP levels, circulating lymphocyte counts, and lymphocyte subpopulations will be performed. After the second dose of BNTCV, 50 pts have currently been tested, with only 25 additional pts seroconverted. The median levels of the AcAS response for pts were 310 AU/mL (range 62-11760) for the AdviseDX test as compared to 12 normal subjects (mean 6725 AU/mL, range 3002-9787), and 1250 U/mL (range 0.87-2500) for the Elecsys test. The 25 patients who were not seroconverted after the 2nd dose received a 3rd dose of BNTCV, including 8 with MM, 9 with NHL, 5 with CLL, 1 with MGUS (with polyneuropathy under daratumumab) and 2 with SMD. Currently, 9 pts were tested after the 3 rd dose. AcAS levels were respectively 268 AU/mL for 1 MM treated by daratumumab, 103 and 313 AU/mL for 2 MM under carfilzomib, 1622 AU/mL for 1 untreated SMD, 29100 AU/mL for 1 untreated MGUS, 537 AU/mL for 1 CLL and 2 negative NHL. In conclusion, there is a need to follow AcAS for pts having HM including SMD after BNTCV aiming to adapt vaccine strategy including a 3 rd dose and eventual recall. As some pts are always negative after a 3 rd dose, vaccination strategy could be discussed by using different combinations of vaccine or the addition of immune adjuvant in a more personalized medicine. In addition, the usage of telemedicine connecting system may help to follow the early tolerance and to improve the pts' adherence. Disclosures Rossi: NPO Petrovax Pharm: Consultancy; LEO Pharma: Consultancy; EUSA Pharma: Consultancy; E-SANA Inc: Other: Co-founder of E-SANA Inc .

Heritability of Hematologic Neoplasms in Twins: An Update

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3636-3636
Author(s):  
Ali Ozhand ◽  
Thomas M. Mack ◽  
Sophia S. Wang ◽  
Ann S. Hamilton ◽  
Amie E. Hwang ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hodgkin Lymphoma ◽  
Lymphocytic Leukemia ◽  
National Death Index ◽  
Hematologic Neoplasms ◽  
Standardized Incidence Ratio ◽  
Expected Number ◽  
Non Hodgkin Lymphoma ◽  
Hematologic Neoplasm

Abstract Abstract 3636 Hodgkin lymphoma, especially the young adult type, is one of the most heritable cancers. We previously reported a high risk of Hodgkin lymphoma to monozygotic (MZ), but not dizygotic (DZ) co-twins of cases, and only a modest difference in risk between MZ and DZ co-twins of non-Hodgkin lymphoma (NHL) cases (Mack, 1995). After an additional 18 years of follow-up, we have now updated the observed occurrence of hematologic malignancies in the initially unaffected co-twins of HL, NHL, multiple myeloma (MM), and chronic lymphocytic leukemia (CLL) twin probands. The number of calendar and age-specific person-years at risk for each co-twin was calculated from the date of diagnosis of the proband to the date of last follow-up of the co-twin, defined by the last date of contact, date of death ascertained directly or from linkage with the National Death Index, or evidence of current vital status from a national tracing program. The expected number of cases was calculated by applying the calendar and age-specific incidence rates by 5-year interval categories for each hematologic neoplasm from the Surveillance, Epidemiology and End-Results Program to the person-years of risk. Diagnoses of hematological neoplasms in the co-twins by age and year were ascertained by direct follow-up augmented by a linkage with the National Death Index, using diagnoses categorized by the ICD-9 codes. The standardized incidence ratio (SIR) was computed as the observed to expected number of cases; 95% confidence intervals (CI) (Breslow and Day, 1987), and the risk ratio (RR) (ratio of the SIR in MZ co-twins compared to that in DZ co-twins) were calculated. Whereas the SIR for DZ co-twins measures the heritable and acquired components of risk to first-degree family members, the RR provides evidence of genetic heritability, based on the additional genomic commonality of MZ twins. A total of 364 (HL), 501 (NHL), 91 (MM), and 45 (CLL) co-twins of probands contributed to the analysis. The risk of developing the same hematologic neoplasm as the proband was generally higher in the MZ compared to the DZ co-twins, with the highest RR observed for HL (13.3) and the lowest for NHL (1.75). Although more than 10,000 person-years were added since the original paper, the RR's for HL and NHL did not change substantially from those reported in 1995. The RR for CLL was 3.3 suggesting moderately strong heritability. One MZ co-twin developed MM producing a large SIR, however chance cannot be easily ruled out. The findings of most interest are the continued very high risk of HL in MZ compared to DZ twins confirming the strong heritability of this neoplasm, and the relatively low RR for NHL. MZ and DZ co-twins of NHL probands had increased but similar SIR's, suggesting that shared environmental factors are more important than heritability. Subtype–specific information on the NHL type was not available from the ICD-9 codes used by the Death Index to identify new cases, so it is possible that stronger NHL heritability would be evident if subtypes were considered separately. Table 1. Occurrence of similar hematologic neoplasms in co-twins of lymphoma and chronic lymphocytic leukemia probands Neoplasm Type Zygosity No. at risk No. Cases Expected No. Cases Observed SIR1 (95% CI2) Risk Ratio: SIR1MZ/SIR1DZ Hodgkin lymphoma MZ 170 0.11 13 114.2 (60.7, 195.3) 13.3 DZ 194 0.12 1 8.6 (0.1, 47.6) Non-Hodgkin lymphoma MZ 213 0.51 6 11.8 (4.3, 25.7) 1.75 DZ 288 0.74 5 6.7 (2.2, 15.7) Multiple myeloma MZ 51 0.03 1 28.8 (0.38, 160,3) NA DZ 40 0.02 0 0 Chronic lymphocytic leukemia MZ 25 0.01 4 260.9 (70.2, 668,0) 3.3 DZ 20 0.01 1 79.8 (1.0, 444.0) 1 Standardized incidence ratio 2 95% Confidence intervals Disclosures: No relevant conflicts of interest to declare.

Immunobeads Test (Antibody Coated Polyacrylamide Beads) in the Immunological Characterization of Lymphoproliferative Disorders

1987 ◽  
Vol 2 (3) ◽  
pp. 173-176
Author(s):  
Teodoro Chisesi ◽  
Michele Vespignani ◽  
Giovanni Capnist
Keyword(s):  
Multiple Myeloma ◽  
Chronic Lymphocytic Leukemia ◽  
Normal Subjects ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Immunological Characterization ◽  
Surface Immunoglobulin ◽  
Non Hodgkin Lymphoma ◽  
Patient Groups

Three groups of patients with immunoproliferative disorders (15 multiple myeloma, 11 non-Hodgkin's lymphoma, 21 chronic lymphocytic leukemia) were studied by immunological characterization and compared to a group of 20 normal subjects (controls) using anti-immunoglobulin coated polyacrylamide beads (T-B Quantigen test, QT), erythrocyte rosettes (ER), surface immunoglobulin (SIg), and monoclonal antibodies for T and B cells (OKT3; OKT11; OKT8; OKT4; IaDR); null cells (NC) and double marker (DM) cells were also considered. The values for normal subjects for T-B, NC and DM cells were comparable. Results for the patient groups strikingly differed. There were progressively larger differences between the T and B percentages obtained with different techniques. The largest differences were seen in patients with chronic lymphocytic leukemia and the smallest in multiple myeloma patients; values were intermediate in non-Hodgkin lymphoma. The different findings were related to the number of DM cells (ER +, SIg+ QT+) and the different tests used. The importance of these findings in the diagnostic appproach to lymphoproliferative disorders is discussed.

Fc Engineered Anti-CD19 Monoclonal Antibodies with Enhanced In Vitro Efficacy Against Multiple Lymphoma Cell Lines.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4747-4747
Author(s):  
Eugene A. Zhukovsky ◽  
Seung Chu ◽  
Matthew Bernett ◽  
Philip Hammond ◽  
Sher Karki ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Plasma Cells ◽  
Lymphoblastic Leukemia ◽  
Unmet Need ◽  
Lymphocytic Leukemia ◽  
Cell Surface Receptor ◽  
Non Hodgkin Lymphoma

Abstract CD19 is a pan-B cell surface receptor that is expressed from early stages of pre-B cell development through terminal differentiation into plasma cells. It is an attractive immunotherapy target for cancers of lymphoid origin since it is also expressed on the vast majority of Non-Hodgkin Lymphoma (NHL) cells. Although the anti-CD20 monoclonal antibody rituximab is efficacious for the treatment of lymphoid tumors, a growing population of rituximab-refractory patients has resulted in an unmet need for alternative B cell-specific immunotherapeutics. Engineered Fc variants that increase the affinity of IgG antibodies for Fc gamma receptors (FcγR) can dramatically enhance antibody-dependent cell-mediated cytotoxicity (ADCC). This technology has been applied to a humanized anti-CD19 antibody (XmAb™ CD19) and demonstrates ADCC against multiple cell lines representative of follicular lymphoma (FL/DOHH-2), chronic lymphocytic leukemia (CLL/MEC-1), B-cell acute lymphoblastic leukemia (B-ALL/VAL), mantle cell lymphoma (MCL/JeKo-1), hairy cell leukemia (HCL/BONNA-12), and Burkitt’s lymphoma (Raji). The ADCC activity observed is in striking contrast with a wild type IgG1 version of the antibody, which mediates little or no ADCC. Moreover, the XmAb™ CD19 activity is comparable to that of rituximab for the majority of cell lines tested and occasionally superior. Fc variants of this antibody are being evaluated in vitro for their ability to conduct ADCC by various effector cell populations, and in relevant in vivo efficacy models. In summary, these data suggest that anti-CD19 Fc variant antibodies with increased effector function could be promising as NHL immunotherapeutics, particularly for rituximab-refractory NHL.

Postural Changes in Essential Hypertension under Treatment and their Effect on the Renogram

1971 ◽  
Vol 10 (01) ◽  
pp. 39-46
Author(s):  
C. Alexandrou ◽  
E. Papadakis ◽  
E. Gyftaki ◽  
J. Darsinos
Keyword(s):  
Renal Function ◽  
Essential Hypertension ◽  
Early Diagnosis ◽  
Postural Hypotension ◽  
Antihypertensive Treatment ◽  
Normal Subjects ◽  
Upright Position ◽  
Postural Changes ◽  
Significant Impairment

SummaryRadioisotope renograms were obtained in the upright and prone position in 9 normal subjects, in 5 patients with untreated essential hypertension and in 21 hypertensives under treatment, showing moderate postural hypotension.No significant renographic change were seen in the two positions in normal subjects and untreated hypertensives. Treated hypertensives with postural hypotension showed significant impairment of renal function in the upright position in 15 cases and no change in 6. Renal creatinine clearance was lower in the group that showed renographic changes. Renography in the upright position is suggested as a convenient test for early diagnosis and follow-up of the adverse effects of antihypertensive treatment.

Evaluation of R-CHOP and R-CVP in the treatment of elderly patient with non-Hodgkin lymphoma

MedPharmRes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 1-6
Author(s):  
Truc Phan ◽  
Tram Huynh ◽  
Tuan Q. Tran ◽  
Dung Co ◽  
Khoi M. Tran
Keyword(s):  
Elderly Patients ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
The Elderly ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Common Sign ◽  
Related Mortality

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.

Restaging of patients with lymphoma

2008 ◽  
Vol 47 (01) ◽  
pp. 37-42 ◽  
Author(s):  
T. Pfluger ◽  
V. Schneider ◽  
M. Hacker ◽  
N. Bröckel ◽  
D. Morhard ◽  
...  
Keyword(s):  
Low Dose ◽  
Non Hodgkin Lymphoma ◽  
Contrast Enhanced ◽  
Pet Ct ◽  
Significant Difference ◽  
18F Fdg ◽  
Sensitivity Specificity ◽  
Fdg Pet Ct

SummaryAim: Assessment of the clinical benefit of i.v. contrast enhanced diagnostic CT (CE-CT) compared to low dose CT with 20 mAs (LD-CT) without contrast medium in combined [18F]-FDG PET/CT examinations in restaging of patients with lymphoma. Patients, methods: 45 patients with non-Hodgkin lymphoma (n = 35) and Hodgkin's disease (n = 10) were included into this study. PET, LD-CT and CECT were analyzed separately as well as side-by-side. Lymphoma involvement was evaluated separately for seven regions. Indeterminate diagnoses were accepted whenever there was a discrepancy between PET and CT findings. Results for combined reading were calculated by rating indeterminate diagnoses according the suggestions of either CT or PET. Each patient had a clinical follow-up evaluation for >6 months. Results: Region-based evaluation suggested a sensitivity/specificity of 66/93% for LD-CT, 87%/91% for CE-CT, 95%/96% for PET, 94%/99% for PET/LD-CT and 96%/99% for PET/CE-CT. The data for PET/CT were obtained by rating indeterminate results according to the suggestions of PET, which turned out to be superior to CT. Lymphoma staging was changed in two patients using PET/ CE-CT as compared to PET/LD-CT. Conclusion: Overall, there was no significant difference between PET/LD-CT and PET/CE-CT. However, PET/CE-CT yielded a more precise lesion delineation than PET/LD-CT. This was due to the improved image quality of CE-CT and might lead to a more accurate investigation of lymphoma.

Expression of P2X7purinoceptors on human lymphocytes and monocytes: evidence for nonfunctional P2X7receptors

2000 ◽  
Vol 279 (4) ◽  
pp. C1189-C1197 ◽  
Author(s):  
B. J. Gu ◽  
W. Y. Zhang ◽  
L. J. Bendall ◽  
I. P. Chessell ◽  
G. N. Buell ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Adhesion Molecule ◽  
Human Lymphocytes ◽  
Normal Subjects ◽  
Cell Types ◽  
Surface Expression ◽  
Lymphocytic Leukemia ◽  
Functional Responses ◽  
Intracellular Expression ◽  
Selective Channel

Lymphocytes from normal subjects and patients with B-chronic lymphocytic leukemia (B-CLL) show functional responses to extracellular ATP characteristic of the P2X7receptor (previously termed P2Z). These responses include opening of a cation-selective channel/pore that allows entry of the fluorescent dye ethidium and activation of a membrane metalloprotease that sheds the adhesion molecule L-selectin. The surface expression of P2X7receptors was measured in normal leucocytes, platelets, and B-CLL lymphocytes and correlated with their functional responses. Monocytes showed four- to fivefold greater expression of P2X7than B, T, and NK lymphocytes, whereas P2X7expression on neutrophils and platelets was weak. All cell types demonstrated abundant intracellular expression of this receptor. All 12 subjects with B-CLL expressed lymphocyte P2X7at about the same level as B lymphocytes from normal subjects. P2X7function, measured by ATP-induced uptake of ethidium, correlated closely with surface expression of this receptor in normal and B-CLL lymphocytes and monocytes ( n = 47, r = 0.70; P< 0.0001). However, in three patients the ATP-induced uptake of ethidium into the malignant B lymphocytes was low or absent. The lack of P2X7function in these B lymphocytes was confirmed by the failure of ATP to induce Ba2+uptake into their lymphocytes. This lack of function of the P2X7receptor resulted in a failure of ATP-induced shedding of L-selectin, an adhesion molecule that directs the recirculation of lymphocytes from blood into the lymph node.

scholarly journals Lymphoproliferative malignancies in patients with neurofibromatosis 1

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Christina Bergqvist ◽  
François Hemery ◽  
Arnaud Jannic ◽  
Salah Ferkal ◽  
Pierre Wolkenstein
Keyword(s):  
General Population ◽  
Medical History ◽  
Hodgkin Lymphoma ◽  
Incidence Rate ◽  
Population Based ◽  
Neurofibromatosis 1 ◽  
Population Based Study ◽  
Non Hodgkin Lymphoma ◽  
History Of

AbstractNeurofibromatosis 1 (NF1) is an inherited, autosomal-dominant, tumor predisposition syndrome with a birth incidence as high as 1:2000. A patient with NF1 is four to five times more likely to develop a malignancy as compared to the general population. The number of epidemiologic studies on lymphoproliferative malignancies in patients with NF1 is limited. The aim of this study was to determine the incidence rate of lymphoproliferative malignancies (lymphoma and leukemia) in NF1 patients followed in our referral center for neurofibromatoses. We used the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital’s electronic health records. We performed a keyword search on clinical notes generated between Jan/01/2014 and May/11/2020 for patients aged 18 years or older. A total of 1507 patients with confirmed NF1 patients aged 18 years and above were identified (mean age 39.2 years; 57% women). The total number of person-years in follow-up was 57,736 (men, 24,327 years; women, 33,409 years). Mean length of follow-up was 38.3 years (median, 36 years). A total of 13 patients had a medical history of either lymphoma or leukemia, yielding an overall incidence rate of 22.5 per 100,000 (0.000225, 95% confidence interval (CI) 0.000223–0.000227). This incidence is similar to that of the general population in France (standardized incidence ratio 1.07, 95% CI 0.60–1.79). Four patients had a medical history leukemia and 9 patients had a medical history of lymphoma of which 7 had non-Hodgkin lymphoma, and 2 had Hodgkin lymphoma. Our results show that adults with NF1 do not have an increased tendency to develop lymphoproliferative malignancies, in contrast to the general increased risk of malignancy. While our results are consistent with the recent population-based study in Finland, they are in contrast with the larger population-based study in England whereby NF1 individuals were found to be 3 times more likely to develop both non-Hodgkin lymphoma and lymphocytic leukemia. Large-scale epidemiological studies based on nationwide data sets are thus needed to confirm our findings.

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