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1.
Microorganisms ; 10(9)2022 Sep 09.
Article in English | MEDLINE | ID: mdl-36144414

ABSTRACT

There is an ongoing need for high-precision serological assays for the quantitation of anti-SARS-CoV-2 antibodies. Here, a trimeric SARS-CoV-2 spike (S) protein was used to develop an ELISA to quantify specific IgG antibodies present in serum, plasma, and dried blood spots (DBS) collected from infected patients or vaccine recipients. The quantitative S-ELISA was calibrated with international anti-SARS-CoV-2 immunoglobulin standards to provide test results in binding antibody units per mL (BAU/mL). The assay showed excellent linearity, precision, and accuracy. A sensitivity of 100% was shown for samples collected from 54 patients with confirmed SARS-CoV-2 infection more than 14 days after symptom onset or disease confirmation by RT-PCR and 58 vaccine recipients more than 14 days after vaccination. The assay specificity was 98.3%. Furthermore, antibody responses were measured in follow-up samples from vaccine recipients and infected patients. Most mRNA vaccine recipients had a similar response, with antibody generation starting 2-3 weeks after the first vaccination and maintaining positive for at least six months after a second vaccination. For most infected patients, the antibody titers increased during the second week after PCR confirmation. This S-ELISA can be used to quantify the seroprevalence of SARS-CoV-2 in the population exposed to the virus or vaccinated.

2.
Haematologica ; 92(12): 1699-702, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18055996

ABSTRACT

RT-PCR detects chimeric BCR-ABL mRNA in approximately 25% of adult acute lymphoblastic leukemia (ALL) cases. Minor breakpoint transcripts (e1a2) are found in about 70% of positive cases and major breakpoint transcripts (e13a2, e14a2) in about 30% of cases. However, other atypical transcripts are sometimes observed. We report experience gained in the GMALL Study Group and identified 8 BCR-ABL-positive adult ALL cases with such atypical transcripts: 5 with e1a3, 2 with e13a3 (b2a3), and 1 with e6a2. This corresponds to a prevalence of 1-2% of all BCR-ABL-positive cases. The clinical courses are reported and diagnostic proposals are made.


Subject(s)
Fusion Proteins, bcr-abl/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , RNA, Messenger/genetics , RNA, Neoplasm/genetics , Adult , Female , Humans , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis
3.
Blood ; 103(4): 1495-8, 2004 Feb 15.
Article in English | MEDLINE | ID: mdl-14576058

ABSTRACT

Imatinib has pronounced but brief antileukemic activity in advanced Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). We assessed the prognostic impact of pretreatment disease features and the early bone marrow (BM) response in 68 consecutive patients with Ph(+)ALL receiving imatinib salvage therapy. A complete hematologic or marrow response was achieved by 92% of patients with BM blasts below 5% on day 14, whereas 62.5% of patients with more than 5% BM blasts on day 14 were nonresponders. Similarly, time to progression (TTP) was superior in patients with a good day 14 response (5.2 versus 0.9 months; P <.0001). Prior complete remission of less than 6 months, white blood cell count of more than 10 x 10(9)/L, circulating peripheral blood blasts at diagnosis, additional Philadelphia chromosomes, or at least 2 Bcr-Abl fusion signals were associated with significantly inferior remission rate and response duration. In patients without poor prognostic features, single-agent imatinib may be appropriate before transplant salvage therapy. Conversely, patients with clinically or cytogenetically defined poor-risk features are candidates for trials of upfront imatinib in combination with other agents.


Subject(s)
Antineoplastic Agents/administration & dosage , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/administration & dosage , Pyrimidines/administration & dosage , Adolescent , Adult , Aged , Antineoplastic Agents/adverse effects , Benzamides , Female , Follow-Up Studies , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Male , Middle Aged , Piperazines/adverse effects , Predictive Value of Tests , Pyrimidines/adverse effects , Recurrence , Remission Induction , Survival Analysis
4.
Blood ; 99(5): 1536-43, 2002 Mar 01.
Article in English | MEDLINE | ID: mdl-11861265

ABSTRACT

The BCR-ABL fusion, the molecular equivalent of the Philadelphia translocation, gains importance for treatment stratification in adult acute lymphoblastic leukemia (ALL). In this prospective study, samples from 478 patients with CD10(+) B-cell precursor ALL (c-ALL and pre-B ALL) underwent BCR-ABL reverse transcription-polymerase chain reaction (RT-PCR) analysis with double testing of positive samples. Patients were stratified according to the PCR result and treated in 2 German Multicenter Trials of Adult ALL. The outcome was followed and the prognostic impact of BCR-ABL was compared to clinical risk features. Of the 478 samples, 432 had an evaluable BCR-ABL result. Thirty-seven percent of the c-ALL and pre-B ALL patients were BCR-ABL(+) (p190, 77%; p210, 20%; simultaneous p190/p210, 3%). BCR-ABL positivity was associated with the high-risk features of older age (45 years versus 30 years median age; P =.0001) and higher white blood cell counts (23 500/microL versus 11 550/microL; P =.0001). Univariate and multivariate analyses revealed BCR-ABL as the leading factor for a poor prognosis (P =.0001) in comparison to clinical risk criteria. Irrespective of the breakpoint, presence of any BCR-ABL transcript predicted a lower chance of initial treatment response (68.4% versus 84.6%; P =.001) and a lower probability of disease-free survival at 3 years (0.13 versus 0.47; P =.0001). This bad outcome was not influenced by postinduction high-dose treatment stratifications. The results show a high prevalence of BCR-ABL fusion transcripts with predominance of p190. BCR-ABL RT-PCR is confirmed as a sensitive, rapid method to diagnose t(9;22), and p190 and p210 are unequivocally demonstrated as the most important predictors of poor long-term survival despite intensified chemotherapy.


Subject(s)
Fusion Proteins, bcr-abl/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Translocation, Genetic/genetics , Adolescent , Adult , Aged , Burkitt Lymphoma/genetics , Burkitt Lymphoma/mortality , Burkitt Lymphoma/pathology , Cytogenetic Analysis , DNA Primers , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Prospective Studies , RNA, Messenger/analysis , Survival Rate , Treatment Outcome
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