scholarly journals Usefulness of real-time PCR in long-term follow-up of follicular lymphoma patients.

2007 ◽  
Vol 54 (1) ◽  
pp. 135-142 ◽  
Author(s):  
Andrzej Tysarowski ◽  
Anna Fabisiewicz ◽  
Ewa Paszkiewicz-Kozik ◽  
Jadwiga Kulik ◽  
Jan Walewski ◽  
...  

The aim of this study was to evaluate the usefulness of quantitative real-time PCR (RQ-PCR) for the monitoring of molecular remission in follicular lymphoma (FL) patients during long-term follow-up. RQ-PCR by the use of TaqMan detection system is a sensitive tool to monitor minimal residual disease (MRD) in FL through amplification of the t(14;18) fusion gene during and post-therapy. In most cases the breakpoint region occurs within the major breakpoint region (MBR). Among 75 patients diagnosed with FL, cells harboring the fusion gene BCL2/JH were found in peripheral blood of 31 patients (41%). We further monitored 30 of these patients in a period varying from 6 months to 5 years by RQ-PCR. In our study the level indicating the possibility of the presence of MRD was established at more than five t(14;18)-positive cells in the background of 83,000 normal cells. The results of this work also confirmed that the presence of MRD detected by RQ-PCR is an indication for careful observation of patients because of a higher risk of disease recurrence.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1373-1373
Author(s):  
Marco Ladetto ◽  
Barbara Mantoan ◽  
Federica De Marco ◽  
Berardino Pollio ◽  
Daniela Drandi ◽  
...  

Abstract Introduction: NLABRs are frequently observed in cancer free-subjects. We recently observed that NLABR-positive clones can persist up to 60 days (Ladetto et al, J Clin Oncol 2003). However the long-term kinetics and potential pre-neoplastic role of NLABR-carrying cells are unknown. To define the natural history of NLABR-positive clones, long term monitoring of cancer-free subjects carrying these lesions has been performed. Methods: 118 subjects undergoing periodical blood examinations for warfarin therapy were screened for the bcl-2/IgH translocation. PCR-positive subjects underwent subsequent monitoring at least once every three months. NLABR-positive clones were monitored using both nested and real time-PCR according to previously published approaches (Ladetto et al Exp Hematol 2001). Sequence homology of NLABRs has always been confirmed by direct sequencing of nested PCR products. Results: 15 NLABR-positive subjects were identified out of 118 (12.7%) subjects. NLABR-positive subjects were monitored for a median time of 13 months (mos) (range 3–30 mos) for a total number of 60 timepoints. In eight subjects (53%), NLABRs detected at study initiation were not detected again in follow-up samples. These eight subjects have been monitored for median period of 12 mos (range 3–28 mos). Follow-up samples in this group were usually PCR-negative, although transient PCR-positivity due to unrelated NLABRs were noticed in two samples. In seven subjects (47%), the same NLABR observed at study initiation was detected one or more times at follow-up. In four subjects, NLABRs detected at diagnosis were amplified in every available follow-up sample (three to seven samples were available for each subject). In three, NLABRs detected at diagnosis were amplified only in a fraction of follow-up samples while the remaining were PCR-negative. Overall, persistent NLABRs were followed on these subjects for a median time of 15 months (range 3–30). The median burden of persistent NLABRs assessed by real-time PCR was 33 rearrangements (rg)/106 diploid genomes (dg) (range <10–760), while the median burden of short-lived NLABRs was <10rg/106 dg (range <10–330). The number of NLABR-positive cells appeared to be rather stable in subjects with persistent NLABR-positive clones. In none of these subjects we could detect differences greater than 1 log among available follow-up samples. Subjects having mixed PCR-positive and PCR-negative results had a smaller tumor burden compared to those constantly PCR-positive. This is consistent with the presence of a small though persistent clonal population. Studies on selected populations showed that NLABR-positive cells were CD19-positive. Discussion: NLABR-positive clones are long-lived cell populations in approximately 50% of cases. Based on this finding it is reasonable to hypothesize the existence of a follicular lymphoma (FL)-related lymphoproliferation of undetermined significance. Since NLABRs occurs in more than than 10% of healthy subjects, this condition is expected to be highly prevalent in the general population (as observed in MGUS and CLUS) and of potential relevance for the pathogenesis of FL.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2198-2198
Author(s):  
Farastuk Bozorgmehr ◽  
Stephanie Laufs ◽  
Eike C. Buss ◽  
Katalina Z. Nagy ◽  
Stephanie E. Sellers ◽  
...  

Abstract Introduction: It is of concern whether the introduction of a transgene into hematopoietic stem cells by retroviral vectors will lead to an alteration of the growth and engraftment characteristics. Earlier studies in mice indicated that retroviral MDR1 gene transfer may be associated with a myeloproliferative disorder. In human or primate cells this could not be reproduced in bulk cell populations. Analyses on the clonal level and a long-term follow-up in a model with more direct relevance to human HSC biology were lacking. Methods: In this study CD34-enriched peripheral blood stem cells from 2 rhesus macaque monkeys were transduced either with a MDR1 gene-retroviral vector (HaMDR1-vector) or a NeoR-retroviral vector (G1Na-vector). After autologous transplantation granulocytes and mononuclear cells of each animal were obtained at different time points and analysed by using a highly sensitive and specific ligation-mediated PCR (LM-PCR) and by quantitative real time PCR. Results: In monkey M120 73 different cell populations (clones) were detected between 8 weeks and 4 years after transplantation; in monkey M038 49 clones could be identified between 16 weeks and 4 years after transplantation. Remarkably, 99 clones descend from the G1Na-vector, whereas only 23 clones descend from the HaMDR1-vector. Quantitative real time PCR analyses support these data: in both animals, the mean proportion of the G1Na-vector and the HaMDR1-vector, respectively, is 2,46%±0,014% and 0,455%±0,003%. Furthermore, single G1Na clones identified with LM-PCR 4 years after transplantation were quantified, showing a copy number between 1.43±0,52 and 7.1±0.34, according to 0.001%±0.0003% and 0.004%±0.0003% of the granulocytes fraction. In the MNC fraction, the G1Na clones were not detectable. At the same time point, 2 HaMDR1 clones were quantified, one in the granulocyte and one in the MNC fraction, respectively. Here, the copy numbers were 2.87±0.56 and 3.52±1.11, according to 0.002%±0.0003% and 0.002%±0.0008% of the granulocyte and MNC fraction, respectively. Conclusions: We conclude that hematopoiesis in these monkeys is polyclonal for prolonged periods after transplantation and that MDR1 gene transfer does not confer a proliferative advantage over vector-control-transduced hematopoietic stem cells.


2003 ◽  
Vol 57 (3) ◽  
pp. 748-754 ◽  
Author(s):  
Chul S Ha ◽  
Joseph S Kong ◽  
Peter McLaughlin ◽  
Susan L Tucker ◽  
Luis E Fayad ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Robert J. Kreitman ◽  
◽  
Claire Dearden ◽  
Pier Luigi Zinzani ◽  
Julio Delgado ◽  
...  

Abstract Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711


2011 ◽  
Vol 140 (5) ◽  
pp. S-874
Author(s):  
Hiroyuki Okada ◽  
Katsuyoshi Takata ◽  
Yoshiro Kawahara ◽  
Masahumi Inoue ◽  
Seiji Kawano ◽  
...  

1996 ◽  
Vol 75 (3) ◽  
pp. 171-173 ◽  
Author(s):  
Gordon Soo ◽  
Anthony Chan ◽  
Dennis Lam ◽  
Victor Abdullah ◽  
C. Andrew van Hasselt

A case of extramedullary plasmacytoma with its unusual appearance is reported. This is the second reported case in world literature affecting the paranasal sinuses with intracranial extension. The role of surgery is to obtain tissue for diagnosis and to excise residual disease. Radiotherapy is the treatment of choice and long-term follow-up is necessary for monitoring disease recurrence. The overall 10-year survival is about 50%. The case is discussed with a general review of the management of this pathology.


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