Publications by authors named "Elsa Poullot"

17 Publications

  • Page 1 of 1

A Comprehensive Clinicopathologic and Molecular Study of 19 Primary Effusion Lymphomas in HIV-infected Patients.

Am J Surg Pathol 2021 Sep 23. Epub 2021 Sep 23.

Departments of Pathology Clinical Immunology Hematological Cytogenetics Laboratory Hematology Laboratory, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) University of Paris, Paris Department of Pathology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) INSERM U955, University Paris-Est Créteil, Créteil, France.

Primary effusion lymphoma (PEL) is associated with human herpesvirus 8 and frequently with Epstein-Barr virus (EBV). We report here a single-center series of 19 human immunodeficiency virus-associated PELs, including 14 EBV+ and 5 EBV- PELs. The objectives were to describe the clinicopathologic features of PELs, with a focus on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, to search for genetic alterations by targeted deep sequencing analysis, and to compare the features between EBV+ and EBV- cases. All the patients were male, and the median age at diagnosis was 47 years old (interquartile range: 40 to 56 y). Reflecting the terminal B-cell differentiation, immunophenotypic profiles showed low expression levels of B-cell markers, including CD19 (0/19), CD20 (1/19), CD79a (0/19), PAX5 (1/19), BOB1 (3/19), and OCT2 (4/19), contrasting with a common expression of CD38 (10/19), CD138 (7/19), and IRF4/MUM1 (18/19). We observed a frequent aberrant expression of T-cell markers, especially CD3 (10/19), and less frequently CD2 (2/19), CD4 (3/19), CD5 (1/19), and CD8 (0/19). Only 2 cases were PD-L1 positive on tumor cells and none PD-1 positive. With respect to immune cells, 3 samples tested positive for PD-L1 and 5 for PD-1. Our 36-gene lymphopanel revealed 7 distinct variants in 5/10 PELs, with either a single or 2 mutations per sample: B2M (n=2), CD58 (n=1), EP300 (n=1), TNFAIP3 (n=1), ARID1A (n=1), and TP53 (n=1). Finally, we did not observe any major clinical, pathologic, or immunohistochemical differences between EBV+ and EBV- PELs and the outcome was similar (2-y overall survival probability of 61.9% [95% confidence interval, 31.2-82.1] vs. 60.0% [95% confidence interval, 12.6-88.2], respectively, P=0.62).
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http://dx.doi.org/10.1097/PAS.0000000000001813DOI Listing
September 2021

Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement.

PLoS One 2021 15;16(9):e0257189. Epub 2021 Sep 15.

The French Cardiac Amyloidosis Reference Center, GRC Amyloid Research Institute, Réseau amylose Mondor, and DHU A-TVB, Créteil, France.

Background: Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP levels can double within 24h of dexamethasone administration, suggesting a deleterious impact on cardiac function. In this study, we evaluate the role of dexamethasone in early cardiovascular mortality during treatment.

Methods And Findings: We retrospectively assessed 100 de novo cardiac AL patients (62% male, mean age 68 years) treated at our institute between 2009 and 2018 following three chemotherapy regimens: CyBorDComb (all initiated on day 1; 34 patients), DCyBorSeq (D, day 1; Cy, day 8; Bor, day 15; 17 patients), and CyBorDSeq (Cy, day 1; Bor, day 8; D, day 15; 49 patients). The primary endpoint was cardiovascular mortality and cardiac transplantation at days 22 and 455. At day 22, mortality was 20.6% with CyBorDComb, 23.5% with DCyBorSeq, and 0% with CyBorDSeq (p = 0.003). At day 455, mortality was not significantly different between regimens (p = 0.195). Acute toxicity of dexamethasone was evaluated on myocardial function using a rat model of isolated perfused heart. Administration of dexamethasone induced a decrease in left ventricular myocardium contractility and relaxation (p<0.05), supporting a potential negative inotropic effect of dexamethasone in AL-CA patients with severe cardiac involvement.

Conclusion: Delaying dexamethasone during the first chemotherapy cycle reduces the number of early deaths without extending survival. It is clear that dexamethasone is beneficial in the long-term treatment of patients with AL-CA. However, the initial introduction of dexamethasone during treatment is critical, but may be associated with early cardiac deaths in severe CA. Thus, it is important to consider the dosage and timing of dexamethasone introduction on a patient-severity basis. The impact of dexamethasone in the treatment of AL-CA needs further investigation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257189PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443042PMC
September 2021

Identification of an EML4-ALK rearrangement in an intrahepatic cholangiocarcinoma.

Pathol Int 2021 Sep 7;71(9):630-632. Epub 2021 Jul 7.

Department of Pathology, University Hospital Henri Mondor, AP-HP, Créteil, France.

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http://dx.doi.org/10.1111/pin.13138DOI Listing
September 2021

Detection of Gene Fusion Transcripts in Peripheral T-Cell Lymphoma Using a Multiplexed Targeted Sequencing Assay.

J Mol Diagn 2021 08 18;23(8):929-940. Epub 2021 Jun 18.

INSERM U955, Université Paris-Est, Créteil, France; Pathology Department, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France. Electronic address:

The genetic basis of peripheral T-cell lymphoma (PTCL) is complex and encompasses several recurrent fusion transcripts discovered over the past years by means of massive parallel sequencing. However, there is currently no affordable and rapid technology for their simultaneous detection in clinical samples. Herein, we developed a multiplex ligation-dependent RT-PCR-based assay, followed by high-throughput sequencing, to detect 33 known PTCL-associated fusion transcripts. Anaplastic lymphoma kinase (ALK) fusion transcripts were detected in 15 of 16 ALK-positive anaplastic large-cell lymphomas. The latter case was further characterized by a novel SATB1_ALK fusion transcript. Among 239 other PTCLs, representative of nine entities, non-ALK fusion transcripts were detected in 24 samples, mostly of follicular helper T-cell (TFH) derivation. The most frequent non-ALK fusion transcript was ICOS_CD28 in nine TFH-PTCLs, one PTCL not otherwise specified, and one adult T-cell leukemia/lymphoma, followed by VAV1 rearrangements with multiple partners (STAP2, THAP4, MYO1F, and CD28) in five samples (three PTCL not otherwise specified and two TFH-PTCLs). The other rearrangements were CTLA4_CD28 (one TFH-PTCL), ITK_SYK (two TFH-PTCLs), ITK_FER (one TFH-PTCL), IKZF2_ERBB4 (one TFH-PTCL and one adult T-cell leukemia/lymphoma), and TP63_TBL1XR1 (one ALK-negative anaplastic large-cell lymphoma). All fusions detected by our assay were validated by conventional RT-PCR and Sanger sequencing in 30 samples with adequate material. The simplicity and robustness of this targeted multiplex assay make it an attractive tool for the characterization of these heterogeneous diseases.
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http://dx.doi.org/10.1016/j.jmoldx.2021.04.013DOI Listing
August 2021

Rituximab plus gemcitabine and oxaliplatin (R-GemOx) in refractory/relapsed diffuse large B-cell lymphoma: a real-life study in patients ineligible for autologous stem-cell transplantation.

Leuk Lymphoma 2021 09 25;62(9):2161-2168. Epub 2021 Mar 25.

Lymphoid Malignancies Unit, Hôpital Henri Mondor, AP-HP, Créteil, France.

There is no established standard treatment for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in patients who are not eligible to receive an intensive treatment. The combination of rituximab gemcitabine and oxaliplatin (R-GemOx) is widely used in this population but data are scarce. We retrospectively collected the data of 196 patients with R/R DLBCL treated with R-GemOx in two French centers over a period of 15 years. The median age of the population was 72 years (range, 24-89), 63% of the patients had an international prognostic index of 3 or higher and 57% were refractory to the last treatment. At the end of R-GemOx treatment, 33% of the patients obtained a complete response. The median progression-free survival (PFS) of the population was 5 months and the median overall survival (OS) was 10 months. Several factors were predictors of unfavorable survival: age over 75 years, international prognostic index of 2 or higher, refractory disease and de novo DLBCL. The median PFS and OS of the patients who obtained a complete response were 22 months and 40 months, respectively. The most significant toxicities were grade 3-4 hematological toxicities (31% of patients). Given its efficacy and tolerability, R-GemOx can be used in patients ineligible for intensive treatment and serve as a basis for new regimen combinations.
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http://dx.doi.org/10.1080/10428194.2021.1901090DOI Listing
September 2021

[Cardiac amyloidosis].

Ann Pathol 2021 Feb 6;41(1):25-37. Epub 2021 Jan 6.

Centre français de référence de l'amylose cardiaque (CRAC), réseau Cardiogen, GHU Henri-Mondor, Assistance publique-Hôpitaux de Paris, Créteil, France; Département de Cardiologie, GHU Henri-Mondor, Assistance publique-Hôpitaux de Paris, Créteil, France.

Different types of amyloid deposits involve the heart. Transthyretin and light chain amyloidosis are the most frequent. Diagnostic performance, typing and treatments have improved in the last decade, and prognosis of cardiac amyloidosis is now significantly better thanks to targeted therapies. In this article, we will describe the clinical manifestations of cardiac amyloidosis, the diagnostic approach and detail the characteristics and specific treatments of the most frequent types of cardiac amyloidosis. We will focus on the histopathological aspects, especially on the importance of amyloid typing.
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http://dx.doi.org/10.1016/j.annpat.2020.11.010DOI Listing
February 2021

Natural history and impact of treatment with tafamidis on major cardiovascular outcome-free survival time in a cohort of patients with transthyretin amyloidosis.

Eur J Heart Fail 2021 02 9;23(2):264-274. Epub 2020 Nov 9.

AP-HP (Assistance Publique-Hôpitaux de Paris), Cardiology Department, DHU-ATVB, Henri Mondor University Hospital, Créteil, France.

Aims: Hereditary (ATTRv) and wild-type (ATTRwt) transthyretin amyloidosis are severe and fatal systemic diseases, characterised by amyloid fibrillar accumulation principally in the heart or peripheral nerves (or both). Since 2012, tafamidis has been used in France to treat patients with ATTRv with neuropathy (alone or combined with cardiomyopathy). Recently, the Phase III ATTR-ACT trial showed that tafamidis decreased the relative risk of mortality in ATTR amyloidosis with cardiomyopathy. The aims of this study were to assess the clinical characteristics of ATTR amyloidosis in a real-life population in comparison to the population included in the ATTR-ACT trial and to assess the impact of tafamidis treatment on major cardiovascular outcome (MCO)-free survival time without cardiac decompensation, heart transplant, or death.

Methods And Results: From June 2008 to November 2018, 648 patients with ATTR amyloidosis (423 ATTRwt and 225 ATTRv) consecutively referred to the French Referral Center for cardiac amyloidosis were included. A total of 467 (72%) patients matched the inclusion criteria of the ATTR-ACT trial. For the 631 patients with cardiomyopathy, tafamidis treatment was associated with a longer median MCO-free survival time (n = 98): 1565 (1010-2400) days vs. 771 (686-895) days without treatment (log-rank P < 0.001). This association was confirmed after considering confounding factors (age at inclusion, N-terminal pro-B-type natriuretic peptide and amyloidosis type) with a propensity score (hazard ratio 0.546; P = 0.0132).

Conclusion: In a large cohort of ATTRwt and ATTRv patients, representative of the inclusion criteria of the ATTR-ACT trial, the present results show an association between tafamidis treatment and a lower occurrence of cardiovascular outcomes in a real-life population.
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http://dx.doi.org/10.1002/ejhf.2028DOI Listing
February 2021

Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use.

J Am Soc Nephrol 2019 07 21;30(7):1206-1219. Epub 2019 Jun 21.

Nephrology and Transplantation Department, Cancerology-Immunity-Transplantation-Infectiology, Clinical Investigation Center-Biotherapies, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, INSERM U955, Paris-Est-Créteil University, Paris, France;

Background: Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production.

Methods: To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant.

Results: The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; <0.05) and prolonged renal graft survival (28.0 days versus 5.2 days; <0.01). However, the reduction in donor-specific antibodies was not maintained because all recipients demonstrated rapid rebound of antibodies, with profound T cell-mediated rejection. In the two clinical patients, a combined heart and kidney transplant recipient with refractory antibody-mediated rejection and a highly sensitized heart transplant candidate, we also observed a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and to heart graft access.

Conclusions: Targeting CD38 with daratumumab significantly reduced anti-HLA antibodies and anti-HLA donor-specific antibodies in a nonhuman primate model and in two transplant clinical cases before and after transplant. This supports investigation of daratumumab as a potential therapeutic strategy; however, further research is needed regarding its use for both antibody-mediated rejection and desensitization.
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http://dx.doi.org/10.1681/ASN.2018121254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622431PMC
July 2019

Clinical spectrum, evolution, and management of autoimmune cytopenias associated with angioimmunoblastic T-cell lymphoma.

Eur J Haematol 2019 Jul 30;103(1):35-42. Epub 2019 May 30.

Service de médecine interne, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est, Créteil, France.

Objective: Angioimmunoblastic T-cell lymphoma (AITL) is frequently associated with autoimmune cytopenia (AIC). Whether such patients have a particular phenotype and require particular management is unclear.

Method: Angioimmunoblastic T-cell lymphoma patients from the multicentric database of the Lymphoma Study Association presenting with AIC during disease course were included and matched to AITL patients without AIC (1/5 ratio).

Results: At diagnosis, AIC patients (n = 28) had more spleen and bone marrow involvement (54% vs 19% and 71% vs 34%, P < 0.001), Epstein-Barr virus replication (89% vs 39%, P < 0.001), gamma globulin titers (median 23 vs 15 g/L, P = 0.002), and proliferating B cells and plasmablasts in biopsies, as compared to control patients (n = 136). The 28 AIC patients had 41 episodes of AIC, diagnosed concomitantly with AITL in 23 (82%) cases. After a median follow-up of 24 months (range 3-155), 10 patients relapsed, all associated with AITL relapse.

Conclusion: Our results provide new insight into AIC associated with AITL by highlighting the significant interplay between AITL and B-cell activation leading to subsequent autoimmunity.
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http://dx.doi.org/10.1111/ejh.13239DOI Listing
July 2019

Multiple Ways to Detect IDH2 Mutations in Angioimmunoblastic T-Cell Lymphoma from Immunohistochemistry to Next-Generation Sequencing.

J Mol Diagn 2018 09 5;20(5):677-685. Epub 2018 Jul 5.

INSERM U955 Équipe 9, Institut Mondor de Recherche Biomédicale, Créteil, France; Université Paris Est, Créteil, France; Département de Pathologie, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France.

Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma associated with chemoresistance and a poor prognosis. Various nonsynonymous mutations in the R172 residue of IDH2 are present in 20% to 30% of AITL patients. In addition to their diagnostic value, these mutations are potentially targetable, especially by isocitrate dehydrogenase (IDH) 2 inhibitor, and therefore their identification in a routine setting is clinically relevant. However, in AITL, the neoplastic cells may be scarce, making the identification of molecular anomalies difficult. We evaluated the diagnostic value of different methods to detect IDH2 mutations in formalin-fixed, paraffin-embedded tumor samples. Immunohistochemistry with an anti-IDH2 R172K antibody, Sanger sequencing, high-resolution melting PCR, allele-specific real-time quantitative PCR, and next-generation sequencing (NGS) were applied to biopsy specimens from 42 AITL patients. We demonstrate that the IDH2 R172K antibody is specific to this amino acid substitution and highly sensitive for the detection of the IDH2 variant, the most frequent substitution in this disease. In our study, NGS and allele-specific real-time quantitative PCR displayed a good sensitivity, detecting 96% and 92% of IDH2 mutations, respectively, in contrast to Sanger sequencing and high-resolution melting PCR, which showed a significantly lower detection rate (58% and 42%, respectively). These results suggest that a combination of immunohistochemistry and AS-PCR or NGS should be considered for the identification of IDH2 mutations in AITL in a routine setting.
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http://dx.doi.org/10.1016/j.jmoldx.2018.05.012DOI Listing
September 2018

[Mysterious gingival ulcers].

Ann Pathol 2017 Apr 28;37(2):198-201. Epub 2016 Nov 28.

Laboratoire d'anatomie et cytologie pathologique, CHU Pontchaillou, 2, rue Henri-le-Guilloux, 35000 Rennes, France. Electronic address:

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http://dx.doi.org/10.1016/j.annpat.2016.09.003DOI Listing
April 2017

[A terrible endoscopy].

Ann Pathol 2015 Apr 9;35(2):174-6. Epub 2015 Mar 9.

Service d'anatomie et cytologie pathologiques, CHU Pontchaillou, 2, rue Henri-le-Guilloux, 35033 Rennes cedex 9, France. Electronic address:

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http://dx.doi.org/10.1016/j.annpat.2015.01.008DOI Listing
April 2015
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