The most prevalent etiologies of splenomegaly (SM) are easily detected in routine clinical practi... more The most prevalent etiologies of splenomegaly (SM) are easily detected in routine clinical practice. However, after these first-line diagnoses have been ruled out, many cases remain unexplained. Frequently, signs and symptoms are non-specific hiding rare etiologies such as Lysosomal Storage Diseases (LSD) (e.g., Gaucher disease (GD), Niemann-Pick disease type B). SplenoMegaly Study (SMS) aims to estimate the prevalence of different etiologies in unexplained SM and to describe their diagnostic work-up. We present here the final results of the study. SMS is a prospective, observational, multi-center, longitudinal study performed in France. All patients with unexplained SM, aged ≥15 years, consulting to the French hematology or internal medicine departments were invited to take part of the study. SM was confirmed by echography or CT-scan with a craniocaudal length ≥13 cm; unexplained was defined as negative clinical and biological routine workup. All conducted exams and tests for diagnosis purpose were under each physician's responsibility. For each patient, last visit took place when an etiology was identified or up to 12 months after inclusion. From Sept-2015 to Apr-2020, 505 patients were enrolled by 87 centers (secondary centers [71.3%] and tertiary centers [28.7%]). Physicians were mainly internists (52.9%) or hematologists (46.0%). Patients characteristics at inclusion were as follows: male gender, 61.2%; median age, 51.0 years old (16-94 years old); median spleen length, 15.0 cm (13-30 cm); heterogeneous spleen structure, 11.1%. A total of 501 patients completed the study. After a median duration of 6.6 months, 232 patients (46.3%) received a diagnosis. When compared to patients without diagnosis, patients with diagnosis were older (median age 59.5 vs 45.0; p<0.001), had more often a massive SM (≥18 cm) (25.2% vs 10.7%; p<0.001) and heterogeneous spleen structure (15.9% vs 6.6%; p=0.002). Their biological test results (hemoglobin, leucocytes, CRP, albumin) were also significantly altered and they showed more constitutional (48.3% vs 37.3%) and digestive symptoms (41.9% vs 28.4%) compared to patients without diagnosis. The proportion of diagnosed patients was higher in tertiary than secondary centers (55.2% vs 32.6%). Hematological (lymphoid and myeloid) malignancies represented only 38.7% (n=87) of established diagnoses (Figure 1). Non-malignant diseases, accounted for 61.3% of diagnosis, were: autoimmune disorders (20.0%, n=45), portal hypertension (12.0%, n=27), infectious diseases (11.6%, n=26), LSD (4.4% [n=10], including type 1 Gaucher Disease (GD1) [n=4]; Niemann-Pick disease type B [n=3] and type C [n=2]; and Fabry disease [n=1]), other disorders (13.3%, n=30) and non-specified (3%, n=7). Hematological malignancies were more common in elderly patients (median age 66.0, p<0.001) with massive SM (p<0.001). Compared to other diagnoses, a large proportion of patients diagnosed with portal hypertension were obese (51.9%) and had ongoing metabolism or nutrition disorders (40.7%). Patients with autoimmune disorders had higher CRP levels (median value, 11.5 mg/L) and showed more osteoarticular symptoms (34.8%). All 4 GD1 patients had thrombocytopenia (≤100G/L platelets). Among the tests contributing to diagnosis, biopsies were performed in 34.3% (n=172) of patients, mainly bone marrow trephine biopsy (BMTB) (20.8%, n=104). Half of patients with BMTB received a diagnosis. Splenectomy was performed in 19 patients (4.0%) and was conclusive in 14 of them. β-Glucocerebrosidase activity assay to test for GD was performed in 79.8% of patients. Among patients without diagnosis, 22.7% of them were not tested for GD. In SMS, patients at inclusion had unexplained SM despite routine clinical and biologic analysis. The diagnostic yield improved after further medical evaluations reaching an etiologic diagnosis in 46% of patients. Patients with an established diagnosis were older, had a larger spleen and altered biological parameters compared to patients without diagnosis. Interestingly, non-malignant diseases accounted for 61.3% of diagnoses. It is noteworthy the diversity of LSD etiologies obtained: 10 patients (4%) were diagnosed with LSD, including 4 GD1 patients. This study provides useful new information to optimize the diagnostic strategy of splenomegaly poorly explained by routine workup. SMS is sponsored by Sanofi-Genzyme. Figure 1 Figure 1. Denis: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Séné: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Costello: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Michaud: Sanofi: Honoraria, Research Funding. Hellé: Sanofi: Current Employment. Lagadec: Sanofi: Current Employment.…
Aims: The onset of blast crisis (BC) in initially chronic phase (CP) CML patients that entered tr... more Aims: The onset of blast crisis (BC) in initially chronic phase (CP) CML patients that entered treatment-free remission (TFR) after TKI is an exceptional event, however, there is emerging evidence that this may occur in such patients (pts), although the pathogenesis remains unclear to date. Methods: Anonymous clinical case retrospective data collection from patients&amp;#39; datafiles, after written agreement of living patients, centralisation of available frozen nucleic acid collection from diagnosis and from blast crisis and reanalysis by Next-Generation Sequencing of samples (ASXL1, ASXL2, BCOR, CALR, CBL, CEBP alpha , CSF3R, DNMT3A, EP300, ETNK1, ETV6, EZH2, FLT3, GATA2, IDH1, IDH2 JAK2, KIT, , KRAS,MPL, NPM1, NRAS, PHF6, PTPN11 , RAD2, RUNX1, SETBP1, SF3B1, SH2B3, SMC1A, SMC3, SRSF2, STAG1, STAG2, TET2, TP53, U2AF1, WT1 and ZRSR2 genes analysed) on Illumina platform. CNV analysis were performed using VisCAp or in-house pipelines and/or by Multiplex Ligation Dependant Probe Amplification (MLPA). ABL1 tyrosine kinase domain mutations were screened by NGS on cDNA or directly on DNA. BCR-ABL1 transcripts are expressed in % (IS) with at least 32,000 copies of ABL1 as control. All patients discontinued their TKI after 2 years of MR4.5 and a TKI was resumed in case of MMR loss. Results: Along 15-year experience of TFR in our country and ≥ ~800 patients experiencing a TKI cessation attempt, informations from 4 (~0.5%) TFR CML patients entering BC have been collected. All patients harboured Major BCR transcripts. The chronic phase characteristics are mentioned in Table 1. All these long-lasting CP CML pts were ELTS risk score low, and 1 was harbouring ACA at diagnosis. One pt was mutated for ASXL2 and 2 mutations for EP300, found again at BC. Three pts had IFN-a prior to imatinib for all. Three out of 4 lost their MMR after a first cessation attempt at 12, 10 and 3 months after cessation. Pt #1 experienced a 2 nd cessation attempt 52 months after re-initiation of TKIs and entered lymphoid BC 6 months after a second resumption of TKI for a 2 nd MMR loss. The BC characteristics are mentioned in Table 2. Three out of 4 BC were lymphoid, one had ACA different from those at CP diagnosis. Two pts explored had multiple mutations in Runx1, U2AF1, EP300 and ASXL2 genes, not present at CP diagnosis, in addition to multiple ABL1 mutations in 2 out of 4 pts (2 T315I, 3 P-Loop mutations). All pts underwent chemotherapy + various TKI leading to complete remission (CR) in all and 3 out of 4 pts could be allotransplanted in CR, one relapsed shortly after transplant, and a second one 34 months after transplant. Overall 3 pts are alive with 1 in controlled relapse. Conclusions: The onset of BC after TFR for sustained deep molecular response remains an exceptional event and is probably not induced by this therapeutic procedure. These 4 cases underline the need for a sustained long-lasting molecular follow-up of pts in TFR, although the majority of these BC seem sudden. Figure 1 Figure 1. Disclosures Bauduer: Sanofi: Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees, Research Funding. Rea: Novartis: Consultancy, Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees. Nicolini: Novartis: Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees, Other: travel, accommodations, expenses, Research Funding; Sun Pharma Ltd.: Consultancy, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Kartos Therapeutics: Consultancy, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Incyte Biosciences: Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; BMS: Honoraria.
Introduction La plupart des etiologies courantes de splenomegalies (SMG) sont facilement identifi... more Introduction La plupart des etiologies courantes de splenomegalies (SMG) sont facilement identifiees en pratique clinique courante. Cependant, une fois ces diagnostics de premiere intention ecartes, la demarche diagnostique est alors un vrai defi, la SMG pouvant etre associee a des etiologies plus rares comme les maladies de surcharge lysosomale (MSL). L’etude SMS (SplenoMegaly Study) est une etude francaise prospective, observationnelle, multicentrique et longitudinale, qui a pour objectif d’estimer la prevalence des differentes etiologies de SMG inexpliquees. Les resultats intermediaires presentes ici portent sur les caracteristiques des patients et les tests et diagnostics etablis lors du suivi. Patients et methodes Depuis 2015, tout patient âge de 15 ans et plus et adresse vers un service d’hematologie ou de medecine interne des 118 hopitaux participants, avec une SMG d’etiologie inexpliquee (definie comme d’origine inconnue apres exclusion des diagnostics de premiere intention sur la base d’un interrogatoire, d’un examen clinique et d’un bilan biologique de routine) ont ete inclus. Pour chaque patient, la derniere visite a lieu lorsqu’une etiologie est identifiee ou jusqu’a 12 mois apres l’inclusion. Comme il n’existe pas de definition precise de SMG, l’application Splenocalc [Chow and al., 2016], a ete utilisee pour confirmer la SMG. L’objectif est d’inclure 500 patients. Resultats En septembre 2019, 374 patients (60 % d’hommes) ont ete inclus, avec un âge median de 53 ans (16–94 ans), une longueur mediane de la rate de 15 cm (13–30 cm) et une structure homogene de la rate pour 88 % d’entre eux. Une echographie et un scanner ont ete realises pour confirmer la SMG chez respectivement 53 % et 46 % des patients. Au total, 276 patients (74 %) ont termine l’etude, dont 138 (50 %) ont eu un diagnostic etabli. Par rapport aux patients restes sans diagnostic, les patients avec un diagnostic sont plus âges (âge median 62,0 ans contre 45,5 ans ; p Conclusion La SMG inexpliquee semble etre un challenge diagnostique pour lequel l’interniste et l’hematologue ont un role cle. Apres 12 mois d’investigations regulieres, 50 % des patients sont restes sans diagnostic. Les patients avec un diagnostic etabli, en particulier ceux avec des hemopathies malignes, sont plus âges et ont une rate de taille plus importante que les patients restes sans diagnostic. La BOM semble etre un examen utile dans la demarche diagnostique. Les pathologies non malignes representent 65 % des diagnostics. Ces resultats intermediaires doivent etre interpretes avec prudence car la population cible n’a pas encore ete atteinte. Les resultats definitifs sont attendus en 2021. Cette etude SMS est sponsorisee par Sanofi Genzyme.
The case of a 37-year-old male who developed multiple asynchronous extramedullary plasmocytoma lo... more The case of a 37-year-old male who developed multiple asynchronous extramedullary plasmocytoma localizations is reported. The first site involved was the cecum. Other tumors successively arose in the chest wall, testis, buttock, nasal cavity, skin, and mediastinum. The patient died 59 months after initial diagnosis. Light microscopy and ultrastructural studies disclosed a substantial proportion of immature plasmocytes in the different tumors, explaining in part the poor activity of radiotherapy and chemotherapy. Although in many cases this clinical pattern indicates multiple myeloma, investigations failed to detect this condition in the patient reported here. Shortly before the fatal outcome, a peak of IgA kappa globulin was detected in the serum. This immunoglobulin was also identified on tumor cells using immunoperoxidase labeling.
We report a study on 809 births and 885 deaths collected from the civil registries of the Pyrenea... more We report a study on 809 births and 885 deaths collected from the civil registries of the Pyrenean village of Beost, Ossau Valley, Bearn, France, during the entire 19th century. Among the studied parameters, some give us interesting data on the population history. Thus, the rate of mortality under 1 year of age (110,7 per thousand), the global longevity of this population (mean age at death: 45,8 years) and the absence of significant increase in mortality during the winter months and periods of difficulty for food availability argue in favor of a quite satisfactory sanitary level. Nevertheless, the reduced longevity of illegitimate children (nine deaths often before the age of 7) suggests an absence of care for this population category who was socially rejected. Furthermore, the proportion of women dying between 21 and 40 years of age was twice than that of men, which could be explained by maternity-related medical complications. The seasonality of births (and therefore of conceptions) is less typical than in the other mountain populations. Finally, we may note an increased mortality at the end of 1856 due to a cholera epidemic and in 1870 because of small pox.
The therapeutic strategy in multiple myeloma depends on age and tumor mass. Stage I must not be t... more The therapeutic strategy in multiple myeloma depends on age and tumor mass. Stage I must not be treated. The Melphalan Prednisone regimen is the reference for induction therapy because polychemotherapies are generally not superior. At this phase, the addition of Interferon alpha seems to be interesting. This drug has an important role during the steady-state phase. VAD represents the most efficient chemotherapy. Body hemi-irradiation is also useful. The analgesic effect and the decrease in the tumoral mass are the striking effects of this treatment. In young patients, high dose chemotherapy with bone marrow transplantation is proposed. Verapamil and anti-IL6 antibodies are currently being evaluated. Symptomatic treatment is essential in this non curable disease.
In this study the authors compare two automated coagulation instruments: the koagulab-40A (Orthod... more In this study the authors compare two automated coagulation instruments: the koagulab-40A (Orthodiagnostics Systems) and l'ACL-100 (Instrumentation Laboratory) using two different methods of detection, photo-optical and nephelemetric respectively. The three parameters studied are: prothrombin time (PT) (82 samples), activated partial thromboplastin time (APTT) (86 samples) and fibrinogenemia (FIB) (109 samples). For each test, they use two reagents of different origins. Samples come from people without any haemostatic disorder and from patients showing abnormal levels of these parameters (heparins or antivitamins K treatments, hypo or hyperfibrinogenemias). For the tree parameters examined, they obtain coefficients of correlation: 0.94 to 0.99 between the two instruments. These values are not noticeably modified by reagent substitution. For fibrinogenemia, the coefficient of variation (CV) is about 4%. Finally, in comparison with the photooptical classical method, the ACL-100 is more rapid, more economical (reduced volumes of reagents) and more feasible (dilutions of plasmas and tubulure changing are not necessary for fibrinogen).
Our knowledge about ancient Egyptian medicine (throughout more than three millennia) comes from s... more Our knowledge about ancient Egyptian medicine (throughout more than three millennia) comes from some papyri, as those of Ebers and Smith, thousands of mummies or skeletons and multiple temples and tumbs decorations. Doctors were initially priests and embalmers which explain their good level in anatomy. The most famous of all, imhotep, who was also architect and minister, became a god of medicine. First hospitals developed from temples. Modern investigation tools are useful for studying on human remains the most prevalent diseases at these times which are comparable with our current medical problems. An increasing number of scientific data, which some examples are reported herein, argue in favor of a fascinating level of advancement of ancient Egyptian medicine in the field of diagnosis and therapy.
Autoimmune neutropenia (AIN) is a rare hematological disorder for which no standard treatment has... more Autoimmune neutropenia (AIN) is a rare hematological disorder for which no standard treatment has been established so far. A brief review of the literature is presented herein concerning the use of G-CSF in this indication. The good results in terms of neutrophils increment and infection prophylaxis render G-CSF attractive for treating AIN. Hypotheses explaining its mechanisms of action are also discussed.
We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old wom... more We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old woman with chronic myeloid leukemia (CML), 6 years after allogeneic bone marrow transplantation (BMT) following total body irradiation (TBI) (12 Gy) and cyclophosphamide 120 mg/kg. The first attempt at implantation with her own cryopreserved ovocytes was unsuccessful. Thereafter, she became pregnant after donated oocyte implantation using estradiol and progesterone support replacing the defective ovarian function. The baby was normal. Unfortunately, 6 months later, she relapsed in chronic phase of CML.
Background: The nutritional status of older persons suffering from various medical or surgical co... more Background: The nutritional status of older persons suffering from various medical or surgical conditions has been well reported. However, studies focusing on hematology patients are very rare. Objective: Our aim was to obtain a photographic picture of the nutritional profile of a sample population treated for miscellaneous blood disorders, to compare our results with those obtained in other types of diseases and to isolate risk-factors for undernutrition. Design: One hundred-twenty free living hematology patients aged over 60-year were prospectively and randomly tested the day of their admission to either our out- or inpatient clinic (department of clinical hematology from a French general hospital) using the mininutritional assessment (MNA). We compared our data with those from the literature and the role of various risk-factors was evaluated using the chi-square or the Fisher exact test. Results: The sex ratio was 1 and the median age 74 (range: 60-97). The majority of this population suffered from malignant disorders (101 cases, 84%) and fifty-three of them received chemotherapy. Eighty individuals (66%) were tested at the outpatient unit. The mean MNA score was 22.8 (range: 7.5-30). Sixteen patients (13%) were categorized as in poor nutritional status (MNA< 17). In this subgroup, more than 3 drugs intake (p < 0.01) and recent weight loss (p = 0.015) were the most important MNA parameters predicting malnutrition (age, sex, disease type or duration being no significant risk-factors). Our MNA results compared favorably with those obtained in other medical or surgical specialties. Conclusion: Undernutrition does not appear more prevalent in the elderly hematology population in comparison with patients suffering from other diseases. However, because nutritional status may influence the outcome, especially in case of blood neoplasms, MNA (or other more sophisticated biological tools) should be included in the evaluation of this population.
We have studied the kinetics of the N-terminal peptide of type III procollagen (NP3P) after BMT a... more We have studied the kinetics of the N-terminal peptide of type III procollagen (NP3P) after BMT as a marker for the development of hepatic fibrosis in veno-occlusive disease (VOD). Four patients with clinically apparent VOD were retrospectively assayed and demonstrated a very high NP3P level. NP3P was also prospectively monitored at the beginning of conditioning and every week (8 patients) or every other day (14 patients) from the day of BMT (day 0) to day +28. Before conditioning the NP3P level (15.5 +/- 5.5 ng/ml) was twice normal and increased during the course of BMT in patients without VOD (21 ng/ml; range 6-35 ng/ml). In four patients who experienced VOD, the NP3P level exceeded 40 ng/ml by day 0 in two. The early rise of NP3P indicates that it is a valuable marker for the development of VOD before it becomes clinically apparent. These data suggest that VOD develops during preparation for BMT and that prophylaxis should therefore be started at this time.
The most prevalent etiologies of splenomegaly (SM) are easily detected in routine clinical practi... more The most prevalent etiologies of splenomegaly (SM) are easily detected in routine clinical practice. However, after these first-line diagnoses have been ruled out, many cases remain unexplained. Frequently, signs and symptoms are non-specific hiding rare etiologies such as Lysosomal Storage Diseases (LSD) (e.g., Gaucher disease (GD), Niemann-Pick disease type B). SplenoMegaly Study (SMS) aims to estimate the prevalence of different etiologies in unexplained SM and to describe their diagnostic work-up. We present here the final results of the study. SMS is a prospective, observational, multi-center, longitudinal study performed in France. All patients with unexplained SM, aged ≥15 years, consulting to the French hematology or internal medicine departments were invited to take part of the study. SM was confirmed by echography or CT-scan with a craniocaudal length ≥13 cm; unexplained was defined as negative clinical and biological routine workup. All conducted exams and tests for diagnosis purpose were under each physician's responsibility. For each patient, last visit took place when an etiology was identified or up to 12 months after inclusion. From Sept-2015 to Apr-2020, 505 patients were enrolled by 87 centers (secondary centers [71.3%] and tertiary centers [28.7%]). Physicians were mainly internists (52.9%) or hematologists (46.0%). Patients characteristics at inclusion were as follows: male gender, 61.2%; median age, 51.0 years old (16-94 years old); median spleen length, 15.0 cm (13-30 cm); heterogeneous spleen structure, 11.1%. A total of 501 patients completed the study. After a median duration of 6.6 months, 232 patients (46.3%) received a diagnosis. When compared to patients without diagnosis, patients with diagnosis were older (median age 59.5 vs 45.0; p<0.001), had more often a massive SM (≥18 cm) (25.2% vs 10.7%; p<0.001) and heterogeneous spleen structure (15.9% vs 6.6%; p=0.002). Their biological test results (hemoglobin, leucocytes, CRP, albumin) were also significantly altered and they showed more constitutional (48.3% vs 37.3%) and digestive symptoms (41.9% vs 28.4%) compared to patients without diagnosis. The proportion of diagnosed patients was higher in tertiary than secondary centers (55.2% vs 32.6%). Hematological (lymphoid and myeloid) malignancies represented only 38.7% (n=87) of established diagnoses (Figure 1). Non-malignant diseases, accounted for 61.3% of diagnosis, were: autoimmune disorders (20.0%, n=45), portal hypertension (12.0%, n=27), infectious diseases (11.6%, n=26), LSD (4.4% [n=10], including type 1 Gaucher Disease (GD1) [n=4]; Niemann-Pick disease type B [n=3] and type C [n=2]; and Fabry disease [n=1]), other disorders (13.3%, n=30) and non-specified (3%, n=7). Hematological malignancies were more common in elderly patients (median age 66.0, p<0.001) with massive SM (p<0.001). Compared to other diagnoses, a large proportion of patients diagnosed with portal hypertension were obese (51.9%) and had ongoing metabolism or nutrition disorders (40.7%). Patients with autoimmune disorders had higher CRP levels (median value, 11.5 mg/L) and showed more osteoarticular symptoms (34.8%). All 4 GD1 patients had thrombocytopenia (≤100G/L platelets). Among the tests contributing to diagnosis, biopsies were performed in 34.3% (n=172) of patients, mainly bone marrow trephine biopsy (BMTB) (20.8%, n=104). Half of patients with BMTB received a diagnosis. Splenectomy was performed in 19 patients (4.0%) and was conclusive in 14 of them. β-Glucocerebrosidase activity assay to test for GD was performed in 79.8% of patients. Among patients without diagnosis, 22.7% of them were not tested for GD. In SMS, patients at inclusion had unexplained SM despite routine clinical and biologic analysis. The diagnostic yield improved after further medical evaluations reaching an etiologic diagnosis in 46% of patients. Patients with an established diagnosis were older, had a larger spleen and altered biological parameters compared to patients without diagnosis. Interestingly, non-malignant diseases accounted for 61.3% of diagnoses. It is noteworthy the diversity of LSD etiologies obtained: 10 patients (4%) were diagnosed with LSD, including 4 GD1 patients. This study provides useful new information to optimize the diagnostic strategy of splenomegaly poorly explained by routine workup. SMS is sponsored by Sanofi-Genzyme. Figure 1 Figure 1. Denis: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Séné: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Costello: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Michaud: Sanofi: Honoraria, Research Funding. Hellé: Sanofi: Current Employment. Lagadec: Sanofi: Current Employment.…
Aims: The onset of blast crisis (BC) in initially chronic phase (CP) CML patients that entered tr... more Aims: The onset of blast crisis (BC) in initially chronic phase (CP) CML patients that entered treatment-free remission (TFR) after TKI is an exceptional event, however, there is emerging evidence that this may occur in such patients (pts), although the pathogenesis remains unclear to date. Methods: Anonymous clinical case retrospective data collection from patients&amp;#39; datafiles, after written agreement of living patients, centralisation of available frozen nucleic acid collection from diagnosis and from blast crisis and reanalysis by Next-Generation Sequencing of samples (ASXL1, ASXL2, BCOR, CALR, CBL, CEBP alpha , CSF3R, DNMT3A, EP300, ETNK1, ETV6, EZH2, FLT3, GATA2, IDH1, IDH2 JAK2, KIT, , KRAS,MPL, NPM1, NRAS, PHF6, PTPN11 , RAD2, RUNX1, SETBP1, SF3B1, SH2B3, SMC1A, SMC3, SRSF2, STAG1, STAG2, TET2, TP53, U2AF1, WT1 and ZRSR2 genes analysed) on Illumina platform. CNV analysis were performed using VisCAp or in-house pipelines and/or by Multiplex Ligation Dependant Probe Amplification (MLPA). ABL1 tyrosine kinase domain mutations were screened by NGS on cDNA or directly on DNA. BCR-ABL1 transcripts are expressed in % (IS) with at least 32,000 copies of ABL1 as control. All patients discontinued their TKI after 2 years of MR4.5 and a TKI was resumed in case of MMR loss. Results: Along 15-year experience of TFR in our country and ≥ ~800 patients experiencing a TKI cessation attempt, informations from 4 (~0.5%) TFR CML patients entering BC have been collected. All patients harboured Major BCR transcripts. The chronic phase characteristics are mentioned in Table 1. All these long-lasting CP CML pts were ELTS risk score low, and 1 was harbouring ACA at diagnosis. One pt was mutated for ASXL2 and 2 mutations for EP300, found again at BC. Three pts had IFN-a prior to imatinib for all. Three out of 4 lost their MMR after a first cessation attempt at 12, 10 and 3 months after cessation. Pt #1 experienced a 2 nd cessation attempt 52 months after re-initiation of TKIs and entered lymphoid BC 6 months after a second resumption of TKI for a 2 nd MMR loss. The BC characteristics are mentioned in Table 2. Three out of 4 BC were lymphoid, one had ACA different from those at CP diagnosis. Two pts explored had multiple mutations in Runx1, U2AF1, EP300 and ASXL2 genes, not present at CP diagnosis, in addition to multiple ABL1 mutations in 2 out of 4 pts (2 T315I, 3 P-Loop mutations). All pts underwent chemotherapy + various TKI leading to complete remission (CR) in all and 3 out of 4 pts could be allotransplanted in CR, one relapsed shortly after transplant, and a second one 34 months after transplant. Overall 3 pts are alive with 1 in controlled relapse. Conclusions: The onset of BC after TFR for sustained deep molecular response remains an exceptional event and is probably not induced by this therapeutic procedure. These 4 cases underline the need for a sustained long-lasting molecular follow-up of pts in TFR, although the majority of these BC seem sudden. Figure 1 Figure 1. Disclosures Bauduer: Sanofi: Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees, Research Funding. Rea: Novartis: Consultancy, Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees. Nicolini: Novartis: Honoraria, Membership on an entity&amp;#39;s Board of Directors or advisory committees, Other: travel, accommodations, expenses, Research Funding; Sun Pharma Ltd.: Consultancy, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Kartos Therapeutics: Consultancy, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Incyte Biosciences: Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; BMS: Honoraria.
Introduction La plupart des etiologies courantes de splenomegalies (SMG) sont facilement identifi... more Introduction La plupart des etiologies courantes de splenomegalies (SMG) sont facilement identifiees en pratique clinique courante. Cependant, une fois ces diagnostics de premiere intention ecartes, la demarche diagnostique est alors un vrai defi, la SMG pouvant etre associee a des etiologies plus rares comme les maladies de surcharge lysosomale (MSL). L’etude SMS (SplenoMegaly Study) est une etude francaise prospective, observationnelle, multicentrique et longitudinale, qui a pour objectif d’estimer la prevalence des differentes etiologies de SMG inexpliquees. Les resultats intermediaires presentes ici portent sur les caracteristiques des patients et les tests et diagnostics etablis lors du suivi. Patients et methodes Depuis 2015, tout patient âge de 15 ans et plus et adresse vers un service d’hematologie ou de medecine interne des 118 hopitaux participants, avec une SMG d’etiologie inexpliquee (definie comme d’origine inconnue apres exclusion des diagnostics de premiere intention sur la base d’un interrogatoire, d’un examen clinique et d’un bilan biologique de routine) ont ete inclus. Pour chaque patient, la derniere visite a lieu lorsqu’une etiologie est identifiee ou jusqu’a 12 mois apres l’inclusion. Comme il n’existe pas de definition precise de SMG, l’application Splenocalc [Chow and al., 2016], a ete utilisee pour confirmer la SMG. L’objectif est d’inclure 500 patients. Resultats En septembre 2019, 374 patients (60 % d’hommes) ont ete inclus, avec un âge median de 53 ans (16–94 ans), une longueur mediane de la rate de 15 cm (13–30 cm) et une structure homogene de la rate pour 88 % d’entre eux. Une echographie et un scanner ont ete realises pour confirmer la SMG chez respectivement 53 % et 46 % des patients. Au total, 276 patients (74 %) ont termine l’etude, dont 138 (50 %) ont eu un diagnostic etabli. Par rapport aux patients restes sans diagnostic, les patients avec un diagnostic sont plus âges (âge median 62,0 ans contre 45,5 ans ; p Conclusion La SMG inexpliquee semble etre un challenge diagnostique pour lequel l’interniste et l’hematologue ont un role cle. Apres 12 mois d’investigations regulieres, 50 % des patients sont restes sans diagnostic. Les patients avec un diagnostic etabli, en particulier ceux avec des hemopathies malignes, sont plus âges et ont une rate de taille plus importante que les patients restes sans diagnostic. La BOM semble etre un examen utile dans la demarche diagnostique. Les pathologies non malignes representent 65 % des diagnostics. Ces resultats intermediaires doivent etre interpretes avec prudence car la population cible n’a pas encore ete atteinte. Les resultats definitifs sont attendus en 2021. Cette etude SMS est sponsorisee par Sanofi Genzyme.
The case of a 37-year-old male who developed multiple asynchronous extramedullary plasmocytoma lo... more The case of a 37-year-old male who developed multiple asynchronous extramedullary plasmocytoma localizations is reported. The first site involved was the cecum. Other tumors successively arose in the chest wall, testis, buttock, nasal cavity, skin, and mediastinum. The patient died 59 months after initial diagnosis. Light microscopy and ultrastructural studies disclosed a substantial proportion of immature plasmocytes in the different tumors, explaining in part the poor activity of radiotherapy and chemotherapy. Although in many cases this clinical pattern indicates multiple myeloma, investigations failed to detect this condition in the patient reported here. Shortly before the fatal outcome, a peak of IgA kappa globulin was detected in the serum. This immunoglobulin was also identified on tumor cells using immunoperoxidase labeling.
We report a study on 809 births and 885 deaths collected from the civil registries of the Pyrenea... more We report a study on 809 births and 885 deaths collected from the civil registries of the Pyrenean village of Beost, Ossau Valley, Bearn, France, during the entire 19th century. Among the studied parameters, some give us interesting data on the population history. Thus, the rate of mortality under 1 year of age (110,7 per thousand), the global longevity of this population (mean age at death: 45,8 years) and the absence of significant increase in mortality during the winter months and periods of difficulty for food availability argue in favor of a quite satisfactory sanitary level. Nevertheless, the reduced longevity of illegitimate children (nine deaths often before the age of 7) suggests an absence of care for this population category who was socially rejected. Furthermore, the proportion of women dying between 21 and 40 years of age was twice than that of men, which could be explained by maternity-related medical complications. The seasonality of births (and therefore of conceptions) is less typical than in the other mountain populations. Finally, we may note an increased mortality at the end of 1856 due to a cholera epidemic and in 1870 because of small pox.
The therapeutic strategy in multiple myeloma depends on age and tumor mass. Stage I must not be t... more The therapeutic strategy in multiple myeloma depends on age and tumor mass. Stage I must not be treated. The Melphalan Prednisone regimen is the reference for induction therapy because polychemotherapies are generally not superior. At this phase, the addition of Interferon alpha seems to be interesting. This drug has an important role during the steady-state phase. VAD represents the most efficient chemotherapy. Body hemi-irradiation is also useful. The analgesic effect and the decrease in the tumoral mass are the striking effects of this treatment. In young patients, high dose chemotherapy with bone marrow transplantation is proposed. Verapamil and anti-IL6 antibodies are currently being evaluated. Symptomatic treatment is essential in this non curable disease.
In this study the authors compare two automated coagulation instruments: the koagulab-40A (Orthod... more In this study the authors compare two automated coagulation instruments: the koagulab-40A (Orthodiagnostics Systems) and l'ACL-100 (Instrumentation Laboratory) using two different methods of detection, photo-optical and nephelemetric respectively. The three parameters studied are: prothrombin time (PT) (82 samples), activated partial thromboplastin time (APTT) (86 samples) and fibrinogenemia (FIB) (109 samples). For each test, they use two reagents of different origins. Samples come from people without any haemostatic disorder and from patients showing abnormal levels of these parameters (heparins or antivitamins K treatments, hypo or hyperfibrinogenemias). For the tree parameters examined, they obtain coefficients of correlation: 0.94 to 0.99 between the two instruments. These values are not noticeably modified by reagent substitution. For fibrinogenemia, the coefficient of variation (CV) is about 4%. Finally, in comparison with the photooptical classical method, the ACL-100 is more rapid, more economical (reduced volumes of reagents) and more feasible (dilutions of plasmas and tubulure changing are not necessary for fibrinogen).
Our knowledge about ancient Egyptian medicine (throughout more than three millennia) comes from s... more Our knowledge about ancient Egyptian medicine (throughout more than three millennia) comes from some papyri, as those of Ebers and Smith, thousands of mummies or skeletons and multiple temples and tumbs decorations. Doctors were initially priests and embalmers which explain their good level in anatomy. The most famous of all, imhotep, who was also architect and minister, became a god of medicine. First hospitals developed from temples. Modern investigation tools are useful for studying on human remains the most prevalent diseases at these times which are comparable with our current medical problems. An increasing number of scientific data, which some examples are reported herein, argue in favor of a fascinating level of advancement of ancient Egyptian medicine in the field of diagnosis and therapy.
Autoimmune neutropenia (AIN) is a rare hematological disorder for which no standard treatment has... more Autoimmune neutropenia (AIN) is a rare hematological disorder for which no standard treatment has been established so far. A brief review of the literature is presented herein concerning the use of G-CSF in this indication. The good results in terms of neutrophils increment and infection prophylaxis render G-CSF attractive for treating AIN. Hypotheses explaining its mechanisms of action are also discussed.
We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old wom... more We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old woman with chronic myeloid leukemia (CML), 6 years after allogeneic bone marrow transplantation (BMT) following total body irradiation (TBI) (12 Gy) and cyclophosphamide 120 mg/kg. The first attempt at implantation with her own cryopreserved ovocytes was unsuccessful. Thereafter, she became pregnant after donated oocyte implantation using estradiol and progesterone support replacing the defective ovarian function. The baby was normal. Unfortunately, 6 months later, she relapsed in chronic phase of CML.
Background: The nutritional status of older persons suffering from various medical or surgical co... more Background: The nutritional status of older persons suffering from various medical or surgical conditions has been well reported. However, studies focusing on hematology patients are very rare. Objective: Our aim was to obtain a photographic picture of the nutritional profile of a sample population treated for miscellaneous blood disorders, to compare our results with those obtained in other types of diseases and to isolate risk-factors for undernutrition. Design: One hundred-twenty free living hematology patients aged over 60-year were prospectively and randomly tested the day of their admission to either our out- or inpatient clinic (department of clinical hematology from a French general hospital) using the mininutritional assessment (MNA). We compared our data with those from the literature and the role of various risk-factors was evaluated using the chi-square or the Fisher exact test. Results: The sex ratio was 1 and the median age 74 (range: 60-97). The majority of this population suffered from malignant disorders (101 cases, 84%) and fifty-three of them received chemotherapy. Eighty individuals (66%) were tested at the outpatient unit. The mean MNA score was 22.8 (range: 7.5-30). Sixteen patients (13%) were categorized as in poor nutritional status (MNA< 17). In this subgroup, more than 3 drugs intake (p < 0.01) and recent weight loss (p = 0.015) were the most important MNA parameters predicting malnutrition (age, sex, disease type or duration being no significant risk-factors). Our MNA results compared favorably with those obtained in other medical or surgical specialties. Conclusion: Undernutrition does not appear more prevalent in the elderly hematology population in comparison with patients suffering from other diseases. However, because nutritional status may influence the outcome, especially in case of blood neoplasms, MNA (or other more sophisticated biological tools) should be included in the evaluation of this population.
We have studied the kinetics of the N-terminal peptide of type III procollagen (NP3P) after BMT a... more We have studied the kinetics of the N-terminal peptide of type III procollagen (NP3P) after BMT as a marker for the development of hepatic fibrosis in veno-occlusive disease (VOD). Four patients with clinically apparent VOD were retrospectively assayed and demonstrated a very high NP3P level. NP3P was also prospectively monitored at the beginning of conditioning and every week (8 patients) or every other day (14 patients) from the day of BMT (day 0) to day +28. Before conditioning the NP3P level (15.5 +/- 5.5 ng/ml) was twice normal and increased during the course of BMT in patients without VOD (21 ng/ml; range 6-35 ng/ml). In four patients who experienced VOD, the NP3P level exceeded 40 ng/ml by day 0 in two. The early rise of NP3P indicates that it is a valuable marker for the development of VOD before it becomes clinically apparent. These data suggest that VOD develops during preparation for BMT and that prophylaxis should therefore be started at this time.
Uploads
Papers by frederic bauduer