Background: Epidemiological data on MDS is scarce in France, and registries from other countries ... more Background: Epidemiological data on MDS is scarce in France, and registries from other countries do not provide data on the daily practice management of MDS in 2008. Methods: GFM centers were asked to collect characteristics of ongoing or recent treatments in all MDS patients (pts) seen at their clinic (as in or outpatients) during the Jan 28th–Feb 3rd, 2008 period (one week).Results: 919 pts from 74 centers were included, 57% males, mean age (+/− SD), 73 (±11) years, with 2.8%, 19% and 28% of pts aged <50, <65 and >80 years, respectively (resp).13% of pts were hospitalized >24h (4.5% for infections or bleeding and 8.5 % for “active” treatments), 46% were seen in the day care facility (40% for transfusions), and 41% as consultations (for staging, follow up or ambulatory treatment). 93% of patients had PS ≤2. Median interval from diagnosis to survey was 29.2 months. FAB at time of survey was: 35.1% RA, 18.5% RARS, 39.1% RAEB, 7.4% CMML; WHO was: 17.4% RA, 13.3% RARS, 14% ...
With TKIs, the management of CML has radically changed. Here we present the case of a woman diagn... more With TKIs, the management of CML has radically changed. Here we present the case of a woman diagnosed with CML during two pregnancies. Medullary and complete cytogenetic remission was achieved with Imatinib. However, she developed major muscular intolerance. This patient expressed the wish to have children. Hematology experts advised to delay her plan to become pregnant. According to BCR/ABL transcripts levels, they also decided to substitute Imatinib for Dasatinib. A major molecular response was subsequently observed with disappearance of muscular toxicity. It was then decided to interrupt Dasatinib treatment and to substitute with pegylated interferon for the duration of the pregnancy. After a normal full term pregnancy, she gave birth to a baby boy. Dasatinib treatment was reintroduced. A year later, the patient became pregnant for a second time. Dasatinib treatment was interrupted and substituted with pegylated interferon. After a normal pregnancy, she gave birth to a baby girl. Dasatinib treatment was then reintroduced. This case report highlights the possibility for CML patients whose disease is stabilized to interrupt Dasatinib treatment and substitute with pegylated interferon during pregnancy without jeopardizing the patient outcome or exposing the fetus to TKI associated teratogen risks.
A 71-year-old female patient with no major history of infection had presented with recurrent chro... more A 71-year-old female patient with no major history of infection had presented with recurrent chronic purulent sinusitis over the past 3 years. These recurrent infections started in 2000 with otolaryngologists' support before diagnosis of IgG4 deficiency be asked. The patient was treated with increasingly extensive courses of antibiotics and underwent several maxillary and sphenoidal sinus washouts. She continued to present with purulent nasal discharge containing Staphylococcus epidermidis. The blood and immune work-ups were normal. Her antinuclear antibody count was 1/320, with no unusual types. The total immunoglobulin (Ig)E, serology, CD4 count, and lymphocyte B phenotype results were all normal. No humoral immune deficiency was detected. The analyses confirmed an underlying specific IgG4 deficiency with values of 3-4 mg/L over 4 months. The patient was treated in March 2011 with prophylactic antibiotic therapy, sinus drainage, and IV infusions of enriched immunoglobulins (IV...
Paroxysmal nocturnal hemoglobinurea (PNH) is a rare disorder of complement regulation due to soma... more Paroxysmal nocturnal hemoglobinurea (PNH) is a rare disorder of complement regulation due to somatic mutation of PIGA (phosphatidylinositol glycan anchor) gene. We herewith report a case who developed a symptomatic PNH long after an allogenic marrow transplant. Some reasonable arguments concerning the origin of PNH clone have been discussed. The molecular studies revealed presence of JAK2 and TET2 mutations without a BCOR mutation. The literature review has been performed to probe into the complex interplay of autoimmunity and clonal selection and expansion of PNH cells, which occurs early in hematopoietic differentiation. The consequent events such as hypoplastic and/or hemato-oncologic features could further be explained on the basis of next-generation sequencing (NGS) studies. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder of hematopoietic stem cells, characterized by a somatic mutation of the phosphatidylinositol glycan-class A (PIGA). The PIGA gene products...
L'erythropoietine recombinante est produite depuis 1988. Son utilisation constitue un progres... more L'erythropoietine recombinante est produite depuis 1988. Son utilisation constitue un progres significatif, en particulier pour les insuffisants renaux, victimes d'anemie severe qui necessitait auparavant la realisation de transfusions repetees. L'erythropoietine recombinante est aujourd'hui employee de maniere de plus en plus frequente dans les anemies de certaines maladies hematologiques comme les myelodysplasies ou dans les suites de certaines chimiotherapies anti-neoplasiques. L'erythropoietine accelere de maniere efficace la production des globules rouges. L'augmentation de la masse globulaire circulante permet un meilleur transport de l'oxygene a destination des tissus. Le transport d'oxygene est un facteur significatif de l'augmentation de la production d'energie a travers la filiere aerobie. Il y a donc une correlation positive entre l'augmentation des globules rouges circulant et l'amelioration des qualites sportives dans les ...
We report data about 50 caucasian top-level cyclists (45 males, 5 women, aged between 16 and 36 y... more We report data about 50 caucasian top-level cyclists (45 males, 5 women, aged between 16 and 36 years, mean 25 +/- 4.5). Recruitment was by controlling top-level athletes in order to follow their blood cell counts to detect variation in haemoglobin concentration and hematocrit level (prevention of erythropoietin abuse). All samples were drawn in the morning, when the cyclists were at rest, according to a standardized protocol. Erythroblastic serie was abnormal in several cases (4 anaemias, 3 macrocytosis, 6 low haematocrit level, 10 mean cell haemoglobin higher than 32 pg, low reticulocyte count). White blood cells showed a trend toward low counts for neutrophils and lymphocytes. Two cyclists had platelets counts below 150.109/l. Our data indicated that top-level cyclism had some effects on the blood cell counts, which is likely to indicate an effect of intense aerobic training on physiological status.
We report data about 50 caucasian top-level cyclists (45 males, 5 womens, aged between 16 and 36 ... more We report data about 50 caucasian top-level cyclists (45 males, 5 womens, aged between 16 and 36 years, mean 25 ± 4.5). Recruitment was by controling top-level athletes in order to follow their blood cell counts to detect variation in haemoglobin concentration and hematocrit level (prevention of erythropoietin abuse). All samples were drawn in the morning, when the cyclists were at rest, according to a standardized protocol. Erythroblastic serie was abnormal in several cases (4 anaemias, 3 macrocytosis, 6 low haematocrit level, 10 mean cell haemoglobin higher than 32 pg, low reticulocyte count). White blood cells showed a trend toward low counts for neutrophils and lymphocytes. Two cyclists had platelets counts below 150.109/l. Our data indicated that top-level cyclism had some effects on the blood cell counts, which is likely to indicate an effect of intense aerobic training on physiological status.
Day care is a potential alternative to inpatient care of cancer patients. Using day care reduces ... more Day care is a potential alternative to inpatient care of cancer patients. Using day care reduces medical costs substantially compared to inpatient care, which is driving the transfer of many inpatient chemotherapy protocols to day care hospitals (DCHs). However, in contrast to inpatient management, day care provides limited observation time, which could increase the risk of renal toxicity when using these protocols. We present a case report of acute kidney injury following high-dose methotrexate administration in a DCH. Based on a review of the current literature on acid-base balance, we also discuss appropriate patient selection and judicious hydration and urine alkalinization so as to prevent toxicity in the day care setting.
Background Myelodysplastic syndrome (MDS) is a pre-leukemia disease affecting the erythroid, myel... more Background Myelodysplastic syndrome (MDS) is a pre-leukemia disease affecting the erythroid, myeloid and megakaryocytic bone marrow production. MDS patients are classified according to the WHO classification of myeloid neoplasms. During the past 15 years management of MDS patients has been stratified according to the International Prognostic Scoring System (IPSS) risk score. Recently a revised version of IPSS has been introduced (IPSS-R). One quarter of LR-MDS in this new IPSS-R were reclassified as having a higher risk and a substantial subset of high risk-MDS (HR-MDS) were reclassified as lower risk. In LR-MDS a differentiation block is observed in the erythroid lineage. The diagnosis and follow up of cytopenias in particular anemia must be the main objective (1). The soluble transferrin receptor (sTfR) directly reflects the erythropoietic activity in individuals without iron defiency and may appreciate ineffective dysplastic erythropoiesis in LR-MDS. In LR-MDS there is also an in...
International journal of sports physiology and performance, Jan 9, 2018
To examine the effects of an intensified tournament on workload, perceptual and neuromuscular fat... more To examine the effects of an intensified tournament on workload, perceptual and neuromuscular fatigue, and muscle-damage responses in an international under-20 rugby union team. Players were subdivided into a high-exposure group (HEG, n = 13) and a low-exposure group (LEG, n = 11) according to match-play exposure time. Measures monitored over the 19-d period included training session (n = 10) and match (n = 5) workload determined via global positioning systems and session rating of perceived exertion. Well-being scores, countermovement jump height performance, and blood creatine kinase concentrations were collected at various time points. Analysis of workload cumulated across the tournament entirety for training and match play combined showed that high-speed running distance was similar between groups, while a very likely larger session rating of perceived exertion load was reported in HEG vs LEG. In HEG, high-speed activity fluctuated across the 5 successive matches, albeit with no...
The potential cardiotoxicity of chemotherapic drugs is well known. For example anthracycline-base... more The potential cardiotoxicity of chemotherapic drugs is well known. For example anthracycline-based regimens are extremely effective for various hematological malignancies. The main disadvantage is cardiotoxicity particularly, in elderly patients who are frequently treated with a consequent dose reduction. The diagnosis and prognosis in patients with suspected heart failure needs a specific monitoring by echocardiography during and after chemotherapy regimens. We tested the interest of NT-proBNP as alternative marker for the detection of left ventricular dysfunction. Brain or B-type natriuretic peptide (BNP) and N-terminal fragment of B-type natriuretic peptide (NT-proBNP) are considered to be valuable biomarkers for the detection of disease state in patients with suspected heart failure. Methods During 1 year, blood samples of 31 patients with hematological malignancies, treated with usual chemotherapy were selected on a routine basis. Patients had the diagnosis of acute leukemia (A...
Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-a... more Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m 2 for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5°C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid. High-resolution computed tomography of the chest disclosed diffuse bilateral opacities with ground-glass shadowing and pleural effusion bilaterally. Mediastinal and hilar lymph nodes were moderately enlarged. polymerase chain reaction for Mycobacterium tuberculosis, Pneumocystis jiroveci, and cytomegalovirus were negative. Cultures including viral and fungal were all negative. A diagnosis of drug-induced pneumonitis was considered and, given the negative bronchoalveolar lavage in terms of an infection, corticosteroid therapy was given at a dose of 1 mg/kg body weight. Within 4 weeks, the patient became afebrile and was discharged from hospital. Development of symptoms with respect to drug administration, unexplained fever, negative workup for an infection, and marked response to corticosteroid therapy were found in our case. An explanation could be a delayed type of hypersensitivity (type IV) with activation of CD8 T cell which could possibly explain most of the symptoms. We have developed a decision algorithm in order to anticipate timely diagnosis of 5-azacitidine-induced pneumonitis, and with the aim to limit antibiotics abuse and to set up emergency treatment.
Background: Epidemiological data on MDS is scarce in France, and registries from other countries ... more Background: Epidemiological data on MDS is scarce in France, and registries from other countries do not provide data on the daily practice management of MDS in 2008. Methods: GFM centers were asked to collect characteristics of ongoing or recent treatments in all MDS patients (pts) seen at their clinic (as in or outpatients) during the Jan 28th–Feb 3rd, 2008 period (one week).Results: 919 pts from 74 centers were included, 57% males, mean age (+/− SD), 73 (±11) years, with 2.8%, 19% and 28% of pts aged <50, <65 and >80 years, respectively (resp).13% of pts were hospitalized >24h (4.5% for infections or bleeding and 8.5 % for “active” treatments), 46% were seen in the day care facility (40% for transfusions), and 41% as consultations (for staging, follow up or ambulatory treatment). 93% of patients had PS ≤2. Median interval from diagnosis to survey was 29.2 months. FAB at time of survey was: 35.1% RA, 18.5% RARS, 39.1% RAEB, 7.4% CMML; WHO was: 17.4% RA, 13.3% RARS, 14% ...
With TKIs, the management of CML has radically changed. Here we present the case of a woman diagn... more With TKIs, the management of CML has radically changed. Here we present the case of a woman diagnosed with CML during two pregnancies. Medullary and complete cytogenetic remission was achieved with Imatinib. However, she developed major muscular intolerance. This patient expressed the wish to have children. Hematology experts advised to delay her plan to become pregnant. According to BCR/ABL transcripts levels, they also decided to substitute Imatinib for Dasatinib. A major molecular response was subsequently observed with disappearance of muscular toxicity. It was then decided to interrupt Dasatinib treatment and to substitute with pegylated interferon for the duration of the pregnancy. After a normal full term pregnancy, she gave birth to a baby boy. Dasatinib treatment was reintroduced. A year later, the patient became pregnant for a second time. Dasatinib treatment was interrupted and substituted with pegylated interferon. After a normal pregnancy, she gave birth to a baby girl. Dasatinib treatment was then reintroduced. This case report highlights the possibility for CML patients whose disease is stabilized to interrupt Dasatinib treatment and substitute with pegylated interferon during pregnancy without jeopardizing the patient outcome or exposing the fetus to TKI associated teratogen risks.
A 71-year-old female patient with no major history of infection had presented with recurrent chro... more A 71-year-old female patient with no major history of infection had presented with recurrent chronic purulent sinusitis over the past 3 years. These recurrent infections started in 2000 with otolaryngologists' support before diagnosis of IgG4 deficiency be asked. The patient was treated with increasingly extensive courses of antibiotics and underwent several maxillary and sphenoidal sinus washouts. She continued to present with purulent nasal discharge containing Staphylococcus epidermidis. The blood and immune work-ups were normal. Her antinuclear antibody count was 1/320, with no unusual types. The total immunoglobulin (Ig)E, serology, CD4 count, and lymphocyte B phenotype results were all normal. No humoral immune deficiency was detected. The analyses confirmed an underlying specific IgG4 deficiency with values of 3-4 mg/L over 4 months. The patient was treated in March 2011 with prophylactic antibiotic therapy, sinus drainage, and IV infusions of enriched immunoglobulins (IV...
Paroxysmal nocturnal hemoglobinurea (PNH) is a rare disorder of complement regulation due to soma... more Paroxysmal nocturnal hemoglobinurea (PNH) is a rare disorder of complement regulation due to somatic mutation of PIGA (phosphatidylinositol glycan anchor) gene. We herewith report a case who developed a symptomatic PNH long after an allogenic marrow transplant. Some reasonable arguments concerning the origin of PNH clone have been discussed. The molecular studies revealed presence of JAK2 and TET2 mutations without a BCOR mutation. The literature review has been performed to probe into the complex interplay of autoimmunity and clonal selection and expansion of PNH cells, which occurs early in hematopoietic differentiation. The consequent events such as hypoplastic and/or hemato-oncologic features could further be explained on the basis of next-generation sequencing (NGS) studies. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder of hematopoietic stem cells, characterized by a somatic mutation of the phosphatidylinositol glycan-class A (PIGA). The PIGA gene products...
L'erythropoietine recombinante est produite depuis 1988. Son utilisation constitue un progres... more L'erythropoietine recombinante est produite depuis 1988. Son utilisation constitue un progres significatif, en particulier pour les insuffisants renaux, victimes d'anemie severe qui necessitait auparavant la realisation de transfusions repetees. L'erythropoietine recombinante est aujourd'hui employee de maniere de plus en plus frequente dans les anemies de certaines maladies hematologiques comme les myelodysplasies ou dans les suites de certaines chimiotherapies anti-neoplasiques. L'erythropoietine accelere de maniere efficace la production des globules rouges. L'augmentation de la masse globulaire circulante permet un meilleur transport de l'oxygene a destination des tissus. Le transport d'oxygene est un facteur significatif de l'augmentation de la production d'energie a travers la filiere aerobie. Il y a donc une correlation positive entre l'augmentation des globules rouges circulant et l'amelioration des qualites sportives dans les ...
We report data about 50 caucasian top-level cyclists (45 males, 5 women, aged between 16 and 36 y... more We report data about 50 caucasian top-level cyclists (45 males, 5 women, aged between 16 and 36 years, mean 25 +/- 4.5). Recruitment was by controlling top-level athletes in order to follow their blood cell counts to detect variation in haemoglobin concentration and hematocrit level (prevention of erythropoietin abuse). All samples were drawn in the morning, when the cyclists were at rest, according to a standardized protocol. Erythroblastic serie was abnormal in several cases (4 anaemias, 3 macrocytosis, 6 low haematocrit level, 10 mean cell haemoglobin higher than 32 pg, low reticulocyte count). White blood cells showed a trend toward low counts for neutrophils and lymphocytes. Two cyclists had platelets counts below 150.109/l. Our data indicated that top-level cyclism had some effects on the blood cell counts, which is likely to indicate an effect of intense aerobic training on physiological status.
We report data about 50 caucasian top-level cyclists (45 males, 5 womens, aged between 16 and 36 ... more We report data about 50 caucasian top-level cyclists (45 males, 5 womens, aged between 16 and 36 years, mean 25 ± 4.5). Recruitment was by controling top-level athletes in order to follow their blood cell counts to detect variation in haemoglobin concentration and hematocrit level (prevention of erythropoietin abuse). All samples were drawn in the morning, when the cyclists were at rest, according to a standardized protocol. Erythroblastic serie was abnormal in several cases (4 anaemias, 3 macrocytosis, 6 low haematocrit level, 10 mean cell haemoglobin higher than 32 pg, low reticulocyte count). White blood cells showed a trend toward low counts for neutrophils and lymphocytes. Two cyclists had platelets counts below 150.109/l. Our data indicated that top-level cyclism had some effects on the blood cell counts, which is likely to indicate an effect of intense aerobic training on physiological status.
Day care is a potential alternative to inpatient care of cancer patients. Using day care reduces ... more Day care is a potential alternative to inpatient care of cancer patients. Using day care reduces medical costs substantially compared to inpatient care, which is driving the transfer of many inpatient chemotherapy protocols to day care hospitals (DCHs). However, in contrast to inpatient management, day care provides limited observation time, which could increase the risk of renal toxicity when using these protocols. We present a case report of acute kidney injury following high-dose methotrexate administration in a DCH. Based on a review of the current literature on acid-base balance, we also discuss appropriate patient selection and judicious hydration and urine alkalinization so as to prevent toxicity in the day care setting.
Background Myelodysplastic syndrome (MDS) is a pre-leukemia disease affecting the erythroid, myel... more Background Myelodysplastic syndrome (MDS) is a pre-leukemia disease affecting the erythroid, myeloid and megakaryocytic bone marrow production. MDS patients are classified according to the WHO classification of myeloid neoplasms. During the past 15 years management of MDS patients has been stratified according to the International Prognostic Scoring System (IPSS) risk score. Recently a revised version of IPSS has been introduced (IPSS-R). One quarter of LR-MDS in this new IPSS-R were reclassified as having a higher risk and a substantial subset of high risk-MDS (HR-MDS) were reclassified as lower risk. In LR-MDS a differentiation block is observed in the erythroid lineage. The diagnosis and follow up of cytopenias in particular anemia must be the main objective (1). The soluble transferrin receptor (sTfR) directly reflects the erythropoietic activity in individuals without iron defiency and may appreciate ineffective dysplastic erythropoiesis in LR-MDS. In LR-MDS there is also an in...
International journal of sports physiology and performance, Jan 9, 2018
To examine the effects of an intensified tournament on workload, perceptual and neuromuscular fat... more To examine the effects of an intensified tournament on workload, perceptual and neuromuscular fatigue, and muscle-damage responses in an international under-20 rugby union team. Players were subdivided into a high-exposure group (HEG, n = 13) and a low-exposure group (LEG, n = 11) according to match-play exposure time. Measures monitored over the 19-d period included training session (n = 10) and match (n = 5) workload determined via global positioning systems and session rating of perceived exertion. Well-being scores, countermovement jump height performance, and blood creatine kinase concentrations were collected at various time points. Analysis of workload cumulated across the tournament entirety for training and match play combined showed that high-speed running distance was similar between groups, while a very likely larger session rating of perceived exertion load was reported in HEG vs LEG. In HEG, high-speed activity fluctuated across the 5 successive matches, albeit with no...
The potential cardiotoxicity of chemotherapic drugs is well known. For example anthracycline-base... more The potential cardiotoxicity of chemotherapic drugs is well known. For example anthracycline-based regimens are extremely effective for various hematological malignancies. The main disadvantage is cardiotoxicity particularly, in elderly patients who are frequently treated with a consequent dose reduction. The diagnosis and prognosis in patients with suspected heart failure needs a specific monitoring by echocardiography during and after chemotherapy regimens. We tested the interest of NT-proBNP as alternative marker for the detection of left ventricular dysfunction. Brain or B-type natriuretic peptide (BNP) and N-terminal fragment of B-type natriuretic peptide (NT-proBNP) are considered to be valuable biomarkers for the detection of disease state in patients with suspected heart failure. Methods During 1 year, blood samples of 31 patients with hematological malignancies, treated with usual chemotherapy were selected on a routine basis. Patients had the diagnosis of acute leukemia (A...
Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-a... more Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m 2 for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5°C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid. High-resolution computed tomography of the chest disclosed diffuse bilateral opacities with ground-glass shadowing and pleural effusion bilaterally. Mediastinal and hilar lymph nodes were moderately enlarged. polymerase chain reaction for Mycobacterium tuberculosis, Pneumocystis jiroveci, and cytomegalovirus were negative. Cultures including viral and fungal were all negative. A diagnosis of drug-induced pneumonitis was considered and, given the negative bronchoalveolar lavage in terms of an infection, corticosteroid therapy was given at a dose of 1 mg/kg body weight. Within 4 weeks, the patient became afebrile and was discharged from hospital. Development of symptoms with respect to drug administration, unexplained fever, negative workup for an infection, and marked response to corticosteroid therapy were found in our case. An explanation could be a delayed type of hypersensitivity (type IV) with activation of CD8 T cell which could possibly explain most of the symptoms. We have developed a decision algorithm in order to anticipate timely diagnosis of 5-azacitidine-induced pneumonitis, and with the aim to limit antibiotics abuse and to set up emergency treatment.
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Papers by Gerard Dine