Context
Acute myeloid leukemia (AML) is a rare disease in children, with only 50% to 60% event‐free survival. Among patients with AML, 10% do not respond to first‐line chemotherapy. There is no ...recommendation concerning second‐line treatments. Gemtuzumab ozogamicin (GO) is a monoclonal antibody targeting CD33, linked to calicheamicin. We report the efficacy and tolerance of a salvage regimen of fludarabin, cytarabine, and GO (FLA‐GO) in patients refractory to first‐line treatment.
Methods
Eight patients (median age 14.5 years), who had more than 2% minimal residual disease (MRD) by flow cytometry (MRD flow), received gemtuzumab 3 mg/m² on days 1, 4, 7, associated with cytarabine 2000 mg/m² and fludarabin 30 mg/m² on days 1 to 5.
Results
Six patients achieved complete remission (CR) (blast count morphology ≤5 × 10−2, CR‐MRD flow <1 × 10−3 for four patients). Five patients received a second course. We observed 11 episodes of febrile neutropenia, including 6 septicemias without complication. There was no fungal infection or toxic death. Two patients received granulocyte colony stimulating factor. One patient had partial platelet recovery; one, prolonged pancytopenia. All patients received hematopoietic stem cell transplantation (HSCT). We observed five mild‐to‐severe sinusoidal obstruction syndromes during HSCT procedures, particularly in patients who did not receive defibrotide prophylaxis. At the date of last contact (median follow‐up: 58 months; range: 22‐78), six patients were in continuous CR with negative MRD. Two patients died of post‐HSCT relapse.
Conclusion
FLA‐GO is a good salvage regimen for pediatric refractory AML, with significant but acceptable toxicity. HSCT is mandatory to achieve sustained CR in these patients.
Abstract Introduction Pneumatic tube system (PTS) in hospitals is commonly used for the transport of blood samples to clinical laboratories, as it is rapid and cost-effective. The aim was to compare ...the effects on haematology samples of a newly acquired ~ 2 km-long PTS that links 2 hospitals with usual transport (non-pneumatic tube system, NPTS). Methods Complete blood cell count, routine coagulation assays, platelet function tests (PFT) with light-transmission aggregometry and global coagulation assays including ROTEM® and thrombin generation assay (TGA) were performed on blood samples from 30 healthy volunteers and 9 healthy volunteers who agreed to take aspirin prior to blood sampling. Results The turnaround time was reduced by 31% (p < 0.001) with the use of PTS. No statistically significant difference was observed for most routine haematology assays including PFT, and ROTEM® analysis. A statistically significant, but not clinically relevant, shortening of the APTT after sample transport by PTS was found (mean ± SD: 30 s ± 1.8 vs. 29.5 s ± 2.1 for NPTS). D-dimer levels were 7.4% higher after transport through PTS but were not discordant. A statistically significant increase of thrombin generation was found in both platelet poor- and platelet rich- plasma samples after PTS transport compared to NPTS transport. Conclusion PTS is suitable for the transport of samples prior to routine haematology assays including PFT, but should not be used for samples intended for thrombin generation measurement.
Dexamethasone could be more effective than prednisolone at similar anti-inflammatory doses in the treatment of childhood acute lymphoblastic leukemia. In order to check if this "superiority" of ...dexamethasone might be dose-dependent, we conducted a randomized phase III trial comparing dexamethasone (6 mg/m(2)/day) to prednisolone (60 mg/m(2)/day) in induction therapy. All newly diagnosed children and adolescents with acute lymphoblastic leukemia in the 58951 EORTC trial were randomized on prephase day 1 or day 8. The main endpoint was event-free survival; secondary endpoints were overall survival and toxicity. A total of 1947 patients with acute lymphoblastic leukemia were randomized. At a median follow-up of 6.9 years, the 8-year event-free survival rate was 81.5% in the dexamethasone arm and 81.2% in the prednisolone arm; the 8-year overall survival rates were 87.2% and 89.0% respectively. The 8-year incidences of isolated or combined central nervous system relapse were 2.9% and 4.5% in the dexamethasone and prednisolone arms, respectively. The incidence of grade 3-4 toxicities during induction and the frequency of osteonecrosis were similar in the two arms. In conclusion, dexamethasone and prednisolone, used respectively at the doses of 6 and 60 mg/m(2)/day during induction, were equally effective and had a similar toxicity profile. Dexamethasone decreased the 8-year central nervous system relapse incidence by 1.6%. This trial was registered at www.clinicaltrials.gov as #NCT00003728.
Despite the ongoing development of automated hematology analyzers to optimize complete blood count results, platelet count still suffers from pre-analytical or analytical pitfalls, including ...EDTA-induced pseudothrombocytopenia. Although most of these interferences are widely known, laboratory practices remain highly heterogeneous. In order to harmonize and standardize cellular hematology practices, the French-speaking Cellular Hematology Group (GFHC) wants to focus on interferences that could affect the platelet count and to detail the verification steps with minimal recommendations, taking into account the different technologies employed nowadays. The conclusions of the GFHC presented here met with a "strong professional agreement" and are explained with their rationale to define the course of actions, in case thrombocytopenia or thrombocytosis is detected. They are proposed as minimum recommendations to be used by each specialist in laboratory medicine who remains free to use more restrictive guidelines based on the patient's condition.
Les leucémies aiguës myéloïdes (LAM) de l’enfant de moins de 15 ans touchent 65 à 85 patients par an en France. Le diagnostic de la LAM nécessite une analyse morphologique précise des blastes ...leucémiques et de leur environnement cellulaire, un immunophénotypage qui définit le stade de lignage et une analyse cytogénétique et moléculaire complète qui déterminent des facteurs pronostiques et permettent d’établir le niveau de risque et de prédire l’issue de la maladie. La rareté et l’hétérogénéité des LAM pédiatriques rend difficile la caractérisation de facteurs pronostiques sans études collaboratives internationales. Les anomalies génétiques associées aux LAM pédiatriques sont différentes des anomalies associées à celles des patients adultes, de même que la présentation clinique diffère un peu. Certaines anomalies génétiques prédisposent aux LAM ou sont en lien avec un syndrome d’insuffisance médullaire héréditaire. Les LAM rencontrées chez l’enfant de moins de 2 ans, et en particulier les néonatales, celles diagnostiquées chez un enfant atteint d’un syndrome de Down ou encore les aspects morphologiques spécifiques des LAM pédiatriques sont autant de particularités qu’il est nécessaire de connaître pour une prise en charge optimale du diagnostic et du suivi de cette entité clinico-biologique.
Acute myeloid leukaemia (AML) in children under 15 years old affects 65-85 patients per year in France. Diagnosis of AML requires accurate morphological analysis of leukaemic blasts and their cellular environment, immunophenotyping to define the lineage stage and comprehensive cytogenetic and molecular analysis to determine prognostic factors and establish the level of risk and predict the outcome of the disease. The rarity and heterogeneity of paediatric AML makes it difficult to characterise prognostic factors without international collaborative studies. The genetic abnormalities associated with paediatric AML are different from those associated with AML in adult patients, and the clinical presentation differs somewhat from that in adults. Some genetic abnormalities predispose to AML or are associated with an inherited bone marrow failure syndrome. AML in children under 2 years old, including infant AML, AML diagnosed in children with Down syndrome and the specific morphological aspects of paediatric AML are all features that should be known for optimal diagnosis and follow-up management of this entity.
Summary
In children, lymphoblastic lymphomas represent 30% of Non‐Hodgkin lymphomas (NHL), and approximately 15% are precursor B‐cell lymphomas (PBLL). Our study evaluated their main clinical ...characteristics, evolution, and prognosis in three trials. From 1989 to 2008, 53 children with PBLL (median age 7·75 years) were included in three protocols: Malignant Lymphoma Therapy (LMT) 96, European Organization for Research and Treatment of Cancer (EORTC) 58881, and EORTC 58951 using Berlin‐Frankfürt‐Münster‐derived acute lymphoblastic leukaemia (ALL) therapy. There were 10 stage I disease, 9 stage II, 9 stage III and 25 stage IV. Clinical presentation was heterogeneous with a majority of bone lesions and cutaneous or subcutaneous manifestations. At diagnosis 23 patients had bone marrow involvement, and only three had central nervous system involvement. The median follow‐up was 74 months. At last follow‐up, 45 patients were in continuous complete remission, whereas eight had progressed or had relapsed (7 Stages IV and 1 Stage III) and died. Two patients had a secondary neoplasia, and are still alive. Disease stage was a major prognostic factor, with better overall survival (OS) and event‐free survival (EFS) (P < 0·05) rates observed in patients with Stage I to III as compared to those with Stage IV. Treatment with protocols derived from ALL therapy are efficient with an 82% EFS and an 85% OS at 5 years.
Ring sideroblasts are commonly seen in myelodysplastic neoplasms and are a key condition for identifying distinct entities of myelodysplastic neoplasms according to the WHO classification. However, ...the presence of ring sideroblasts is not exclusive to myelodysplastic neoplasms. Ring sideroblasts are as well either encountered in non-clonal secondary acquired disorders, such as exposure to toxic substances, drug/medicine, copper deficiency, zinc overload, lead poison, or hereditary sideroblastic anemias related to X-linked, autosomal, or mitochondrial mutations. This review article will discuss diseases associated with ring sideroblasts outside the context of myelodysplastic neoplasms. Knowledge of the differential diagnoses characterized by the presence of ring sideroblasts in bone marrow is essential to prevent any misdiagnosis, which leads to delayed diagnosis and subsequent management of patients that differ in the different forms of sideroblastic anemia.
La détection de cellules de surcharge et/ou lymphocytes vacuolés dans le sang apporte une aide précieuse à l’orientation diagnostique des maladies de surcharge lysosomale. Cependant cet examen est ...peu prescrit et les aspects cytologiques parfois méconnus. Le Groupe francophone d’hématologie cellulaire (GFHC), a souhaité par le biais d’un questionnaire, faire un état des lieux des pratiques mises en place pour réaliser cette recherche dans les laboratoires de ses membres. Après exploitation des réponses obtenues, devant la grande variabilité des pratiques, il a souhaité établir des recommandations d’harmonisation de cette recherche.
Identification in blood films of storage cells and/or vacuolated lymphocytes is a precious usefulness to diagnose lysosomal storage disease. However, this screening is fully prescribed and cytological aspects sometimes not well known. The French Cellular Hematology Group (GFHC) has decided to investigate members’ practices through a survey. Because of the important variability in screening storage cells on blood film examination, the GFHC, aimed to establish recommendations for practical harmonization.
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