Eva de Berranger

Predicting the risk of severe bacterial infection in children with chemotherapy‐induced febrile neutropenia

The prognosis of febrile neutropenia (FN) in childhood cancer has been considerably improved by the intensification of treatment, including systematic hospitalization and broad‐spectrum antibiotics. As only few children present with a severe bacterial infection (SBI), clinical decision rules have been developed to distinguish those at risk for SBI. The aim of this study was to evaluate the reproducibility of six clinical decision rules proposed in the literature and to compare their performance.

Management of endocrino-metabolic dysfunctions after allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE…). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins… Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach.RésuméLa transplantation allogénique de cellules souches hématopoïétiques est pratiquée dans les dysfonctions de moelle osseuse liées à des hémopathies, mais également dans certaines maladies rares (adrénoleucodystrophie, encéphalomyopathie mitochondriale gastro-intestinale ou MNGIE…). Après quelques décennies, ce traitement a fait la preuve de son efficacité au prix d’un certain nombre d’effets secondaires précoces ou plus tardifs tels qu’infection, réaction greffon-contre-hôte, complications cardiovasculaires et cancers secondaires. Ces complications sont principalement liées au conditionnement, qui requiert une chimothérapie puissante associée à une irradiation corporelle totale (conditionnement myélo-ablatif) ou une immunosuppression (conditionnement non myélo-ablatif). Parmi ces effets secondaires, les complications endocrines peuvent être classées en 1) déficits hormonaux endocrines (particulièrement gonado- and somatotropes) liés aux conséquences de la chimio- et surtout de la radiothérapie, avec ses effets propres sur la croissance, la puberté, l’os et la fertilité; 2) maladies auto-immunes, particulièrement dysthyroidies; 3) tumeurs secondaires impliquant soit les glandes endocrines (cancer thyroidien) ou dépendant du statut hormonal (cancer du sein, méningiome), favorisées par la dysrégulation immunitaire et la radiothérapie; 4) complications métaboliques, spécialement diabètes cortico-induits et dyslipidémies qui s’accompagnent d’un risque cardiovasculaire accru. Ces complications sont intriquées. De plus, l’hormonothérapie substitutive peut moduler le risque cardio-vasculaire et tumoral de ces patients, déjà accru par la radiothérapie et la chimothérapie, notamment les glucocorticoides et les anthracyclines… C’est pourquoi ces personne et leur famille doivent être informées de ces effets secondaires et de l’intérêt d’un suivi multidisciplinaire à long-terme.

Clinical value of pre‐transplant minimal residual disease in childhood lymphoblastic leukaemia: the results of the French minimal residual disease‐guided protocol

Minimal residual disease (MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (ALL). Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non‐ex vivo T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T‐cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high‐risk paediatric ALL enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with MRD <10−3 and the 27 with MRD ≥10−3. Multivariate analysis identified sex match and MRD as being significantly associated with 5‐year survival. MRD ≥10−3 compromised the 5‐year cumulative incidence of relapse (43·6 vs. 16·7%). Complete remission status and stem cell source did not modify the relationship between MRD and prognosis. Thus, pre‐transplant MRD is still a major predictor of outcome for ALL. The MRD‐guided strategy resulted in survival for 72·3% of patients with MRD<10−3 and 40·4% of those with MRD ≥10−3.

SynthèseSéquelles post-allogreffe de cellules souches hématopoïétiquesPost-hematopietic stem cell transplant complications

Under the long-term monitoring of patients treated in childhood or adolescence for cancer, we present in this article the long-term monitoring and therefore possible effects of patients who underwent allergenic hematopoietic stem cell transplantation. This article is based on a collaborative effort organized by the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC), which took place during the 4th day of allograft harmonization practices. Patients affected are children and young adults (0-25 years). We defined the monitoring effects beyond 1 year post-transplant. Our recommendations are based on a literature review, in line with the Leucémie Enfant Adulte (LEA) study cohort of long-term monitoring of patients treated for hematological malignancies in childhood, grafted or not. It became important to determine the nature of problems, their risk factors, frequency and monitoring necessary to implement for their detection. We will not address the therapeutic management of sequelae.

Séquelles post-allogreffe de cellules souches hématopoïétiques

Under the long-term monitoring of patients treated in childhood or adolescence for cancer, we present in this article the long-term monitoring and therefore possible effects of patients who underwent allergenic hematopoietic stem cell transplantation. This article is based on a collaborative effort organized by the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC), which took place during the 4th day of allograft harmonization practices. Patients affected are children and young adults (0-25 years). We defined the monitoring effects beyond 1 year post-transplant. Our recommendations are based on a literature review, in line with the Leucémie Enfant Adulte (LEA) study cohort of long-term monitoring of patients treated for hematological malignancies in childhood, grafted or not. It became important to determine the nature of problems, their risk factors, frequency and monitoring necessary to implement for their detection. We will not address the therapeutic management of sequelae.

Carnet de suivi national : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country. Our article discusses the updates and modifications for the 2016 version of the national patient follow-up care logbook.