[Management of vaccination in children receiving an allogeneic marrow transplant]. / Prise en charge de la vaccination chez les enfants receveurs d'une greffe de moelle allogénique.

Over the last decades, significant advances in the diagnosis and therapeutics have considerably improved success rate from bone marrow transplant in patients suffering from otherwise life-threatening diseases, allowing now for prolonged survival and better quality of life after an allograft. However, infectious diseases remain one of the most serious complication in this population, hence associated with a high morbidity and mortality. Prevention, in particular through vaccination, constitutes a cornerstone of the management of immunocompromised hosts, since this procedure aims to protect them once back to life in community after long periods of hospitalization. If the necessity of vaccinating immunocompromised patients as well as their family is unequivocally recognized among health care workers, some questions remain source of debate. Several famous societies edited guidelines, but those differ from each other and cannot be transposed from a country to another without considering their local epidemiology and implemented vaccination schedule. Moreover, development and availability of new vaccines render recommendations constantly susceptible to adaptations. After exhaustive literature review, this article aims to offer pragmatic answers to the main questions raised by healthcare workers when vaccinating children after a bone marrow transplant. We here review all vaccines available and discuss their modalities of administration considering the timing after transplant, the immunological residual status and the medical history of the child. We also offer clues to optimize vaccination of patients' siblings. In addition to highlight some interrogations about future vaccines formulations, we propose here a vaccination schedule tailored for pediatric bone marrow transplant recipients in Belgium in 2017.

Au cours des dernières années, les progrès faits dans les domaines thérapeutiques et diagnostiques ont permis d'améliorer les performances des traitements par greffes de moelle osseuse, allongeant ainsi significativement l'espérance de vie des patients souffrant de maladies jusqu'alors associées à un sombre pronostic. Cependant, aujourd'hui encore, les infections restent parmi les complications les plus redoutées en termes de morbidité et de mortalité chez ces patients. La prévention et particulièrement la vaccination occupe donc une place primordiale dans la prise en charge de ces hôtes fragiles, visant à les protéger une fois leur retour à la vie en communauté envisagé après de longues périodes d'immunosuppression. Si la nécessité de vacciner les patients transplantés et leur entourage fait l'unanimité au sein des soignants, les modalités de vaccination restent encore sujettes à de maintes interrogations dans la littérature. Plusieurs sociétés réputées font état de recommandations mais celles-ci varient entre elles et ne peuvent être transposées d'un pays à l'autre sans tenir compte de l'épidémiologie locale et du schéma vaccinal préalablement implémenté. Par ailleurs, la mise à disposition constante de nouveaux vaccins nécessite une adaptation perpétuelle des diverses recommandations établies. Sur base d'une revue exhaustive de la littérature, nous tenterons dans cet article d'apporter des réponses pragmatiques aux questions fréquemment soulevées par les soignants en charge des enfants greffés de moelle osseuse. Le document détaille les différents vaccins disponibles, en discute les critères d'administration selon le délai par rapport à la greffe et le statut immunologique du patient et revoit comment optimaliser la vaccination de l'entourage. En plus de souligner certaines interrogations à suivre concernant de nouvelles formulations vaccinales à venir, l'article ci-dessous offre un schéma pratique d'administration des différents vaccins chez les enfants receveurs d'une greffe de moelle en Belgique en 2017.

[Hematopoietic stem cell transplantation for severe sickle cell disease]. / Greffe de cellules souches hématopoïétiques dans la drépanocytose homozygote sévère.

Hematopoietic stem cell transplantation is the sole curative therapy for sickle cell anemia (SCA). This treatment is restricted to severe forms of disease. Lack of HLA-identical sibling donor is the major limiting factor for delivering this therapy. Conditioning regimen should be myeloablative. Post transplantation immunosuppressive medication is necessary for both graft tolerance and graft-versus-host disease (GvHD) control. For the majority of patients, bone marrow is source of stem cells. Alternative sources including related cord blood stem cells are under evaluation and promising. Outcome for 250 grafted patients worldwide is excellent. More than 85 % survive free of SCA and have a good quality of life although GvHD remains the main complication.

Hydroxyurea treatment for sickle cell disease: impact on haematopoietic stem cell transplantation's outcome.

Since 1988, 24 children have undergone haematopoietic stem cell transplantation (HSCT) for severe sickle cell disease (SCD) in our unit, 13 being grafted after having been exposed to hydroxyurea (HU) to control SCD-related complications. Different pre-transplant conditioning regimens were given over time: Bu14/Cy200 in six patients (group 1), Bu16/Cy200/antithymocyte globulin (ATG) in five (group 2) and Bu16/Cy200/ATG with HU prior to HSCT in 13 (group 3). The aim of this study is to compare the outcome after HSCT of these groups of patients, which differ according to pre-transplant drug exposure. Overall, 20 of the 24 transplanted children had stable engraftment and have remained free of SCD-related symptoms after HSCT; 19 of them are currently alive and cured of SCD. In group 1 (HU-, ATG-), we observed one unexplainable late death, one absent engraftment, one late rejection and one mixed stable chimerism. In group 2 (HU-, ATG+), we observed the absence of engraftment in two patients and one early rejection. In group 3 (HU+, ATG+), we observed no cases of either absent engraftment, mixed stable chimerism or late rejection. In our experience, pre-transplant treatment with HU seems to be associated with a lower incidence of rejection/absent engraftment in severe SCD patients. These results need to be confirmed with a larger number of patients.

Total parenteral nutrition in bone marrow transplant: what is the appropriate energy level?

OBJECTIVES: Total parenteral nutrition (TPN), recommended during bone-marrow transplant (BMT), is often withheld following complications. We aim to determine the effective amount of energy supplied and its short-term effects in children requiring BMT. METHODS: Twenty children (11 males, 9 females, mean age 8 years, range 1-18 years) receiving 13 allogenic and 7 autologous BMT for malignant (13) and nonmalignant (7) diseases, were retrospectively evaluated for energy/protein intakes, weight changes, time to engraftment and on TPN, occurrence of complications, and metabolic abnormalities. RESULTS: Each child received approximately 72% of the prescribed calories, an average of 0.87 +/- 0.2 x basal-metabolic rate, 1.14 +/- 0.4 g protein/kg/day, and 176 +/- 34:1 nonprotein calories:nitrogen ratio. Body weight improved during the 35 days (range 14-62) of TPN, with loss thereafter. Engraftment occurred in 20 +/- 7.5 days. Caloric intake and time to engraftment were related (p = 0.002). Ten central-venous-line and 12 gastrointestinal infections occurred. Among laboratory abnormalities, liver function tests resulted temporarily altered in 10 patients, and permanently in 1 child with cholestasis. Eight children developed graft-versus-host disease. Five died of cancer. CONCLUSIONS: The energy supplied with TPN in BMT is less than expected and approximately covers the BMR with mixed effects. Energy intake needs to be calibrated during TPN and adjusted during feeding resumption to expedite recovery.

Unusual findings in two cases of Langerhans' cell histiocytosis.

We report unusual findings in two patients with Langerhans' cell histiocytosis (LCH), namely a cervical mass lesion with extensive destruction of the posterior elements of a cervical vertebra and gastrointestinal lesions as part of multisystem involvement. The aim of our report is threefold. Firstly, LCH can be responsible for osteolysis of the vertebral posterior arches, with or without involvement of the vertebral body, and should be included in the differential diagnoses of cervical mass lesions. Secondly, in a patient with confirmed LCH and additional protein-losing enteropathy, gastrointestinal involvement should be considered as a possibility since it is an important factor for establishing prognosis. Thirdly, LCH lesions can be very extensive and yet have a good response to therapy, whereas less spectacular lesions may not respond or respond only partially to therapy. Thus, an important factor in establishing prognosis is the presence of multisystem involvement at diagnosis, regardless of the extent of a lesion at a particular site.

Magnetic resonance imaging and angiography in cerebral fungal vasculitis.

We report on an 11-year old girl treated for leukemia who developed infarcts in the right lentiform nucleus and temporal lobe. Magnetic resonance angiography (MRA) showed mild intraluminal irregularities in the right carotid syphon and stenosis of the right proximal middle cerebral artery, suggesting vasculitis. Magnetic resonance imaging (MRI) follow-up showed evolution of the initial infarct into an abscess. Stereotactic biopsy disclosed filaments of aspergillus. This report emphasizes the fact that cerebral aspergillosis should be considered if MRA and MRI are indicative of vasculitis and cerebral infarction in immunosuppressed children.

[Bone marrow graft in hereditary diseases]. / La greffe de moelle dans les maladies héréditaires.

Since 1968, bone marrow transplantation became the first line therapy for selected metabolic and immunological hereditary disorders. Actually, advances in the supportive care in bone marrow transplantation and a better knowledge of the immunology of BMT complications has been associated with a better disease correction and an increase in long term survival. New approaches are under investigation and include: hematopoietic growth factors, enzymatic replacement and gene therapy. However at the present time BMT is still the only curative treatment for selected hereditary disorders.

[Autologous bone marrow graft in solid tumors in childhood]. / Greffe de moelle autologue dans les tumeurs solides des enfants.

Curability in children suffering from malignant solid tumor is 50%. Thus, high dose chemotherapy with or without total body irradiation followed by autologous bone marrow transplantation (ABMT) has been proposed to patients suffering from cancer either at initial diagnosis (poor prognosis tumor) or at relapse. Thanks to these studies, drugs having dose effects properties have been selected. In some tumors, ABMT has significantly improved patients median survival. It remains to be determined if: 1. high dose chemotherapy protocols with ABMT are superior to new aggressive chemotherapeutic protocol without ABMT. 2. ABMT increases the curability of high risk patients.

[Indications for bone marrow graft in severe hemoglobinopathies]. / Indications des greffes de moelle dans les hémoglobinopathies graves.

Allogenic bone marrow transplantation (ABMT) is the only curative approach for sickle cell anemia and major beta-thalassemia. In sickle cell anemia, ABMT can be proposed for severe clinical disease. In major beta-thalassemia, it must be proposed to young patients who have an HLA identical familial donor.

Bone marrow transplantation for severe sickle cell anaemia.

Five children with sickle cell anaemia underwent bone marrow transplantation (BMT) for severe clinical disease. The conditioning regimen for BMT was in busulfan plus cyclophosphamide. The allograft contained more than 5 x 10(8) nucleated cells per kg recipient. Prophylaxis of GVHD consisted of methotrexate and cyclosporin A. Therapy was well tolerated. Duration of neutropenia (less than 0.5 x 10(9)/l) was short (14-25 d). Platelet recovery (greater than 50 x 10(9)/l) occurred between day 12 and 45. The patients have been followed up for 8-28 months. No major infections occurred and long-term BMT-related toxicity was limited to mild, chronic GVHD in one patient. Mean haemoglobin levels remained above 10 g/dl. Haemoglobin electrophoresis showed AS patterns in all grafted patients--all marrow donors having sickle cell trait. From our preliminary data, we conclude that BMT or sickle cell anaemia is curative, well tolerated and should be proposed for suitable patients.