Christiane Vermylen

Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium

Fifty patients affected by sickle cell anaemia underwent transplantation of HLA-identical haematopoietic stem cells (bone marrow, 48; cord blood, 2). Two groups of patients were considered for transplantation. Group 1 included 36 permanent residents of a European country who, retrospectively, met the inclusion criteria accepted at a consensus conference held in Seattle in 1990, wherein children were selected because they already had evidence of a morbid course. Group 2 included 14 patients who were transplanted earlier, had not received more than three blood transfusions and were transplanted because they had decided to return to their country of origin. Kaplan–Meier estimates of overall survival, event-free survival and disease-free survival at 11 years of the whole grafted population are 93, 82 and 85%, respectively. In group 1, overall survival, EFS and DFS were 88, 76 and 80% and in group 2, 100, 93 and 93%, respectively. Clinical manifestations of the disease, as well as disease associated haemolytic anaemia, disappeared in all successfully treated patients. Recovery of spleen function was present in seven out of 10 evaluated patients. Adverse events (death, absence of engraftment, mixed chimerism and relapse) occurred more frequently in group 1 than in group 2 (25% vs 7%, Pu2009<u20090.001). acute graft-versus-host disease (gvhd) was present in 20 patients (grade i or ii, 19; grade iii, 1), chronic gvhd in 10 (limited, 7; extensive, 3). one patient developed an acute myeloid leukaemia. gonadal dysfunction was present in all patients (six boys and eight girls) transplanted close to or after puberty, although transient in one adolescent girl.

Safety and Efficacy of Privigen ® , a Novel 10% Liquid Immunoglobulin Preparation for Intravenous Use, in Patients with Primary Immunodeficiencies

PurposeThe present study was designed to evaluate the efficacy and safety of a novel, 10% liquid formulation of intravenous immunoglobulin, stabilized with 250xa0mmol/L l-proline (Privigen®), in patients with primary immunodeficiency disease.Materials and MethodsEighty adults and children diagnosed with common variable immunodeficiency or X-linked agammaglobulinemia received intravenous Privigen® infusions (200–888xa0mg/kg) at 3- or 4-week intervals over a 12-month period, according to their previously established maintenance dose. The primary endpoint was the annual rate of acute serious bacterial infections.ResultsThere were six episodes of acute serious bacterial infections, corresponding to an annual rate of 0.08; the annual rate for all infections was 3.55. Mean serum IgG trough levels were between 8.84 and 10.27xa0g/L. A total of 1,038 infusions were administered, most of them at the maximum rate permitted (8.0xa0mg kg−1 min−1). Temporally associated adverse events, possibly or probably related to study drug, occurred in 9% of infusions, either during or within 72xa0h after infusion end.ConclusionPrivigen® is well tolerated and effective for the treatment of primary immunodeficiency.

A prospective study of minimal residual disease in childhood B-lineage acute lymphoblastic leukaemia: MRD level at the end of induction is a strong predictive factor of relapse.

We prospectively investigated minimal residual disease (MRD) in 51 children with B‐lineage acute lymphoblastic leukaemia (ALL) treated according to the Fralle 93 protocol. PCR follow‐up was performed in children in morphological and cytogenetic complete remission, provided an immunoglobulin (IgH) gene rearrangement could be detected using FR3/JH amplimers. MRD was studied according to our previously described methodology, with a few modifications including the use of a consensus JH probe to control for PCR efficiency variations.

Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone

Background. The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood.Objective. To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period.Materials and methods. Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984–1993).Results. Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n =18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/RBS+ abnormalities (n = 10) were most frequently insignificant.Conclusion. In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed.

The wandering spleen.

The article presents two cases of wandering spleen in the pediatric age group. Both patients were admitted for abdominal pain. In one, the onset was sudden and, on physical examination, a mass was felt in the left hypochondrium. In the other, it was the second episode and a firm mid-abdominal mass was found. The wandering spleen is a specific clinical syndrome which should be taken into account when an abdominal tumor is found. Ultrasonography and isotopic scan are very useful diagnostic tools The wandering spleen is caused by the absence of the splenorenal ligament which allows increased mobility of the splenic hilum. Both children underwent a splenectomy and made an uneventful recovery.

Therapy-related acute myeloid leukemia in a child with Noonan syndrome and clonal duplication of the germline PTPN11 mutation.

A 4‐year‐old girl with Noonan syndrome (NS) and constitutive PTPN11 mutation presented with stage 4 neuroblastoma and was treated by intensive chemotherapy. During the treatment, cytogenetic analysis revealed the development of a hyperdiploid clone with duplication of the germline PTPN11 mutation in a morphologically normal bone marrow. A few months later, the patient developed acute myelomonoblastic leukemia with an additional clonal deletion of 7q. Although, we cannot conclude whether there is an association between NS and neuroblastoma, this case suggests that duplication of germline PTPN11 mutations, potentially induced by chemotherapy, contributes to leukemogenesis in patients with NS. Pediatr Blood Cancer 2007;48:101–104.

Haematological disturbances during long-term valproate therapy.

A 14-year-old boy with mental retardation presented with severe thrombocytopenia, macrocytic anaemia and allergic dermatitis. He had been treated with valproate for seizures since the age of 2 years. Clinical examination showed severe purpura, mucous bleeding and extensive dermatitis. Tests to detect serum direct antiplatelet antibodies were positive and bone marrow examination revealed myelodysplastic abnormalities. Valproate was discontinued and both dermatitis and general condition of the child improved with normalization of the full blood count. This report suggests that valproate may produce both peripheral immune thrombocytopenia and severe bone marrow depression several years after the initiation of the therapy.

Sjögren's syndrome in a child.

Sjögrens syndrome is a relatively uncommon condition in the paediatric age group. The youngest child reported thus far was a 5-year-old girl [4].This article reports the case of a 2-year-old girl admitted for recurrent infections of the respiratory tract with diffuse pulmonary interstitial infiltrations and a progressive swelling of the parotid glands.The clinical features and the results of laboratory investigations, including parotid and hepatic biopsies, chest X-rays and sialography helped to establish the diagnosis of Sjögrens syndrome.Clinical, immunological and genetic characteristics of Sjögrens syndrome are reviewed.

Papillary thyroid carcinoma in a 9-year-old girl with ataxia-telangiectasia.

A 9‐year‐old female with ataxia‐telangiectasia (AT) presenting with papillary thyroid carcinoma and lymph nodes involvement is reported. We discuss this novel association, the general risk of neoplasic complications in these patients, the natural history of thyroid carcinoma in the pediatric population and the potential link between thyroid carcinogenesis and ataxia‐telangiectasia mutated gene (ATM) mutation. We also expose our therapeutic attitude, according to both clinical status and particular genetic background of our patient. Pediatr Blood Cancer 2008;50:1058–1060.

CLONAL MONOSOMY 7 AND 5q IN A CHILD WITH MYELODYSPLASTIC SYNDROME

The authors report the case of a 5-year-old boy referred for thrombocytopenia and neutropenia. Bone marrow examination showed a myelodysplasia with clonal monosomy7. The acceleration of the disease was marked by the appearance of an additional cytogenetic abnormality, i.e., the deletion of the long arm of chromosome 5 in the clonal cells. RAS genemutationwas not detected. Chemotherapy was started to achieve complete remission before a bone marrow transplatation. This treatment was complicated by a prolonged a plasia and the patient died of systemic mycotic infection.