immunodeficiencies haematopoietic stem cell transplantation for severe congenital Cognitive and behavioural abnormalities in children following

Abstract Haematopoietic stem cell transplantation (HSCT) is a highly successful treatment for severe congenital immunodeficiencies. However, some studies have suggested that children may experience cognitive difficulties following HSCT. This large scale study assessed cognitive and behavioural function for the cohort of children treated by HSCT at one centre between 1979 - 2003 to determine the frequency and severity of problems and to identify risk factors. 105 patients were assessed on standardized measures of cognitive and emotional and behavioural function together with a control group of unaffected siblings. The average IQ for the cohort was 85 (95 percent confidence interval 81 - 90), significantly lower than both the population average of 100 (p<0.001) and unaffected siblings. Multivariate analysis indicated that the underlying genetic defect, diagnosis of ADA deficient severe combined immunodeficiency and consanguinity were associated with worse outcome, but that age at transplant and chemotherapy conditioning were not. Children treated by HSCT for severe immunodeficiency have an increased risk of long term cognitive difficulties and associated emotional and behavioural difficulties. The specific genetic diagnosis, consanguinity and severe clinical course are associated with poor outcome. Long term follow up of these patients should include screening to identify and manage these problems more effectively. From bloodjournal.hematologylibrary.org by guest on June 12, 2013. For personal use only.

[1]  U. Pannicke,et al.  Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications. , 2007, Blood.

[2]  F. Rieux-Laucat,et al.  Naturally occurring primary deficiencies of the immune system. , 1997, Annual review of immunology.

[3]  F. Arredondo-Vega,et al.  Hepatic Dysfunction as a Complication of Adenosine Deaminase Deficiency , 1996 .

[4]  C. Conners.  Conners' rating scales-revised : technical manual , 1997 .

[5]  Surveys.,et al.  Standard occupational classification , 1990 .

[6]  A. Fischer,et al.  Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome. , 2005, Blood.

[7]  R. Mulhern,et al.  Cognitive and academic functioning in survivors of pediatric bone marrow transplantation. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  A. Fischer,et al.  Cernunnos, a Novel Nonhomologous End-Joining Factor, Is Mutated in Human Immunodeficiency with Microcephaly , 2006, Cell.

[9]  R. Goodman,et al.  Psychometric properties of the strengths and difficulties questionnaire. , 2001, Journal of the American Academy of Child and Adolescent Psychiatry.

[10]  M. van der Burg,et al.  A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation. , 2005, The Journal of clinical investigation.

[11]  I. Kaitila,et al.  The chondro-osseous dysplasia of adenosine deaminase deficiency with severe combined immunodeficiency. , 1976, The Journal of pediatrics.

[12]  J. Kramer,et al.  Toxicities of total-body irradiation for pediatric bone marrow transplantation. , 1996, International journal of radiation oncology, biology, physics.

[13]  R. Noll,et al.  Social functioning of children surviving bone marrow transplantation. , 1998, Journal of pediatric psychology.

[14]  R. Mulhern,et al.  Psychological effects of bone marrow transplantation on children and adolescents: preliminary report of a longitudinal study. , 1995, Bone marrow transplantation.

[15]  C. Hollis,et al.  Detecting emotional and behavioural problems in paediatric clinics. , 2003, Child: care, health and development.

[16]  J. Goldwein,et al.  Neuropsychological outcome of children undergoing bone marrow transplantation , 1998, Bone Marrow Transplantation.

[17]  D. Rimoin,et al.  Pathologic findings in adenosine deaminase-deficient severe combined immunodeficiency. I. Kidney, adrenal, and chondro-osseous tissue alterations. , 1985, The American journal of pathology.

[18]  G. Mieli-Vergani,et al.  Nonmyeloablative stem cell transplantation for congenital immunodeficiencies. , 2000, Blood.

[19]  R. Goodman,et al.  The extended version of the Strengths and Difficulties Questionnaire as a guide to child psychiatric caseness and consequent burden. , 1999, Journal of child psychology and psychiatry, and allied disciplines.

[20]  J. Kramer,et al.  Cognitive and adaptive behavior 1 and 3 years following bone marrow transplantation , 1997, Bone Marrow Transplantation.

[21]  H. Gaspar,et al.  Cognitive and behavioral abnormalities in adenosine deaminase deficient severe combined immunodeficiency. , 2001, The Journal of pediatrics.

[22]  Badaruddoza,et al.  Inbreeding depression and intelligence quotient among north Indian children , 1993, Behavior genetics.

[23]  U. Heinzmann,et al.  A missense mutation in the WD40 domain of murine Lyst is linked to severe progressive Purkinje cell degeneration , 2006, Acta Neuropathologica.

[24]  P. Veys,et al.  Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen. , 2005, Blood.

[25]  Badaruddoza.  Effect of Inbreeding on Wechsler Intelligence Test Scores among North Indian Children , 2004, Asia-Pacific journal of public health.

[26]  H. Gaspar,et al.  Bilateral sensorineural deafness in adenosine deaminase-deficient severe combined immunodeficiency. , 2004, The Journal of pediatrics.

[27]  H. Meltzer,et al.  Mental health of children and adolescents in Great Britain , 2003, International review of psychiatry.

[28]  A. Smedler,et al.  Neuropsychological deficits in very young bone marrow transplant recipients , 1995, Acta paediatrica.

[29]  G. Dellatolas,et al.  Neuropsychological outcome in long-term survivors of a childhood extracranial solid tumor who have undergone autologous bone marrow transplantation , 2003, Bone Marrow Transplantation.

[30]  A. Smedler,et al.  Total body irradiation: a neuropsychological risk factor in pediatric bone marrow transplant recipients , 1995, Acta paediatrica.

[31]  J. T. Miller,et al.  Cognitive function in patients with chronic granulomatous disease: a preliminary report. , 2004, Psychosomatics.