T. Flood - Academia.edu (original) (raw)

Papers by T. Flood

Journal of Clinical Virology, 2006

Journal of Allergy and Clinical Immunology, 2013

Irish Journal of Medical Science, 1989

101 consecutive cases of culture positive meningococcal infection who presented to Our Lady&a... more 101 consecutive cases of culture positive meningococcal infection who presented to Our Lady's Hospital, Cmmlin, between 1982 and 1987 were reviewed. 52 cases were male and 49 were female, ranging in age from five weeks to 131/2 years. ALl cases were culture positive, 51 ...

Irish Journal of Medical Science, 1990

Perinatal mortality and morbidity following indeterminate antepartum haemorrhage did not seem to ... more Perinatal mortality and morbidity following indeterminate antepartum haemorrhage did not seem to be as high as suggested from published studies (Chamberlain et al, 1978, British Births, 1970. Heinemann, London, pp. 54-79). We carried out a prospective study of cases ...

Clinical Immunology, 2010

Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway. R... more Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway. Raised CD3+TCRαβ+CD4−CD8− double negative T cells and impaired T cell apoptosis are hallmarks of the disease. In contrast, the B cell compartment has been less well studied. We found an altered distribution of B cell subsets with raised transitional B cells and reduced marginal zone B cells, switched memory B cells and plasma blasts in most of 22 analyzed ⁎ Corresponding author. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m C l i n i c a l I m m u n o l o g y w w w . e l s e v i e r . c o m / l o c a t e / y c l i m Clinical Immunology (2010) 137, 357-365

Bone Marrow Transplantation, 2004

Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT),... more Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT), is frequently associated with total body irradiation (TBI) given in the pre-BMT conditioning protocol. We report our preliminary observation of the prevalence of thyroid dysfunction in children transplanted for primary immunodeficiency (PID) who were given cytoreductive conditioning with busulphan and cyclophosphamide, but without TBI. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (fT4) in 83 survivors transplanted between 1987 and 2002. We found nine children (10.8%) with clinical and/or biochemical thyroid dysfunction at 4 months to 4.5 years post-BMT of which three had positive antithyroid microsomal antibodies. Two patients were classified as primary and seven as compensated hypothyroidism (hyperthyrotropinaemia). Four patients with clinical features of hypothyroidism received replacement thyroxine, while five of the seven patients with compensated hypothyroidism remain off thyroxine because we suspect this may be a transient phenomenon. Abnormalities of thyroid function including severe primary hypothyroidism may occur post-BMT in children receiving chemotherapy conditioning without TBI. Thyroid function should be assessed regularly in this group of patients.

Bone Marrow Transplantation, 2014

Blood, 2011

Children with primary immunodeficiency diseases, particularly those less than 1 year of age, expe... more Children with primary immunodeficiency diseases, particularly those less than 1 year of age, experience significant toxicity after hematopoietic stem cell transplantation, with busulfan- or melphalan-based conditioning. Treosulfan causes less veno-occlusive disease than busulfan and does not require pharmacokinetic monitoring. We report its use in 70 children. Children received 42 g/m(2) or 36 g/m(2) with cyclophosphamide 200 mg/kg (n = 30) or fludarabine 150 mg/m(2) (n = 40), with alemtuzumab in most. Median age at transplantation was 8.5 months (range, 1.2-175 months); 46 (66%) patients were 12 months of age or younger. Donors were as follows: matched sibling donor, 8; matched family donor, 13; haploidentical, 4; and unrelated, 45. Median follow-up was 19 months (range, 1-47 months). Overall survival was 81%, equivalent in those age less or greater than 1 year. Skin toxicity was common. Veno-occlusive disease occurred twice with cyclophosphamide. Eighteen patients (26%) had graft-versus-host disease, and only 7 (10%) greater than grade 2. Two patients rejected; 24 of 42 more than 1 year after transplantation had 100% donor chimerism. The remainder had stable mixed chimerism. T-cell chimerism was significantly better with fludarabine. Long-term follow-up is required, but in combination with fludarabine, treosulfan is a good choice of conditioning for hematopoietic stem cell transplantation in primary immunodeficiency disease.

Biology of Blood and Marrow Transplantation, 2012

had worse engraftment compared to congenic wildtype mice. In conclusion, both, vacating of HSC ni... more had worse engraftment compared to congenic wildtype mice. In conclusion, both, vacating of HSC niche space, and the effects of host regulatory cells, that are activated during the TLI procedure appear critical to permit donor HSC engraftment post-TLI/ATG. The dynamics of engraftment after TLI/ATG are unique. Further studies to define the exact roles of host Tregs and NKT cells in engraftment after TLI/ATG and other conditioning modalities are underway.

Biology of Blood and Marrow Transplantation, 2012

Biology of Blood and Marrow Transplantation, 2010

Biology of Blood and Marrow Transplantation, 2010

Archives of Disease in Childhood - Fetal and Neonatal Edition, 2001

To evaluate outcome following neonatal bone marrow transplantation (BMT) for severe combined immu... more To evaluate outcome following neonatal bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) when there is a family history of a previously affected sibling, and to compare results with those published for in utero BMT. A retrospective review of cases referred and transplanted between 1987 and 1999, focusing on infectious and graft versus host disease (GvHD) complications after BMT, and T and B lymphocyte function. Thirteen patients received 18 stem cell transplants: four whole marrow, one cord blood, 10 parental T cell depleted (TCD) haplo-identical, and three TCD unrelated donor BMT. Nine were conditioned with busulphan and cyclophosphamide. All are alive and well (six months to 11.5 years after BMT). Six had grade I-II acute GvHD and two chronic GvHD (now resolved). Three had a top up BMT for poor T cell function, one had a third BMT for graft failure and chronic GvHD, and one had a third BMT for graft failure. Twelve have good in vitro proliferation to T cell mitogens, and all have normal serum IgA levels. Three receive intravenous immunoglobulin; for one of these, it is less than one year since BMT. Nine are above the 2nd centile, and 10 of 12 old enough to be assessed have normal neurodevelopment. These results are better than those published for in utero BMT for SCID. Early postnatal BMT should be the preferred option in neonatal SCID.

Archives of Disease in Childhood, 2003

Archives of Disease in Childhood, 2012

A cluster of four confirmed cases of meningococcal disease was seen in the same nuclear family ac... more A cluster of four confirmed cases of meningococcal disease was seen in the same nuclear family across a 15-week period. The cases were three siblings and a parent and all recovered well. The first case was confirmed by meningococcal PCR only but the subsequent three cases were due to indistinguishable strains of serogroup B (B:NT:P1.19-1,15-11). Contact tracing was initially undertaken and reviewed in detail after each subsequent case. Antibiotic prophylaxis was administered to close family contacts on three separate occasions, including switching of antibiotic agents, with good compliance. Subsequent investigation of the family has not revealed any obvious immunological problem and no further significant infections have been recognised. A cluster of meningococcal disease of this nature and timescale is highly unusual. Details of the cluster, investigation and implications for health protection practice are discussed.

Introduction Patients with congenital agammaglobulinemia, characterized by a defect in B lymphocy... more Introduction Patients with congenital agammaglobulinemia, characterized by a defect in B lymphocyte differentiation causing B alymphocytosis, require lifelong IgG replacement. There is scant literature regarding the effectiveness of IgG treatment at preventing mucosal (particularly sinopulmonary tract) infection and whether current management adequately restores " normal " health and quality of life (QoL). We aimed to document infective episodes pre-and post-commencing IgG replacement, determine any change in lung function and structure and assess respiratory status and QoL in a cohort of patients treated in Newcastle. Methods Clinical data were extracted from medical records of 15 patients identified from the immunology database, focus-ing on infective episodes, serial chest CT and spirometry results. Thirteen patients completed a selection of standardized and validated questionnaires assessing physical health, respiratory health and QoL. Results Pediatric patients on IgG therapy suffered fewer infections per patient year (0.74) than adults (2.13). 6/14 patients showed deteriorating respiratory status despite adequate therapy. Health questionnaires revealed a significant burden of respiratory disease on a patient's life. Conclusion Clinical data showed patients with congenital agammaglobulinemia receiving immunoglobulin therapy retained a higher than average infection rate, most of which affected mucosal barriers. Most patients self-reported worse respiratory symptoms, a lower respiratory-related QoL and a lower general health QoL relative to a healthy population. Most participants had progressive structural lung damage and decreased lung function. These results suggest that current management is not entirely effective at preventing deterioration of respiratory health or restoring QoL.

Journal of Clinical Virology, 2006

Journal of Allergy and Clinical Immunology, 2013

Irish Journal of Medical Science, 1989

101 consecutive cases of culture positive meningococcal infection who presented to Our Lady&a... more 101 consecutive cases of culture positive meningococcal infection who presented to Our Lady's Hospital, Cmmlin, between 1982 and 1987 were reviewed. 52 cases were male and 49 were female, ranging in age from five weeks to 131/2 years. ALl cases were culture positive, 51 ...

Irish Journal of Medical Science, 1990

Perinatal mortality and morbidity following indeterminate antepartum haemorrhage did not seem to ... more Perinatal mortality and morbidity following indeterminate antepartum haemorrhage did not seem to be as high as suggested from published studies (Chamberlain et al, 1978, British Births, 1970. Heinemann, London, pp. 54-79). We carried out a prospective study of cases ...

Clinical Immunology, 2010

Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway. R... more Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway. Raised CD3+TCRαβ+CD4−CD8− double negative T cells and impaired T cell apoptosis are hallmarks of the disease. In contrast, the B cell compartment has been less well studied. We found an altered distribution of B cell subsets with raised transitional B cells and reduced marginal zone B cells, switched memory B cells and plasma blasts in most of 22 analyzed ⁎ Corresponding author. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m C l i n i c a l I m m u n o l o g y w w w . e l s e v i e r . c o m / l o c a t e / y c l i m Clinical Immunology (2010) 137, 357-365

Bone Marrow Transplantation, 2004

Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT),... more Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT), is frequently associated with total body irradiation (TBI) given in the pre-BMT conditioning protocol. We report our preliminary observation of the prevalence of thyroid dysfunction in children transplanted for primary immunodeficiency (PID) who were given cytoreductive conditioning with busulphan and cyclophosphamide, but without TBI. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (fT4) in 83 survivors transplanted between 1987 and 2002. We found nine children (10.8%) with clinical and/or biochemical thyroid dysfunction at 4 months to 4.5 years post-BMT of which three had positive antithyroid microsomal antibodies. Two patients were classified as primary and seven as compensated hypothyroidism (hyperthyrotropinaemia). Four patients with clinical features of hypothyroidism received replacement thyroxine, while five of the seven patients with compensated hypothyroidism remain off thyroxine because we suspect this may be a transient phenomenon. Abnormalities of thyroid function including severe primary hypothyroidism may occur post-BMT in children receiving chemotherapy conditioning without TBI. Thyroid function should be assessed regularly in this group of patients.

Bone Marrow Transplantation, 2014

Blood, 2011

Children with primary immunodeficiency diseases, particularly those less than 1 year of age, expe... more Children with primary immunodeficiency diseases, particularly those less than 1 year of age, experience significant toxicity after hematopoietic stem cell transplantation, with busulfan- or melphalan-based conditioning. Treosulfan causes less veno-occlusive disease than busulfan and does not require pharmacokinetic monitoring. We report its use in 70 children. Children received 42 g/m(2) or 36 g/m(2) with cyclophosphamide 200 mg/kg (n = 30) or fludarabine 150 mg/m(2) (n = 40), with alemtuzumab in most. Median age at transplantation was 8.5 months (range, 1.2-175 months); 46 (66%) patients were 12 months of age or younger. Donors were as follows: matched sibling donor, 8; matched family donor, 13; haploidentical, 4; and unrelated, 45. Median follow-up was 19 months (range, 1-47 months). Overall survival was 81%, equivalent in those age less or greater than 1 year. Skin toxicity was common. Veno-occlusive disease occurred twice with cyclophosphamide. Eighteen patients (26%) had graft-versus-host disease, and only 7 (10%) greater than grade 2. Two patients rejected; 24 of 42 more than 1 year after transplantation had 100% donor chimerism. The remainder had stable mixed chimerism. T-cell chimerism was significantly better with fludarabine. Long-term follow-up is required, but in combination with fludarabine, treosulfan is a good choice of conditioning for hematopoietic stem cell transplantation in primary immunodeficiency disease.

Biology of Blood and Marrow Transplantation, 2012

had worse engraftment compared to congenic wildtype mice. In conclusion, both, vacating of HSC ni... more had worse engraftment compared to congenic wildtype mice. In conclusion, both, vacating of HSC niche space, and the effects of host regulatory cells, that are activated during the TLI procedure appear critical to permit donor HSC engraftment post-TLI/ATG. The dynamics of engraftment after TLI/ATG are unique. Further studies to define the exact roles of host Tregs and NKT cells in engraftment after TLI/ATG and other conditioning modalities are underway.

Biology of Blood and Marrow Transplantation, 2012

Biology of Blood and Marrow Transplantation, 2010

Biology of Blood and Marrow Transplantation, 2010

Archives of Disease in Childhood - Fetal and Neonatal Edition, 2001

To evaluate outcome following neonatal bone marrow transplantation (BMT) for severe combined immu... more To evaluate outcome following neonatal bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) when there is a family history of a previously affected sibling, and to compare results with those published for in utero BMT. A retrospective review of cases referred and transplanted between 1987 and 1999, focusing on infectious and graft versus host disease (GvHD) complications after BMT, and T and B lymphocyte function. Thirteen patients received 18 stem cell transplants: four whole marrow, one cord blood, 10 parental T cell depleted (TCD) haplo-identical, and three TCD unrelated donor BMT. Nine were conditioned with busulphan and cyclophosphamide. All are alive and well (six months to 11.5 years after BMT). Six had grade I-II acute GvHD and two chronic GvHD (now resolved). Three had a top up BMT for poor T cell function, one had a third BMT for graft failure and chronic GvHD, and one had a third BMT for graft failure. Twelve have good in vitro proliferation to T cell mitogens, and all have normal serum IgA levels. Three receive intravenous immunoglobulin; for one of these, it is less than one year since BMT. Nine are above the 2nd centile, and 10 of 12 old enough to be assessed have normal neurodevelopment. These results are better than those published for in utero BMT for SCID. Early postnatal BMT should be the preferred option in neonatal SCID.

Archives of Disease in Childhood, 2003

Archives of Disease in Childhood, 2012

A cluster of four confirmed cases of meningococcal disease was seen in the same nuclear family ac... more A cluster of four confirmed cases of meningococcal disease was seen in the same nuclear family across a 15-week period. The cases were three siblings and a parent and all recovered well. The first case was confirmed by meningococcal PCR only but the subsequent three cases were due to indistinguishable strains of serogroup B (B:NT:P1.19-1,15-11). Contact tracing was initially undertaken and reviewed in detail after each subsequent case. Antibiotic prophylaxis was administered to close family contacts on three separate occasions, including switching of antibiotic agents, with good compliance. Subsequent investigation of the family has not revealed any obvious immunological problem and no further significant infections have been recognised. A cluster of meningococcal disease of this nature and timescale is highly unusual. Details of the cluster, investigation and implications for health protection practice are discussed.

Introduction Patients with congenital agammaglobulinemia, characterized by a defect in B lymphocy... more Introduction Patients with congenital agammaglobulinemia, characterized by a defect in B lymphocyte differentiation causing B alymphocytosis, require lifelong IgG replacement. There is scant literature regarding the effectiveness of IgG treatment at preventing mucosal (particularly sinopulmonary tract) infection and whether current management adequately restores " normal " health and quality of life (QoL). We aimed to document infective episodes pre-and post-commencing IgG replacement, determine any change in lung function and structure and assess respiratory status and QoL in a cohort of patients treated in Newcastle. Methods Clinical data were extracted from medical records of 15 patients identified from the immunology database, focus-ing on infective episodes, serial chest CT and spirometry results. Thirteen patients completed a selection of standardized and validated questionnaires assessing physical health, respiratory health and QoL. Results Pediatric patients on IgG therapy suffered fewer infections per patient year (0.74) than adults (2.13). 6/14 patients showed deteriorating respiratory status despite adequate therapy. Health questionnaires revealed a significant burden of respiratory disease on a patient's life. Conclusion Clinical data showed patients with congenital agammaglobulinemia receiving immunoglobulin therapy retained a higher than average infection rate, most of which affected mucosal barriers. Most patients self-reported worse respiratory symptoms, a lower respiratory-related QoL and a lower general health QoL relative to a healthy population. Most participants had progressive structural lung damage and decreased lung function. These results suggest that current management is not entirely effective at preventing deterioration of respiratory health or restoring QoL.