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Summary:Haemopoietic stem cell transplants (HSCT) cure increasing numbers of primary immunodeficiencies (PID): residual recipient T-cell function increases risk of incomplete or decreasing immune reconstitution, which may resolve following a second, unconditioned, infusion from the same donor (boost infusion). We assessed the outcome of 20 boost infusions in 19/139 patients transplanted for PID patients at our centre since 1987. Boost infusion was given 64-1226 days after the original HSCT. Follow-up was 4-124 months. In all, 12 of 19 patients cleared viral infection (6), or showed sustained increase in donor chimerism, T- and B-cell numbers and function, or other markers (6). In 7/12 patients, immunoglobulin replacement has been discontinued. Four were partially successful with stable low-level chimerism (two patients) or improved T-cell function, but not B cell function (two patients). Four failed with no change in donor chimerism or cell number. No significant association with donor source, T-cell depletion, conditioning regimen, boost infusion stem cell dose or time from original HSCT to boost was found. One patient developed grade III acute graft-versus-host disease despite cyclosporine, and one developed severe pneumonitis; both have recovered. Boost infusion was successful or partially successful in 84%of patients. The risk of adverse effects is low.Bone Marrow Transplantation (2005) 35, 683-689. doi:10.1038/sj.bmt.1704872 Published online 21 February 2005 [ABSTRACT FROM AUTHOR]

More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are associated with T–B + NK + SCID phenotype. Severe immunodeficiency with CHARGE syndrome has been noted only rarely Omenn syndrome is a rare autosomal recessive form of SCID with erythroderma, hepatosplenomegaly, lymphadenopathy and alopecia. Hypomorphic recombination activating genes 1 and 2 mutations were first described in patients with Omenn syndrome. More recently, defects in Artemis, RMRP, IL7Rα and common gamma chain genes have been described. We describe four patients with mutations in CHD7, who had clinical features of CHARGE syndrome and who had T–B + NK + SCID (two patients) or clinical features consistent with Omenn syndrome (two patients). Immunodeficiency in patients with DiGeorge syndrome is well recognized − CHARGE syndrome should now be added to the causes of T–B + NK + SCID, and mutations in the CHD7 gene may be associated with Omenn-like syndrome. [ABSTRACT FROM AUTHOR]

Summary:Primary immunodeficiencies (PID) are an important cause of childhood mortality. Haematopoietic stem cell transplantation (HSCT) is the best treatment for many PID. Umbilical cord stem cells are an alternative source of HSC. There is little data regarding outcome of umbilical cord stem cell transplantation (UCSCT) for PID. Our single centre experience is reported. A retrospective study of 14 of 148 patients transplanted for PID, who have received 15 UCSCT was performed, with specific regard to graft-versus-host disease (GvHD) and immune reconstitution. Eight patients with severe combined immunodeficiency (SCID), and six with other combined immunodeficiencies were treated. Of the patients, 12 received unrelated cords, and two had sibling transplants. Median age at transplant was 3.5 months, median nucleated cell dose was 0.8 × 108/kg. All engrafted. Median time to neutrophil engraftment was 22 days, median time to platelet engraftment was 51 days. One developed significant grade III GvHD post transplantation. In total, 11 patients had full donor T and six full donor B-cell chimerism, six of nine patients >1 year post-BMT had normal IgG levels and specific antibody responses to tetanus and Hib vaccines; two are being assessed. Two patients died of multi-organ failure related to pre-existing infection and inflammatory complications respectively. UCSCT should be considered for patients requiring stem cell therapy for PID.Bone Marrow Transplantation (2005) 36, 295–299. doi:10.1038/sj.bmt.1705054; published online 20 June 2005 [ABSTRACT FROM AUTHOR]

Summary: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 (2004) 33, 949-953. doi:10.1038/sj.bmt.1704456 Published online 8 March 2004 [ABSTRACT FROM AUTHOR]

Aims -- 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. Methods -- 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. Results -- 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 neuro- development. Conclusion -- These results are better than those published for in utero BMT for SCID. Early postnatal BMT should be the preferred option in neonatal SCID. [ABSTRACT FROM AUTHOR]