Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency.

PURPOSE OF REVIEW: Hematopoietic cell transplantation (HCT) is an established curative treatment for children with primary immunodeficiencies. This article reviews the latest developments in conditioning regimens for primary immunodeficiency (PID). It focuses on data regarding transplant outcomes according to newer reduced toxicity conditioning regimens used in HCT for PID. RECENT FINDINGS: Conventional myeloablative conditioning regimens are associated with significant acute toxicities, transplant-related mortality, and late effects such as infertility. Reduced toxicity conditioning regimens have had significant positive impacts on HCT outcome, and there are now well-established strategies in children with PID. Treosulfan has emerged as a promising preparative agent. Use of a peripheral stem cell source has been shown to be associated with better donor chimerism in patients receiving reduced toxicity conditioning. Minimal conditioning regimens using monoclonal antibodies are in clinical trials with promising results thus far. Reduced toxicity conditioning has emerged as standard of care for PID and has resulted in improved transplant survival for patients with significant comorbidities.

A four-point clinical criteria distinguishes immune thrombocytopenia from acute lymphoblastic leukaemia.

Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage.

Neonatal tetanus: a study of five cases in Sandakan, Sabah.

This study aims to study the demographics, clinical presentation, treatment and outcome of neonatal tetanus patients managed at Hospital Duchess of Kent from January 1st 2006 to December 31st 2006. Five neonates were studied. All presented with fever, poor sucking and limb stiffness, with a history of unsterile delivery and uncertain maternal tetanus immunity status. All were nursed in a minimal-stimuli environment and were given IV penicillin G, IM tetanus immunoglobulin and sedatives to control spasms. Nutrition and chest physiotherapy were rendered. Three patients required artificial ventilation. Duration of treatment ranged from 25 to 44 days. All survived. Inadequate maternal immunization, unsterile delivery and inappropriate umbilical cord care are major contributing factors of neonatal tetanus in our study. Supportive measures are the mainstay of treatment in our setting with very limited resources.

Changes in the incidence, patterns and outcomes of graft failure following hematopoietic stem cell transplantation for Hurler syndrome.

Hematopoietic stem cell transplantation (HSCT) is the standard of care in children with Hurler syndrome (HS) as it is the only therapy that can arrest disease progression. We examined the incidence, patterns and outcomes of graft failure in all HS children undergoing first HSCT at the Royal Manchester Children's Hospital or the University of Minnesota Children's Hospital from 1983 to 2016. Implementation of busulfan pharmacokinetic monitoring started in 2004 in both institutions. Two hundred and forty HS children were included in this analysis (historical era (pre-2004), n=131; current era (post 2004), n=109). The proportion of patients with graft failure was significantly lower in the current era compared with the historical era (37.2% vs 10.1%, respectively). Of 49 patients with graft failure in the historical era, 1 had aplasia and 48 had autologous reconstitution. All the 11 graft failures of the current era occurred in recipients of cord blood transplants (7 aplasia and 4 autologous reconstitution). The outcomes of second transplant in these patients has improved, with 89% of such patients alive and engrafted in the current era compared with 58% in the historical era. The pattern of graft failure has changed from autologous reconstitution, likely secondary to inadequate myelosuppression in the historical era, to aplasia in the current era, likely due to imperfect immunosuppression.

Haemophagocytic lymphohistiocytosis in Malaysian children.

OBJECTIVES: To study the clinical presentation, therapy and outcome of children diagnosed with both primary and secondary haemophagocytic lymphohistiocytosis (HLH) at the University of Malaya Medical Centre. METHODS: All patients diagnosed with HLH between 1998 and 2004 were studied. Clinico-pathological data of these patients were prospectively collected and analysed. RESULTS: Thirteen consecutive patients (eight boys) with a median age of 28 months were seen. All patients presented with high-grade unremitting fever and almost all, with hepatosplenomegaly and cytopenias. Neurological manifestations, which ranged from irritability to seizures and coma, were seen in 10 (77%) patients. Other common presenting features include liver dysfunction (46%) and skin rash (38%). All patients were treated using the HLH-94 protocol chemotherapy which consisted of a combination of etoposide, dexamethasone and cyclosporine. Complete response was seen in seven patients while two required bone marrow transplantation and one developed secondary acute myeloid leukaemia. Two patients died before treatment could be commenced. Overall mortality rate in our series was 46%. CONCLUSIONS: Haemophagocytic lymphohistiocytosis is an uncommon disease with a high fatality rate. Due to its protean clinical manifestations, it may be underdiagnosed. Early detection and prompt institution of appropriate therapy is necessary to improve the outcome in affected patients.