Chimerism and tolerance in a recipient of a deceased-donor liver transplant.

Complete hematopoietic chimerism and tolerance of a liver allograft from a deceased male donor developed in a 9-year-old girl, with no evidence of graft-versus-host disease 17 months after transplantation. The tolerance was preceded by a period of severe hemolysis, reflecting partial chimerism that was refractory to standard therapies. The hemolysis resolved after the gradual withdrawal of all immunosuppressive therapy.

Deletion 22q11.2 syndrome--implications for the intensive care physician.

OBJECTIVE: To report on the experience of a pediatric intensive care unit (PICU) with patients with deletion 22q11.2 syndrome: 1) to delineate the clinical characteristics and management of these patients; 2) to assess whether these patients were managed appropriately, especially in terms of blood transfusion; and 3) to make recommendations for PICU management. DESIGN: Retrospective assessment of medical records of patients with fluorescent in situ hybridization-proven 22q11 deletion admitted to the PICU at the Children's Hospital at Westmead, Sydney. SETTING: PICU in a tertiary university-affiliated children's hospital. PATIENTS: Sixty-five consecutive admissions in 40 patients with diagnosis of 22q11 deletion over a 4-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-seven (57%) of 65 admissions were postoperative cardiac surgical and accounted for the most common reason for admission to the PICU. Thirteen (20%) admissions were for velopharyngeal/laryngeal problems. Four (6%) admissions were associated with hypocalcemia, with two being first presentations. Five (12.5%) of 40 patients had immune dysfunction, one of whom developed cytomegalovirus pneumonitis. Twenty-nine (72.5%) patients received blood products either immediately before PICU admission or in the PICU. Of these, 16 received nonirradiated cellular blood products. There were two deaths from complications of congenital heart disease. CONCLUSIONS: PICUs need to be familiar with deletion 22q11.2 syndrome, especially the recommended use of irradiated and cytomegalovirus-seronegative blood components in these immunocompromised patients. The guidelines were inconsistently followed in the cohort of patients reported here. The extent of this problem may be more widespread in PICUs, and we recommend that individual units review their practice in this regard. Hypocalcemia may manifest at any time, and a regular survey of the calcium status is required in the intensive care setting. Admission to PICU should afford the opportunity to invite subspecialty referral and optimize extended care.

Complex phenotypes in the haemoglobinopathies: recommendations on screening and DNA testing.

This document considers a number of scenarios involving complex haemoglobinopathies and provides 28 recommendations at both the clinical and laboratory levels on how these should be managed.

Importance of minimal residual disease testing during the second year of therapy for children with acute lymphoblastic leukemia.

PURPOSE: A high level of minimal residual disease (MRD) after induction chemotherapy in children with acute lymphoblastic leukemia (ALL) is an indicator of relative chemotherapy resistance and a risk factor for relapse. However, the significance of MRD in the second year of therapy is unclear. Moreover, it is unknown whether treatment intervention can alter outcome in patients with detectable MRD. PATIENTS AND METHODS: We assessed the prognostic value of MRD testing in bone marrow samples from 85 children at 1, 12, and 24 months from diagnosis using clone-specific polymerase chain reaction primers designed to detect clonal antigen receptor gene rearrangements. These children were part of a multicenter, randomized clinical trial, which, in the second year of treatment, compared a 2-month reinduction-reintensification followed by maintenance chemotherapy with standard maintenance chemotherapy alone. RESULTS: MRD was detected in 69% of patients at 1 month, 25% at 12 months, and 28% at 24 months from diagnosis. By univariate analysis, high levels of MRD at 1 month, or the presence of any detectable MRD at 12 or 24 months from diagnosis, were highly predictive of relapse. Multivariate analysis showed that MRD testing at 1 and 24 months each had independent prognostic significance. Intensified therapy at 12 months from diagnosis did not improve prognosis in those patients who were MRD positive at 12 months from diagnosis. CONCLUSION: Clinical outcome in childhood ALL can be predicted with high accuracy by combining the results of MRD testing at 1 and 24 months from diagnosis.

Recombinant activated factor VII following pediatric cardiac surgery.

OBJECTIVE: Review the use of recombinant activated Factor VII following cardiac surgery. Specifically, we sought to define our current therapeutic practice indications and outcomes to assess the impact of recombinant activated factor VII on postoperative bleeding. DESIGN: Retrospective case series. SETTING: The study was conducted at the University affiliated pediatric intensive care unit. PATIENTS AND PARTICIPANTS: All postcardiac surgical patients who received recombinant activated Factor VII between June 2002 and July 2006. RESULTS: Cardiac surgery requiring cardiopulmonary bypass was performed on 1010 children during this period. In all, 25 (2.5%) children received recombinant activated factor VII for excessive bleeding. A single dose (180 microg/kg) of recombinant activated factor VII was given to 11 patients and 2 doses of 180 microg/kg to 14 patients. Intercostal drain losses were reduced from 12 (6.7-20.8) mL/kg/h to 3 (1-4.1) mL/kg/h, P = .018 following 1 dose of recombinant activated factor VII. In those receiving 2 doses; initial losses were 19.1 (7.5-31.7) mL/kg/h, after the first dose were 7.5 (3.6-13.7) mL/kg/h, P = .046, and after the second dose were 2 (1-2.9) mL/kg/h, P = .008. The plasma prothrombin time decreased in both the 1 dose, P = .003 and 2 dose, P = .009 groups. The activated partial thromboplastin time also decreased in the 1 dose group, P = .007 and 2 dose group, P = .03. There were no side effects attributable to recombinant activated factor VII. Annual rates of return to the operating theatre for excessive bleeding were coincidentally reduced in association with the routine use of recombinant activated factor VII from 4.3% to 1.5%, P = .019. CONCLUSIONS: Hemostasis occurred in 25 postoperative pediatric cardiac patients after recombinant activated Factor VII was given. In this setting, once conventional hemostatic therapy was optimized, recombinant activated Factor VII 180 microg/kg initially with intercostal losses greater than 10 mL/kg/h and a repeat dose after 2 hours if losses remained greater than 5 mL/kg/h was effective. No complications were found to have occurred and there was a coincidental reduction in annual returns to theatre for excessive bleeding.

Intermittent 20q- and consistent i(7q) in a patient with Shwachman-Diamond syndrome.

Shwachman Diamond syndrome (SDS) is a genetic disorder characterized by pancreatic hypoplasia, recurrent infection and bone marrow dysfunction. Some cases have an abnormality of chromosome 7, such as isochromosome 7q (i(7q)), which may be associated with the development of leukemia. We present a boy who was diagnosed with SDS at 19 months of age. From age 5-14 years, bone marrow cytogenetics has shown a consistent abnormality - i(7q), with an intermittent separate abnormality - deletion 20q, from age 11 years. During this time, the boy has been clinically well without leukemic signs, managed conservatively. We suggest that deletion 20q may be a non random secondary change in SDS with i(7q).