Hematopoietic stem-cell transplantation following solid-organ transplantation in children.

Reports of hematopoietic stem-cell transplantation (HSCT) following solid-organ transplantation have been described in adults mainly as case reports. These reports demonstrate feasibility but likely do not reflect true outcomes due to a positive reporting bias. We report herein the outcomes of all our pediatric recipients of allogeneic HSCT following previous solid-organ transplantation between 2000 and 2009. Four children were identified. Two patients underwent heart transplantation followed by cord-blood allogeneic HSCT for T-cell lymphoma/post transplant lymphoproliferative disease (PTLD) and two patients underwent liver transplantation followed by living-donor allogeneic HSCT for severe aplastic anemia (SAA). The mean time between transplants was 4.2 years (range 1.5-6 years). All patients engrafted; however, all patients died from 37 days to 1 year after HSCT. Causes of death included infections (n=2), multi-organ failure (n=1) and solid-organ graft rejection (n=1). Though three patients survived beyond day+100, multiple complications were observed including EBV re-activation followed by EBV-positive PTLD (n=1) and five episodes of severe infections. The patients transplanted for lymphoma did not have evidence of recurrence at last follow-up. Although feasibilty has been shown with this cohort, we conclude that allogeneic HSCT in immunosuppressed patients following solid-organ transplantation remains a very high risk procedure that results in severe morbidity and mortality in children.

Equivalent outcomes for pediatric heart transplantation recipients: ABO-blood group incompatible versus ABO-compatible.

ABO-blood group incompatible infant heart transplantation has had excellent short-term outcomes. Uncertainties about long-term outcomes have been a barrier to the adoption of this strategy worldwide. We report a nonrandomized comparison of clinical outcomes over 10 years of the largest cohort of ABO-incompatible recipients. ABO-incompatible (n = 35) and ABO-compatible (n = 45) infant heart transplantation recipients (< or =14 months old, 1996-2006) showed no important differences in pretransplantation characteristics. There was no difference in incidence of and time to moderate acute cellular rejection. Despite either the presence (seven patients) or development (eight patients) of donor-specific antibodies against blood group antigens, in only two ABO-incompatible patients were these antibodies implicated in antibody-mediated rejection (which occurred early posttransplantation, was easily managed and did not recur in follow-up). Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe renal dysfunction were identical in both groups. Survival was identical (74% at 7 years posttransplantation). ABO-blood group incompatible heart transplantation has excellent outcomes that are indistinguishable from those of the ABO-compatible population and there is no clinical justification for withholding this lifesaving strategy from all infants listed for heart transplantation. Further studies into observed differing responses in the development of donor-specific isohemagglutinins and the implications for graft accommodation are warranted.

Waiting before birth: outcomes after fetal listing for heart transplantation.

Following fetal diagnosis of a profound heart defect, transplantation (HTx) is an alternative to pregnancy termination or neonatal surgical palliation. Retrospective review of the cardiac and transplant databases of fetal listings for HTx between 1990 and July 2006 was undertaken to describe outcomes after listing. We identified 26 fetal listings (of 269 total listings). Diagnoses included congenital heart disease (n = 24) and cardiomyopathy (n = 2). Seven patients were delisted after birth: in five cases parents opted for surgical palliation, two clinically improved. One patient died wait-listed (stillborn). Time wait-listed as a fetus ranged from 1-41 days (median 19 days). Eighteen patients underwent HTx (median weight 2.8 kg, range 2.1-10.9 kg); median days wait-listed after birth was 22 (4 h-123 days). Two fetuses were surgically delivered at 36 weeks gestation when a donor organ became available; 11 were transplanted as neonates (<30 days). The median age at HTx was 1 month (4 h-2.6 months). Fetal listing for HTx increases the potential window of opportunity for a donor organ to become available; patients had low wait-list mortality and a fair intermediate-term outcome. Well-defined criteria for eligibility for fetal listing and priority allocation to infants over fetuses seem rational approaches for centers that offer fetal listing.

Emerging clinical picture of lymphangioleiomyomatosis.

OBJECTIVE: To provide a comprehensive update of the clinical picture of lymphangioleiomyomatosis (LAM) using two large patient registries. METHODS: A cross sectional questionnaire survey which included questions on 14 LAM symptoms, pneumothorax, tuberous sclerosis complex (TSC), date of diagnosis, and pulmonary function tests (PFTs). RESULTS: The response rate was 70.5% (n = 328). The mean age at the time of the survey was 46.7 years. The mean age at diagnosis was 42.7 years for women diagnosed 1 year before the survey and 35.8 years for women diagnosed 10 years previously. The main symptoms were dyspnoea (74%), fatigue (72%), cough (47%) and chest pain (44%); younger patients (<40 years) were less likely to report dyspnoea (p = 0.02). Patients with TSC (n = 51) were less likely to report dyspnoea (p = 0.05) and 76.5% reported angiomyolipoma (p < 0.0001) compared with patients with sporadic LAM. Patients with pneumothorax (63.0%) were less likely to report dyspnoea or fatigue (p < or = 0.05) than patients without pneumothorax. PFT results showed that low forced expiratory volume in 1 second and carbon monoxide transfer factor were highly associated with dyspnoea (p < 0.0001), but not with fatigue or history of pneumothorax. CONCLUSION: Previously considered a condition of women of childbearing age, more older women (50% without pneumothorax) are now being diagnosed with LAM. LAM should be considered in women over 40 with unexplained dyspnoea. LAM patients with pneumothorax have less fatigue and less dyspnoea than those without pneumothorax. Fatigue has been overlooked as a symptom of LAM and appears across the spectrum of pulmonary function.

Quality of life and function following cardiac transplantation in adolescents.

Quality of life and functional status are important outcome measures following heart transplantation. The present study evaluated the quality of life and function of 10 adolescent heart transplant recipients at the Hospital for Sick Children. Subjects were surveyed using a visual analog quality of life scale, the Children's Depression Inventory, The Pediatric Quality of Life Scale 4.0, and the Functional Status IIR. Results demonstrated excellent perceived quality of life and psychologic well-being, comparable to healthy norms. Subscale results for physical, social, and emotional function provide evidence for positive responses to transplantation. As well, results on factors such as self-esteem, school, interpersonal function, and mood demonstrate gender differences that may influence outcomes. Studies are currently underway to further delineate these important quality of life, function, and psychosocial issues to ensure optimal outcomes are achieved in our patients.

ABO-incompatible heart transplantation in infants.

BACKGROUND: Transplantation of hearts from ABO-incompatible donors is contraindicated because of the risk of hyperacute rejection mediated by preformed antibodies in the recipient to blood-group antigens of the donor. This contraindication may not apply to newborn infants, who do not yet produce antibodies to T-cell-independent antigens, including the major blood-group antigens. METHODS: We studied 10 infants 4 hours to 14 months old (median, 2 months) who had congenital heart disease or cardiomyopathy and who received heart transplants from donors of incompatible blood type between 1996 and 2000. Serum isohemagglutinin titers were measured before and after transplantation. Plasma exchange was performed during cardiopulmonary bypass; no other procedures for the removal of antibodies were used. Standard immunosuppressive therapy was given, and rejection was monitored by means of endomyocardial biopsy. The results were compared with those in 10 infants who received heart transplants from ABO-compatible donors. RESULTS: The overall survival rate among the 10 recipients with ABO-incompatible donors was 80 percent, with 2 early deaths due to causes presumed to be unrelated to ABO incompatibility. The duration of follow-up ranged from 11 months to 4.6 years. Two infants had serum antibodies to antigens of the donor's blood group before transplantation. No hyperacute rejection occurred; mild humoral rejection was noted at autopsy in one of the infants with antibodies. No morbidity attributable to ABO incompatibility has been observed. Despite the eventual development of antibodies to antigens of the donor's blood group in two infants, no damage to the graft has occurred. Because of the use of ABO-incompatible donors, the mortality rate among infants on the waiting list declined from 58 percent to 7 percent. CONCLUSIONS: ABO-incompatible heart transplantation can be performed safely during infancy before the onset of isohemagglutinin production; this technique thus contributes to a marked reduction in mortality among infants on the waiting list.