Human kidney-derived hematopoietic stem cells can support long-term multilineage hematopoiesis.

Long-term multilineage hematopoietic donor chimerism occurs sporadically in patients who receive a transplanted solid organ enriched in lymphoid tissues such as the intestine or liver. There is currently no evidence for the presence of kidney-resident hematopoietic stem cells in any mammal species. Graft-versus-host-reactive donor T cells promote engraftment of graft-derived hematopoietic stem cells by making space in the bone marrow. Here, we report full (over 99%) multilineage, donor-derived hematopoietic chimerism in a pediatric kidney transplant recipient with syndromic combined immune deficiency that leads to transplant tolerance. Interestingly, we found that the human kidney-derived hematopoietic stem cells took up long-term residence in the recipient's bone marrow and gradually replaced their host counterparts, leading to blood type conversion and full donor chimerism of both lymphoid and myeloid lineages. Thus, our findings highlight the existence of human kidney-derived hematopoietic stem cells with a self-renewal ability able to support multilineage hematopoiesis.

Chronic Granulomatous Disease with the McLeod Phenotype: a French National Retrospective Case Series.

BACKGROUND: X-linked chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the CYBB gene (located on Xp21.1). Patients with large deletions on chromosome Xp21.1 can present with the McLeod phenotype and also Duchenne muscular dystrophy or retinitis pigmentosa. The objective of the present study was to describe a series of French patients with CGD and the McLeod phenotype. METHODS: We retrospectively collected data from the medical records of 8 patients with CGD and the McLeod phenotype registered at the French National Reference Center for blood types. RESULTS: The median age at diagnosis of CGD was 1.2 years, the median age at diagnosis of the McLeod phenotype was 4.5 years, and the median length of follow-up was 15.2 years. Four patients displayed allo-immunization, with anti-KEL20 and anti-XK1 (formerly known as anti-KL) antibodies. Five of the 6 patients with available blood smears had acanthocytosis. Neuropsychiatric, muscle-related, and ocular manifestations were present in 4, 2, and 1 of the patients, respectively. Three of the 4 patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT) are alive. Overall, 5 patients are alive, and 3 are alive and well. CONCLUSION: This is the largest yet descriptive study of a series of patients with X-linked CGD and the McLeod phenotype. Although this disease combination is rare, the timely, accurate diagnosis of the McLeod phenotype is critical because of the serious post-transfusion complications. However, HSCT can be considered in these patients.

Lactate clearance in infants undergoing surgery for congenital heart disease.

Measurement of lactate concentrations during cardiac surgery with cardiopulmonary bypass (CPB) is a reliable monitoring tool for the assessment of the adequacy of perfusion, and a predictor of poor outcome. However, increased lactate production, which is multifactorial (anaerobic metabolism, hyperglycemia), increased lactate load by packed red blood cell (PRBC) transfusions, and decreased lactate clearance may all result in hyperlactatemia. The aim of this study was to estimate the clearance of lactate in infants undergoing surgery with CPB, using the lactate load from the PRBCs transfusions received during CPB. Retrospective cohort of infants <1 year of age with repeated lactate measurements during CPB, and a known lactate concentration in the PRBCs used during CPB were evaluated. All patients received PRBCs in the prime and during CPB to maintain hematocrit >35% and venous saturation >70%. Lactate kinetics were estimated across several time intervals between two lactate measurements, using a single compartment model. The lactate load was calculated as the product: PRBC-lactate concentration * volume. The rate of endogenous lactate production was assumed to be unchanged (maintenance of high oxygen deliveries and normoglycemia throughout CPB). Overall, 87 calculations were performed in 27 patients, then averaged per patient. The mean lactate half-life was 12.36 min [10.67-14.06], the mean clearance was 0.09 L/min [0.06-0.11], the indexed lactate clearance was 0.36 L/min/m2 [0.28-0.44]. Lactate clearance increased significantly with age. The half-life of lactate in infants is comparable with that reported in adults with CPB, and lactate clearance is higher. Knowing the high lactate content of PRBCs, lactate clearance rather than absolute concentration is potentially a better indicator of the adequacy of perfusion during CPB in infants.

Transfusion-related adverse events are decreased in pregnant women with sickle cell disease by a change in policy from systematic transfusion to prophylactic oxygen therapy at home: A retrospective survey by the international sickle cell disease observatory.

Sickle cell disease (SCD) in pregnancy can be associated with adverse maternal and perinatal outcomes. Furthermore, complications of SCD can be aggravated by pregnancy. Optimal prenatal care aims to decrease the occurrence of maternal and fetal complications. A retrospective, French, two-center study compared two care strategies for pregnant women with SCD over two time periods. In the first study period (2005-2010), the women were systematically offered prophylactic transfusions. In the second study period (2011-2014), a targeted transfusion strategy was applied whenever possible, and home-based prophylactic nocturnal oxygen therapy was offered to all the pregnant women. The two periods did not differ significantly in terms of the incidence of vaso-occlusive events. Maternal mortality, perinatal mortality, and obstetric complication rates were also similar in the two periods, as was the incidence of post-transfusion complications (6.1% in 2005-2010 and 1.3% in 2011-2014, P = .15), although no de novo alloimmunizations or delayed hemolysis transfusion reactions were observed in the second period. The results of this preliminary, retrospective study indicate that targeted transfusion plus home-based prophylactic nocturnal oxygen therapy is safe and may decrease transfusion requirements and transfusion-associated complications.