Trasplante de progenitores hematopoyéticos en déficit de piruvato cinasa: ¿cuándo indicarlo? / Haematopoietic stem cell transplantation in pyruvate kinase deficiency: When is it indicated?

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National registry of hemoglobinopathies in Spain (REPHem).

BACKGROUND: Although highly prevalent throughout the world, the accurate prevalence of hemoglobinopathies in Spain is unknown. PROCEDURE: This study presents data on the national registry of hemoglobinopathies of patients with thalassemia major (TM), thalassemia intermedia (TI), and sickle cell disease (SCD) in Spain created in 2014. Fifty centers reported cases retrospectively. Data were registered from neonatal screening or from the first contact at diagnosis until last follow-up or death. RESULTS: Data of the 715 eligible patients were collected: 615 SCD (497 SS, 64 SC, 54 SBeta phenotypes), 73 thalassemia, 9 CC phenotype, and 18 other variants. Most of the SCD patients were born in Spain (65%), and 51% of these were diagnosed at newborn screening. Median age at the first diagnosis was 0.4 years for thalassemia and 1.0 years for SCD. The estimated incidence was 0.002 thalassemia cases and 0.03 SCD cases/1,000 live births. Median age was 8.9 years (0.2-33.7) for thalassemia and 8.1 years (0.2-32.8) for SCD patients. Stroke was registered in 16 SCD cases. Transplantation was performed in 43 TM and 23 SCD patients at a median age of 5.2 and 7.8 years, respectively. Twenty-one patients died (3 TM, 17 SCD, 1 CC) and 200 were lost to follow-up. Causes of death were related to transplantation in three patients with TM and three patients with SCD. Death did not seem to be associated with SCD in six patients, but nine patients died secondary to disease complications. Overall survival was 95% at 15 years of age. CONCLUSIONS: The registry provides data about the prevalence of hemoglobinopathies in Spain and will permit future cohort studies and the possibility of comparison with other registries.

Immunomagnetic T Cell Depletion: an Analysis of Variables Affecting Final Cell Yield.

BACKGROUND: Only little detailed information has been published by a small number of centers on experiences with the technical aspects of "in vitro" large-scale graft manipulation technologies. METHODS: We report our experiences with the graft engineering procedures performed and the results obtained after T cell depletion. We have analyzed data from 212 procedures (108 CD34+ cell selection and 104 CD3+/CD19+ cell depletion). RESULTS: We conclude that the final cell products after selection or depletion were completely different with regard to CD34+ cell purity (95.8% vs. 1.52%). The CD34+ cell recovery after CD34+ cell selection is negatively affected when the initial leukocyte and/or CD34+ cell counts exceed the threshold defined by the manufacturer (68.9% vs. 45.2%, p < 0.01). However, the cell count threshold defined for the depletion technique could be exceeded without seriously affecting final results (86.1% vs. 86.4% for those with more or less than 40 x 109 leukocyte before the procedure; p = 0.7). Another important conclusion from this study is that in both CD34+ cell selection and CD3+/CD19+ cell depletion better results were reached after having gained experience by performing the procedures several times. This means that a learning process can be expected when using these in vitro graft manipulation procedures. CONCLUSIONS: It is extremely important to have experienced staff to perform these procedures. The expected results are different with each procedure so the decision on which of these T cell depletion approaches are used should be based on the characteristics of the final product wanted.

Defining "poor mobilizer" in pediatric patients who need an autologous peripheral blood progenitor cell transplantation.

The definition of poor mobilizers is not clear in pediatric patients undergoing autologous peripheral blood hematopoietic progenitor cell (HPC) mobilization. Most studies conducted in children define those variables related to the collection of HPC after leukapheresis, but the information regarding exclusively the mobilization process is scarce. In our experience, most children (92.2%) reach the target CD34(+) cell dose for autologous peripheral blood progenitor cell transplantation if CD34(+) cell count was higher than 10/µL. No differences were observed between those with >20 CD34(+) cells/µL and 11-20 CD34(+) cells/µL. In this study, we analyzed the variables that influence CD34(+) cell count; we found that prior use of radiotherapy was the main variable related to poor mobilization. Patients diagnosed with Ewing sarcoma, treated with radiotherapy and mobilized with standard doses of granulocyte colony-stimulating factor (G-CSF) were also at a high risk of mobilization failure. In these patients, we should consider mobilization with high dose G-CSF and be prepared with new mobilization agents to avoid delay on their course of chemotherapy.

Predicting factors for admission to an intensive care unit and clinical outcome in pediatric patients receiving hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: In children, hematopoietic stem cell transplantation (HSCT) implies life-threatening complications and some patients need admission to a pediatric intensive care unit (PICU). Few studies have been reported analyzing this issue in a pediatric population and most focused on risk factors predicting survival following PICU admission. DESIGN AND METHODS: We examined data of 240 pediatric patients who received HSCT (100 allogeneic and 140 autologous) in order to ascertain the incidence of life-threatening complications requiring PICU admission, the contributing risk factors and the patients' long-term survival. RESULTS: Forty-two (17.5%) (25 males and 17 females) of the transplanted children were admitted to the PICU. Twenty-nine of them (69%) had received an allogeneic transplant and thirteen (31%) an autologous transplant. Their median age was 7 years (range; 1-18). The most frequent reason for admission was respiratory failure (37 cases, 88%). The overall probability of developing complications requiring PICU admission was 21.2% (33.5% for allogeneic transplantation and 10.1% for patients receiving autologous grafts, p=0.0002). On univariate analysis, only the type of transplantation was significantly associated with PICU admission (allogeneic vs autologous RR 1.92, 95% CI: 1.46-2.53)(p = 0.0001). In allogeneic transplants, only the underlying disease (non-malignant) and the status of disease at transplantation within malignant diseases (advanced phase) were pretransplant variables associated with PICU admission. Post-transplantation risk factors were presence of graft-versus-host disease (GvHD) (p = 0.046) and its grade (II-IV) (p = 0.002), as well as the presence of multiorgan dysfunction during the early post-infusion phase especially when the lung was the first failing organ (p = 0.0001). However, on multivariate analysis, only severe GvHD was statistically significant. In the autologous transplantation group, the underlying disease (solid tumor, p = 0.07) and status at transplantation (advanced phase, p = 0.0029) were the only risk factors. In the post-transplant phase, patients who develop multiorgan dysfunction during the neutropenic period and those with engraftment syndrome had an increased risk of requiring critical care. The overall event-free survival (EFS) at 3 years was 15.3%, (18.4% for autologous transplant recipients and 13.7% for those receiving an allogeneic graft, p = 0.4). Using a Cox regression model, multiorgan failure (MOF) present at admission was the only variable that had a negative impact on EFS (4.28% vs 35.71% for patients with no MOF, p = 0.016). INTERPRETATION AND CONCLUSIONS: Despite high mortality, intensive care support can be beneficial for pediatric patients with life-threatening complications following HSCT. However, for patients with multiorgan failure involving the lungs, admission to the PICU should be avoided.