BackgroundThe presence of minimal residual disease detected by polymerase chain reaction techniques prior to allogeneic hematopoietic stem cell transplantation has proven to be an independent prognostic factor for poor outcome in children with acute lymphoblastic leukemia. Design and MethodsThe aim of this study was to ascertain whether the presence of minimal residual disease detected by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation is related to outcome in children acute lymphoblastic leukemia. Minimal residual disease was quantified by multiparametric flow cytometry at a median of 10 days prior to hematopoietic stem cell transplantation in 31 children (age range, 10 months to 16 years) with acute lymphoblastic leukemia. Thirteen patients were transplanted in first remission. Stem cell donors were HLA-identical siblings in 8 cases and matched unrelated donors in 23. Twenty-six children received a total body irradiation-containing conditioning regimen. According to the level of minimal residual disease, patients were divided into two groups: minimal residual diseasepositive (≥0.01%) (n=10) and minimal residual disease-negative (<0.01%) (n=21). ResultsEstimated event-free survival rates at 2 years for the minimal residual disease-negative andpositive subgroups were 74% and 20%, respectively (P=0.004) and overall survival rates were 80% and 20%, respectively (P=0.005). Bivariate analysis identified pre-transplant minimal residual disease as the only significant factor for relapse and also for death (P<0.01). ConclusionsThe presence of minimal residual disease measured by multiparametric flow cytometry identified a group of patients with a 9.5-fold higher risk of relapse and a 3.2-fold higher risk of death than those without minimal residual disease. This study supports the strong relationship between pre-transplantation minimal residual disease measured by multiparametric flow cytometry and outcome following allogeneic hematopoietic stem cell transplantation and concur with the results of previous studies using polymerase chain reaction techniques.Key words: minimal residual disease, hematopoietic stem cell transplantation, polymerase chain reaction. Citation: Elorza I, Palacio C, Dapena JL, Gallur L, Sanchez de Toledo J, and Diaz de Heredia C.Relationship between minimal residual disease measured by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation and outcome in children with acute lymphoblastic leukemia. Haematologica 2010;95:936-941. doi:10.3324/haematol.2009 Relationship between minimal residual disease measured by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation and outcome in children with acute lymphoblastic leukemia

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.

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Immune reconstitution is crucial to the success of allogeneic hematopoietic stem cell transplantation. Umbilical cord blood transplantation (UCBT) has been associated with delayed immune reconstitution. We characterized the kinetics and investigated the risk variables affecting recovery of the main lymphocyte subsets in 225 consecutive pediatric and adult patients (males, n = 126; median age, 15; range, .3 to 60; interquartile range, 4 to 35) who underwent myeloablative single UCBT between 2005 and 2015 for malignant and nonmalignant disorders. Low CD4 and CD8 T cell counts were observed up to 12 months after UCBT. In contrast, B and natural killer cells recovered rapidly early after transplantation. In a multivariate regression model, factors favoring CD4 T cell recovery ≥ 200 cells/µL were lower dose antithymocyte globulin (ATG) (hazard ratio [HR], 3.93; 95% confidence interval [CI], 2.3 to 5.83; P = .001), negative recipient cytomegalovirus (CMV) serostatus (HR, 3.76; 95% CI, 1.9 to 5.74; P = .001), and younger age (HR, 2.61; 95% CI, 1.01 to 3.47; P = .03). Factors favoring CD8 T cell recovery ≥ 200 cells/µL were lower dose ATG (HR, 3.03; 95% CI, 1.4 to 5.1; P = .03) and negative recipient CMV serostatus (HR, 1.9; 95% CI, 1.63 to 2.15; P = .01). Our results demonstrate the significant negative impact of ATG on lymphocyte recovery. A reduction of the dose or omission of ATG could improve immune reconstitution and perhaps reduce opportunistic infections after UCBT.

Congenital erythropoietic porphyria (CEP), or Günther's disease, is an inborn error of metabolism produced by a deficiency of uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthesis pathway. This enzymatic defect induces the accumulation of isomer I porphyrins in erythrocytes, skin, and tissues, producing various clinical manifestations. Severe cases are characterized by extreme photosensitivity, causing scarring and mutilations, and by hemolytic anemia, reducing life expectancy. CEP is caused by mutations in the UROS gene, and one of the most severe forms of the disease is associated with a cysteine to arginine substitution at residue 73 of the protein (C73R). CEP has been successfully treated only by the transplantation of hematopoietic precursors. We report the case of a male infant with severe postdelivery symptoms diagnosed with CEP and found to be homozygous for the C73R mutation. He underwent successful allogeneic bone marrow transplantation from a matched unrelated donor at 7 months of age. The hemolytic anemia was corrected and the porphyrin overproduction was significantly reduced. The patient remained asymptomatic after 1 year. This new case confirms that patients with severe CEP can benefit from early postnatal hematopoietic stem cell transplantation.