Introduction: New generation osmotic gradient ektacytometry has become a powerful

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

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Summary Blinatumomab and inotuzumab ozogamycin represent promising alternatives to conventional chemotherapy in acute lymphoblastic leukaemia (ALL). We analysed data from 29 children with ALL treated under compassionate use with blinatumomab, inotuzumab or both. The complete remission (CR) rate in a heavily pretreated population with overt relapse was 47·6%. At earlier stages (first/second CR), both antibodies represented a useful tool to reduce minimal residual disease, and/or avoid further toxic chemotherapy until stem cell transplantation. Six patients developed grade 3 reversible non‐haematological toxicity. The 12‐month overall survival and event‐free survival rates were 50·8 ± 26·4% and 38·9 ± 25·3% with blinatumomab, 45·8 ± 26% and 27·5 ± 25% with inotuzumab.

Children with Noonan syndrome (NS) are at increased risk of developing juvenile myelomonocytic leukemia (JMML) or a myeloproliferative disorder associated with NS (MPD/NS) resembling JMML in the first weeks of life; whereas JMML is an aggressive disorder requiring hematopoietic stem cell transplantation, MPD/NS may resolve without treatment and cases with spontaneous remission have also been reported. Two cases of NS with hematologic disorders are described. Diagnosis of the syndrome was confirmed by the identification of earlier reported germline missense mutations in the PTPN11 gene. Splenomegaly in 1 patient and leukocytosis, monocytosis and "in vitro" culture assays consistent with JMML in both were the most salient hematologic features. After a 24-month follow-up, these 2 infants continue to improve and JMML has been ruled out. Splenomegaly persists in 1 patient and monocytosis in both, but without signs of malignancy, thereby suggesting abnormal hematopoiesis or MPD/NS, as described in NS.