Prognostic role of minimal residual disease before and after hematopoietic stem cell transplantation in childhood acute lymphoblastic leukemia

More than 80% of children with acute lymphoblastic leukemia (ALL) can be cured through intensive and risk-oriented chemotherapy protocols. Allogeneic hematopoietic stem cell transplantation (HSCT) is considered bene\ufb01cial for approximately 10% of the patients who are at veryhigh risk at frontline therapy and for the majority of patients after relapse. Consequently, it is critically important to identify prognostic factors in this group of patients in order to tailor risk-adapted therapy. In this retrospective study, we aimed to assess the prognostic role of minimal residual disease (MRD) before HSCT and at di\ufb00erent time points after transplantation in children with ALL

Introduction: non-theatrical film festivals

The idea for this publication stemmed from the Reframing Film Festivals conference that the curators of this special issue were organised in Venice in February 2020, which was conceived to foster research engagement with the histories of film festivals and their relationship with film historiography and canons. During this two-day event, among the contributions dedicated to the micro-histories of a variety of festivals based in Central and Eastern Europe, South America and South-East Asia, several artists, curators, archivists and historians from France, Austria, Italy, Chile and Spain presented research focused on non-theatrical cultures and related festivals. This strand of research ranged 10 from historical analysis of international competitions for amateur filmmakers to theorisations of the festivals dedicated to analog video art and time-based art, from the study of the historical developments of national non-fiction festivals to the mapping of ethnographic film festival circuits. Hence, in this special issue dedicated to non-theatrical film festivals, readers will find a combination of voices representing film cultures that have been developing outside of movie theatres and away from the logic of theatrical distribution, as the title implies

Positron scattering from formic acid

We report on measurements of total cross sections for positron scattering from the fundamental molecule formic acid (HCOOH). In this case, the energy range of our experimental work is 0.3-50.2 eV. Our interpretation of these data was somewhat complicated by the fact that at room temperature, formic acid vapor consists of about 95% monomer and 5% dimer forms, so that the present cross sections represent an average for that ensemble. To assist us in interpreting the data, rigorous Schwinger multichannel level calculations for positron elastic scattering from the formic acid monomer were also undertaken. These calculations, incorporating an accurate model for the target polarization, are found to be in good qualitative agreement with our measured data, particularly when allowance is made for the target beam mixture (monomer versus dimer) in the experiment

T cell therapy with EBV-specific cytotoxic T-lymphocytes for patients with nasopharyngeal carcinoma

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HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with fanconi anemia

Abstract We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given T cell–depleted, CD34 + positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5% to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%), respectively. The conditioning regimen was well tolerated, with no fatal regimen-related toxicity and 3 cases of grade III regimen-related toxicity. The cumulative incidence of transplant-related mortality was 17% (95% CI, 5% to 59%). The 5-year overall survival, event-free survival, and disease-free survival were 83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to 100%), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of T cell–depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date

Autoimmune hematological diseases after allogeneic hematopoietic stem cell transplantation in children: An Italian multicenter experience

AbstractAutoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations

BACKGROUND AND OBJECTIVES: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL). Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been reported to depend on the severity of the c-MPL functional defect. To improve our knowledge in this field, we studied clinical and biological features of five new patients. DESIGN AND METHODS: We diagnosed five CAMT patients, identified c-MPL mutations, including five novel alterations and investigated relationships between mutations and their clinical-biological consequences. RESULTS: In all cases, platelet c-MPL and bone marrow colonies were reduced, while serum TPO levels were elevated. We also documented that the percentage of bone marrow cells expressing tumor necrosis factor-a and interferon-g was increased during pancytopenia as compared to in controls, suggesting that, as in other bone marrow failure diseases, these inhibitory cytokines contributed to the pancytopenia. Contrary to previously published data, we found no evidence of correlations between different types of mutations and the clinical course. INTERPRETATION AND CONCLUSIONS: These results suggest that therapies, such as hematopoietic stem cell transplantation, which are potentially curative although associated with a risk of treatment-related mortality, should not be postponed even in those CAMT patients whose c-MPL mutations might predict residual activity of the TPO receptor