Preliminary data suggest that ex vivo T cell-depleted matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is feasible and confers a clinically beneficial reduction in graft-versus-host disease. Classically, T cell-depleted grafts were associated with reduction of the graft-versus-leukemia (GVL) effect because of delayed T cell immune reconstitution. However, natural killer (NK) cell alloreactivity is also critical for an early GVL effect as well as for lymphocyte immune reconstitution. Here, we study the role of NK cells in MRD T cell-depleted HSCT, which is still poorly understood. Given that MRD ligands for inhibitory killer cell immunoglobulin-like receptors (KIRs) are matched, we focused on activating KIR receptors. We retrospectively analyzed KIR genotyping in patients and MRDs in 40 ex vivo T cell-depleted pediatric HSCTs. The log-rank test and Cox proportional risk test were performed to correlate genotype with clinical outcome (relapse rate, disease-free survival, and overall survival) and immune reconstitution. The statistical analysis revealed poorer overall survival when donors have a KIR-B content score of ≥2, a best/better subtype, or present the KIR2DS1 gene. The patient's relapse rate was higher when donors present the KIR2DL5A gene, as well as a poorer probability of disease-free survival when the donor is classified with a best/better subtype. Regarding immune reconstitution, donor KIR haplotype A or the presence of inhibitory KIR genes promote best recovery of T lymphocytes, whereas donor KIR haplotype B or the presence of activating KIR genes confer better expansion of NK cells. These findings suggest that the selection of MRDs with an inhibitory KIR phenotype improve T cell expansion as well as the clinical outcome after pediatric ex vivo T cell-depleted HSCT.
Thrombocytosis is usually found by chance in children. Reactive or secondary thrombocytosis is the more common form, with infectious diseases being the most prevalent cause of it. Regarding the number of platelets there are four degrees of thrombocytosis; in its extreme degree the number of platelets exceeds 1,000,000/mm 3 . We describe a case of extreme reactive thrombocytosis in a healthy 6-year-old child. He required critical care admission for diagnosis and treatment (maximum number of platelets 7,283,000/mm 3 ). We review the different causes of thrombocytosis in childhood, the differential diagnosis, and the available treatments in case of extreme thrombocytosis.Extreme reactive thrombocytosis in a healthy 6 year-old child 319 de plaquetas de 7.283.000/mm 3 ). Se revisan las diferentes causas de trombocitosis en la infancia, se describe el diagnóstico diferencial y se discute sobre los diferentes tratamientos disponibles ante un caso como el descrito.
Treatment targeting CD19 by a chimeric antigen receptor expressed on T cells (anti-CD19 CAR-T) has led to a breakthrough in the management and treatment of relapsed and refractory B- cell acute lymphoblastic leukemia (B-ALL). After infusion, the efficacy of anti-CD19 CAR-T is monitored by bone marrow negative minimal residual disease and the absence of peripheral CD19+ B lymphocytes (B-cell aplasia). In patients who have received an allogenic Hematopoietic Stem Cell Transplantation (HSCT) prior to treatment with anti-CD19 CAR-T, monitoring lineage-specific chimerism could be helpful. We found that on 4 patients who received anti-CD19 CAR-T cells after HSCT and achieved early complete response, CD19+ lineage mixed chimerism but not CD3+ lineage mixed chimerism monitored by molecular techniques anticipated earlier than B-cell aplasia determined by flow cytometry, lack of effectiveness of anti-CD19 CAR-T and leukemia relapse. Donor lymphocyte infusions (DLIs) did not prevent relapse but recovered CD3+ full donor chimerism. We suggest that continuous lineage chimerism analysis should be done routinely in patients who receive anti-CD19 CAR-T cells after HSCT and achieve complete remission because it can support early treatment intervention. However, the role of DLI in this setting is unclear, so further prospective studies should be developed.
Thrombocytosis is usually a casual finding in children. Reactive or secondary thrombocytosis is the more common form, being the infections diseases the most prevalent cause of it. Regarding the number of platelets there are four degrees of thrombocytosis; in its extreme degree the number of platelets exceeds 1,000,000/mm(3). We describe a case of extreme reactive thrombocytosis in a healthy 6-year-old child. He required critical care admission for diagnosis and treatment (maximum number of platelets 7,283,000/mm(3)). We review the different causes of thrombocytosis in childhood, the differential diagnosis, and the available treatments in case of extreme thrombocytosis.
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