In β-thalassemia/HbE, PS-exposing RBCs, fragmented RBCs, and RMPs all differed in their numbers and their intensity of PS expression. The effects of these differences among PS-exposing populations on the pathophysiology of the disease require further investigation.
Background:The UniCel® DxH-800 is an automated cell counter widely used in laboratories. However, the effects of increased nucleated red blood cells (NRBCs) on the lymphocyte counts obtained using the UniCel DxH-800 have not been fully elucidated.Objective: The study's objective was to compare lymphocyte counts obtained using the DxH-800 and those obtained using flow cytometry in various ranges of NRBCs. Methods:This cross-sectional study analyzed 25 healthy volunteers and 69 β-thalassemia/HbE patients. The numbers of lymphocytes were determined using a UniCel DxH-800 and a standard flow cytometer using counting beads.Results: In healthy volunteers, regression analysis of the lymphocyte counts using the two approaches showed an r 2 0.85 and a p < 0.0001, and a Bland-Altman plot showed mean bias of +264 cells/μL. In β-thalassemia/HbE patients, regression analysis of the lymphocyte counts obtained using an automated cell counter and a flow cytometer showed an r 2 of 0.06, a p = 0.028, and a Bland-Altman plot showed the mean bias of +1,509 cells/μL. In addition, a high degree of discrepancy in the lymphocyte counts was observed in β-thalassemia/HbE patients who had NRBCs > 100,001 cells/μL. Conclusions:The present study demonstrated that the UniCel DxH-800 performed well in enumerating lymphocytes in specimens that contained various numbers of NRBCs. However, a high number of NRBCs may interfere with lymphocyte counts obtained using the counter.
Background: 6-Mercaptopurine (6-MP), a thiopurine agent, is an indispensable medication for treating pediatric acute lymphoblastic leukemia (ALL). However, its side effects of neutropenia and hepatotoxicity might interrupt treatment, resulting in poor outcomes. Inosine triphosphate pyrophosphatase (ITPA), an enzyme in the thiopurine pathway, may prevent the accumulation of toxic thiopurine metabolites. Studies on ITPA and thiopurine-associated toxicities are scarce. Methods: This study retrospectively investigated 1- to 15-year-old children with ALL who received 6-MP during the maintenance phase of treatment between 2000 and 2020. Toxicity during the first year of maintenance therapy and the mean dose of 6-MP were analyzed. Results: The 209 patients had a median age of 4.8 (0.3-14.8) years. Of these, 124 patients (59.3%) had wildtype ITPA, 73 patients (34.9%) had heterozygous ITPA 94C>A (hetITPA), and 12 patients (5.7%) had homozygous ITPA 94C>A (homITPA), with an allele frequency of 0.23. The incidence of neutropenia among ITPA polymorphisms did not significantly differ (P = 0.813). In patients harboring homITPA, transaminitis was more frequent than other polymorphisms but without a significant difference (P = 0.063). The mean dose of 6-MP for patients with homITPA was significantly lower than that for patients with hetITPA or wildtype ITPA (P = 0.016). Conclusions: HomITPA had a higher incidence of transaminitis and required a significantly larger dose reduction of 6-MP than wildtype ITPA. Further study is warranted to elucidate the effects of ITPA polymorphisms on toxicity in patients with ALL treated with 6-MP.
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