Multivariate Analysis of Immune Reconstitution and Relapse Risk Scoring in Children Receiving Allogeneic Stem Cell Transplantation for Acute Leukemias.

A timely and effective immune reconstitution after hematopoietic stem cell transplantation (HSCT) is of crucial importance to enhance graft-versus-leukemia reaction in hematological malignancies. Several factors can influence the yield of this process, and new mathematical models are needed to describe this complex phenomenon. METHODS: We retrospectively analyzed immune reconstitution in the early post-HSCT period in a multicenter cohort of 206 pediatric patients affected by acute lymphoblastic leukemia, acute myeloblastic leukemia, and myelodysplastic syndrome who received their first allo-HSCT. All patients were in complete morphological remission at transplantation and were followed-up at least 26 mo post-HSCT. Blood samples for analysis of lymphocyte subset numbers were collected at day 100 (±20 d). RESULTS: The 2-y cumulative incidence of relapse was 22.2% (95% confidence interval [CI], 17.3-27). Using principal component analysis, we identified based on 16 input variables a new multivariate model that enables patients' description in a low-dimensional model, consisting of the first 2 principal components. We found that the numbers of CD3+/CD4+/CD8+ lymphocyte subsets at day 100 post-HSCT and acute graft-versus-host disease had the greatest impact in preventing relapse. We ultimately derived a risk score defining high- or medium-low-risk groups with 2-y cumulative incidence of relapse: 35.3% (95% CI, 25.6-45) and 15.6% (95% CI, 10.1-20.7), respectively (P = 0.001*). CONCLUSIONS: Our model describes immune reconstitution and its main influencing factors in the early posttransplantation period, presenting as a reliable model for relapse risk prediction. If validated, this model could definitely serve as a predictive tool and could be used for clinical trials or for individualized patient counseling.

Clinical and laboratory outcomes following total or partial splenectomy in patients with hereditary spherocytosis.

This study compared outcomes following total (TS) or partial splenectomy (PS) among patients with hereditary spherocytosis. Seventy-nine patients (TS = 33, PS = 46) were identified. The follow-up period was longer after PS (59.6 vs. 24.9 months, p < .001). Long-term adverse events occurred more frequently following PS (50% vs. 29%, p = .001). Anemia, jaundice, and fatigue recurred in six patients with PS, leading to five completion splenectomies. Hemoglobin was not different between PS and TS by 5 years post-procedure (12.3 vs. 13.4 g/dL, p = .25). Both PS and TS ameliorate symptoms and improve hematologic parameters. The rate of secondary surgery following PS should be considered when planning the initial surgical procedure.

Heterozygous Mutation in Adenosine Deaminase Gene in a Patient With Severe Lymphopenia Following Corticosteroid Treatment of Autoimmune Hemolytic Anemia.

We describe a previously healthy 14-year-old girl with acute onset autoimmune hemolytic anemia, associated with severe but transient lymphopenia during corticosteroid therapy, without infectious episodes during follow-up. After detailed investigations to rule out an underlying immunodeficiency, we detected a heterozygous ADA gene mutation. This was associated with slightly increased blood levels of adenosine and deoxyadenosine nucleotides and with reduced ADA activity in red blood cells, but within the normal range. This observation suggests that heterozygous ADA mutation might be a predisposing factor for lymphopenia in patients receiving corticosteroid therapy.