ABSTRACT
Background: Interstitial lymphocytic lung disease (ILLD), a recently recognized complication of primary immunodeficiencies (PID), is caused by immune dysregulation, abnormal bronchus-associated lymphoid tissue (BALT) hyperplasia, with subsequent progressive loss of pulmonary function. Various modes of standard immunosuppressive therapy for ILLD have been shown as only partially effective. Objectives: To retrospectively evaluate the safety and efficacy of abatacept or rituximab in treatment of ILLD in children with PID. Methods: 29 children (median age 11 years) with various forms of PID received one of the two therapy regimens predominantly based on the lesions' immunohistopathology: children with prevalent B-cell lung infiltration received rituximab (n = 16), and those with predominantly T-cell infiltration received abatacept (n = 17). Clinical and radiological symptoms were assessed using a severity scale developed for the study. Results: The targeted therapy with abatacept (A) or rituximab (R) enabled long-term control of clinical (A 3.4 ± 1.3 vs. 0.6 ± 0.1; R 2.8 ± 1 vs. 0.7 ± 0.05, p < 0.01) and radiological (A 18.4 ± 3.1 vs. 6.0 ± 2.0; R 30 ± 7.1 vs. 10 ± 1.7, p < 0.01) symptoms of ILLD in both groups and significantly improved patients' quality of life, as measured by the total scale (TS) score of 57 ± 2.1 in treatment recipients vs. 31.2 ± 1.9 before therapy (p < 0.01). Conclusions: ILLD histopathology should be considered when selecting treatment. Abatacept and rituximab are effective and safe in differential treatment of ILLD in children.
Subject(s)
Abatacept/administration & dosage , Lung Diseases, Interstitial/drug therapy , Primary Immunodeficiency Diseases/drug therapy , Quality of Life , Rituximab/administration & dosage , Abatacept/adverse effects , Adolescent , Child , Child, Preschool , Female , Humans , Lung Diseases, Interstitial/immunology , Male , Primary Immunodeficiency Diseases/immunology , Rituximab/adverse effectsABSTRACT
We evaluated the depletion of TCR-alpha/beta cells from the graft of children with high-risk AML, who received transplantation from unrelated (n=20) and haploidentical donors (n=13). The preparative regimen included treosulfan, melphalan, fludarabine and anti-thymocyte globulin. Grafts were PBSC engineered by TCR-alpha/beta and CD19 depletion. The graft contained a median of 9 × 10(6)/kg of CD34+ and 20 × 10(3)/kg of αß-T cells. Post-transplant immune suppression included tacrolimus till day +30 and Mtx in 21 patients, tacrolimus in 5, Mtx in 2 and no prophylaxis in 5 patients. Sixteen patients received native or TCR-alpha/beta-depleted donor lymphocytes at a median of 47 (40-204) days. Median follow-up is 1.76 years. Primary engraftment was achieved in 33 patients (100%). Cumulative incidence of acute GvHD (aGvHD) grade 2-3 was 39 (26-60)%, half of them had skin-only aGvHD. Cumulative incidence of chronic GvHD was 30(18-50)%. Transplant-related mortality is 10(4-26)%. Event-free survival (EFS) is 60(43-76)% and overall survival (OS) is 67(50-84)% at 2 years. In a subgroup of patients, who received transplantation in CR, EFS is 66(48-84)% and OS-72(53-90)% at 2 years. Our data suggest that TCR-alpha/beta and CD19 depletion is a robust method of graft manipulation, which can be used to engineer grafts for children with AML.
