Clinical Outcome and Quality of Life in Patients with ARPC1B Deficiency Managed Conservatively or with Allogeneic Hematopoietic Stem Cell Transplantation

Background ARPC1B deficiency leads to a combined immunodeficiency characterized by early clinical onset, recurrent infections, and platelet abnormalities with bleeding tendency. Although most patients with ARPC1B mutations tolerate transplant conditioning, with a high rate of immunodeficiency resolution, there is a lack of studies comparing the clinical outcome and quality of life of patients undergoing transplantation or treated conservatively. The aim of the study is to compare ARPC1B patients managed conservatively and with HSCT assessing clinical outcome and quality of life. Methods The study was approved by ESID, EBMT, and CIS inborn error working parties. The inclusion criteria are patients with ARPC1B deficiency genetically confirmed and treated conservatively or with HSCT. Clinical data including symptoms, genetics, IDDA 2.1 score at last follow-up, and HSCT-related features were collected by local physicians and anonymized. Patients included in the study completed age-related quality of life questionnaires: PedsQL 4.0 and SDQ for children and SF 12 for adults, respectively. Results Thirteen centers from nine countries have been involved, collecting data from 20 patients. Clinical onset was early in all patients (median age 1 month [0-36]). The most frequent homozygous variant was c.311G>C (20%). Eight out of the 20 patients (40%) received allo-HSCT at a median age of 8.8 years [0.76-16.2]. The main clinical features are summarized in Table 1. At last available follow-up, 17 out of 20 patients are alive (85%), with 3 out of 8 patients dead after transplant. The median age at follow-up was 10.41 (1.58-36) for non-transplanted and 14.85 years (0.83-22.2) for transplanted patients. At the time of writing, 10 out of 17 patients (58.8%) had completed the QoL questionnaire (8/12 not transplanted, 2/5 transplanted). Preliminary results from the quality of life questionnaires are highlighted in Figure 1A-B. Table 1. HSCT No-HSCT Total n n=8 100% n=12 % n=20 (100) Infections 8 100 11 92 19 (95%) Recurrent AOM 4 50 9 75 13 (65%) URTI 5 62.5 3 25 8 (40%) LRTI 5 62.5 6 50 11 (55%) Sepsis 3 37.5 0 0 6 (30%) CNS infections 0 0 1 8 3 (15%) Skin infections 6 75 9 75 15 (75%) Severe Warts 2 25 4 33 6 (30%) Acute/Chronic CMV 2 25 4 33 7 (35%) Bleeding 3 37.5 8 67 11 (55%) Enterorrhagia 3 37.5 7 58 10 (50%) Recurrent epistaxis 0 0 2 17 2 (10%) ITP 3 37.5 3 25 6 (30%) Severe eczema 6 75 8 67 14 (70%) Skin vasculitis 2 25 5 42 7 (35%) Arthritis 2 25 4 33 6 (30%) Lymphoproliferation 2 25 1 8 3 (15%) IBD-like 2 25 4 33 6 (30%) Last follow-up IDDA 2.1 score 32.9 [4.1-174] 33.9 [6.9-66] 32.9 [4.1-174] HSCT: Hematopoietic Stem Cell Transplantation; AOM: Acute Otitis Media; URTI: Upper Respiratory Tract Infection; LRTI: Lower Respiratory Tract Infection; CNS: Central Nervous System; CMV: Cytomegalovirus; ITP: Immune Thrombocytopenic Purpura; IBD: Inflammatory Bowel Disease; IDDA: Inflammatory Disease Damage Assessment Figure 1. Patient (A) and proxy (B) PedsQL 4.0 scales scores of pediatric patients with ARPC1B deficiency. Scores are compared with children with healthy pediatric population. Conclusion Preliminary results confirm that HSCT in ARPC1B deficiency is feasible and effective. Even if preliminary, QoL was significantly reduced in patients treated conservatively compared with healthy donors. Notably, there is a marked reduction in the frequency of bleeding, eczema, and autoimmune/autoinflammatory symptoms in the HSCT group. More data are needed to determine its impact on patient outcomes and quality of life.