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Immunosuppressive therapy (IST) using horse antithymocyte globulin (h-ATG) combined with cyclosporine (CsA) and eltrombopag is the standard care for aplastic anemia (AA) in patients without a suitable matched donor. However, in many countries, h-ATG use has been discontinued, leaving rabbit ATG (r-ATG), which has a lower response rates and poorer survival, as the only alternative. In previous studies, alemtuzumab (ALZ), a humanized monoclonal antibody targeting CD52, combined with CsA resulted in an adequate ORR in AA patients. This study describes a multicenter, international retrospective analysis of ALZ for treating AA. We analyzed a series of patients who received subcutaneous ALZ for AA in four centers in Brazil and the United Kingdom from March 2009 to January 2024. We analyzed 64 ALZ treatments in 61 AA adult patients, 76% with SAA or very severe aplastic anemia (VSAA). Overall response rate (ORR) was 59.4% at 12 months (complete: 21.9%, partial: 37.5%). Cumulative incidence (CI) of response was 54.7% at 6 months, and 59.4% at 12 months. Younger patients (under 65) had higher CI of response (67% vs. 31%, P=0.03), as well as patients treated with a total dose of 103 mg (70% vs. 38%, P=0.02). Overall survival (OS) was 86% at 1 year, 78% at 2 years, and 70% at 4 years, significantly higher in responders (90% vs. 44%, P<0.0001). Adverse events were of low grade, and infectious events were infrequent. Subcutaneous ALZ is a feasible, effective, and safe alternative to r-ATG for AA patients requiring immunosuppressive treatment where h-ATG access is limited., (Copyright © 2024 American Society of Hematology.)

Background: Fanconi Anemia (FA) is a rare and heterogeneous genetic syndrome. It is associated with short stature, bone marrow failure, high predisposition to cancer, microcephaly and congenital malformation. Many genes have been associated with FA. Previously, two adult patients with biallelic pathogenic variant in Breast Cancer 1 gene (BRCA1) had been identified in Fanconi Anemia-like condition., Clinical Report: The proband was a 2.5 year-old girl with severe short stature, microcephaly, neurodevelopmental delay, congenital heart disease and dysmorphic features. Her parents were third degree cousins. Routine screening tests for short stature was normal., Methods: We conducted whole exome sequencing (WES) of the proband and used an analysis pipeline to identify rare nonsynonymous genetic variants that cause short stature., Results: We identified a homozygous loss-of-function BRCA1 mutation (c.2709T > A; p. Cys903*), which promotes the loss of critical domains of the protein. Cytogenetic study with DEB showed an increased chromosomal breakage. We screened heterozygous parents of the index case for cancer and we detected, in her mother, a metastatic adenocarcinoma in an axillar lymph node with probable primary site in the breast., Conclusion: It is possible to consolidate the FA-like phenotype associated with biallelic loss-of-function BRCA1, characterized by microcephaly, short stature, developmental delay, dysmorphic face features and cancer predisposition. In our case, the WES allowed to establish the genetic cause of short stature in the context of a chromosome instability syndrome. An identification of BRCA1 mutations in our patient allowed precise genetic counseling and also triggered cancer screening for the patient and her family members., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)