BackgroundThe simultaneous presence of a heterozygous β-thalassemia with α-gene triplication may cause anything from a thalassemia trait to thalassemia intermedia of mild to moderate severity.Case presentationAn 8-month-old ethnic Gypsy male infant with failure to thrive from birth, mild jaundice and splenomegaly. Clinical signs were compatible with severe microcytic anemia requiring bi-monthly blood transfusions. The β-thalassemia gene analysis found homozygous mutation IVS-I-110 (G>A) (c.93-21G>A) in intron 1 of the hemoglobin beta globin gene and a non-pathogenic sequence variant (single nucleotide polimorfism (SNP) Rs1609812). In addition, the patient had α gene triplication (αααanti 3.7/αα) caused by double heterozygosity for a 3.7 kb fragment that contained only the hemoglobin alpha globin gene-2 gene. This finding led to screening and follow up in first-degree relatives, twin brothers and a sister and parents to provide them with appropriate genetic counseling. Nowadays, new horizons could open a new therapeutic management until definitive cure of these diseases through gene therapy or mutation-specific genome editing.ConclusionsGenetic testing can provide an early diagnosis and facilitates the search for a suitable donor for transplantation.
Treatment of steroid‐refractory chronic graft‐versus‐host disease (cGVHD) is a challenge. Here, we describe a retrospective analysis of 66 patients with steroid‐refractory cGVHD treated with imatinib (starting dose of 100 mg in 70% of patients; maximum dose of 100‐200 mg in 74%). Most patients had multi‐organ involvement (≥2 organs, 83%), with the most affected being skin (85%), oral mucosa (55%), eyes (42%), and lungs (33%). The overall response rate was 41% (21 partial and three complete responses). The organ with the best response rate was the skin (46%), followed by gastrointestinal tract (43%), liver (41%), the oral mucosa (36%), eyes (29%), and lungs (18%). Imatinib led to steroid tapering in 17/38 patients. Twenty‐five (38%) patients experienced imatinib‐related adverse events, comprising extra‐hematologic toxicity (n = 24, 36%) and hematologic toxicity (n = 6, 9%). No cases of grade 4‐5 toxicity were reported. The main causes of imatinib discontinuation were treatment failure (52%) and toxicity (9%). After a median follow‐up of 41 months, the 3‐year overall survival was 81%, with no difference between imatinib responders and non‐responders. These real‐life results show that imatinib is safe and has moderate efficacy in patients with heavily pre‐treated cutaneous sclerotic cGVHD; however, activity against lung cGVHD is very limited.
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