Luspatercept is a recent breakthrough in the therapy of anemia in low-risk MDS.
From January 2021 to October 2023, 44 patients (median age 77, M/F 25/19, WHO 2016 classification: MDS-RS-MLD 28, ...MDS-MLD -4, RARS-T 8, CMML- 0 2, 5q- + RS 2, IPSS-R: very low 2, low 33, Intermediate 9, IPSS-M (35 pts): very low + low 18, moderate low 11, moderate high 2, high 2, very high 2) were treated with luspatercept. Median follow-up was 13 months (range 1-42). The median number of cycles was 15 (2-42). Transfusion dependency (TD) before luspatercept initiation ranged from 2 transfusion units (TU) to 12 TU/8 weeks. All patients were tested for SF3B1 mutation.
We evaluated 42 patients. Twenty-four (57 %) patients reached TI (>12weekes), 6 (14 %) patients have had a reduction in transfusion need (HI, according to IWG criteria 2006). There were differences in response according to transfusion burden. Significant more responders belonged to lower IPSS-R, IPSS-M categories. In 17 patients, we added ESA (± prednisone), which led to the improvement of response in 12 cases with 9 TI. Four patients died (2-disease progression, 2 for comorbidity). There were no adverse effects of Grade II or more.
We did observed better responses in patients bearing single mutation in SF3B1, in lower IPSS-R and IPSS-M risk categories, patients with LTB and lower initial baseline EPO levels. The higher response rate in our follow-up may be influenced by the combination with ESA and rapid dose escalation.
Hereditary haemorrhagic telangiectasia (HHT) exhibits considerable phenotypic heterogeneity. Therefore, precise mutation screening and evaluation of patient risk must be determined in every HHT ...family. We present an HHT-2 case with an initial life-threatening bleeding episode that led to identification of a relatively large HHT family. Exome sequencing of the family members determined HHT-associated ACVRL1C1120T variant resulting in Arg374Trp substitution at the Ser/Thr-kinase domain region. The affected members display typical epistaxis symptomatology from early childhood resulting in sideropoenia. In addition, the HHT patients also displayed dermatology findings such as facial teleangiectasias and trunk/limb white spots representing post-inflammatory hypopigmentation. Interestingly, co-segregating with modifying cytochrome P450 (CYP2C) variant in the HHT patients led to NSAID intolerance marked by increased frequency of bleeding episodes. No arterial-venous malformation of the visceral organs and brain or association with cancer were observed. The heterogeneity of clinical presentation and the role of other variants support the need of regular patient monitoring and development of a nation-wide patient registry.
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