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L‐leucine improves anemia and growth in patients with transfusion‐dependent Diamond‐Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond‐Blackfan Anemia Registry
Author(s) -
Vlachos Adrianna,
Atsidaftos Evangelia,
Lababidi Mohammad Lutfi,
Muir Ellen,
Rogers Zora R.,
Alhushki Waseem,
Bernstein Jonathan,
Glader Bertil,
Gruner Barbara,
Hartung Helge,
Knoll Christine,
Loew Thomas,
Nalepa Grzegorz,
Narla Anupama,
Panigrahi Arun R.,
Sieff Colin A.,
Walkovich Kelly,
Farrar Jason E.,
Lipton Jeffrey M.
Publication year - 2020
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.28748
Subject(s) - medicine , diamond–blackfan anemia , anemia , bone marrow failure , short stature , fanconi anemia , hematopoietic stem cell transplantation , pediatrics , gastroenterology , transplantation , haematopoiesis , stem cell , rna , biochemistry , chemistry , genetics , biology , dna repair , gene , ribosome
Background Diamond‐Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, short stature, congenital anomalies, and cancer predisposition. Most cases are due to mutations in genes encoding ribosomal proteins (RP) leading to RP haploinsufficiency. Effective treatments for the anemia of DBA include chronic red cell transfusions, long‐term corticosteroid therapy, or hematopoietic stem cell transplantation. In a small patient series and in animal models, there have been hematologic responses to L‐leucine with amelioration of anemia. The study objectives of this clinical trial were to determine feasibility, safety, and efficacy of L‐leucine in transfusion‐dependent patients with DBA. Procedure Patients ≥2 years of age received L‐leucine 700 mg/m 2 orally three times daily for nine months to determine a hematologic response and any improvement in growth (NCT01362595). Results This multicenter, phase I/II study enrolled 55 subjects; 43 were evaluable. There were 21 males; the median age at enrollment was 10.4 years (range, 2.5‐46.1 years). No significant adverse events were attributable to L‐leucine. Two subjects had a complete erythroid response and five had a partial response. Nine of 25, and 11 of 25, subjects experienced a positive weight and height percentile change, respectively, at the end of therapy. Conclusions L‐leucine is safe, resulted in an erythroid response in 16% of subjects with DBA, and led to an increase in weight and linear growth velocity in 36% and 44% of evaluable subjects, respectively. Further studies will be critical to understand the role of L‐leucine in the management of patients with DBA.