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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/m2 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.

Background Tacrolimus is an immunosuppressive drug that is used to lower the activity of the patient’s immune system to prevent organ rejection. Unfortunately, there is limited data regarding the therapeutic equivalency of generic tacrolimus formulations especially in children. We report the case of a pediatric patient having an inability to achieve a therapeutic trough level for tacrolimus after conversion from brand name to the generic formulation. Case presentation A 17-month-old male patient diagnosed with T-cell acute lymphoblastic leukemia underwent allogeneic stem cell transplantation. The patient initially received intravenous (IV) tacrolimus for graft-versus-host disease (GVHD) prophylaxis and achieved therapeutic levels. The patient was then switched to an oral brand formulation of tacrolimus, and was able to maintain trough levels within the therapeutic range. After being discharged, the patient received the generic formulation of tacrolimus from an outside pharmacy and the care team was unable to reach therapeutic levels despite multiple dose escalations. Returning to brand name tacrolimus resulted in prompt achievement of therapeutic levels. Conclusions A likely etiology for the inability to achieve therapeutic trough levels in this patient is the change in formulation from brand formulation to generic version. Other factors including drug-drug interaction, preparation of the medication by a different pharmacy, drug-food interaction and genetic factors were also considered. Physicians and pharmacists must be aware of the inability to achieve targeted therapeutic concentrations of tacrolimus resulting from the conversion of brand name to the generic formulation until these generic formulations are tested in clinical trials in a pediatric population.