Metoclopramide Treatment in Patients with Diamond-Blackfan Anemia: Preliminary Results of a French Prospective Trial.
Authors: Leblanc Thierry , Marie Isabelle , Debre Marianne , Da Costa Lydie , Bordigoni Pierre , Demolis Pierre , Tchernia Gil ,   the SHIP DBA Working Group
Published: April 2020

Abstract
Metoclopramide has been shown to be a potential new therapeutic approach for Diamond-Blackfan anemia (DBA) affected individuals and has been hypothetized to stimulate erythropoiesisis through the induction of prolactin release. Among 15 transfusion-dependent patients enrolled in a previous pilot study, 9 completed 16 weeks of treatment, 3 of whom reaching a complete and sustained response (Abkowitz et al, Blood 2002). In order to further assess the drug efficacy we performed a prospective study in patients included in the French DBA registry. Patients over 2 years of age and dependent on regular transfusions were randomized at inclusion either to be treated immediately after a transfusion (Arm B), or 6 weeks later (Arm A), the comparison of these 2 groups aiming to provide a more accurate determination in the delay of response. All patients were prescribed metoclopramide for 16 or 22 weeks: 10 mg x 3/d in adults and 0.2 mg/kg x 3/d in children (weight &lt; 50 kg). Packed Red Blood Cell transfusions were prescribed for hemoglobin values &lt; 80g/L. The definition of response relied on Hb levels, reticulocyte counts, and the intervals between transfusions. Prolactin as well as other hormones levels were assessed. The study was initiated in October 2003. 7 adults and 22 children have been included so far (13F, 16M): 17 in A and 16 in B arms, respectively; 4 additional pts are planned to be included within a month. The treatment had to be prematurely discontinued in 2 pts because of severe side effects: nervous breakdown (8w of treatment) and anaphylaxis (14w of treatment). Other side effects were mild. Most patients complained of asthenia and drowsiness which both decreased after the 1st weeks of treatment; amenorrhoea (2 pts) and bulimia (3 pts) were also observed. No increase in transfusion need occurred. An update of the trial was performed on August 1st: at that time 21 pts had completed at least 16w of treatment. None of them experienced a complete response, as defined by a transfusion independence. In two a partial response, as defined by an increase in the transfusion interval was obtained: In one patient it evolved from 3–4 to 8 w, and in the other from 6–8 to 10–11w. Both are still on treatment. Lastly, it has to be emphasized that the 2 French responder patients previously included in the pilot study are still transfusion independent more than 5 yr after the initiation of metoclopramide treatment.
CONCLUSION: metoclopramide may be of interest in some DBA affected individuals, even though we only obtained a low rate of partial responses in the present ongoing trial. We believe that this non toxic, and low cost treatment warrants to be tested in all patients with regular transfusion need or requiring high dose steroids. The duration of response and long term tolerance remain to be determined. Acknowledgments: Maria Daniela Arturi Foundation, DBA foundation and Assistance Publique-Hôpitaux de Paris (DRRC)