Prolactin levels were 2-16 ng/mL (normal, < 20 ng/mL) in patients prior to metoclopramide administration. Responding patients are listed as patients 1, 2, and 3. Although anemia was noted during the first year of his life, Diamond-Blackfan anemia was diagnosed in patient 1 at age 4 years (Hgb, 7.2 g/dL; MCV, 101 fL; marrow demonstrated 4% of RBC precursors). Subsequent testing showed no mutation in the coding sequence of RPS19. At the time of metoclopramide administration, the patient was 32 years old and received prednisone 20 mg daily and RBC transfusions each 5 to 6 weeks. At 15 weeks, 9 weeks past his last transfusion, he met criteria for response. At 16 weeks (the duration of this study), his Hct was 29% (Hgb, 9.9 g/dL). At 6 months with continued therapy, his Hct was 36% (Hgb, 12.2 g/dL). With a prednisone taper, the Hgb decreased to 7.3 g/dL. Prednisone (20 mg daily) was restarted and the Hgb remains more than 12 g/dL for 16 months. He currently takes 10 mg metoclopramide twice a day. Diamond-Blackfan anemia was diagnosed in patient 2 when she was 1 year old (Hct, 21%; MCV, 94 fL; 9% of nucleated marrow cells were RBC precursors). Subsequent studies showed a normal HgbF and no abnormality in the coding sequence of RPS19. She initially responded to steroids (1971-1978), required no therapies between 1980 and 1990 (adolescence), but relapsed in 1990 with steroid-resistant disease. She then failed trials of IL-3 and cyclosporine and required RBC transfusions every 5 weeks. Her Hct (obtained 7 days after transfusion) was 22% and hemoglobin was 7.5 g/dL. After 14 weeks of metoclopramide therapy, her transfusion interval increased, meeting response criteria. At 7 months of therapy, she became transfusion independent (Hgb, 10 g/dL). The Hgb has remained more than 9 g/dL for 2 years (on metoclopramide 20 mg daily). Patient 3 (3-year-old boy) has been steroid dependent since his diagnosis at age 16 months. At that time, his Hct was 15.3%, MCV 103 fL, marrow had 7% erythroid precursors, ADA level was elevated at 1.57, and HgbF was 19.9%. RPS19 status is uncertain. At the time of study, he required daily prednisone at a dose of 5 mg alternating with 10 mg to maintain the Hgb at 6.8 g/dL. After 12 weeks of metoclopramide (0.2 mg/kg 3 times a day), his Hgb was 9.6 g/dL, meeting response criteria. At 16 weeks, the Hgb was 9.9 g/dL and the prednisone dose was tapered to 5 mg daily, then 5 mg alternating with 2 mg daily (Hgb values, 8.4-8.9 g/dL). When the metoclopramide dose was decreased to once a day (at 9 months), the Hgb fell to 6.7 g/dL, but recovered after restarting the 3-times-a-day dose. Because serum prolactin levels were measured at unknown times relative to 3-times-a-day metoclopramide ingestion, or just prior to metoclopramide ingestion, it is unlikely that values reflect peak responses. Three patients (ages 12, 21, and 30) discontinued therapy at weeks 12, 8, and 12, respectively because of toxicity (fatigue). Three patients (ages 4, 12, and 16) were noncompliant and removed from the study at weeks 9, 8, and 3. Their presentations and clinical characteristics were similar to evaluable patients.

A indicates androgens; P, prednisone or methylprednisolone; C, cyclosporine; Tx, RBC transfusions.