BACKGROUND Alloantibodies against more than 50 non‐ABO blood group antigens have been implicated in hemolytic disease of the fetus and newborn (HDFN) and are expected to wane within weeks after delivery. Persistent anemia leads to the hypothesis of continued exposure to red blood cell (RBC) alloantibodies via breast milk, which has been shown in a murine model and suggested in rare case reports. CASE REPORT We report three cases of prolonged HDFN in two neonates with anti‐D HDFN and one with anti‐Jka HDFN. Patient 1 demonstrated 4+ anti‐D serologic testing beyond 2 months; therefore, antibody testing was performed on maternal breast milk. METHODS Maternal serum samples were tested for the presence of unexpected antibodies using standard Ortho gel card and 37 °C 60 minutes with anti‐human globulin (AHG) tube saline methods. Antibody titrations were performed using the standard 37 °C 60 minutes to AHG tube saline method. Fresh breast milk samples were tested using the standard 37 °C 60 minutes to AHG tube saline method for both unexpected antibodies and titration study. Fresh breast milk from an O‐positive, antibody‐negative donor was used as control for any reactivity that may have been due to milk solids or proteins alone. RESULTS Using a known methodology applied in a novel way to test breast milk for RBC alloantibodies, antibodies against fetal RBCs were identified in the maternal breast milk of three patients. CONCLUSION Maternal RBC alloantibodies are present in breast milk and may be clinically significant in patients with prolonged recovery from HDFN.
Purpose: Simultaneously targeting the tumor and tumor microenvironment may hold promise in treating children with refractory solid tumors. Pexidartinib, an oral inhibitor of tyrosine kinases including colony stimulating factor 1 receptor (CSF-1R), KIT, and FLT3, is FDA approved in adults with tenosynovial giant cell tumor. A phase I trial was conducted in pediatric and young adult patients with refractory leukemias or solid tumors including neurofibromatosis type 1–related plexiform neurofibromas. Patients and Methods: A rolling six design with dose levels (DL) of 400 mg/m2, 600 mg/m2, and 800 mg/m2 once daily for 28-day cycles (C) was used. Response was assessed at regular intervals. Pharmacokinetics and population pharmacokinetics were analyzed during C1. Results: Twelve patients (4 per DL, 9 evaluable) enrolled on the dose-escalation phase and 4 patients enrolled in the expansion cohort: median (lower, upper quartile) age 16 (14, 16.5) years. No dose-limiting toxicities were observed. Pharmacokinetics appeared linear over three DLs. Pharmacokinetic modeling and simulation determined a weight-based recommended phase II dose (RP2D). Two patients had stable disease and 1 patient with peritoneal mesothelioma (C49+) had a sustained partial response (67% RECIST reduction). Pharmacodynamic markers included a rise in plasma macrophage CSF (MCSF) levels and a decrease in absolute monocyte count. Conclusions: Pexidartinib in pediatric patients was well tolerated at all DL tested, achieved target inhibition, and resulted in a weight-based RPD2 dose.
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