No abstract

The 5-year progression-free and total survival rates for the 13 children were 46 +/- 14% and 54 +/- 14%, respectively. Seven patients suffered a relapse at the primary site, four of whom also had leptomeningeal metastases. Seven of the 13 patients (54%) remain alive at the time of this report at a median of 76 months (range 51-93 months) from study entry. Six patients died between 8 and 38 months after diagnosis, all with active disease. Intensification of therapy may further improve outcome in this high-risk population.

Methotrexate can influence the central nervous system through several metabolic toxic pathways. These effects can be categorized as immediate, acute to subacute, or chronic neurologic syndromes. The acute to subacute syndrome occurs frequently in acute lymphoblastic leukemia treatment protocols, generally manifesting with focal neurologic signs and changes seen on magnetic resonance imaging and single photon emission computed tomography. While in some patients the neurotoxicity is transient and benign and allows for continuation of chemotherapy, in others it can be quite severe and debilitating, leading to permanent neurologic deficits. The need to modify the treatment protocols when neurotoxicity appears is not fully established. It is also unknown whether the use of sufficient amounts of leucovorin can overcome the toxic effects of the drug.

This is the first report of maternal hypercalcemia caused by a CYP24A1 mutation, showing that not only infants are at risk for this complication. Our findings emphasize the importance of recognition, genetic diagnosis and proper treatment of this recently identified hypercalcemic disorder in this era of widespread vitamin D supplements.