ABSTRACT
6-Mercaptopurine (6-MP) is the mainstay of treatment for acute lymphoblastic leukemia and lymphoblastic lymphoma. It is metabolized into the pharmacologically active, 6-thioguanine nucleotide (6-TGN), and 6-methyl mercaptopurine nucleotides (6-MMPN), which is associated with hepatotoxicity that jeopardizes antileukemic therapy. Allopurinol alters the metabolism of 6-MP to increase 6-TGN levels and decreases 6-methyl mercaptopurine nucleotides levels. We report 2 cases in which combination therapy of allopurinol with 6-MP was used successfully to avoid hepatotoxicity while delivering adequate 6-TGN levels. We suggest that this combination therapy can be used safely to change the metabolite production in patients who develop excessive hepatotoxicity.
Subject(s)
Allopurinol/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites/administration & dosage , Mercaptopurine/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/metabolism , Child , Humans , Liver/drug effects , Maintenance Chemotherapy/methods , Male , Mercaptopurine/administration & dosage , Mercaptopurine/metabolismABSTRACT
We sought to determine if maternal use of selective serotonin reuptake inhibitors (SSRIs) in the second half of pregnancy is associated with persistent pulmonary hypertension of the newborn (PPHN). We performed a case-controlled study (1:6 ratio) of infants delivered at Madigan Army Medical Center with primary PPHN from 2003 through 2009. Study and control patients were compared for the following clinical factors: SSRI use after 20 weeks gestation, mode of delivery, maternal disease, body mass index, tobacco use, fetal gender, maternal age, and parity. We identified 20 cases of primary PPHN out of 11,923 births for an incidence of 0.17%. Mode of delivery was the only factor we found to be associated with PPHN. Specifically, cesarean delivery (CD) prior to the onset of labor increased the risk for PPHN: odds ratio (OR) = 4.9, confidence interval (CI) 1.7 to 14.0. Importantly, use of SSRIs in the second half of pregnancy was identified in 5% of the controls but none of the cases (OR = 0, CI 0 to 3). PPHN is associated with CD prior to the onset of labor but not with SSRI use in the second half of pregnancy. Previous studies linking PPHN to SSRI use relied on after-the-fact patient interviews and incomplete records. Additional studies are needed to verify these results.
