Results
Forty-two patients were eligible for inclusion in our chart review. All patients in this cohort had wild type TPMT genotypes. The demographic information of this cohort can be found in Table 1. Of these, 30 patients (71.4%) were under the age of 10. There was a predominance of males, 28 (66.6%) and Caucasians, 29 (69%). The diagnoses treated included B cell ALL (78.6%), T cell ALL (14.3%), and LL (7.1%). We documented when the following laboratory values were out of the identified normal ranges at any time during maintenance chemotherapy treatment (and the number of occurrences): ALT, glucose, immunoglobulin G, amylase, lipase, and the 6-MP metabolites 6-MMPN and 6-TGN. Table 2 displays the toxicities experienced in our cohort. Seventy four percent of patients had a least one episode of documented hypoglycemia and 88% had at least one episode of elevated ALT >3 times the upper limit of normal. Shunting of 6-MP to the toxic metabolite 6-MMPN was observed in 54% of the patients (Table 3). Allopurinol was used in 12 patients; most had improvement in clinical course and metabolite profiles (Figure 2, Table 3). For those who were treated with allopurinol, the ratio of 6-MMPN/6-TGN changed from a mean of 92 (standard deviation 16.8) to a mean of 8.6 standard deviation 12.9). Forty five percent (17/38) of all males reviewed were shunters, while only 25% (6/24) of females experienced shunting (Table 1). When evaluated by age, 41% (18/44) patients ≤ 10 years were shunters, while only 27% (5/18) of those > 10 years experiencing shunting (Table 1).
The series of 12 patients who received allopurinol demonstrated safety and efficacy. These patients experienced no direct side effects from the allopurinol, nor did they experience any increased toxicity of chemotherapy as a result of the allopurinol. All patients treated with allopurinol remain alive and in remission as of 1 Jun 2019, the longest being 6 years post-treatment. Transaminitis resolved for all twelve patients. Three patients with symptomatic hypoglycemia related to mercaptopurine therapy had improvement not only in symptoms but also in measured glucose levels during clinic encounters. All three patients with acute pancreatitis during maintenance had experienced acute pancreatic episodes prior to the start of maintenance therapy. Two of these went on to develop chronic pancreatitis that flared during maintenance.