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.