PMID- 33750748
OWN - NLM
STAT- MEDLINE
DCOM- 20210519
LR  - 20230918
IS  - 1536-3678 (Electronic)
IS  - 1077-4114 (Linking)
VI  - 43
IP  - 3
DP  - 2021 Apr 1
TI  - Allopurinol to Prevent Mercaptopurine Adverse Effects in Children and Young 
      Adults With Acute Lymphoblastic Leukemia.
PG  - 95-100
LID - 10.1097/MPH.0000000000002117 [doi]
AB  - Mercaptopurine (6MP) is used to treat acute lymphoblastic leukemia (ALL) and is 
      metabolized by hypoxanthine guanine phosphoribosal transferase to form 
      6-thioguanine nucleotide (6TGN). It is also metabolized by thiopurine 
      methyl-transferase to produce 6-methylmercaptopurine (6MMP). Elevated levels of 
      6MMP have been associated with toxic effects that may interfere with therapy. 
      Allopurinol is known to inhibit thiopurine methyl-transferase which reduces red 
      cell 6MMP and increases 6TGN. Allopurinol has been utilized successfully in adult 
      and pediatric patients with inflammatory bowel disease who have experienced 6MMP 
      related gastrointestinal toxicity. Between August 2015 and August 2018 we started 
      25 patients with ALL in maintenance on allopurinol in combination with a reduced 
      dose of 6MP. They all had unacceptable side-effects from elevated 6MMP, including 
      abdominal pain, nausea, vomiting, decreased appetite, hypoglycemia, fatigue, and 
      liver toxicity. In addition many had a facial rash. All patients showed 
      resolution of symptoms within a few weeks after starting allopurinol. The red 
      cell levels of 6MMP rapidly declined in the first month. The red cell levels of 
      6TGN transiently increased in spite of the lower 6MP dose. There was no decrease 
      in absolute neutrophil count or hemoglobin. Platelets decreased slightly not 
      requiring therapy modification. Elevated bilirubin normalized, and alanine 
      aminotransferase decreased significantly with most normalizing. All patients 
      continued on allopurinol with reduced dose 6MP until completing therapy. 
      Allopurinol, in conjunction with a reduced dose of 6MP, effectively resolves 6MMP 
      related side-effects in ALL patients on maintenance chemotherapy. This approach 
      may lead to increased adherence to oral 6MP during ALL maintenance in patients 
      with 6MMP induced side-effects.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Kamojjala, Ruchika
AU  - Kamojjala R
AD  - Children's Hospitals and Clinics of Minnesota, Minneapolis, MN.
FAU - Bostrom, Bruce
AU  - Bostrom B
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pediatr Hematol Oncol
JT  - Journal of pediatric hematology/oncology
JID - 9505928
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Enzyme Inhibitors)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - E7WED276I5 (Mercaptopurine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Allopurinol/*therapeutic use
MH  - Antimetabolites, Antineoplastic/adverse effects/*therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Enzyme Inhibitors/*therapeutic use
MH  - Female
MH  - Humans
MH  - Male
MH  - Mercaptopurine/adverse effects/*therapeutic use
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy
MH  - Retrospective Studies
MH  - Young Adult
COIS- The authors declare no conflict of interest.
EDAT- 2021/03/23 06:00
MHDA- 2021/05/20 06:00
CRDT- 2021/03/22 18:33
PHST- 2020/03/01 00:00 [received]
PHST- 2021/01/19 00:00 [accepted]
PHST- 2021/03/22 18:33 [entrez]
PHST- 2021/03/23 06:00 [pubmed]
PHST- 2021/05/20 06:00 [medline]
AID - 00043426-202104000-00003 [pii]
AID - 10.1097/MPH.0000000000002117 [doi]
PST - ppublish
SO  - J Pediatr Hematol Oncol. 2021 Apr 1;43(3):95-100. doi: 
      10.1097/MPH.0000000000002117.