Evidence map›Paper›PMID 18685564›Full record

ArticleClinical pharmacology and therapeutics2009

Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia.

G Stocco, M H Cheok, K R Crews, T Dervieux, D French, D Pei, W Yang, C Cheng, C-H Pui, M V Relling and 1 more

Registry-linked trialOpen access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology and therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 97 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 5 pooled it
16.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00137111 phase3completednot on this map

Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

TypeinterventionalSponsorSt. Jude Children's Research HospitalRan2000 to 2014Enrolled501ConditionsLymphoblastic Leukemia, AcuteArmsPrednisone, Dexamethasone, Vincristine, Daunorubicin, Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase, Methotrexate, Cyclophosphamide, Cytarabine, Etoposide, Mercaptopurine, Imatinib, chemotherapy, intrathecal chemotherapy
3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 5 syntheses or guidelines pooled it, 217 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Guideline
  4. Pooled it
  5. Guideline
  6. Trial
  7. Trial
  8. Trial
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

G StoccoDepartment of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
M H Cheok
K R Crews
T Dervieux
D French
D Pei
W Yang
C Cheng
C-H Pui
M V Relling
W E Evans
St. Jude Children's Research Hospital · USIRCCS Materno Infantile Burlo Garofolo · IT

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Whole GenomeU01GM061393 · NIGMS · UNIVERSITY OF CHICAGO · PI COX, NANCY J, DOLAN, MARY EILEEN · 2000 to 2014
$39.0M
PHARMACOGENOMICS OF CHILDHOOD LEUKEMIA (ALL)R37CA036401 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI EVANS, WILLIAM E · 1987 to 2014
$9.7M
PHARMACODYNAMICS OF ANTILEUKEMIC AGENTS IN CHILDRENR01CA078224 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SPARREBOOM, ALEXANDER · 1998 to 2007
$3.6M
P450 METABOLISM OF EPIPODOPHYLLOTOXINS IN CHILDRENR01CA051001 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI RELLING, MARY V. · 1996 to 2006
$2.7M
NCI NIH HHS CA21765NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA051001NCI NIH HHS R01 CA078224NCI NIH HHS R01 CA51001NCI NIH HHS R01 CA78224NCI NIH HHS R37 CA036401NCI NIH HHS R37 CA36401NIGMS NIH HHS U01 GM061393NIGMS NIH HHS U01 GM61393
6 · The paper itself

Abstract

The influence of genetic polymorphism in inosine triphosphate pyrophosphatase (ITPA) on thiopurine-induced adverse events has not been investigated in the context of combination chemotherapy for acute lymphoblastic leukemia (ALL). This study investigated the effects of a common ITPA variant allele (rs41320251) on mercaptopurine metabolism and toxicity during treatment of children with ALL. Significantly higher concentrations of methyl mercaptopurine nucleotides were found in patients with the nonfunctional ITPA allele. Moreover, there was a significantly higher probability of severe febrile neutropenia in patients with a variant ITPA allele among patients whose dose of mercaptopurine had been adjusted for TPMT genotype. In a cohort of patients whose mercaptopurine dose was not adjusted for TPMT phenotype, the TPMT genotype had a greater effect than the ITPA genotype. In conclusion, genetic polymorphism of ITPA is a significant determinant of mercaptopurine metabolism and of severe febrile neutropenia, after combination chemotherapy for ALL in which mercaptopurine doses are individualized on the basis of TPMT genotype.

Indexed as

AdolescentChildChild, PreschoolFemaleGastrointestinal DiseasesHumansInfantInosine TriphosphataseMaleMercaptopurineNeutropeniaPolymorphism, GeneticPrecursor Cell Lymphoblastic Leukemia-LymphomaPyrophosphatasesInosine TriphosphataseITPA protein, humanMercaptopurinePyrophosphatases

Identifiers

PMID18685564
PMCPMC2762405
OpenAlexW2168795023

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.