Abstract
Aim: To evaluate compliance in children with acute lymphoblastic leukaemia (ALL).
Methods: Compliance was assessed through specific interviews, annotations from medical charts, and erythrocytic determination of 6-mercaptopurine metabolites.
Results: A total of 39 patients who had concluded maintenance phase of chemotherapy were included in the study. Mothers were responsible for delivering 6-MP in 87% of cases. Thirty five interviewees said that medical prescription was well understood and that the main reason for non-compliance was forgetfulness. Non-compliance was detected through interviews (33.3% of the cases), reports from medical charts (30.7%), and drug determination (16.6%); 53.8% of children were found to be non-compliant. Non-compliance was significantly associated with chronic undernourishment. Although not statistically significant, there was a trend for the group of non-compliant children to be associated with low per capita family income. No significant associations of non-compliance with age at diagnosis, gender, parents' schooling level, number of family members, power consumption, and medians of absolute leucocyte or neutrophil blood counts were detected. A short follow up period precluded valid analysis on outcome. In the non-compliant group (n = 21), seven children relapsed, contrasting with three relapses in the compliant group (n = 18).
Conclusions: Results suggest that non-compliance is one of the mechanisms which underlies the adverse influence of socioeconomic factors on the outcome of children with ALL. Additional studies are necessary to confirm this hypothesis. Comprehensive approaches to the problem of non-compliance are urgently needed.
Full Text
The Full Text of this article is available as a PDF (62.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Azeemuddin S., Israili Z. H., Bharmal F. M. Rapid method for evaluating compliance of 6-mercaptopurine therapy in children with leukemia. J Chromatogr. 1988 Aug 19;430(1):163–169. doi: 10.1016/s0378-4347(00)83147-3. [DOI] [PubMed] [Google Scholar]
- Bonilla M., Moreno N., Marina N., deReyes G., Shurtleff S. A., Downing J. R., Behm F. G., Harrison P. L., Ribeiro R. C., Peña O. Acute lymphoblastic leukemia in a developing country: preliminary results of a nonrandomized clinical trial in El Salvador. J Pediatr Hematol Oncol. 2000 Nov-Dec;22(6):495–501. doi: 10.1097/00043426-200011000-00004. [DOI] [PubMed] [Google Scholar]
- Cameron C. Patient compliance: recognition of factors involved and suggestions for promoting compliance with therapeutic regimens. J Adv Nurs. 1996 Aug;24(2):244–250. doi: 10.1046/j.1365-2648.1996.01993.x. [DOI] [PubMed] [Google Scholar]
- Davies H. A., Lennard L., Lilleyman J. S. Variable mercaptopurine metabolism in children with leukaemia: a problem of non-compliance? BMJ. 1993 May 8;306(6887):1239–1240. doi: 10.1136/bmj.306.6887.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davies H. A., Lilleyman J. S. Compliance with oral chemotherapy in childhood lymphoblastic leukaemia. Cancer Treat Rev. 1995 Mar;21(2):93–103. doi: 10.1016/0305-7372(95)90022-5. [DOI] [PubMed] [Google Scholar]
- Dervieux T., Boulieu R. Simultaneous determination of 6-thioguanine and methyl 6-mercaptopurine nucleotides of azathioprine in red blood cells by HPLC. Clin Chem. 1998 Mar;44(3):551–555. [PubMed] [Google Scholar]
- Dibley M. J., Goldsby J. B., Staehling N. W., Trowbridge F. L. Development of normalized curves for the international growth reference: historical and technical considerations. Am J Clin Nutr. 1987 Nov;46(5):736–748. doi: 10.1093/ajcn/46.5.736. [DOI] [PubMed] [Google Scholar]
- Festa R. S., Tamaroff M. H., Chasalow F., Lanzkowsky P. Therapeutic adherence to oral medication regimens by adolescents with cancer. I. Laboratory assessment. J Pediatr. 1992 May;120(5):807–811. doi: 10.1016/s0022-3476(05)80256-2. [DOI] [PubMed] [Google Scholar]
- Haynes R. B., McKibbon K. A., Kanani R. Systematic review of randomised trials of interventions to assist patients to follow prescriptions for medications. Lancet. 1996 Aug 10;348(9024):383–386. doi: 10.1016/s0140-6736(96)01073-2. [DOI] [PubMed] [Google Scholar]
- Kalwinsky D. K., Rivera G., Dahl G. V., Roberson P., George S., Murphy S. B., Simone J. V. Variation by race in presenting clinical and biologic features of childhood acute lymphoblastic leukaemia: implications for treatment outcome. Leuk Res. 1985;9(6):817–823. doi: 10.1016/0145-2126(85)90300-5. [DOI] [PubMed] [Google Scholar]
- KyngAs H. A., Kroll T., Duffy M. E. Compliance in adolescents with chronic diseases: a review. J Adolesc Health. 2000 Jun;26(6):379–388. doi: 10.1016/s1054-139x(99)00042-7. [DOI] [PubMed] [Google Scholar]
- Lancaster D., Lennard L., Lilleyman J. S. Profile of non-compliance in lymphoblastic leukaemia. Arch Dis Child. 1997 Apr;76(4):365–366. doi: 10.1136/adc.76.4.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lansky S. B., Smith S. D., Cairns N. U., Cairns G. F., Jr Psychological correlates of compliance. Am J Pediatr Hematol Oncol. 1983 Spring;5(1):87–92. [PubMed] [Google Scholar]
- Lau R. C., Matsui D., Greenberg M., Koren G. Electronic measurement of compliance with mercaptopurine in pediatric patients with acute lymphoblastic leukemia. Med Pediatr Oncol. 1998 Feb;30(2):85–90. doi: 10.1002/(sici)1096-911x(199802)30:2<85::aid-mpo3>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
- Lennard L. Assay of 6-thioinosinic acid and 6-thioguanine nucleotides, active metabolites of 6-mercaptopurine, in human red blood cells. J Chromatogr. 1987 Dec 25;423:169–178. doi: 10.1016/0378-4347(87)80340-7. [DOI] [PubMed] [Google Scholar]
- Lennard L., Singleton H. J. High-performance liquid chromatographic assay of the methyl and nucleotide metabolites of 6-mercaptopurine: quantitation of red blood cell 6-thioguanine nucleotide, 6-thioinosinic acid and 6-methylmercaptopurine metabolites in a single sample. J Chromatogr. 1992 Nov 27;583(1):83–90. doi: 10.1016/0378-4347(92)80347-s. [DOI] [PubMed] [Google Scholar]
- Lennard L., Welch J., Lilleyman J. S. Intracellular metabolites of mercaptopurine in children with lymphoblastic leukaemia: a possible indicator of non-compliance? Br J Cancer. 1995 Oct;72(4):1004–1006. doi: 10.1038/bjc.1995.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lilleyman J. S., Lennard L. Non-compliance with oral chemotherapy in childhood leukaemia. BMJ. 1996 Nov 16;313(7067):1219–1220. doi: 10.1136/bmj.313.7067.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDougall L. G., Wilson T. D., Cohn R., Shuenyane E. N., McElligott S. E. Compliance with chemotherapy in childhood leukaemia in Africa. S Afr Med J. 1989 May 20;75(10):481–484. [PubMed] [Google Scholar]
- Macdougall L. G., McElligott S. E., Ross E., Greeff M. C., Poole J. E. Pattern of 6-mercaptopurine urinary excretion in children with acute lymphoblastic leukemia: urinary assays as a measure of drug compliance. Ther Drug Monit. 1992 Oct;14(5):371–375. doi: 10.1097/00007691-199210000-00005. [DOI] [PubMed] [Google Scholar]
- Matsui D. M. Drug compliance in pediatrics. Clinical and research issues. Pediatr Clin North Am. 1997 Feb;44(1):1–14. doi: 10.1016/s0031-3955(05)70459-4. [DOI] [PubMed] [Google Scholar]
- Mora J. O. A new method for estimating a standardized prevalence of child malnutrition from anthropometric indicators. Bull World Health Organ. 1989;67(2):133–142. [PMC free article] [PubMed] [Google Scholar]
- Paes Cybele A., Viana Marcos B., Freire Ricardo V., Martins-Filho Olindo A., Taboada Diana C., Rocha Vanderson G. Direct association of socio-economic status with T-cell acute lymphoblastic leukaemia in children. Leuk Res. 2003 Sep;27(9):789–794. doi: 10.1016/s0145-2126(03)00010-9. [DOI] [PubMed] [Google Scholar]
- Powell J. E., Mendez E., Parkes S. E., Mann J. R. Factors affecting survival in White and Asian children with acute lymphoblastic leukaemia. Br J Cancer. 2000 May;82(9):1568–1570. doi: 10.1054/bjoc.1999.1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pui C. H., Sallan S., Relling M. V., Masera G., Evans W. E. International Childhood Acute Lymphoblastic Leukemia Workshop: Sausalito, CA, 30 November-1 December 2000. Leukemia. 2001 May;15(5):707–715. doi: 10.1038/sj.leu.2402111. [DOI] [PubMed] [Google Scholar]
- Relling M. V., Hancock M. L., Rivera G. K., Sandlund J. T., Ribeiro R. C., Krynetski E. Y., Pui C. H., Evans W. E. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst. 1999 Dec 1;91(23):2001–2008. doi: 10.1093/jnci/91.23.2001. [DOI] [PubMed] [Google Scholar]
- Rogers A. S., Miller S., Murphy D. A., Tanney M., Fortune T. The TREAT (Therapeutic Regimens Enhancing Adherence in Teens) program: theory and preliminary results. J Adolesc Health. 2001 Sep;29(3 Suppl):30–38. doi: 10.1016/s1054-139x(01)00289-0. [DOI] [PubMed] [Google Scholar]
- Smith S. D., Rosen D., Trueworthy R. C., Lowman J. T. A reliable method for evaluating drug compliance in children with cancer. Cancer. 1979 Jan;43(1):169–173. doi: 10.1002/1097-0142(197901)43:1<169::aid-cncr2820430125>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
- Spinetta John J., Masera Giuseppe, Eden Tim, Oppenheim Daniel, Martins Antonio Gentil, van Dongen-Melman Jeanette, Siegler Mark, Eiser Christine, Ben Arush Myriam Weyl, Kosmidis Helen Vasiliatou. Refusal, non-compliance, and abandonment of treatment in children and adolescents with cancer: a report of the SIOP Working Committee on Phychosocial Issues in Pediatric Oncology. Med Pediatr Oncol. 2002 Feb;38(2):114–117. doi: 10.1002/mpo.1283. [DOI] [PubMed] [Google Scholar]
- Tebbi C. K., Cummings K. M., Zevon M. A., Smith L., Richards M., Mallon J. Compliance of pediatric and adolescent cancer patients. Cancer. 1986 Sep 1;58(5):1179–1184. doi: 10.1002/1097-0142(19860901)58:5<1179::aid-cncr2820580534>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
- Viana M. B., Fernandes R. A., de Oliveira B. M., Murao M., de Andrade Paes C., Duarte A. A. Nutritional and socio-economic status in the prognosis of childhood acute lymphoblastic leukemia. Haematologica. 2001 Feb;86(2):113–120. [PubMed] [Google Scholar]
- Wright E. C. Non-compliance--or how many aunts has Matilda? Lancet. 1993 Oct 9;342(8876):909–913. doi: 10.1016/0140-6736(93)91951-h. [DOI] [PubMed] [Google Scholar]