Adherence to treatment with imatinib in chronic myeloid leukemia: a study of
          the first decade of responses obtained at a Brazilian hospital

Reis, Samuel Roosevelt Campos dos; Quixadá, Acy Telles de Souza; Nunes, Sammara Tavares; Cid, Danielle Maria Camelo; Souza, Jacqueline Holanda de; Costa, Clara Maria Bastos Eloy da; Silveira, Carolina Bizelli; Cid, David Antonio Camelo; Oliveira, Mariana Fátima Cabral de

doi:10.5581/1516-8484.20130053

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Original Articles • Rev Bras Hematol Hemoter 35 (3) • June 2013 • https://doi.org/10.5581/1516-8484.20130053 copy

Adherence to treatment with imatinib in chronic myeloid leukemia: a study of the first decade of responses obtained at a Brazilian hospital

Authorship SCIMAGO INSTITUTIONS RANKINGS

Objetive:

The aim of this study was to identify the reasons for failure in adherence to imatinib mesylate treatment in chronic myeloid leukemia.

Methods:

A retrospective review was performed of 100 non-electronic records of patients with Ph⁺ chronic myeloid leukemia treated with imatinib mesylate. The study period was from January 2001 to January2011. Data were analyzed by Chi-Square and Correspondence analysis using the Statistical Analysis System software package.

Results:

At the beginning of treatment 41% of patients were in advanced stages of the disease. The unavailability of the drug (44.8%) and myelotoxicity (25.7%) were the most frequent reasons for interruption. The adherence rate was < 90% in 47% of the cases. The low adherence influenced the cytogenetic response (p-value = 0.020) and molecular response (p-value = 0.001). Very high adherence (> 95%) induced complete cytogenetic response, major cytogenetic response and major molecular response.

Conclusion:

The population of this study obtained lower-than-expected therapeutic responses compared to other studies.

Characteristics
Age at diagnosis - median (range)		44.5 (13-77)
Gender - %
	Male	50
	Female	50
Stage of disease at diagnosis - %
	Chronic	96
	Accelerated	2
	Blast crisis	2
Stage of the disease at start of treatment with IM - %
	Chronic	59
	Accelerated	28
	Blast crisis	13
Treatment prior to IM - %
	Hydroxyurea (hydroxycarbamide)	28
	Busulfan and hydroxyurea	2
	Busulfan, hydroxyurea and interferon	3
	Hydroxyurea and interferon	58
	Hydroxyurea and anagrelide	1
	Busulfan, hydroxyurea, interferon and allogeneic BMT	1
	Hydroxyurea and Relapsed ALL Protocol - 1996	1
	Hydroxyurea and allogeneic BMT	2
	Interferon	1
	No record	2
Initial dose of IM - %
	300	1
	400	78
	600	21
Distance between patient's home and outpatient clinic - %
	< 100 km	66
	101 - 200 km	14
	201 - 300 km	8
	301 - 400 km	7
	401 - 500 km	3
	> 501 km	2

Reasons for interruption
Unintentional	RF (%)	Intentional	RF (%)
Unavailability of medication at healthcare service	44.8	Missed appointment	2.5
Suspension due to thrombocytopenia	9.4	Took less than the prescribed dose	2.5
Suspension due to thrombocytopenia and leukopenia	8.1	Interruption due to social events	1.1
Adverse reaction (except hematologic and GIT)	7.4	Abandonment	0.7
Suspension due to leukopenia	5.1	Suspension due to pregnancy or suspected pregnancy	0.7
Intolerance of GIT	3.6	Took more than the prescribed dose	0.4
Forgot	3.3	Stopped taking the medication because symptoms improved	0.2
Suspension due to thrombocytopenia, leukopenia and anemia	1.8
Complication from other pathology(ies); Suspended by physician at specialized healthcare service	1.6
Complication from other pathology(ies); Suspended by physician at other healthcare service	1.3
Complication from other pathology(ies); Suspended by the patient	1.3
Other	1.3
Dependence on third parties	1.1
Suspension due to anemia	1.1
Financial difficulties	0.5
Suspension due to thrombocytosis	0.2

		Intermediate 50-90% (n = 47)	High 90-95% (n = 22)	Very high > 95% ( n = 31)	Total (n = 100)
Hematologic response (p-value = 0.826)
	Complete hematologic response	43	21	29	93
	Partial hematologic response	2	-	2	4
	Absent hematologic response	1	1	-	2
Cytogenetic response (p-value = 0.020)
	Complete cytogenetic response	11	9	18	38
	Major cytogenetic response	4	4	1	9
	Minor cytogenetic response	2	2	-	4
	Minimal cytogenetic response	2	-	1	3
	Absent cytogenetic response	13	6	8	27
Molecular response (p-value = 0.001)
	Complete molecular response	1	2	5	8
	Major molecular response	5	5	13	23
	Absent molecular response	17	11	6	34

Study	Method used	Non-adherence rate (%)	Consequence of non-adherence
Noens et al.⁽¹⁹⁾	Questionnaire and pill count	32.7	Increased risk of suboptimal responses
Marin et al.⁽¹⁶⁾	Electronic monitoring device	26	Reduced possibility of achieving major and complete molecular response
Darkow et al.⁽¹³⁾	Electronic data on dispensation	31	Increased healthcare costs
Ganesan et al.⁽¹⁷⁾	Patient's return for dispensation	29	Reduced event-free survival
Present study	Data from non-electronic medical records	47	Reduced possibility to achieve and maintain hematologic, cytogenetic and molecular response

Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular R. Dr. Diogo de Faria, 775 cj 114, 04037-002 São Paulo/SP/Brasil, Tel. (55 11) 2369-7767/2338-6764 - São Paulo - SP - Brazil
E-mail: secretaria@rbhh.org

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[1] Corresponding author: David Antonio Camelo Cid, Universidade Federal do Ceará - UFC Rua Capitão Francisco Pedro, 1290 - Rodolfo Teófilo 60430-370 Fortaleza, CE, Brazil davidcid86@yahoo.com.br