Risk of stroke in patients with mycosis fungoides: A nationwide population-based cohort study

Abstract

Dear editor,

Hematologic malignancies increase the risk of ischemic or hemorrhagic stroke and lead to co-morbidities.¹ Mycosis fungoides (MF) is a rare malignant T-cell lymphoma that primarily involves skin and commonly disseminates to internal organs.^2,3 As MF involving the central nervous system is rare, only few studies to date have examined the neurological consequences of MF on these patients.^4,5 Moreover, the incidence and risk of stroke in MF patients remain unknown.

In this cohort study, we investigated incidence rates and risks of stroke in patients with MF by using National Health Insurance Research Database in Taiwan. This study received approval from the Institutional Review Board at China Medical University Hospital (CMUH104-REC2-115). From 1998 to 2010, a total of 1783 MF patients and 7132 age- and sex-matched normal controls were identified. The mean age of the MF cohort was 51.6 years (SD, 20.6 years); 61% of the patients were male. The overall incidence rate of stroke was 1.47-fold higher in the MF cohort than in the non-MF cohort (12.2 vs. 8.29 per 10,000 person-years) with an adjusted hazard ratio (HR) of 1.51 (95% confidence interval (CI), 1.17–1.96) (Table 1). MF patients in older age group and those with more co-morbidities, including diabetes, hypertension, hyperlipidemia, coronary heart disease, atrial fibrillation, congestive heart failure, had higher risk of stroke (Table 1). The risk of ischemic stroke among the MF patients was significantly higher by 1.56-fold (95% CI, 1.11–2.20) compared with the non-MF cohort.

Table 1.

Incidence rates and risk of stroke stratified by sex, age, and co-morbidity in a multivariate Cox proportional hazards regression model for patients with mycosis fungoides compared to those without mycosis fungoides

	Mycosis fungoides
	No			Yes
Variables	Event	PY	Rate^a	Event	PY	Rate^a	IRR (95% CI)	Adjusted HR^b (95% CI)
All	267	32,217	8.29	74	6060	12.2	1.47 (1.28, 1.70)***	1.51 (1.17, 1.96)**
Sex
Female	89	13,537	6.57	27	2581	10.5	1.59 (1.27, 2.00)***	1 (reference)
Male	178	18,680	9.53	47	3479	13.5	1.42 (1.18, 1.71)***	1.19 (0.95, 1.49)
Age
≤40	4	10,400	3.8	5	2256	22.2	5.76 (4.43, 7.50)***	1 (reference)
40–60	34	11,187	30.4	14	2105	66.5	2.19 (1.72, 2.78)***	4.75 (2.33, 9.70)***
60–80	175	9185	190.5	41	1452	282.4	1.48 (1.16, 1.89)***	23.4 (11.9, 45.8)***
>80	54	1445	373.7	14	248	564.5	1.51 (0.95, 2.42)	38.5 (18.9, 78.4)***
Number of co-morbidities
0	173	29,175	59.3	39	5100	76.5	1.29 (1.09, 1.53)**	1 (reference)
1	44	1751	251.3	22	623	353.1	1.41 (0.97, 2.03)	1.94 (1.46, 2.59)***
≥2	50	1292	387.0	13	337	385.8	1.00 (0.61, 1.63)	2.35 (1.75, 3.15)***

HR: hazard ratio; CI: confidence interval; IRR: incidence rate ratio; PY: person-year.

Note: Event: stroke.

p < 0.05, **p < 0.01, ***p < 0.001.

Rate: incidence rate, per 10,000 person-years.

Adjusted HR: multivariable analysis including age, sex, and co-morbidities (diabetes, hypertension, hyperlipidemia, coronary heart disease, atrial fibrillation, congestive heart failure).

Footnotes

Patients with MF have a higher risk of stroke, especially ischemic stroke. Physicians should be more aware of the possibility of cerebrovascular disease in cancer patient with neurologic signs and symptoms and establish stroke-related intervention programs for patients with MF to improve their long-term outcomes.

Authors’ contributions

Jeng-Dau Tsai, Yu-Ping Hsiao, and Chang-Ching Wei conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted.

Cheng-Li Lin and Henry J Tsai carried out the initial analysis, reviewed and revised the manuscript, and approved the final manuscript as submitted.

Chang-Ching Wei coordinated and supervised data collection, critically reviewed the manuscript, and approved the final manuscript as submitted.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019), China Medical University Hospital, Academia Sinica Taiwan Biobank, Stroke Biosignature Project (BM104010092), NRPB Stroke Clinical Trial Consortium (MOST 103-2325-B-039-006), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.

References

Haller

Lyrer

. Malignancy and stroke. Semin Cerebrovasc Dis Stroke 2005; 5: 47–54.

Weinstock

Horm

. Mycosis fungoides in the United States. Increasing incidence and descriptive epidemiology. JAMA 1998; 260: 42–46.

Hothali

GIA

. Review of the treatment of mycosis fungoides and Sézary syndrome: a stage-based approach. Int J Health Sci 2013; 7: 220–239.

Duvic

. Central nervous system involvement in patients with mycosis fungoides and cutaneous large-cell transformation. J Am Acad Dermatol 2008; 59: S16–S22.

Benner

Jansen

Vermeer

Willemze

. Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood 2012; 119: 1643–1649.