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1586 Increased Prevalence of Prior Malignancies and Autoimmune Diseases in Patients Diagnosed with Chronic Myeloid LeukemiaClinically Relevant Abstract

Chronic Myeloid Leukemia: Therapy
Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

Niklas Gunnarsson, MD1*, Martin Hoglund, MD, PhD2, Leif Stenke, MD, PhD3, Solveig Wallberg Jonsson, MD, PhD4*, Fredrik Sandin, PhD5*, Magnus Bjorkholm, MD, PhD6, Arta Dreimane, MD, PhD7*, Mats Lambe, MD, PhD8*, Berit Markevarn, MD9*, Ulla Olsson-Stromberg, MD, PhD10*, Hans Wadenvik, MD, PhD11*, Johan Richter, MD, PhD12* and Anders Sjalander, MD, PhD13*

1Department of Public Health and Clinical Medicine, UmeA University, Gavle, Sweden
2Uppsala University, Department of Medical Sciences, Section of Hematology, Uppsala, Sweden
3Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
4Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden
5Regional Cancer Centre, Uppsala-Orebro, Uppsala, Sweden
6Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
7Departement of Hematology, Linkoping University Hospital, Linkoping, Sweden
8Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
9Department of Hematology, Umea University Hospital, Umea, Sweden
10Department of Medical Science and Division of Hematology, Uppsala University Hospital, Uppsala, Sweden
11Department of Hematology, Sahlgrenska University Hospital, Göteborg, Sweden
12Department of Hematology and Vascular Disorders, Skane University Hospital, Lund, Sweden
13Department of Public Health and Clinical Medicine, Umea University, Sundsvall, Sweden

Background: In a recent, large population-based study we identified an increased risk of a second malignancy in patients following a diagnosis of Chronic Myeloid Leukemia (CML), as compared to an age- and gender-matched control cohort (Gunnarsson et al, Br J Haematol. 2015 Jun; 169(5): 683-8). If CML patients have an increased congenital or acquired susceptibility to develop any cancer, the prevalence of other prior malignancies would be expected to be increased already at the time of CML diagnosis.

There is a known association between autoimmune disease (AD) or chronic inflammatory disease (CID) and the development of some hematological malignancies. However, to date, studies on the prevalence of AD or CID detected prior to the CML diagnosis are few and inconclusive.

Our aim was to estimate the prevalence of other malignancies, AD or CID in CML patients at or before the time point of the CML diagnosis.

Materials and methods: We used the population-based Swedish CML Register to identify patients diagnosed with CML in Sweden between 2002-2013. This cohort was linked to the Swedish Cancer Register to retrieve information about malignancies reported before the diagnosis of CML and the Swedish National Patient Register to retrieve information about AD and CID.

For each of the 984 patients with CML, five age-, gender- and county of residence-matched controls were selected from the general population. All controls had to be free of CML and alive at the time of CML diagnosis for the corresponding case patient.

Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI).  We excluded diagnoses registered during the year prior to the CML diagnosis to avoid detection bias. In separate steps, analyses were also performed based on diagnoses of AD, CID or cancer three years before the date of CML diagnosis.

Results: A total of 984 CML patients were assessed with regard to a prior diagnosis of malignancy, AD or CID excluding the year immediately prior to their CML diagnosis, representing more than 45.000 person-years of follow-up. Compared to the matched population controls, the prevalence of prior malignancies and AD were elevated in CML patients: OR 1.47 (95%CI 1.20-1.82) and 1.55 (1.21-1.98), respectively. Breast-, gastrointestinal- and urinary tract cancers and melanomas were common cancer types and were all significantly more prevalent in the CML cohort, table I. After implementing a three-year exclusion period before the date of CML diagnosis, prior malignancies remained more prevalent in CML patients. Assessment of ADs was hampered by small numbers, sarcoidosis was the only AD with increased prevalence: OR 13.43; 95 % CI 3.56 – 50.73. No association was detected between CML and previous CID.

Conclusions: Based on a large population-based cohort, our findings indicate that CML patients have an increased prevalence of other malignancies and AD prior to the diagnosis of CML, suggesting that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.

Table I. Odds Ratios for malignancies prior to CML among 984 Swedish CML patients diagnosed between 2002 and 2013. Diagnoses of malignancy during the year immediately prior to CML diagnosis excluded to avoid detection bias.

Participants

Latency More Than 3 Years

Before CML Diagnosis

Variable

CML

n=984

Controls

n = 4920

OR

95% CI

CML

n=984

Controls

n = 4920

OR

95% CI

Overall

128

453

1.47

1.20 - 1.82

113

381

1.55

1.24 – 1.93

Men

58

184

1.61

1.19 - 2.18

50

146

1.75

1.26 – 2.43

Women

70

269

1.32

1.01 - 1.74

63

235

1.36

1.02 – 1.82

Age <60 years

66

221

1.53

1.15 – 2.03

60

209

1.46

1.09 – 1.97

Age ≥ 60 years

62

232

1.36

1.02 – 1.81

53

172

1.57

1.15 – 2.16

Second cancer type

Gastrointestinal

21

62

1.71

1.04 - 2.82

19

50

1.92

1.13 – 3.27

Breast

32

88

1.85

1.22 - 2.78

24

65

1.87

1.16 – 3.00

Gynecological

28

132

1.06

0.70 - 1.61

25

130

0.96

0.62 – 1.48

Ear-nose-throat

1

12

0.42

0.05 - 3.20

1

6

0.83

0.10 – 6.93

Endocrine Gland

9

13

3.48

1.49 - 8.17

7

11

3.20

1.24 – 8.27

Lung

1

7

0.71

0.09 - 5.81

1

4

1.25

0.14 – 11.20

Urinary tract

14

37

1.90

1.03 - 3.54

11

29

1.91

0.95 – 3.83

Malignant melanoma

13

32

2.05

1.07 - 3.91

12

21

2.88

1.41 – 5.87

Prostate

20

84

1.19

0.73 - 1.95

18

64

1.41

0.83 – 2.40

Non-Hodgkin Lymphoma

1

7

0.71

0.09 – 5.81

1

4

1.25

0.14 – 11.20

Chronic Lymphatic Leukemia

3

2

7.52

1.25 – 45.06

1

1

5.00

0.31 – 80.07

Polycythemia Vera

1

3

1.67

0.17 – 16.05

1

2

2.50

0.23 – 27.62

Central Nervous System

3

10

1.50

0.41 – 5.47

3

9

1.67

0.45 – 6.18

Testicle

2

3

3.34

0.56 – 20.00

2

2

5.01

0.70 – 35.60

Disclosures: Richter: Ariad: Honoraria ; Bristol-Myers Squibb: Honoraria ; Novartis: Honoraria . Sjalander: Novartis: Honoraria .

*signifies non-member of ASH