Does chronic lymphocytic leukemia increase the risk of osteoporosis?

Transcription

1 Does chronic lymphocytic leukemia increase the risk of osteoporosis? Amrita Desai, MD Internal Medicine Residency Program Adam Olszewski, MD Department of Hematology and Oncology Memorial Hospital of Rhode Island Alpert Medical School of Brown University

2 Outline Introduction Aims Methodology Results Limitations Conclusions

3 Chronic Lymphocytic Leukemia (CLL) Most common lymphoproliferative disorder seen in the elderly Incidence rates are 6.7 and 3.6 cases per 100,000 population/year Indolent course Excessive osteoclastic resorption leading to bone demineraliztion Cancer Causes Control 2008; 19:379.

4 Osteoporosis Skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fractures. Prevalence is estimated to increase from 10 million to >14 million people in 2020 Current medical costs are estimated at $ billion. Journal of Bone and Mineral Research Volume 22, Issue 3, March 2007

5 Literature Search Osteoporosis is a known complication: Treated pediatric lymphomas. J Clin Oncol. 1998;16(12): Post- chemotherapy for non-hodgkin lymphoma ASH Annual Meeting Abstracts. 2006;108(11):4607 Unknown whether presence of a bone marrowreplacing process such as CLL is a significant risk factor for osteopenia or osteoporosis

6 Aims Investigate the prevalence of osteoporosis, osteopenia and compression fractures in patients with CLL treated at MHRI + RIH Identify risk factors for compression fractures Investigate if patients with CLL have increased risk of osteoporosis

7 Methodology A retrospective cohort study

8 Inclusion Criteria Case selection: - Patients at RIH and the MHRI Cancer Center - Diagnosis of CLL on the basis of flow cytometry/bone marrow biopsy - Adequate medical information (follow up, physician problem list or radiology evaluations) - Patients with absolute lymphocyte count<5000/mm3 were excluded Controls: - Family Medicine Practice and Internal Medicine patients at MHRI. - ( 2:1)matched on age, gender, race and BMI

9 Data Collection Demographics: Age at diagnosis and last follow up Ethnicity not available in majority of cases Height, weight and calculated BMI Tobacco use status (current, past, never smoker)

10 Data Collection Clinical/Laboratory data: Confirmation with flow cytometry CD38 status Available CLL FISH studies Adenopathy Splenomegaly White blood cell count (WBC) Absolute lymphocyte count (ALC) Hemoglobin Platelets Beta-2-microglobulin Lactate dehydrogenase (LDH)

11 Endpoints: DEXA (dual-energy x-ray absorptiometry) bone density scan results. Evidence of osteoporosis (physician notation, CT scan result) Evidence of osteopenia (physician notation, CT scan result) Evidence of compression fracture (physician notation, report of the CT scan) Composite endpoint (any of the above)

12 Results cases Controls MHRI (87) RIH (53) MHRI (120) Excluded 27 Included 60 Excluded 17 Included 36 4: ALC < : Different diagnosis ( rule out CLL, family history of CLL, LGL leukemia, leukocytosis) 12: inadequate follow up information 1: prisoner 9: ALC < : Different diagnosis ( rule out CLL, family history of CLL, LGL leukemia, leukocytosis) 6: inadequate follow up information

13 Results for: The prevalence of osteoporosis, osteopenia and compression fractures in patients with CLL treated at MHRI Cancer Center and at RIH

14 Demographics Cases N= 96 Age (median) 71yrs Gender( Females) 48% BMI (median) 26 Absolute Lymphocyte Count (median) 40,850/mm 3 Hemoglobin (mean) LDH (mean) Vitamin D level (mean) Median follow up time 12.4 g/dl 202 IU/L 30.7 ng/ml 2.9 yrs

15 Prevalence of osteoporosis in CLL patients osteoporosis 12, 11% 96, 89%

16 Prevalence of osteoporosis +osteopenia in CLL patients osteoporosis 12, 13% 5, 5% osteopenia 79, 82%

17 Prevalance of compression fractures in CLL patients 7, 7% Compression fractures 96, 93%

18 Discussion Low prevalence of osteoporosis High prevalence of compression fractures

19 Results for: Identification of risk factors for compression fractures

20 Risk factors for Compression Fractures in CLL patients HR CI p Osteopenia/osteoporosis %CI , p=0.004 Anemia %CI P=0.01 ALC> 100,000/mm %CI P=0.04

21 Risk factors for compression fractures in CLL patients

22 Discussion More disease burden increases risk of compression fracture Need for early screening

23 Results for: Do patients with CLL have increased risk of osteoporosis?

24 CT scans Fisher's exact = 0.327

25 DEXA scans p<0.001

26 Prevalence of osteoporosis Fisher's exact = 0.107

27 Compression Fracture odds ratio 1.0, 95%CI , p=1.0

28 Discussion More DEXA scans in controls In some cases men got fewer DEXA scans compared to women Informant bias? More CT scans in cases

29 Limitations Retrospective study Small cohort Single centre study Paucity of data available on imaging studies

30 Conclusion The incidence of osteoporosis in CLL patients was 12% The incidence of compression fractures was 7% Compression fractures were higher with osteoporosis/osteopenia and with heavier burden of disease.

31 References 1. Cabanillas ME, Lu H, Fang S, Du XL. Elderly patients with non-hodgkin lymphoma who receive chemotherapy are at higher risk for osteoporosis and fractures. Leuk Lymphoma. 2007;48(8): Thompson MA, Huen A, Ayers GD, et al. Baseline Osteopenia and Osteoporosis in Untreated Non- Hodgkin's Lymphoma Patients. ASH Annual Meeting Abstracts. 2006;108(11): Haddy TB, Mosher RB, Reaman GH. Osteoporosis in survivors of acute lymphoblastic leukemia. Oncologist. 2001;6(3): Nysom K, Holm K, Michaelsen KF, Hertz H, Muller J, Molgaard C. Bone mass after treatment for acute lymphoblastic leukemia in childhood. J Clin Oncol. 1998;16(12): Leone J, Vilque JP, Jolly D, et al. Effect of chlorambucil on bone mineral density in the course of chronic lymphoid leukemia. Eur J Haematol. 1998;61(2): Molica S, Digiesi G, Antenucci A, et al. Vitamin D insufficiency predicts time to first treatment (TFT) in early chronic lymphocytic leukemia (CLL). Leuk Res Shanafelt TD, Drake MT, Maurer MJ, et al. Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia. Blood. 2011;117(5): Lecouvet FE, Vande Berg BC, Michaux L, et al. Early chronic lymphocytic leukemia: prognostic value of quantitative bone marrow MR imaging findings and correlation with hematologic variables. Radiology. 1997;204(3): Asomaning K, Bertone-Johnson ER, Nasca PC, Hooven F, Pekow PS. The association between body mass index and osteoporosis in patients referred for a bone mineral density examination. J Womens Health (Larchmt). 2006;15(9): De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005;16(11):