'Does chronic lymphocytic leukemia increase the … chronic lymphocytic leukemia increase the risk...
Transcript of 'Does chronic lymphocytic leukemia increase the … chronic lymphocytic leukemia increase the risk...
Does chronic lymphocytic leukemia increase the risk of osteoporosis?Amrita Desai, MD Internal Medicine Residency ProgramAdam Olszewski, MD Department of Hematology and OncologyMemorial Hospital of Rhode IslandAlpert Medical School of Brown University
Outline Introduction
Aims
Methodology
Results
Limitations
Conclusions
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.
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 $13.7–20.3 billion.
Journal of Bone and Mineral ResearchVolume 22, Issue 3, March 2007
Literature Search
Osteoporosis is a known complication: Treated pediatric lymphomas.
Post- chemotherapy for non-Hodgkin lymphoma
Unknown whether presence of a bone marrow-replacing process such as CLL is a significant risk factor for osteopenia or osteoporosis
J Clin Oncol. 1998;16(12):3752-3760.
ASH Annual Meeting Abstracts. 2006;108(11):4607
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
Methodology
A retrospective cohort study
Inclusion CriteriaCase 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
Data Collection
Demographics:Age at diagnosis and last follow upEthnicity – not available in majority of casesHeight, weight and calculated BMITobacco use status (current, past, never smoker)
Data Collection
Clinical/Laboratory data:Confirmation with flow cytometryCD38 statusAvailable CLL FISH studiesAdenopathySplenomegalyWhite blood cell count (WBC)Absolute lymphocyte count (ALC)HemoglobinPlateletsBeta-2-microglobulinLactate dehydrogenase (LDH)
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)
cases
MHRI(87)
RIH(53)
Excluded 27
Included 60
Excluded 17
Included 36
Controls
MHRI(120)
4: ALC < 500010: Different diagnosis (“rule out CLL”, “family history of CLL”, “LGL leukemia”, leukocytosis) 12: inadequate follow up information 1: prisoner
Results
9: ALC < 5000 2: Different diagnosis (“rule out CLL”, “family history of CLL”, “LGL leukemia”, leukocytosis) 6: inadequate follow up information
Results for:
The prevalence of osteoporosis, osteopenia and compression fractures in patients with CLL treated at MHRI Cancer Center and at RIH
Demographics
Cases N= 96
Age (median) 71yrs
Gender( Females) 48%BMI (median) 26Absolute Lymphocyte Count (median) 40,850/mm3
Hemoglobin (mean) 12.4 g/dLLDH (mean) 202 IU/LVitamin D level (mean) 30.7 ng/mLMedian follow up time 2.9 yrs
12, 11%
96, 89%
Prevalence of osteoporosis in CLL patients
osteoporosis
Prevalence of osteoporosis +osteopenia in CLL patients
79, 82%
12, 13%5, 5% osteopenia
osteoporosis
7, 7%
96, 93%
Prevalance of compression fractures in CLL patients
Compression fractures
Discussion
Low prevalence of osteoporosis
High prevalence of compression fractures
Results for:
Identification of risk factors for compression fractures
Risk factors for Compression Fractures in CLL patients
HR CI p
Osteopenia/osteoporosis 12.8 95%CI 1.5-109, p=0.004
Anemia 8.9 95%CI 1.1-74 P=0.01
ALC> 100,000/mm3 5.1 95%CI 1.1-23.7 P=0.04
Risk factors for compression fractures in CLL patients
Discussion
More disease burden increases risk of compression fracture
Need for early screening
Results for:
Do patients with CLL have increased risk of osteoporosis?
CT scans
Fisher's exact = 0.327
DEXA scans
p<0.001
Prevalence of osteoporosis
Fisher's exact = 0.107
Compression Fracture
odds ratio 1.0, 95%CI 0.32-2.84, p=1.0
Discussion
More DEXA scans in controls
In some cases men got fewer DEXA scans compared to women
Informant bias?
More CT scans in cases
Limitations
Retrospective study
Small cohort
Single centre study
Paucity of data available on imaging studies
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.
References
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2. 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):4607-.
3. Haddy TB, Mosher RB, Reaman GH. Osteoporosis in survivors of acute lymphoblastic leukemia. Oncologist. 2001;6(3):278-285.
4. 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):3752-3760.
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6. 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. 2011.
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8. 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):813-818.
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10. 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):1330-1338.