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Chronic Lymphocytic Leukemia: A Contemporary Perspective on Diagnosis and Assessment Part 1: Diagnosis, Staging, and Prognosis Compliments of Bayer HealthCare.

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Presentation on theme: "Chronic Lymphocytic Leukemia: A Contemporary Perspective on Diagnosis and Assessment Part 1: Diagnosis, Staging, and Prognosis Compliments of Bayer HealthCare."— Presentation transcript:

1 Chronic Lymphocytic Leukemia: A Contemporary Perspective on Diagnosis and Assessment Part 1: Diagnosis, Staging, and Prognosis Compliments of Bayer HealthCare Pharmaceuticals Inc.

2 Diagnosis: NCI vs IWCLL guidelines for CLL VariableNCIIWCLL Diagnosis Lymphocytes (x 10 9 /L)≥5; ≥ B-cell Marker (CD19, CD20, CD23) + CD5 ≥10 + B phenotype or bone marrow involved <10 + both of above Atypical cells (%)<55Not stated Duration of lymphocytosisNone requiredNot stated Bone marrow lymphocytes (%) ≥30>30 Staging Modified Rai, correlate with Binet IWCLL 1. Cheson BD, et al. Blood. 1996;87:

3 Diagnosis: NCI vs IWCLL guidelines for CLL VariableNCIIWCLL Response criteria CR Physical exam Normal SymptomsNone Lymphocytes (x 10 9 /L)≤4<4 Neutrophils (x 10 9 /L)≥1.5>1.5 Platelets (x 10 9 /L)>100 Hemoglobin (g/dL)>11 (untransfused)Not stated Bone marrow lymphs (%)<30, no nodules Normal, allowing nodules or focal infiltrates PR Physical exam (nodes and/or liver, spleen) ≥50% decreaseDownshift in stage Plus ≥1 of: Neutrophils (x 10 9 /L)≥1.5 Platelets (x 10 9 /L)>100 Hemoglobin (g/dL) >11 or 50% improvement Duration of CR or PR ≥2 monthsNot stated

4 Staging: Rai and Binet staging systems for CLL Clinical staging systems for CLL Stage ValueRaiBinetMedian survival Lymphocytosis (>15,000/mm 3 ) months (12.5 years) Lymphocytosis plus nodal involvement IA <3 node groups months (8.5-9 years) Lymphocytosis plus organomegaly IIB >3 node groups months (5-6 years) Anemia (RBCs) III Hgb <11 g/dL C Hgb <10 g/dL months (1.5-2 years) Lymphocytosis plus thrombocytopenia (platelets) IV PLT <100,000/mm 3 PLT <100,000/mm 3 1. Rai KR, et al. Blood. 1975;46: Binet JL, et al. Cancer. 1981;48: Binet JL, et al. Cancer. 1977;40:

5 Comparison of CLL and PLL B-CLL CLL-PLL CLLPLL slg+++ CD19++ CD20++ CD5++-/+ Courtesy of Randy Gascoyne, MD. 1. Bennett JM, et al. J Clin Pathol. 1989;42:

6 Immunophenotype scoring system Scoring system for B-CLL Membrane marker Points 10 SmlgWeakModerate/strong CD5PositiveNegative CD23PositiveNegative FMC7NegativePositive CD79b (SN8)NegativePositive 1. Matutes E, et al. Leukemia. 1994;8: Moreau EJ, et al. Am J Clin Pathol. 1997;108:

7 Prognosis: histologic bone marrow patterns The different bone marrow patterns probably reflect variations in amount of lymphoid accumulation during the natural course of the disease Interstitial (low risk) Diffuse (high risk) Nodular (low risk) Courtesy of Randy Gascoyne, MD. 1. Montserrat E, et al. Cancer. 1984;54:

8 Prognosis: lymphocyte doubling time Survival time according to LDT (all stages) Months Probability of survival Doubling time ≤12 months Doubling time >12 months 1. Montserrat E, et al. Br J Haematol. 1986;62:

9 Prognosis with serum markers: the effect of  2-microglobulin on survival in untreated CLL Effect of  2 -microglobulin on survival in untreated CLL PtsDied 2M2M < >4.0 Years Proportion surviving Keating M. Unpublished data. 2. Hallek M, et al. Leuk Lymphoma. 1996;22: Sarfati M, et al. Blood. 1996;88: Fayad L, et al. Blood. 2001;97:

10 Genetic abnormalities in CLL Genetic abnormality Incidence (%) Median survival (months)Clinical correlation 13q Typical morphology Mutated V H genes Stable disease Atypical morphology Progressive disease del 11q Bulky lymphadenopathy Unmutated V H genes Progressive disease Early relapse post autograft p53 loss/mutation Atypical morphology Unmutated V H genes Advanced disease Drug resistance 1. D Ö hner H, et al. N Engl J Med. 2000;343: Oscier DG, et al. Blood. 2002;100:

11 Effect of genetic abnormalities on survival 1 Effects of genetic abnormalities on survival in patients with CLL (N=325) 1 1. Döhner H, et al. N Engl J Med. 2000;343: In CLL

12 Unmutated V H gene Median = 117 months Mutated V H gene Median = 293 months Hamblin TJ, et al. Blood. 1999;94: Percent surviving (%) Months Prognosis: effect of V H gene mutations on survival

13 Prognosis: V H gene/p53 concordance Months V H gene/p53 multivariate analysis 1. Krober A, et al. Blood. 2002;100: Crespo M, et al. N Engl J Med. 2003;348: Oscier DG, et al. Blood. 2002;100: Unmutated V H gene Median = 119 months Mutated V H gene Median = 310 months p53 loss/mutation Median = 47 months Probability of survival (%)

14 Prognosis: effect of CD38 expression on survival Months 1. Orchard JA, et al. Lancet. 2004;363: Percent surviving (%) CD38 ≥30% Mean = months CD38 <30% Mean = 288 months N=162 P=

15 Probability of survival (%) 1. Crespo M, et al. N Engl J Med. 2003;348: Prognosis: effect of ZAP-70 on survival of patients with Binet stage A CLL Years after diagnosis <20% ZAP-70-positive cells N=44 P=.01 ≥20% ZAP-70-positive cells

16 Months Probability 1. Sarfati M, et al. Blood. 1996;88: ≤574 U/mL >574 U/mL Prognosis with serum markers: effect of sCD23 level on survival


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