Jan Emmerechts23/04/16

Monoklonale B-cellymfocytoseMBL

Definitionstitel

• Clonal B-cell population in PB

• B-cell count < 5 x 109/L

• No evidence of lymphoma/infection/autoimmune disease

International Familial CLL Consortium (2005)

International Working Group of CLL (2008)

Introductiontitel

Strati, Shanafelt. Blood 2015;126:454-462

Prevalencetitel

• Increases with age (standard sensitivity assays)

<40y: 0.2-0.3%

40-60y: 3.5-6.7%

>60y: 5-9%

• Increases in case of familial predisposition

Familial CLL (2 1st degree relatives with CLL):

>40y: 15%

Sporadic CLL:

>60y: 15,6%

• Increases with assay sensitivity

PrevalenceSensitivity of technique

D’Arena, Musto. Transl Med 2015; 8:75-79

>40y: 12%

>60y: >20%

>90y: 75%

Nieto et al. Blood 2009;114:33-37

>70y: ~100% if 45mL blood would

be analyzed

Almeida et al. Leukemia 2011;25:718-722

• Based on phenotype:

CLL-like MBL: CD5+/CD20dim/CD23+

atypical CLL-like MBL: CD5+/CD20+/CD23- or dim

non-CLL MBL: CD5-

• Based on number of clonal B-cells:

high-count MBL (clinical MBL)

low-count MBL (population screening MBL)

ClassificationSensitivity of technique

75%

25%

Classificationtitel

Rawstron et al. Cytometry B Clin Cytom 2010;78:S19-S23

500/µL 5000/µL

LC-MBL HC-MBL CLL

Median:

1/µL

Median:

2900/µL

Vardi et al. Blood 2013;121:4521-4528

Classificationtitel

Single study, n=333

Biological characteristicstitel

Kaldapakis et al. BioMed Res Int 2014; 1-11

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Biological characteristicstitel

Kostopoulos et al. Genes Chromosomes & Cancer 2015;54:210-221

N=75 HC-MBL

Biological characteristicstitel

Kaldapakis et al. BioMed Res Int 2014; 1-11

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Which HC-MBL cases progress to CLL?

Ghia, Caligaris-Cappio. Blood 2012;119:4358-4362

Disease progressionPathophysiology

Disease progressionRisk factors

Strati, Shanafelt Blood 2015;126:454-462

Disease progressionB-cell count

Rawstron et al. N Engl J Med 2008;359:575-583

Disease progressionB-cell count

Kaldapakis et al. BioMed Res Int 2014; 1-11

Disease progressionPrognosis

Rawstron. Curr Hematol Malig Rep 2013;8:52-59

Disease progressionChange in classification?

Scarfo et al. Hematol Oncol Clin N Am 2013; 251-265

Recommendationstitel

• LC-MBL– Risk of progression is negligible

– Do not inform patients (?)

– No monitoring necessary

• HC-MBL– Risk of progression 1-2% per year

– Inform patients that risk is low, but not negligible

– Yearly hematologic consultation (CBC, physical examination)

Introductiontitel

• BM involvement– Median BM infiltration: 28% (5-85%)

– No correlation between extent of BM infiltration and B-cell count in PB

• ‘Nodal MBL’– Subset of patients with MBL and focal/subtle CLL-like infiltration in LN

– LN: <1,5 cm and no proliferation centers

– Indolent course

– ‘tissue involvement by CLL/SLL-like cells of uncertain significance’

• Atypical CLL-MBL & non-CLL MBL:– Atypical CLL:

• Exclude t(11;14)

– Non-CLL:

• often (splenic) MZL-like or non-classifiable

• Prevalence: 1-2%, increases with age

• Up to 1/3 is transient

• Usually indolent course

Gibson et al. Haematologica 2011;96:1144-52

Jan Emmerechts

23/04/16

Questions?