Radiation Oncology/NHL/CLL-SLL

Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL)

Overview

 * CLL is the most common leukemia among adults in Western world
 * It is characterized by accumulation of mature B-cells
 * CLL molecular phenotype: CD5+, CD23+, surface Ig weak, CD79b weak/absent, FMC7 neg.
 * Diagnosis: lymphocytosis (often >5 x 10^9 / L, but not an absolute cutoff)
 * Risk factors are male sex, advanced age, white race, and family history of CLL or lymphoproliferative disorders
 * Cause and pathogenesis are largely unknown
 * Peripheral blood of some healthy adults shows circulating B-cell clones with surface phenotypes similar to CLL
 * Monocloncal B-cell lymphomatosis (MBL) indicates presence of such B-cells in blood at <5000 per cubic millimeter
 * Prevalence of MBL may be 3-5% in general population over 50 years of age
 * It appears that these circulating B-cell clones may be present in blood of for years prior to development of CLL, and that the light chain re-arrangement is the same
 * Thus, it may be reasonable to consider MBL a precursor state to CLL, in a similar fashion as MGUS is a precursor state to multiple myeloma
 * CLL and SLL are histologically and immunophenotypically identical
 * By definition, CLL has more marked peripheral blood involvement
 * CLL: absolute lymphocyte count >=5 x109/L
 * SLL: absolute lymphocyte count <5 x109/L
 * Clinical course varies widely, but frequently characterized by indolent behavior
 * Treatment commonly deferred while patients asymptomatic
 * No consensus on best treatment, but nucleoside analogues and Rituxan have led to improved outcomes

Staging
Rai Staging

Binet Staging

Classification

 * MD Anderson; 2007 (1985-2005) PMID 17925562 -- "Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center." (Tsimberidou AM, J Clin Oncol. 2007 Oct 10;25(29):4648-56.)
 * Retrospective. 2126 consecutive CLL/SLL patients
 * Outcome: rates of response, OS, and FFS not different among different groups
 * Predictive factors: deletion of 17p or 6q, age >60, b2-microglobulin >2, albumin <3.5, creatinine >1.6
 * Conclusion: Patients with CLL or SLL can be treated similarly

Richter's transformation

 * Named for Maurice N. Richter who described it in 1928
 * Development of high grade NHL (typically diffuse large B-cell lymphoma) in the setting of CLL
 * May be triggered by viral infections (e.g. EBV) or by genetic defects acquired by the malignant clone
 * Occurs in ~4% of CLL patients
 * Response rates to chemotherapy are low, up to ~40%; median OS is ~8 months


 * 1993 PMID 7693038, 1993 &mdash; "Common clonal origin of chronic lymphocytic leukemia and high-grade lymphoma of Richter's syndrome." Cherepakhin V et al. Blood. 1993 Nov 15;82(10):3141-7.
 * 1975 PMID 1096589, 1975 &mdash; "Richter's syndrome. A terminal complication of chronic lymphocytic leukemia with distinct clinicopathologic features." Long JC et al. Am J Clin Pathol. 1975 Jun;63(6):786-95.
 * Original description; 1928 PMID 19969796, 1928 &mdash; "Generalized reticular cell sarcoma of lymph nodes associated with lymphatic leukemia." Richter MN et al. Am J Pathol. 1928; 4:285.

Radiation Therapy

 * Please see spleen irradiation

Reviews

 * 2006 PMID 16983131 -- "Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia." (Shanafelt TD, Ann Intern Med. 2006 Sep 19;145(6):435-47.)
 * 2006 PMID 16901035 -- "Chronic lymphocytic leukemia: diagnosis and treatment." (Yee KW, Mayo Clin Proc. 2006 Aug;81(8):1105-29.)