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

Rai Stage	Criteria	Survival (yr)
0	lymphocytosis only. no other abnormality	> 13
I	lymphocytosis and lymph node enlargement. no other abnormality	8
II	lymphocytosis and spleen or liver enlargement (w/ or w/o lymph node enlargement). no other abnormality	5
III	lymphocytosis and anemia (Hgb < 11 g/dL); w/ or w/o spleen / liver / lymph node enlargement. no platelet abnormality	2
IV	lymphocytosis and thrombocytopenia (plts < 100,000 /µL)	1

Binet Staging

Binet Stage	Criteria	Survival (yr)
A	<3 lymph node areas; no anemia or thrombocytopenia	12
B	3 or more lymph node areas; no anemia or thrombocytopenia	5
C	Anemia (Hgb < 11) or thrombocytopenia (< 100,000 /µL)	2

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 — "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 — "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 — "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.)