# Radiation Oncology/NHL/CLL-SLL

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
* Non-Hodgkin lymphoma: Main Page | Randomized
* Overview: Overview |
* Follicular |
* Diffuse large B-cell |
* MALT |
* Nodal marginal zone |
* Mantle cell |
* CLL/SLL |
* Lymphoblastic |
* Burkitt |
* NK/T cell |
* Anaplastic large cell |
* Primary CNS Lymphoma
* Treatment:
* Aggressive |
* Specific sites |
* Radioimmunotherapy
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 x10$^9$/L
** SLL: absolute lymphocyte count <5 x10$^9$/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.)