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Chronic Lymphocytic Leukemia


A preoperative evaluation performed shortly before a 66-year-old man is scheduledto undergo coronary artery bypass graft (CABG) surgery reveals a peripheralblood leukocyte count of 23,500/μL with 28% neutrophils, 70% lymphocytes,and 2% monocytes. The patient’s hemoglobin level is 14.5 g/dL; plateletcount is 265,000/μL.

Case 1:

Incidental Finding ofLymphocytosis in an Older Man

A preoperative evaluation performed shortly before a 66-year-old man is scheduledto undergo coronary artery bypass graft (CABG) surgery reveals a peripheralblood leukocyte count of 23,500/?L with 28% neutrophils, 70% lymphocytes,and 2% monocytes. The patient's hemoglobin level is 14.5 g/dL; plateletcount is 265,000/μL.


The patient has had type 2 diabetes mellitus for many years, and for thepast 18 months he has required insulin. He had had no history of cardiacsymptoms until 3 months ago, when he began to experience mild, reproduciblechest pain on exertion. Although nitrates and β-blockers were prescribed,the pain continued to occur even at reduced levels of effort. CABG was scheduledafter a coronary angiogram revealed 90% stenosis in the proximal left anteriordescending coronary artery and 75% stenosis in the mid circumflexcoronary arteries.


Results of a chest examination are normal; no rales, gallops, or murmursare audible. No lymph nodes are palpable in the neck, axillae, or groin. Thereis no hepatosplenomegaly.


Examination of the peripheral smear confirms a large population of maturelymphocytes without blast forms. Results of a serum chemistry panel arenormal. A CT scan shows no liver or spleen enlargement.

Which of the following statements is most likely to be truefor this patient?


His operation should be cancelled; he needs immediate therapy for hisblood dyscrasia.


His expected survival is less than 5 years.


His disease represents a clonal proliferation of B cells and can best bediagnosed by flow cytometry.


He is likely to have hypergammaglobulinemia.


His disease will transform into acute lymphoblastic leukemia.

Case 1:


In this patient with asymptomatic lymphocytosis, the largepopulation of mature lymphocytes without blast formsseen on a peripheral blood smear strongly suggests

chroniclymphocytic leukemia



The vast majority of patients with CLLhave a clonal proliferation of B lymphocytes, which currentlyis most easily diagnosed by flow cytometry of theperipheral blood. Thus, choice C is correct. A monoclonalpopulation of CD5+ and CD20+ lymphocytes is consistentwith this diagnosis. In many patients, flow cytometry canbe used in place of the once obligatory marrow examination--although marrow biopsy is often helpful for stagingand prognosis.


Staging and prognosis. Accurate and clinically usefulstaging criteria have been developed for CLL. The Raistaging system is frequently used.


This consists of:

  • Stage 0, lymphocytosis only (31% of new cases).
  • Stage I, lymphocytosis and lymphadenopathy (35% ofnew cases).
  • Stage II, splenomegaly (26% of new cases).
  • Stage III, anemia (6% of new cases).
  • Stage IV, thrombocytopenia (2% of new cases).

The prognosis deteriorates as the stages advance:stage 0 is associated with low risk of death and a mediansurvival of more than 11 years; stages I and II, with intermediaterisk and a median survival of 5 to 7 years; stagesIII and IV, with high risk and a median survival of lessthan 2 years. This patient has only lymphocytosis--noclinical adenopathy, splenomegaly, or cytopenias. Thus,his disease is stage 0. Early-stage CLL has a good prognosis,and the expected survival is more than a decade.Choice B is incorrect.Consequently, important therapies for other conditions(such as coronary artery disease [CAD]) should notbe withheld. A recent editorial emphasized that approximatelya third of CLL patients never require therapy anddie of causes unrelated to CLL, while another third have along initial period of indolent disease before any progressionis evident.


Thus, choice A is not correct. This man's2-vessel CAD in the setting of diabetes takes precedenceover his early-stage CLL.

Complications of advanced disease.

Eventually, CLLprogresses to a stage where significant complications arelikely, morbidity is increased, and therapy is required. Inthe advanced stages of the disease--when lymphadenopathyis usually marked--hypogammaglobulinemia may develop,which results in an increased risk of infection fromencapsulated organisms. This infectious diathesis is amajor source of morbidity in late-stage CLL.


(choice D) occurs in a related B-cell disorder,multiple myeloma, but is rare in CLL.CLL may occasionally transform into an aggressiveform of large cell lymphoma (Richter syndrome). However,transformation into acute lymphoblastic leukemia(choice E) is extremely rare.


A variety of effective agents are now availableto treat patients with more advanced disease (such asthose with cytopenias). Chlorambucil is still useful. Thepurine analog fludarabine yields even higher responserates and longer progression-free survival--although itdoes not improve overall survival. Newer agents, such asthe immunotherapeutic agent rituxamib, are also showinggreat promise in therapy for B-cell neoplasms.


Outcome of this case.

The patient underwent successfulCABG surgery with mammary artery grafts. Amarrow specimen was obtained at surgery that demonstrateda 30% infiltration by mature B cells but no geneticor chromosomal markers that would signal a poor prognosis.Serial blood counts from the following year haveshowed no change except for a minor elevation in lymphocytecount (to 18,000/?L). The patient currently has noangina. He will continue to be followed with serial examinationsand blood counts.




Rozman C, Montserrat E. Chronic lymphocytic leukemia.

N Engl J Med.



Dighiero G, Maloum K, Desablens B, et al. Chlorambucil in indolent chroniclymphocytic leukemia.

N Engl J Med.



Dighiero G, Binet JL. When and how to treat chronic lymphocytic leukemia.

N Engl J Med.



Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucilas primary therapy for chronic lymphocytic leukemia.

N Engl J Med.



Byrd JC, Waselenko JK, Keating M, et al. Novel therapies for chronic lymphocyticleukemia in the 21st century.

Semin Oncol.


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