Chapter 32 Chronic Lymphocytic Leukemia
Initial Evaluation of Young Patients With Chronic Lymphocytic Leukemia
Only 10% of patients diagnosed with CLL are younger than 50 years of age, and these patients often present a diagnostic and therapeutic dilemma to hematologists initially evaluating them. The great majority of patients diagnosed before the age of 50 years will have early-stage CLL with a slightly higher predisposition to a prior first-generation relative with this disease. Additionally, these patients are generally of a higher economic status or have chronic fatigue or medical illnesses for which they have been undergoing routine blood testing, leading to diagnosis of CLL. When the diagnosis of CLL is made, these younger patients have a more challenging time understanding how the disease will impact them. For patients with no symptoms referable to CLL, we generally discuss complications of the disease during the first visit and have a detailed discussion regarding assessment of genetic risk factors predisposing to early disease progression, including select interphase chromosomal abnormalities [del(17p13.1) and del(11q22.3)] and IgVH mutational status (unmutated). During this time, it is important to counsel patients that identification of high-risk genomic features can actually increase anxiety because no treatment intervention is indicated in the absence of symptoms, regardless of genomic profile, outside of a clinical trial. In our experience, the great majority of patients desire this testing. Despite the potential benefit of allogeneic SCT in younger patients with CLL, we generally mention this only as one treatment option used in this disease and do not pursue consultation or tissue typing of patients or siblings until patients are truly symptomatic from their disease. We provide considerable discussion about the promising new kinase inhibitors coming forward in the treatment of CLL, analogous to how imatinib impacted treatment of CML. During the second visit 4 to 6 weeks later, we review the results of these prognostic factors and answer additional questions that have arisen. Ultimately, the majority of patients have low-risk disease, and knowing this allows patients to take partial control of their disease and move on with their lives. Serial assessment of the psychological well-being of patients with CLL during this first year is incredibly important. At no place during the evaluation do we refer to CLL as being a good or favorable leukemia. In our experience, the most common reason for dissatisfaction toward the initial hematology evaluation is lack of explanation of the disease process or the minimization of CLL as a “good leukemia to have.”
For young patients presenting with other chronic medical problems who are asymptomatic from their CLL, we follow the approach outlined above. More commonly, these patients have fatigue, mild anemia, or other symptoms that could be referable to the CLL. Additionally, this group is more commonly overweight or obese. In either setting, it is important to first think like an internist and pursue other causes for symptoms potentially referable to CLL. In particular, encouragement of both weight loss and a fixed exercise plan should be encouraged for fatigue and often improve quality of life and in other medical comorbidities. It is very important to note that younger patients with CLL can often go a decade or more without therapy, and early treatment of this patient group in the absence of symptoms still offers no proven long-term advantage. For this reason, our group remains very conservative on starting therapy for young patients with CLL.
Figure 32-1 CHRONIC LYMPHOCYTIC LEUKEMIA (CLL).
The peripheral blood smear (A) typically shows lymphocytosis and increased smudge cells as a result of the fragility of the CLL cells (see also smudge cell in C, right side). These can be avoided by making a preparation of blood and bovine serum albumin (22%) at a ratio of 11 drops of blood and 1 drop of albumin before preparing the slide (B). Cytologic features of CLL cells differ. Classic cells have a small nucleus with a “soccer ball” chromatin pattern (C). Some cases have increased large cells, or prolymphocytes, with more open chromatin and prominent “punched-out” nucleoli (D; prolymphocyte, right side). Other cases, sometimes referred to as “atypical,” have clefted cells and large cells (E). The bone marrow can show nodular infiltrates of CLL cells (F), an interstitial infiltrate, or a diffuse infiltrate (G).