Originally published as JCO Early Release 10.1200/JCO.2007.13.7844 on November 5 2007

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Value of Computed Tomography in the Monitoring of Patients With Chronic Lymphocytic Leukemia

Moores Cancer Center, University of California, San Diego, CA

In this issue of the Journal of Clinical Oncology, Blum et al¹ conducted retrospective analyses of the medical records of patients with chronic lymphocytic leukemia (CLL) to evaluate the relative value of computed tomography (CT) in assessing the response to therapy. Unlike the guidelines for assessing the response to therapy for most other types of non-Hodgkin's lymphomas (NHL), the widely-used National Cancer Institute–sponsored Working Group (NCI-WG) guidelines for patients with CLL do not incorporate use of CT scans in the response-assessment algorithm.² Nevertheless, CT scans increasingly are being used, not only to assess the response to treatment, but also for routine disease monitoring, a practice that has been largely discouraged.³ In their study, Blum et al found that the use of CT scans, as per NHL response definitions, had little value over the established NCI-WG criteria for assessing the response of CLL patients to therapy or for predicting post-treatment progression-free survival.

CLL is a systemic disease. Generally, lymphadenopathy detected at one anatomic site also can be found at other locations, giving rise to the notion that the disease can be followed by physical exam, the CBC, and other blood or marrow tests. However, a recent study published earlier in the Journal challenged this notion.⁴ This study found that CT scans could help stratify patients with early, stage 0 disease into two groups that had significantly different risks for disease progression. Thirty-eight of 140 patients who were not found to have enlarged lymph nodes by physical exam (hence the stage 0 classification) were found to have enlarged lymph nodes by CT scan, albeit of less than 2 cm in diameter except in five patients. Surprisingly, 13 patients (9% of the total) also were found to have splenic enlargement on CT scan that was not appreciated by physical exam.⁴ Patients who had evidence for lymph node enlargement in this study had a shorter time to initial treatment and poorer survival than did patients without detectable abnormalities on the CT scan. As such, this study challenged the notion that the physical exam for lymphadenopathy or splenomegaly can suffice for accurately staging patients with CLL.

However, an important question that needs to be addressed is whether CT scans can improve on our ability to predict outcome when other diagnostic and laboratory studies are available. In the former study by Muntanola et al,⁴ a significantly higher proportion of patients who had enlarged lymph nodes detectable only by CT scan also were found to have other known adverse prognostic indicators, such as leukemia cell expression of ZAP-70 or short lymphocyte-doubling times, than did patients without lymphadenopathy on CT evaluation. These other risk parameters also could delineate a subgroup of patients who had a relatively short median time from diagnosis to initial therapy independent of the results obtained by CT scans. In the retrospective study presented in this issue, Blum et al noted that achievement of either a complete response or partial response by NCI-WG criteria had a significant bearing on the ability to predict overall survival regardless of the results obtained via CT. Moreover, the NHL-CT assessment of response did not perform better than standard NCI-WG criteria in predicting the length of progression-free survival.

More studies are needed to evaluate the relative value of CT scans in monitoring patients with CLL. The need for this is particularly apparent with the advent of therapy with alemtuzumab, an anti-CD52 monoclonal antibody with therapeutic efficacy in inducing complete responses in CLL that appears inversely proportional to the extent of lymphadenopathy, which more often is being assessed with CT scans before therapy. ⁵ Because of the need for further study, the upcoming revision in the guidelines for treatment-response assessment will suggest that CT scans be performed before and after treatment in clinical trials involving patients with CLL. The prospective analyses of the value of CT scans relative to that of other CLL-associated risk indicators in predicting outcome will be necessary before making recommendations to use, or not to use, CT scans in the routine clinical evaluation and monitoring of patients with this disease.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

ACKNOWLEDGMENTS

Supported in part by Grant No. PO1CA081534 from the National Institutes of Health to the CLL Research Consortium (CRC).

REFERENCES

1. Blum KA, Young D, Broering S, et al: Computed tomography scans do not improve the predictive power of 1996 National Cancer Institute working group chronic lymphocytic leukemia response criteria. J Clin Oncol 25:5624-5629, 2007[Abstract/Free Full Text]

2. Cheson BD, Bennett JM, Grever M, et al: National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: Revised guidelines for diagnosis and treatment. Blood 87:4990-4997, 1996[Free Full Text]

3. Binet JL, Caligaris-Cappio F, Catovsky D, et al: Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia. Blood 107:859-861, 2006[Abstract/Free Full Text]

4. Muntañola A, Bosch F, Arguis P, et al: Abdominal computed tomography predicts progression in patients with Rai stage 0 chronic lymphocytic leukemia. J Clin Oncol 25:1576-1580, 2007[Abstract/Free Full Text]

5. James DF, Kipps TJ: Alemtuzumab in chronic lymphocytic leukemia. Future Oncol 3:29-42, 2007[CrossRef][Medline]

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