Risk for Second Nonlymphoid Neoplasms in Chronic Lymphocytic Leukemia

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Risk for Second Nonlymphoid Neoplasms in Chronic Lymphocytic Leukemia

Written by Ramaz Mitaishvili

Thursday, 27 December 2007

Constantin A. Dasanu, MD, PhD; Doru T. andrescu, MD

Abstract

Major advances have occurred in understanding the biology, immunology, and

modalities of treatment of chronic lymphocytic leukemia (CLL) in the last

decade. B-cell CLL is the most common type of leukemia occurring in the US and

Western nations. B-cell CLL is characterized by progressive defects in both

cell-mediated and humoral-mediated immunity. B-lymphocyte defects, low

gammaglobulin levels, and quantitative and functional T-cell defects have been

documented in the setting of CLL. In concert with each other, they account for

the increased susceptibility of the CLL patients to infectious agents. Moreover,

several recent surveys have pointed out that CLL patients are at high risk of

developing a large variety of second malignant neoplasms. Different therapeutic

modalities used for CLL may further exacerbate immunosuppression by depleting

both T- and B-immune effectors, thus favoring various infectious diseases and

perhaps altering the immune surveillance. The occurrence of 2 or more second

cancers is increasingly reported in the context of CLL. Increased awareness of

this association is warranted. Future development of surveillance strategies may

be needed for a growing population of surviving patients who are at risk for

second nonlymphoid neoplasms.

Historical Perspectives and Early Data

Long before the purine analogs became available for the treatment of

chronic lymphocytic leukemia (CLL), a few reports indicated that patients with

CLL are at increased risk for lymphoid malignancies, and may be at increased

risk for subsequent nonlymphoid malignant neoplasms as well ( Table 1 ).

In the United States, an early retrospective analysis in 1975 by Manusow

and Weinerman[1] on 102 patients with CLL admitted between 1955 and 1974 at the

University of Manitoba, Winnipeg, Manitoba, Canada, suggested that the incidence

of second cancers was elevated when compared with that in the general population

of Manitoba of the same age and sex distribution. The risk for all cancers

developing in patients with CLL was found to be 3-fold that for the age- and

sex-matched population, 8-fold for skin cancers, and 2-fold for all cancers --

excluding skin cancer.

At about the same time, Santoro and colleagues,[2] at Instituto Nazionale

Tumori of Milan, Italy, reported on the incidence of a second primary neoplasm

in 82 consecutive cases of CLL. In 19.5% of patients, an associated neoplasm was

diagnosed either subsequently or concurrently to CLL. Head and neck carcinomas

and breast cancer had the highest incidence. The results of this study further

supported the hypothesis that patients with CLL are prone to develop subsequent

cancers.

A large retrospective study performed in 1978 by Greene and colleagues[3]

at the National Cancer Institute in Bethesda, land, looked at the outcome of

4869 patients with CLL. Second primary cancers developed in 234 patients

compared with 204.9 expected. The risk was significantly elevated for malignant

melanoma, soft-tissue sarcomas, and lung cancer. The study authors concluded

that immunologic defects in CLL may be involved in the etiology of the excess

risk for these sites, in part because a similar array of nonlymphoid tumors was

seen following therapeutic immunosuppression among renal transplant recipients.

Full article (very long)

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