Chronic lymphocytic leukemia

This is the commonest leukemia in adults and predominantly affects the elderly. A full description of CLL and its molecular abnormalities is provided in Chapter 10. Most are B-cell neoplasms (95%), which demonstrate a variety of cytogenetic abnormalities that are of value for molecular diagnosis and residual disease detection. Karyotypic abnormalities include trisomy 12 and deletions or translocations of chromosomes 11 and 13. Since these tumors are of B-cell origin, rearranged IgH genes may be used to confirm clonality and to detect re sidual tumor following chemotherapy and, in younger poor-risk patients, BMT.

Bone marrow transplantation is generally precluded in most patients with CLL due to the advanced age of the patients affected. However, recent studies of younger patients with aggressive disease who have undergone either autologous or allogeneic BMT have shown that PCR-detectable disease is often present at, or shortly after, transplantation, but this does not predict relapse. In the largest single-center study, the methods used for the analysis involved PCR amplification of the IgH locus with sequencing of the CDR3 products, before constructing patient-specific oligonucleotide probes, which were then used to probe the PCR products from marrow or blood samples taken after transplantation. Data suggest that patients who remain PCR-positive in the months following transplantation or become PCR-positive, having been PCR-negative initially, tend to relapse. Those that remain PCR-negative or become negative remain in clinical and morphological remission (Figure 6.11). Obviously, with an indolent, slow-growing disease like CLL, we must wait some years before the data can be interpreted fully, since it may be that ultimately all patients will relapse.

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