Terminal transformation in B-cell chronic lymphocytic leukaemia

Terminal transformation of chronic lymphocytic leukaemia (CLL) comparable to the blast-cell transformation which is responsible for almost all deaths in the chronic myeloid leukaemias is a rare event because the majority of CLL patients die without a major or easily recognised morphological transformation of the leukaemia cells having occurred. However, a substantial proportion of these patients die with progressive treatment-resistant disease or from intractable infections resulting from CLL-related immunodeficiency. In many of these patients biological transformation of the leukaemia cells can be associated with the appearance of complex chromosomal changes not present earlier or additional to the commonly present trisomy 12(1). In a broad sense, therefore, all of these patients may be said to undergo lethal transformation of their disease in contrast to the, admittedly substantial numbers, especially of elderly males who die from causes totally unrelated to their CLL, especially cardiovascular and cerebrovascular diseases, and other malignant diseases. In the narrow sense the term 'terminal transformation' is usually restricted to those conditions in which the terminal event is the proliferation of a new population of lymphoid cells of enhanced malignancy. There are three well-known types of transformation. One, 'prolymphrocytoid' transformation is relatively low-grade, while the other two, 'Richter's syndrome' and 'immunoblastic transformation' are rapidly progressive conditions. The last two account for about 5% of all deaths in CLL, but the slowly progressive prolymphocytoid transformation has been described too recently to permit reliable estimates of its frequency in unselected series to CLL. It may be of the order of 10%.