Optimal pharmacotherapeutic management of acute lymphoblastic leukaemia in the elderly.

The main characteristic of acute lymphoblastic leukaemia (ALL) in the elderly is its dismal prognosis. However, other than a lower incidence of T-cell ALL and a greater likelihood of unfavourable chromosomal abnormalities, the clinical and biological characteristics of Philadelphia chromosome-negative (Ph-) ALL in the elderly at diagnosis are no different from those observed in younger adults, and do not account, per se, for its poor prognosis. Rather, the latter is explained to a large extent by a high rate of treatment-induced mortality and/or by the use of less toxic but comparatively less effective drug regimens. Ph- ALL patients are offered treatments ranging from palliative care to intensive chemotherapy, but the survival of patients given palliative or minimally active chemotherapy is extremely poor. However, a valid comparison with patients given more intensive chemotherapy is lacking, as, in most cases, minimally active chemotherapy is used in patients with poor performance status at diagnosis. When more intensive chemotherapy is used, unacceptably high early mortality rates (up to 50%) have been reported, with complete-response rates ranging from 40% to 80% and 5-year survival consistently below 20%. Clearly, the results of therapy are unsatisfactory in Ph- ALL patients, which should encourage the development of innovative approaches, such as the use of new monoclonal antibodies. On the other hand, the availability of imatinib and second-generation tyrosine kinase inhibitors (TKIs) has improved the prognosis of Philadelphia-positive (Ph+) ALL in older patients. Impressive response rates have been reported, even in patients given imatinib and corticosteroids without additional chemotherapy, at the cost of manageable toxicity. Paradoxically, in the imatinib era, elderly patients with Ph+ leukaemia (which is clearly associated with an adverse prognosis in younger adults) seem to survive longer than Ph- elderly patients, although long-term survivors still remain relatively few. Whether new TKIs, such as dasatinib or nilotinib, will improve the prognosis of Ph+ ALL in the elderly is being prospectively assessed in several countries.