Growth factors in the treatment of acute lymphoblastic leukemia

The safety of G-CSF and GM-CSF in adult and pediatric patients with ALL has been well established. In addition, prophylactic administration of G-CSF was shown to significantly accelerate neutrophil recovery in most clinical trials. This was associated with a substantially reduced incidence and duration of febrile neutropenia and of severe infections in selected high risk patients receiving multiple treatment cycles, whereas the clinical benefit appears to be negligible in patients at low risk of infectious complications. There is currently insufficient evidence to support the use of GM-CSF as an adjunct to treatment for ALL outside of clinical trials. Apart from patient characteristics and type of CSF, it has become evident that scheduling of growth factor administration in relation to the type of chemotherapy, and use of different study end points influence the clinical efficacy of HGF administration. Although no studies have so far shown that use of growth factors is associated with reduced mortality, higher complete remission rates or superior survival, improvements in other clinical endpoints, e.g. infection rate, duration of i.v. antibiotics, and length of hospital stays were frequently perceived as clinically important and felt to contribute substantially to the patient's quality of life. It will become increasingly important to select those patients likely to benefit from growth factor support and to identify additional predictive criteria. Scheduling of CSFs, e.g. early versus delayed and prophylactic versus interventional administration, the type of growth factor used and the duration of administration need to be optimized in the context of specific treatment protocols. Although myeloid growth factors presently can not be expected to have a major impact on overall treatment outcome in patients with ALL, they facilitate important incremental improvement; in supportive care when appropriately applied. As the remaining open questions are resolved, clinical benefits may be achieved consistently and with a favorable cost benefit ratio.