Treatment of hematological malignancies with allogeneic nonmyeloablative stem cell transplantation: conditioning regimens with fludarabine

Allogeneic stem cell transplantation (alloSCT) is an accepted therapeutic option for various hematological malignancies. For many years, alloSCT was based on the concept that a myeloablative dose of chemoradiotherapy was necessary to allow successful donor stem cell engraftment. These high-dose regimens cause considerable toxicity in graft recipients and even the most intensive conditioning regimens do not reliably eliminate all malignant cells. During the last decade, it became clear that the curative potential of alloSCT was not solely due to the conditioning regimen but also to an immune response of donor cells against the malignancy, termed the graft-versus-leukemia (GVL) effect. The increasing evidence that the GVL effect is essential for the eradication of host tumor cells has led to the development of a new concept in alloSCT: the use of reduced intensity, nonmyeloablative conditioning regimens that allow exploitation of the GVL effect without the toxicity of myeloablative therapy. The purine analog fludarabine is immunosuppressive and has activity against many hematological malignancies. The introduction of nonmyeloablative fludarabine-based conditioning regimens has facilitated alloSCT, while limiting regimen-related morbidity and mortality in patients with susceptible hematological malignancies. This potentially curative approach extends the use of alloSCT to older patients and to those with comorbidities that preclude high-dose chemoradiotherapy. The purpose of this review is to summarize the results obtained with fludarabine-based nonmyeloablative conditioning regimens and alloSCT in patients with malignant hematological disorders.