(marketed as fludarabine phosphate
under the trade name Fludara
) is a chemotherapy
drug used in the treatment of hematological malignancies
Fludarabine is highly effective in the treatment of chronic lymphocytic leukemia, producing higher response rates than alkylating agents
such as chlorambucil
Fludarabine is used in various combinations with cyclophosphamide
in the treatment of indolent non-Hodgkins lymphomas
. As part of the FLAG
regimen, fludarabine is used together with cytarabine
and granulocyte colony-stimulating factor
in the treatment of acute myeloid leukaemia
. Because of its immunosuppressive effects, fludarabine is also used in some conditioning regimens prior to non myeloablative allogeneic stem cell transplant
Fludarabine is a purine analog
, and can be given both orally and intravenously. Fludarabine inhibits DNA synthesis
by interfering with ribonucleotide reductase
and DNA polymerase
. It is active against both dividing and resting cells.
Fludarabine is associated with profound lymphopenia, and as a consequence, increases the risk of opportunistic infections
significantly. Patients who have been treated with fludarabine will usually be asked to take co-trimoxazole
or to use monthly nebulised pentamidine
to prevent Pneumocystis jiroveci pneumonia
. The profound lymphopenia caused by fludarabine renders patients susceptible to transfusion-associated graft versus host disease
, a fatal complication of blood transfusion
. For this reason, all patients who have ever received fludarabine should only be given irradiated
Fludarabine causes anemia, thrombocytopenia and neutropenia, requiring regular blood count monitoring. Some patients require blood and platelet transfusion, or G-CSF injections to boost neutrophil counts.
Fludarabine is associated with the development of severe autoimmune hemolytic anemia in a proportion of patients.
Difficulties are often encountered when harvesting peripheral blood stem cells from patients previously treated with fludarabine.