In acute myeloid leukaemia (AML), age has a definite effect on the biology of the disease and also determines the outcome of
chemotherapy. AML cells constitutively express
mRNA and produce several haematopoietic
cytokines. The haematopoietic
cytokines: SCF,
IL-3,
GM-CSF and
G-CSF induce leukaemic colonies or activate
DNA synthesis in about 80% of AML cases. Both
M-CSF and
thrombopoietin stimulated AML cell proliferation is seen in vitro in about 50% of cases. Both
IL-6 and
IL-11 showed little proliferative activity on primary AML cells. The combinations of these
cytokines were synergistic in stimulating the proliferation of AML cells. On the other hand, the inhibitory haematopoietic
cytokines:
TNF-alpha,
TGF-beta, IFN-gamma and
IL-4 have shown multiple effects on AML blast cell proliferation. In several in vitro systems, haematopoietic
cytokines have failed to induce maturation of AML blasts. Only in AML with t(8;21),
G-CSF has induced granulocytic maturation of AML blasts in vitro. AML cells with
chromosomal abnormalities involving the 21q22 region differentiate in vitro into eosinophils in the presence of
IL-5.
IL-6 and IFN-alpha have induced megakaryocytic differentiation of blast cells from
acute megakaryoblastic leukemia (M7) patients. The haematopoietic
cytokines: SCF,
IL-3 and GMCSF have protected in vitro AML cells from
chemotherapy-induced apoptosis. Many clinical studies have been recently reported evaluating the effect of the haematopoietic
cytokines:
GM-CSF,
G-CSF,
IL-3 and PIXY321 as adjuncts to the
chemotherapy of AML patients. Most studies have shown these haematopoietic
cytokines to be well-tolerated and effective in augmenting neutrophil recovery in elderly AML patients when given after
chemotherapy. On the other hand, considerable number of studies using these
cytokines before and during
chemotherapy to recruit AML cells into cell cycle and thus make them more susceptible to
chemotherapy have reaveled no benefit. Several clinical trials have shown promising results after the use of
IL-2 either as
remission induction therapy in refractory and/or relapsed AML patients or as post-remission consolidative
immunotherapy. Haematopoietic
cytokines administered after
chemotherapy can shorten the duration of
neutropenia and hospitalisation without a significant effect on treatment outcome. On the other hand, their use before and during
chemotherapy has yielded no benefit, and instead have led to delay of platelet recovery and worse survival rate in some elderly AML patients.