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References

Recurrence of the original disease (relapse)

The combination of chemotherapy and intense conditioning does not necessarily eradicate the last leukemic cell in the patient and therefore, the risk of relapse remains. Nevertheless, a HSCT can cure a malignant disease entirely owed to the Graft-vs-Leukemia (GVL)-effect of the allogeneic T cells of the donor co-transfused with the graft. It remains under debate whether GVL can be separated from GVHD or whether the 2 are just two different consequences of the attack by donor T cells on the tissues of the patient. Whatever it may be, the efficacy of the GVL is always proportional to the extent of the GVHD. Hence, the risk of relapse is inversely related to the grade of GVHD and as a consequence, all efforts to decrease the risk of GVHD increase the risk of relapse.

Probability of relapse according to HLA matching, T cell depletion and occurrence of GVHD.

Decreasing the risk of GVHD / Increasing the risk of relapse

The best known examples of factors that decrease the risk of GVHD but concomitantly increase the risk of relapse are:

  • An high degree of compatibility between patient and donor. Patients transplanted with HSC from a monozygotic twin are at higher risk than those transplanted with the HSC of their HLA identical sibling who are at higher risk than those transplanted with the HSC of an HLA-mismatched donor.
  • GVHD prophylaxis such as T cell depletion or severe immunosuppression.

Leukemias differ considerably with respect to their sensitivity to GVL. Chronic myeloid leukemia (CML) appears to be the most sensitive and the rules mentioned above and depicted in the figure are most clear for CML. Nevertheless, other leukemias may follow the same rules.

The GVL effect can also be exploited when a patient relapses after transplantation by infusing T cells from his original donor (DLI). This causes a GVHD that is usually milder than after transplantation and the freshly infused T cells may exert the necessary GVL/allogeneic effect to eradicate the leukemia. This treatment is particularly efficient in CML.