Stem cell transplantation
Mrs S was 40 years old when originally diagnosed with chronic myeloid leukaemia (CML) in 2004. She began treatment with Imatinib but had an incomplete cytogenetic response. Other tyrosine kinase inhibitors (TKIs) were not an option at that point, although many have subsequently been developed and licensed.
She therefore went on to have a Fludarabine, Melphlan, Alemtuzumab conditioned sibling allograft in 2007. At day 100, a bone marrow aspirate confirmed molecular remission (BCR-ABL ratio 0), with peripheral blood chimerism of CD15 99%/T cells 46% donor. Following two donor lymphocyte infusions (DLIs) in 2008, she converted to full donor myeloid chimerism, and remained BCR-ABL negative. She had no significant graft versus host disease (GVHD).
In 2015, the CML relapsed, and she was treated with Dasatinib, a second generation TKI. She suffered some haematological toxicity from this, such that she was frequently not able to tolerate full dose treatment.
In 2018, she re-commenced a DLI programme (peripheral blood chimerism 30/98, BCR-ABL ratio 11%, when started).
With a combination of Dasatinib and escalating DLI (capped at CD3 1×10^7/kg, nine DLI doses in total), her chimerism slowly converted back to full donor, and her BCR-ABL ratio is now 0.
She has had no significant GVHD. She continues reduced dose Dasatininb, and remains extremely well in herself.
This case illustrates the important role the Newcastle advanced therapies team often play in the long term care of patients. More than ten years after preparation of the original graft, DLIs were still being used in the patient’s care.