While collecting a fax off the machine the other day I stumbled across a report on an old patient of mine. I had treated her about 10 years ago for follicular lymphoma but now she had developed acute myeloid leukemia. It is becoming apparent that the successful treatments for various cancers, themselves leave secondary cancers in their wake. Thinking back over my career of 35 years of treating cancer patients, the numbers are beginning to mount up.
I can remember another woman of a similar age who developed her secondary leukemia five years after the lymphoma treatment. There was a woman with splenic marginal zone lymphoma who developed her leukemia after chlorambucil. This is the only time I have seen chlorambucil responsible. There was a man with an autoimmune condition, Wegener's granulomatosis, who developed first myelodysplastic syndrome (MDS) then acute myeloid leukemia (AML) after cyclophosphamide, and another woman with systemic lupus erythematosus who had a cyclophosphamide induced acute leukemia.
It is well established that cytotoxic drugs can cause both MDS and AML. The alkylating agents - mustine, cyclophosphamide, melphalan, thiotepa, chlorambucil and busulphan are well known to do so. Often they cause a loss of all or part of chromosomes 5 and 7, and the type of leukemia is usually difficult to treat and frequently fatal. Less well known is the fact that another type of cytotoxic drug, those that act as topoisomerase inhibitors (such as adriamycin and etoposide)can also cause leukemia, though these drugs induce chromosomal translocations like t(8;21), t(15;17) and inv 16.
In my experience cyclophophamide is more likely to induce leukemia than other cytotoxic drugs. This is paradoxical because it is less likely to induce permanent bone marrow damage than the others. Perhaps the others do not allow partially damaged cells to survive.
There is also some suggestion that the type of tumor being treated might influence whether or not secondary leukemias occur. We know that MDS and AML can occur with other lymphomas and leukemia even if no treatment is given. Myeloma is associated with MDS. In the 1980s I reported 20 patients with various B cell malignancies who developed MDS or AML without any treatment. I have seen AML develop in CLL patients twice; on both occasions the patient had received no treatment for the CLL. I have seen three patients who developed chronic myeloid leukemia (CML) to complicate their CLL even though they had had no treatment for their CLL.
The patient who had Wegener's Granulomatosis had a brother with kidney cancer. The woman with systemic lupus erythematosus was treated at the same time as another with the same diagnosis, only this woman was treated with plasma exchange rather than cytotoxic drugs. She developed kidney cancer.
To me this all suggests a genetic tendency to develop multiple disorders of the blood and immune systems. Treatment toxicity may synergize with this.
Why some patients develop secondary cancers and others do not, despite having teh same disease and the same treatment is a mystery. It is agood subject for research.