Transformation & Myelodysplasia

Transformation & Myelodysplasia


Because WM is a slow-growing lymphoma, it is not uncommon for patients to have it for several years. In a small percentage of patients, having WM for a long time may increase their chances for developing a transformation of their disease into a more aggressive lymphoma, such as diffuse large B-cell lymphoma. This may occur because the cancerous WM cells acquire additional mutations over time that cause them to change. The percentage of patients who undergo this transformation has been variously cited as approximately 6%–13%. It has also been suggested that treatment with nucleoside analogs such as fludarabine and cladribine (2CdA) may contribute to the development of transformation.

Signs of transformation to a more aggressive lymphoma include worsening constitutional symptoms (weakness, fatigue, fever, weight loss, night sweats); rapidly enlarging lymph nodes, liver, and spleen; signs of disease outside the bone marrow; and profound cytopenias (reductions in the number of blood cells).  There are treatments that can be quite effective for more aggressive lymphoma, but they must be started promptly.


There is evidence to suggest that prolonged treatment with alkylating agents such as chlorambucil and with nucleoside analogs such as fludarabine and cladribine can cause myelodysplasia and/or acute myelogenous leukemia. Myelodysplasia, also known as myelodysplastic syndrome, was once known as “pre-leukemia” and is characterized by inefficient and disorderly production of myeloid blood cells such as neutrophils or monocytes. Such situations likely occur because these drugs can cause DNA damage, leading to the development of mutations that can potentially become cancerous. While it is important to recognize these possibilities, it does not mean that such treatments should not be given. Hematologist-oncologists and their WM patients should weigh the risks versus benefits of these particular agents.