Although three patients have been treated in the pilot study of this new gene therapy treatment of CLL, the authors of the NEJM article give a single case report on one patients who would have been expected to do badly with further treatment because of a TP53 problem. I have attempted to simplify the case report for a lay-audience.
The patient was diagnosed as Rai stage I CLL in 1996 but did not need treatment until6 years of watch and wait had passed. The reason for treatment was a progressive increase in white cell count and in lymph node size. In 2002, he was treated with two cycles of rituximab plus fludarabine (FR) which normalized his blood count and shrunk his lymph nodes, though they could still be felt. This would have been a partial remission. In 2006, he received a further four cycles of FR for disease progression, again with normalization of blood counts and partial regression of his lymph nodes. This response was followed by a 20-month progression-free interval and a 2-year treatment-free interval.
In February 2009, he had a rapidly progressive rise in white cell count and recurrent enlargement of his lymph nodes. At this stage his bone marrow was extensively infiltrated with CLL. Cytogenetic analysis showed 20% of his cells contained a deletion of chromosome 17p, but much more sensitive FISH testing showed an 85% deletion involving TP53 on chromosome 17p. He received rituximab with bendamustine (BR) for one cycle and three additional cycles of bendamustine without rituximab (because of a severe allergic reaction). This treatment resulted in only transient improvement in lymphocytosis and a CT scan showed that the enlarged lymph nodes were getting bigger.
In December 2009, his own T-cells were collected by leukapheresis and preserved in liquid nitrogen. The patient then received alemtuzumab (which actually works in TP53 disordered CLL) for 11 weeks, with improved blood cell production and a partial resolution of his enlarged lymph nodes. Over the next 6 months, he had stable disease but with persistent, extensive marrow involvement and diffuse lymph node enlargement (with multiple 1- to 3-cm lymph nodes). In July 2010, the patient was enrolled in a phase 1 clinical trial of chimeric antigen receptor–modified T-cells.