Observation

Because of its indolent nature, chemotherapy is not indicated for asymptomatic or minimally affected patients with CLL, and observation is the generally accepted approach.[1] Because the rate of progression may vary, with long periods of stability and sometimes spontaneous regressions, frequent and careful observation is required to monitor the clinical course. One nomogram to predict time-to-first treatment relies on the number of lymph node sites, size of cervical lymph nodes, lactate dehydrogenase level, the IGH mutational status, and the presence of del(11q) or del(17p) established by fluorescence in situ hybridization analysis.[2] Spontaneous regression, manifested by a sustained reduction of the malignant clone without therapy, occurs in less than 5% of patients. These patients almost exclusively have hypermutation of IGH.[3]

Evidence (observation):

Despite many therapeutic options, observation should be considered for asymptomatic or minimally affected patients, even in the context of adverse prognostic findings. Therapy begins when patients develop profound cytopenias or when symptoms adversely impact quality of life.

There are no clinical trial results that confirm that immediate treatment of asymptomatic or minimally affected patients with the B-cell receptor inhibitors or BCL2 inhibitors is superior to observation.

Clinical trials will need to establish improved outcomes using the newer biological therapies in asymptomatic patients before observation or watchful waiting is discontinued.