HCL Protocol Treatment Algorithm. Newly diagnosed HCL patients typically receive a purine analog, most commonly cladribine in five daily doses, less commonly pentostatin in six to 12 biweekly doses. Newly diagnosed or once-relapsed patients may receive repeat courses of single-agent purine analog, but at MD Anderson and the NIH, are also eligible for protocol treatment with rituximab and cladribine (CDAR). At the NIH, multiply relapsed HCL/HCLv patients eligible for moxetumomab pasudotox receive that option (also available in other centers), while ineligible patients may receive LMB-2, BRAF inhibition, ibrutinib, and BRPR (bendamustine-rituximab vs pentostatinrituximab) in that order of priority. Common off-protocol options for multiply-relapsed HCL include repeat courses of single-agent purine analog, single-agent rituximab, and pentostatin-rituximab. Splenectomy and even splenic radiation can have palliative benefit at least for a limited period of time.