Because CLL occurs mainly in the elderly and is often associated with comorbidities that prevent a significant proportion of patients from receiving regular chemoimmunotherapy, meroval in combination with conventional lumecanine has become the treatment of choice for this group of patients in recent years. In addition, investigators are exploring more effective and well-tolerated treatment options. A Czech group reported the results of applying low doses of FC+R in the treatment of older or comorbid CLL. They applied half a dose of fludarabine (12 mg/m2 i.v. or 20 mg/m2 orally, d1-3) in combination with a 60% dose of cyclophosphamide (150 mg/m2 i.v./p.o. d1-3). There was no change in the dose of rituximab. A total of 93 patients were treated, of which 56% were treated in first line and 44% in second line. Patients Rai stage III-IV accounted for 62%, IGHV unmutated group 74%;, 11q-32%, 17p-5%. As a result, the CR rate was 39% for first-line treatment and 27% for second-line treatment, while the incidence of grade III-IV granulocytopenia, thrombocytopenia and anemia was 54%, 13% and 11%, respectively, and the incidence of severe infection was 13%. The investigators concluded that the reduced-dose FCR regimen was satisfactory and had a better safety profile for patients who could not receive the full dose of FCR. In patients with relapsed refractory CLL and poor general condition, treatment is more difficult. Two Italian study groups have reported the results of applying low-dose alemtuzumab treatment separately. The first group applied alemtuzumab 10 mg subcutaneously three times a week (30 mg once a week in 18 patients with reduced lymphocytes) for 18 weeks in 39 patients refractory to fludarabine, resulting in an ORR of 44% and a CRR of 8%, while the rate of grade III-IV infection was only 7% and the rate of CMV activation 27%. Another group was a retrospective study using <45 mg< font=""> per week <600 mg< font=""> total dose as a criterion for low dose and found an ORR of 56% and a CRR of 22% . The median follow-up was 42.2 months, with median OS and PFS of 39 and 19.4 months, respectively. the incidence of grade III-IV granulocytopenia, thrombocytopenia, and anemia was 29%, 6%, and 6%, respectively. The incidence of serious infections was 7%, CMV activation was 34%, and CMV disease developed in one case. Both studies concluded that the use was equally effective with a better safety profile, especially in the elderly and frail. Cladribine, as a nucleoside analogue, is comparable to fludarabine in the treatment of CLL. How effective and safe is the combination of rituximab? Researchers, also from Italy, reported data on the treatment of 67 patients with CLL or SLL. Of these, 45 were primary patients and 65 were evaluable, with an OR rate of 85%, a CR rate of 45%, a median follow-up of 27.6 months and a median time to treatment failure of 36.7 months; grade III-IV granulocytopenia, thrombocytopenia and anemia occurred in 10, 3 and 2 patients, respectively. Thus, it is evident that R-cladribine combination therapy is comparable in efficacy and better in safety to more potent chemotherapy and warrants further study. It is thus evident that in elderly and frail individuals, dose reduction based on conventional chemoimmunotherapy is commonly used, and new combinations may offer additional options.