Combinations of fludarabine with alkylating agents (cyclophosphamide) produce higher response rates and longer progression-free survival than single agents:

FC (fludarabine with cyclophosphamide)
FR (fludarabine with rituximab)
FCR (fludarabine, cyclophosphamide, and rituximab)
CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)Although the purine analogue fludarabine was shown to give superior response rates to chlorambucil as primary therapy, no evidence shows early use of fludarabine improves overall survival, and some clinicians prefer to reserve fludarabine for relapsed disease. Chemoimmunotherapy with FCR has shown to improve response rates, progression-free survival, and overall survival in a large randomized trial in CLL patients selected for good physical fitness. This has been the first clinical trial demonstrating that the choice of a first-line therapy can improve the overall survival of people with CLL.Alkylating agents approved for CLL include bendamustine and cyclophosphamide. Targeted therapy
Targeted therapy attacks cancer cells at a specific target, with the aim of not harming normal cells. Targeted drugs used in CLL include venetoclax (a Bcl-2 inhibitor), ibrutinib (a Brutons tyrosine kinase inhibitor), idelalisib and duvelisib (inhibitors of some forms of the enzyme phosphoinositide 3-kinase), as well as monoclonal antibodies against CD20 (rituximab, ofatumumab and obinutuzumab)  and CD52 (alemtuzumab). Notably, some of the effects of the targeted therapies such as BCR inhibitors can be attributed to disrupting the interaction of CLL cells with tumour promoting T cells. Stem cell transplantation
Autologous stem cell transplantation, using the recipients own cells, is not curative. : 1458   Younger individuals, if at high risk for dying from CLL, may consider allogeneic hematopoietic stem cell transplantation (HSCT).
Myeloablative (bone marrow killing) forms of allogeneic stem cell transplantation, a high-risk treatment using blood cells from a healthy donor, may be curative, but treatment-related toxicity is significant. : 1458  An intermediate level, called reduced-intensity conditioning allogeneic stem cell transplantation, may be better tolerated by older or frail patients. Refractory CLL
"Refractory" CLL is a disease that no longer responds favorably to treatment within 6 months following the last cancer therapy. In this case, more aggressive targeted therapies, such as BCR or BCL2 pathway inhibitors, have been associated with increased survival. During pregnancy
Leukemia is rarely associated with pregnancy, affecting only about one in 10,000 pregnant women. Treatment for chronic lymphocytic leukemias can often be postponed until after the end of the pregnancy. If treatment is necessary, then giving chemotherapy during the second or third trimesters is less likely to result in pregnancy loss or birth defects than treatment during the first trimester. Prognosis
Prognosis can be affected by the type of genetic mutation that the person with CLL has. Some examples of genetic mutations and their prognoses are: mutations in the IGHV region are associated with a median overall survival (OS) of more than 20–25 years, while no mutations in this region is associated with a median OS of 8–10 years; deletion of chromosome 13q is associated with a median OS of 17 years; and trisomy of chromosome 12, as well as deletion of chromosome 11q, is associated with a median OS of 9–11 years.