**8.2 CLL and AIHA**

CLL is frequently associated with autoimmune phenomena, the most common being autoimmune hemolytic anemia (AIHA) [75]. Up to 33% of CLL cases have a positive direct antiglobulin test (DAT) during the course of disease, but overt AIHA occurs much less frequently. In a report of 1203 patients with CLL consecutive cases reported from a single institution, 52 (4.3%) cases of AIHA were observed, 19 at the time of diagnosis [76]. The prevalence of AIHA in patients with CLL have been reported in the range of 4–10%. It increases with disease stage. The autoantibodies that cause AIHA can be produced by nonmalignant B cells or, less commonly, by the malignant CLL clone itself [77, 78]. In practice, AIHA may occur in patients with no other requirement for treatment, or in patients in whom chemotherapy treatment is imminent or already started. Factors associated with an increased risk of development of AIHA at diagnosis included a high white blood count, older age, and male sex. AIHA alone was not itself associated with poor prognosis. The diagnosis of

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*Chronic Lymphocytic Leukemia: Rapidly Changing Treatment Landscape*

AIHA is usually based on the presence of an isolated fall in hemoglobin associated with a positive DAT, increased reticulocytes, and serum bilirubin. There have been no controlled trials of treatment for AIHA in CLL and the treatment approach is based on personal and institutional experience. In general, AIHA is responsive to CLL treatment, but if there is no indication to treat CLL, AIHA should be treated as a separate entity with steroids and other immune suppressants, the details of which is beyond the scope of this chapter. There has been controversy whether some chemotherapy agents, particularly purine analogs, induce or worsen AIHA. In a trial comparing outcomes of treatments using chlorambucil, fludarabine, or fludarabine in combination with cyclophosphamide, a positive DAT was found in 14%, and AIHA occurred in 10% of patients [75]. AIHA occurred more often in patients treated with chlorambucil than fludarabine, and occurred least frequently in patients receiving the combination of fludarabine and cyclophosphamide. For patients requiring therapy, a positive DAT test had poor prognostic significance, even in the absence of AIHA. The results suggest that the most successful treatment of AIHA in patients requiring chemotherapy treatment is the treatment associated

In summary, there has been a significant change in how we manage patients in CLL over the last 5 years. We have shifted away from chemoimmunotherapy towards novel agents such as BTK, PIK3, and BCL-2 inhibitors, which are not only more efficacious but are also safer and better tolerated. New prognostic models are being developed, and it appears that MRD directed therapy will become the norm in the future. Many clinical trials are looking at various combinations of novel therapies, with a defined period of treatment based on MRD analysis, to enable patients to have a period of treatment-free remission instead of continuous therapy.

Department of Hematology and Cellular Therapy, Allegheny Health Network, West

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*DOI: http://dx.doi.org/10.5772/intechopen.88070*

with the best response rate.

**9. Future directions**

**Author details**

Yazan Samhouri, Rupin Shah and Cyrus Khan

provided the original work is properly cited.

\*Address all correspondence to: clarasilvestr@gmail.com

Penn Hospital, Pittsburgh, USA

*Chronic Lymphocytic Leukemia: Rapidly Changing Treatment Landscape DOI: http://dx.doi.org/10.5772/intechopen.88070*

AIHA is usually based on the presence of an isolated fall in hemoglobin associated with a positive DAT, increased reticulocytes, and serum bilirubin. There have been no controlled trials of treatment for AIHA in CLL and the treatment approach is based on personal and institutional experience. In general, AIHA is responsive to CLL treatment, but if there is no indication to treat CLL, AIHA should be treated as a separate entity with steroids and other immune suppressants, the details of which is beyond the scope of this chapter. There has been controversy whether some chemotherapy agents, particularly purine analogs, induce or worsen AIHA. In a trial comparing outcomes of treatments using chlorambucil, fludarabine, or fludarabine in combination with cyclophosphamide, a positive DAT was found in 14%, and AIHA occurred in 10% of patients [75]. AIHA occurred more often in patients treated with chlorambucil than fludarabine, and occurred least frequently in patients receiving the combination of fludarabine and cyclophosphamide. For patients requiring therapy, a positive DAT test had poor prognostic significance, even in the absence of AIHA. The results suggest that the most successful treatment of AIHA in patients requiring chemotherapy treatment is the treatment associated with the best response rate.
