**6. Role of minimal residual disease (MRD) testing in CLL**

MRD in CLL is assessed most commonly using multiparametric flow cytometry with a sensitivity to detect <1 CLL cell in 10,000 leukocytes. MRD – undetectable (MRD-U) has been defined detection of <1 CLL cell per 10,000 leukocytes [2].

**109**

**Figure 3.**

*Richter transformation. Adapted by ASH education handbook [73].*

*Chronic Lymphocytic Leukemia: Rapidly Changing Treatment Landscape*

MRD-U in the blood or bone marrow strongly correlates with longer PFS in the patients treated with chemoimmunotherapy has been noted in numerous studies [30, 57, 64]. However, MRD- U is rarely achieved in patients who are on ibrutinib, a drug that offers significant clinical benefit in PFS and survival in CLL patients [66]. So, there is consensus that while MRD- U is generally a favorable outcome for patients but its exact use case scenario in clinical practice is yet to be determined. As of now the potential use of MRD status in CLL patients is in the context of clinical trials, as a surrogate for PFS depending on the type of treatment used and possibly as a replacement for clinical and radiographic response assessments in the future.

Maurice Richter initially described the transformation of CLL into an more aggressive form of lymphoma and since then this has been recognized as Richter's Transformation (RT) [67]. In most cases RT consists of transformation of CLL into Diffuse Large B Cell Lymphoma (DLBCL), however other aggressive lymphomas have been reported. As of now the reported incidence of RT in the era of novel agents is not very different from the incidence of RT in the chemoimmunotherapy era [68, 69] with incidence rates varying from 3–20% among various studies. RT is suspected when there is rapid clinical deterioration, worsening discordant lymphadenopathy to new onset cytopenia. However, its presentation can be varied. When RT is suspected a comprehensive evaluation with a PET/CT, image guided biopsy as well as a bone marrow biopsy is required. SUV of greater than 10 can distinguish RT form CLL with high sensitivity (91%) and specificity (95%) [70]. However, this has been disputed in the setting of novel agents and thus a concern for RT necessitates a biopsy of the index lesion preferably. RT primarily arises in the background of TP53 disruption and complex karyotype. MYC activation and CDKN2A/B likely play an important role in RT. Clonally related RT patients (>80% of RT DLBCL) respond very poorly to traditional chemotherapy for DLBCL, whereas clonally unrelated DLBCL RT patients respond to traditional chemotherapy just as de novo DLBCL. Thus, determination of clonal evolution is important but difficult to determine [71].Trials performed prior to the use of novel agents used R-CHOP or similar

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

**7. Richter's transformation**

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

MRD-U in the blood or bone marrow strongly correlates with longer PFS in the patients treated with chemoimmunotherapy has been noted in numerous studies [30, 57, 64]. However, MRD- U is rarely achieved in patients who are on ibrutinib, a drug that offers significant clinical benefit in PFS and survival in CLL patients [66]. So, there is consensus that while MRD- U is generally a favorable outcome for patients but its exact use case scenario in clinical practice is yet to be determined. As of now the potential use of MRD status in CLL patients is in the context of clinical trials, as a surrogate for PFS depending on the type of treatment used and possibly as a replacement for clinical and radiographic response assessments in the future.
