**5. Role of transplant in CLL**

In the setting of approval of novel agents in the treatment of CLL the number of transplants that are being performed in Europe and the United States are decreasing. In the chemoimmunotherapy era, patients with TP53 deletion/mutation, fludarabine refractoriness, early relapse (<24 months) after FCR treatment were in the highest risk group. Allogeneic Stem Cell Transplant (SCT) would be considered in these patients as the only viable treatment option. Today however, these patients have ibrutinib, idelalisib and venetoclax and various combination of novel agents with immunotherapy as possible treatment options. There are no randomized clinical trials that compare the outcomes of allogeneic SCT with conventional chemotherapy, chemoimmunotherapy or novel therapy regimens. Most transplants offered for CLL use reduced intensity conditioning (RIC), however no trials have been conducted to compare it to myeloablative conditioning. RIC resulted in reduced toxicity without compromising engraftment and anti-tumor activity [60]. Follow up results for studies with RIC indicate that about 40% of patients achieve long term disease control and RIC also overcomes the negative prognostic effect of TP53, fludarabine refractoriness as well as that of SF3B1 and NOTCH gene mutations [61–63]. Generally, allogeneic transplants are no longer offered to patients with del(17p) in first remission. In the relapsed setting the role of SCT must be weighed against the comorbidities, prior therapies, and duration of response to prior therapies as well as current mutation status including TP53, NOTCH1 and SF3B1. Patient must be informed about the side effect profile and non-relapse mortality associated with allogeneic transplant compared to the toxicity and side effect profile of novel agents. (**Figure 2**).

**Figure 2.** *Hematopoietic SCT for CLL by year [64, 65].*
