Five patients were in resistant relapse and three others were in sensitive or untreated relapse of RS. The median number of previous therapies was 4. Six patients received the transplant from an HLA identical sibling and two patients received the transplant from an unrelated donor. Three patients achieved durable disease remissions and were free of disease Droxinostat at 14 months, 47 months, and 67 months, including 2 patients who received non myeloablative preparative regimens. Five patients died of treatment related toxicities. According to a non randomized comparison of two RS cohorts, the estimated cumulative survival at 3 years  who received allogeneic SCT after a CR, CRu or PR, compared to 27% for patients who responded to initial therapy but received no allogeneic SCT.
96 Remarkably, allogeneic SCT has no benefit in RS patients who are refractory to induction regimens. In view of the poor prognosis of Richter,s Syndrome, patients should be entered into clinical trials whenever possible. The UKCLL NCRN group is currently recruiting into a Phase II study using ofatumumab in induction in combination with CHOP followed by ofatumumab maintenance for one year. Perspective CLL treatment has changed dramatically in the past decade and thanks to chemo immunotherapy remission durations of several years with improvement in overall survival have been achieved. However, not all patients benefit from current treatment strategies. Future efforts have to focus on evaluating the plethora of new anti cancer agents now available for tolerability in older patients with co morbidities.
Their efficacy has to be assessed after genetically informed risk stratification and response prediction that directs targeted therapies to the right patient. In view of their favourable safety profile, the combination of antibodies with BCR inhibitors might represent an attractive and tangible option for these patients. In the longer term, the recent WGS and WES data have revealed novel pathways of relevance in CLL such as Notch1 and the spliceosome. Inhibitors of these pathways are already undergoing pre clinical and early clinical evaluation. Besides, we need to establish complementary ways of assessing response by focussing on quality of life and activities of daily living assessments in addition to survival curves.
We hope that in future, these personalized approaches will further improve outcomes and maybe even cure patients with CLL. Developing an effective inhibitor to phosphatidylinositol 3 kinase / Akt signaling has become one of the most sought after goals of pharmaceutical companies and academia alike. Such compounds are seen as possessing the potential to have a significant impact on the treatment of human disease, the largest application being in oncology, but certainly encompassing a variety of other pathological conditions. The field has gone from a handful of archetypal inhibitors which dominated the field for upwards of ten years, to a range of small molecules that are progressing rapidly towards, and through early clinical testing. Just a few years ago the general opinion was that broad spectrum inhibitors of the class I PI3Ks would almost certainly have unacceptable toxicity if administered continuously.