The duration of such response can be long, and there are available treatments and clinical trial options for these patients should they relapse or be intolerant of BCRi or venetoclax. how allo-SCT fits into the treatment algorithm in the era of novel agents. Introduction In any disease, the choice of an allogeneic SCT (allo-SCT) must weigh both the risks of the morbidity of the transplant and its outcome compared with what can be achieved using other treatment approaches. Based upon these criteria, in 2007, a consensus paper recognized groups of patients with chronic lymphocytic leukemia (CLL) who were considered at sufficiently high risk to undergo allo-SCT, namely, those patients whose CLL cells harbored del(17p) (deletion 17 p) or mutations or those who were refractory to (or relapsing within 2 years of receiving) purine analog combination treatment.1 Rabbit Polyclonal to MOBKL2B These recommendations were widely accepted, and allo-SCT was considered the treatment of choice for patients with such high-risk disease and the only treatment that offers curative intent in CLL.1 However, the treatment algorithm for CLL has changed markedly over the past decade, 2 firstly with chemoimmunotherapy replacing chemotherapy3,4 and more recently with the licensing for the treatment of CLL of the novel B-cell receptor inhibitors (BCRis) ibrutinib5,6 and idelalisib7 as well as the BCL2 inhibitor venetoclax.8-11 The availability of these novel brokers and their high efficacy in those patients who previously were considered to be at high risk have changed the treatment scenery and altered the criteria for transplant in CLL from those defined in 2007.1,12 It is in this establishing, where there is now common availability of novel brokers, that we now have to make treatment decisions regarding who is a suitable candidate for allo-SCT and when in the course of disease is the optimal time to consider transplantation. CLL is not the only disease in which new drug development has had an impact on SCT. The chronic leukemias have already seen the biggest impact of novel brokers on the use of transplantation, and imatinib has already largely replaced allo-SCT in the treatment of chronic myeloid leukemia.13 Here, I outline my approach to the clinical management of high-risk CLL patients on the basis of currently available treatment options. Treatment of CLL and the role of transplant CLL is an extremely heterogeneous disease, and patients do not merit treatment until their disease has progressed and become symptomatic.14 A number of prognostic factors have been AM251 identified that can help predict time from initial diagnosis to time of treatment and help identify patients more likely to require early treatment (Determine 1). Some of these factors can also be used to start to determine which more youthful CLL patients merit concern for allo-SCT at some stage in their clinical course. None of these prognostic factors represent in themselves an indication to treat patients with CLL, and many clinicians perform analyses of these factors only at the time when patients have fulfilled the criteria for indication for treatment.14 Under these circumstances, these factors are being examined for their predictive value to determine response to treatment rather than as a prognostic factor. For more youthful, fit patients, the chemoimmunotherapy treatment of choice remains fludarabine, cyclophosphamide, and rituximab (FCR), based on the results of the German CLL Study Group CLL8 study, which exhibited a survival advantage with FCR chemoimmunotherapy compared with fludarabine and cyclophosphamide chemotherapy alone.3 Many patients with CLL are too frail to be considered candidates for FCR, and other approved treatment approaches for these patients include bendamustine and rituximab,15 obinutuzumab and chlorambucil,4 or ibrutinib.6 A number of ongoing clinical trials are examining the role of chemoimmunotherapy vs novel agents alone or in combination. The results of these studies will help define the optimal front-line treatment of different individual groups in the future. As front-line treatments have improved, the number of patients with front-line refractory disease (previously a concern for suitability for allo-SCT) has decreased. Open in a separate window Physique 1. Selected prognostic markers in CLL. A number of factors have been shown to have prognostic significance in CLL, and a number of these are shown here. Identification of high-risk patients with CLL Standard treatment approaches are not considered to be curative in CLL, although 2 recent studies have exhibited that patients with mutated immunoglobulin heavy chain variable (status and trisomy 12 with no evidence of del(17p) or TP53 mutation. He was commenced on treatment with FCR and completed 6 cycles. He had prolonged thrombocytopenia and low-level but detectable minimal residual disease (MRD) at his end result assessment. His disease was showing evidence of progression at his AM251 next medical center visit 5 months following completion of FCR. I met him with his family in medical center and discussed his poor prognosis. We performed tissue typing on him and his 3 brothers and recognized an HLA-matched sibling. His disease progressed, and I repeated his cytogenetics and discovered that his CLL experienced acquired del(17p). At that time, he was treated AM251 with alemtuzumab and proceeded to a reduced intensity allo-SCT. He engrafted well, achieved.