Clinical Practice Recommendations for Use of Allogeneic Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation

Abstract

We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations. We followed the Grading of Recommendations Assessment, Development and Evaluation methodology. For standard-risk CLL we recommend allo-HCT in the absence of response or if there is evidence of disease progression after B cell receptor (BCR) inhibitors. For high-risk CLL an allo-HCT is recommended after failing 2 lines of therapy and showing an objective response to BCR inhibitors or to a clinical trial. It is also recommended for patients who fail to show an objective response or progress after BCR inhibitors and receive BCL-2 inhibitors, regardless of whether an objective response is achieved. For Richter transformation, we recommend allo-HCT upon demonstration of an objective response to anthracycline-based chemotherapy. A reduced-intensity conditioning regimen is recommended whenever indicated. These recommendations highlight the rapidly changing treatment landscape of CLL. Newer therapies have disrupted prior paradigms, and allo-HCT is now relegated to later stages of relapsed or refractory CLL.

Guideline for the treatment of chronic lymphocytic leukaemia

“…Although patients with relapsed CLL and TP53 disruption benefit significantly from BCRi compared to historical data, most patients relapse within 3 years (Sharman et al , ; Byrd et al , ; O'Brien et al , ; Schetelig et al , ) and the optimal treatment for patients who fail BCRi is uncertain. For patients with Richter transformation at any stage, prognosis remains very poor and alloSCT remains the standard of care for patients achieving remission to induction chemotherapy (Kharfan‐Dabaja et al , ).…”

Ibrutinib as a bridge to transplant in high-risk chronic lymphocytic leukemia: A case report and review of the literature

“…In a recent publication, the American Society for Blood and Marrow Transplantation has maintained its recommendation to alloHCT in high-risk CLL patients after failing two lines of therapy and showing an objective response to BCR-inhibitors, and in patients refractory to or progressing after BCR-inhibitors and subsequently treated by BCL-2 antagonist [22] . In a recent survey by the EBMT, Dreger et al showed the feasibility of alloHCT after ibrutinib exposure, with a 1-year NRM of 9%; the outcome was better in ibrutinib-sensitive compared to refractory disease (1-year relapse rate 29% versus 60%) [23] , [24] .…”

Znaczenie oceny minimalnej choroby resztkowej u chorych na przewlekłą białaczkę limfocytową

“…Również uzyskanie głębokich odpowiedzi mierzonych z wykorzystaniem FLC wiąże się z dłuższym czasem PFS w przypadkach r/r CLL u chorych leczonych alemtuzumabem w monoterapii czy w skojarzeniu z wysokodawkowanym metyloprednizolonem [45,46]. Ocena MRD znalazła również zastosowanie w monitorowaniu odpowiedzi u chorych poddanych procedurze allo--HSCT i jest zalecana przez ASBMT (American Society for Blood and Marrow Transplantation) [47]. Uzyskanie niskiego poziomu MRD mierzonej w szpiku kostnym za pomocą FLC lub metodami molekularnymi 12 miesięcy po allo-HSCT wiązało się z dłuższym czasem wolnym od wznowy (EFS, event-free survival) [25,[48][49][50].…”