Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus

Abstract

The aim of this project was to identify situations where allogeneic stem cell transplantation (allo-SCT) might be considered as a preferred treatment option for patients with B-cell chronic lymphocytic leukemia (CLL). Based on a MED-LINE search and additional sources, a consented proposal was drafted, refined and approved upon final discussion by an international expert panel. Key elements of the consensus are (1) allo-SCT is a procedure with evidence-based efficacy in poor-risk CLL; (2) although definition of 'poor-risk CLL' requires further investigation, allo-SCT is a reasonable treatment option for younger patients with (i) non-response or early relapse (within 12 months) after purine analogues, (ii) relapse within 24 months after having achieved a response with purineanalogue-based combination therapy or autologous transplantation, and (iii) patients with p53 abnormalities requiring treatment; and (3) optimum transplant strategies may vary according to distinct clinical situations and should be defined in prospective trials. This is the first attempt to define standard indications for allo-SCT in CLL. Nevertheless, whenever possible, allo-SCT should be performed within disease-specific prospective clinical protocols in order to continuously refine transplant indications according to new developments in risk assessment and treatment of CLL.

Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study

“…Eligible patients were in need of treatment 26 with poor-risk CLL according to one of the following modified EBMT Consensus criteria 17 : fludarabine refractoriness (defined as no response or relapse o 12 months after the last administration of fludarabine), or relapsed o24 months after the last administration of fludarabine combined with a monoclonal antibody, or refractory or relapsed and having del(17p). Patients had to be 18-70 years inclusive with a WHO performance ⩽ 2 and a hematopoietic cell transplantation-comorbidity index (HCT-CI) ⩽ 2.…”

“…1,8,15,16 Therefore, alloSCT was proposed for patients with poor survival with non-transplant treatments: (1) purine analog refractory/relapsing (R/R) o12 months, or (2) R/R o2 years after purine-analog-based combination therapy or (3) del(17p)/ TP53 abnormalities present (EBMT Transplant Consensus on alloSCT in CLL). 17 High disease burden and chemorefractory disease at the time of alloSCT have been identified as negative predictors of PFS. 1,18,19 Therefore, before alloSCT effective remission-induction treatment is mandatory, but as of today no standard regimen exists.…”

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

“…In particular, for 17p-patients, alternative more toxic therapeutic approaches are generally recommended, such as immunotherapy, high-dose methylprednisolone (HDMP), or allogeneic hematopoietic cell transplantation (alloHCT) [6,7]. The overall response rate (OR) to the anti-CD52 antibody alemtuzumab in the relapsed setting was 34%, with OR of 39% in patients with 17p-, 30% in patients with 11q-, and a median progression-free survival (PFS) of 7.7 months [5].…”

Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review

“…According to iwCLL, patients with resistant disease (defined as a short time to progression after the first treatment) and/or leukemia cells with del 17p should be offered alternative treatment approaches such as alloHSCT. According to the EBMT consensus, patients with non-response or early relapse (within 12 months) after purine analogue treatment relapse within 24 months of having achieved a response with purine-analogue-based combination therapy, or autologous transplantation and TP53 abnormalities requiring treatment are potential candidates for alloHSCT [55].…”