Allogeneic transplantation in high-risk chronic lymphocytic leukemia: a single-center, intent-to-treat analysis

Although allogeneic hematopoietic stem cell transplantation (HCT) is still the only documented curative treatment option for patients with high-risk chronic lymphocytic leukemia (CLL), the advent of pathway inhibitors has substantially altered its role in the treatment landscape of CLL. In 2014, the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT) proposed a transplant algorithm for patients with high-risk CLL taking into account use of the B-cell receptor inhibitors ibrutinib and idelalisib as well as the BCL-2 inhibitor venetoclax. Patients can enter the ERIC/EBMT algorithm at two different levels. Level 1 (L1) includes patients with CLL harboring TP53 abnormalities and/or del(11q) who have relapsed after or are refractory to chemoimmunotherapy but are responding to treatment with a first pathway inhibitor. At this level allogeneic HCT is only suggested as an option for those patients who have a low transplant risk, i.e. availability of a well-matched donor and absence of comorbidity. Level 2 (L2) is defined by disease that has relapsed after or is refractory to both chemoimmunotherapy and the first pathway inhibitor. Patients on L2 are considered to have a higher disease-specific risk, justifying allogeneic HCT even with mismatched donors or comorbidity. A recent refinement of the ERIC/EBMT algorithm eliminated del(11q) as a high-risk criterion but retained the two-level risk grading. The purpose of the present study was to explore whether the ERIC/EBMT algorithm is generally feasible and whether allogeneic HCT can still be performed successfully at L2. Patients with CLL who were referred to our institution between January 2014 and October 2017 and matched the criteria for inclusion in the algorithm, thus triggering a donor search, were eligible for entry into this study. Survival times were calculated on an intent-totreat basis from entry into the algorithm unless indicated otherwise. The analysis was performed according to the Declaration of Helsinki and upon approval by the institutional ethics review committee. In total, 21 patients were included. Nineteen patients entered the algorithm at L1 and two patients at L2. Of the 19 patients entering at L1, 11 patients met the eligibility criteria for allogeneic HCT, whereas eight patients did not (6 did not have a 10/10 donor, 1 had comorbidity, 1 refused allogeneic HCT) (Figure 1). These 19 L1 patients (13 males, 6 females) had a median age of 58 years (range, 38-63 years). TP53 lesions were present in 14 patients and del(11q) without TP53 lesions in five. All patients were on their first pathway inhibitor, which was ibrutinib in 13 patients, idelalisib in four, and venetoclax in two. Prior to pathway inhibitor treatment, patients had received a median of three (range, 1-8) treatment lines. There were no significant difference in baseline characteristics between the 11 patients meeting transplant eligibility criteria and the eight patients who did not. At a median follow-up of 48 months (range, 21-57 months) after algorithm entry, disease progression had occurred in L1 in seven patients (Figure 1). In the absence