Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation for T-Cell Prolymphocytic Leukemia – a Study on Behalf of the Chronic Malignancies Working Party of the EBMT

Introduction T-cell prolymphocytic leukemia is a rare subtype of mature T-cell lymphoma, associated with poor outcomes. The standard approach is to bring eligible patients to allogeneic hematopoietic cell transplantation (allo-HCT) in the first line. The most effective available treatment for achieving this point in remission is alemtuzumab. Autologous hematopoietic cell transplantation is also an option but with no demonstrable curative potential (Drozd-Sokolowska, 2024). Unfortunately, even allo-HCT is followed by at least 40% risk of relapse, which does not include long-term analysis. Here we report, for the first time, long-term outcomes with follow-up exceeding 10 years.

Methods: Patients aged ≥18 years old with a T-PLL diagnosis who underwent first allo-HCT between 1995 and 2012, included in two studies previously reported by CMWP (Wiktor-Jedrzejczak, 2012; Wiktor-Jedrzejczak, 2019) were selected for the current analysis. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier methods. Cumulative incidence of relapse (RI) and non-relapse mortality (NRM) were analysed together in a competing risks framework. Prognostic factors for the outcomes of interest were evaluated in univariate analyses.

Results Seventy-seven patients were included, 70% males. Median age at allo-HCT was 53.6 years (IQR, 47.6-59.6). KPS at allo-HCT was ≤80 in 29.7 %. Regarding CMV serostatus, the donor was positive in 46.2% cases; 26.9 % of cases were negative for CMV both in the donor and the recipient. Among the 46 patients (60%) with available information on pre-allo-HCT treatment, 67.4 % patients received solely 1 line of therapy, including 58.7% who received alemtuzumab (41.3% monotherapy). Alemtuzumab was given mostly in the first line of treatment (78.2%). At time of allo-HCT, 80.5% patients were in remission, either partial or complete.

Median calendar year of allo-HCT was 2006 (IQR 2004-2008). Conditioning was myeloablative in 51.4% patients. TBI was administered to 44.7% patients. The donor was an identical sibling in 45.5% cases. Source of stem cells was peripheral blood in 85.7%. T-cell depletion was used in 56.1% patients; ATG in 53% of them. Primary graft failure was experienced by 1% (95% CI 0-4%) and the cumulative incidence of secondary graft failure within 12 months was 3% (95% CI 0-6%).

With a median follow-up of 12.5 (95% CI, 6.8 to 14.4; IQR 6.0 to 14.4) years; the 6-year probability of OS was 29% (95% CI, 18-39%), PFS 20% (95% CI, 10-29%), NRM 38% (95% CI, 27-49%). Overall, the cumulative incidence of relapse was 22% (95% CI 13-31%) at 1-year, 36% (95% CI 25-46%) at 3-years, 42% (95% CI 31-54%) at 6-years and 49% (95% CI 37-61%) at 10-years. For patients who proceeded to allo-HCT directly after the first-line alemtuzumab, the respective 6-year outcomes amounted at 43% (24-62%) for OS, 24% (7-40%) for PFS, 53% (34-72%) for RI and 23% (7-39%) for NRM, non-significantly different from patients who had more than 1 pre-treatment line or non-alemtuzumab first line. 76.6% patients succumbed during the follow-up period. The most frequent causes of deaths were relapse/ progression (44.2 %), infection (23.1 %), and GvHD (15.4 %). Factors predictive for OS were calendar year of allo-HCT (<2005 vs. ≥2005), status of T-PLL at allo-HCT, with patients transplanted in CR having superior outcomes (6-yr OS 48 vs. 18%; log-rank p=0.03). Status of T-PLL did also impact on PFS (6-yr PFS 33 vs. 12% for CR versus other; log-rank p=0.02), while calendar year of allo-HCT (6-yr 29 vs 59%; Gray’s test p=0.01) and age of the donor (6-yr 23 vs 51%; Gray’s test p=0.04) on NRM. Relapse incidence was influenced solely by TBI implementation in conditioning, with patients receiving TBI having a significantly lower RI (6-yr RI 27 vs. 55%; Gray’s test p=0.03).

Conclusions Long-term outcomes of patients with T-PLL remain dismal, nevertheless a small proportion of patients can potentially be cured. Both NRM, with high rate of infections and relapse incidence lead to treatment failure. Infectious complication rate can potentially be lowered with appropriate preventive/ therapeutic measures. This pattern and rate of relapse post allo-HCT, appears to be markedly higher than in most other mature T disorders, and remains unexplained to this day. The deleterious impact of alemtuzumab, strongly suspected, remains unproven. Strategies to counter the significant relapse rates remain an urgent unmet clinical need.