Allogeneic stem cell transplant for T-prolymphocytic leukemia: A single center analysis

Abstract

Abstract Introduction: T-prolymphocytic leukemia (T-PLL) is a rare subtype of mature T-cell leukemia that is associated with poor outcomes, including after allogeneic stem cell transplant (allo-SCT) in patients in first complete remission (CR1). Standard frontline treatment includes intravenous alemtuzumab followed by allo-SCT in CR1 among eligible patients. While initial remission rates are over 80%, the risk of relapse following allo-SCT remains over 40%, with reported 3-year progression-free survival (PFS) rates of approximately 25%. Methods: We retrospectively analyzed patients with T-PLL who underwent allo-SCT at our institution between 2003-2024. Overall survival (OS) and PFS were analyzed using the Kaplan-Meier method. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were analyzed in a competing risks framework. Prognostic factors for the outcomes of interest were evaluated in univariate analysis. Multivariate analysis could not be completed due to sample size constraints. Results: Forty-nine patients were included in this analysis, 61% of whom were male. At diagnosis, the median WBC count was 40x109/L (range 2.7-470). Median age at allo-SCT was 59 years (range, 36-78). Median HCT-CI score at transplant was 2 (range, 0-8). All patients received alemtuzumab as upfront induction. At time of allo-SCT, 29 patients (59%) were in CR1/CR2. The median calendar year that patients underwent allo-SCT was 2018. The conditioning regimen was fludarabine/melphalan-based in 28 patients (57%) and busulfan-based in 15 patients (31%). Graft-versus-host disease (GvHD) prophylaxis included ATG/tacrolimus/methotrexate until 2017, after which the majority received PTCy/tacrolimus +/- MMF. The donor was a fully matched sibling in 16 (33%), matched unrelated (MUD) in 26 (53%) and mismatched (including haploidentical donors) in 9 (18%). The source of stem cells was peripheral blood in 82% (N=40). In-vivo T cell depletion with ATG or alemtuzumab was used in 12 patients (24%) undergoing mismatched transplants, the majority of whom were treated prior to 2018. All patients engrafted, with a median donor chimerism at day +30 of 59% and mixed donor chimerism in 39% of patients. With a median follow-up of 36 months (range, 3.7-111) in the entire cohort, the 3-year probability of OS was 32% (range, 19-46), PFS was 30% (range, 17-43), and NRM was 37% (range, 26-54). CIR was 31% (20-48). Improved outcomes were observed in patients treated during or after 2018 (N=26) compared to those transplanted before 2018 (N=23), which was likely due to better patient selection. Among those who underwent allo-SCT in 2018 or later, 20 (77%) were in CR1/CR2 at time of transplant, compared to only 39% (N=9) of patients who underwent allo-SCT prior to 2018. The OS, PFS, NRM, and progression/relapse rates at 3 years were 48% vs 17% (HR 0.5, p=0.043), 41% vs 17% (HR 0.5, p=0.05), 35% vs 39% (HR 0.9, p=0.8), and 23% vs 39% (HR 0.4, p=0.1) in those transplanted in 2018 or later vs prior to 2018, respectively. Among the patients who underwent allo-SCT prior to 2018, only 2 were long term survivors (107 and 111 months), whereas the median survival in patients transplanted in 2018 or later was 36 months (range, 37-88). 3 yr-OS for patients transplanted in CR1/CR2 was 54% (95% CI 34-70) versus 5% (95% CI 4-22) for those not in CR at the time of transplant. The most frequent causes of deaths in the entire cohort were relapse and progression of the underlying disease (N=16; 47%), infection (N=8, 23%), and GvHD (N=5, 15%). On univariate analysis, not being in CR at time of transplant (p=0.02), transplant before year 2018 (p=0.04), and in-vivo T cell depletion (p=0.02) predicted for worse OS. Due to the small number of patients in the cohort and heterogeneity of the patient and transplant characteristics over time, we were unable to assess predictors of outcomes through multivariate analyses. Conclusions: Overall,long-term outcomes of patients with T-PLL remain suboptimal. However, in recent years an improvement in OS, PFS, and rates of disease progression/relapse have been noted. This may be due to better patient selection (CR vs not). Other factors like improvement in supportive care measures that reduce post-transplant complications may have also contributed.