Allogeneic stem cell transplant results in t-cell prolymphocytic leukemia (T-PLL): A collaborative multi-center study cohort

Abstract Introduction: T-PLL is a rare, aggressive leukemia with poor prognosis and limited therapies. Previous studies on T-PLL patients receiving an allogeneic stem cell transplant (alloSCT) are limited by small numbers with limited data on disease and transplant characteristics. Further, recent data from our large national cohort of patients demonstrated significant survival difference between TCL1A+ and TCL1A- T-PLL, and CD8+ T-PLL vs CD8- T-PLL. In this large multi-center series, utilizing comprehensive disease subtype and alloSCT clinical data, we evaluated prognostic and survival therapeutic outcomes in T-PLL patients that had an alloSCT with a particular focus on T-PLL disease subtypes. Methods: We retrospectively evaluated 572 diagnosed with T-PLL at 21 academic cancer centers throughout the USA between 2000-2023, of which we performed a further evaluation on the169 that proceeded with alloSCT. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier methods and Cox proportional hazard models. Results: Among n=169 alloSCT recipients with T-PLL, the median follow-up time was 20.9 months post-alloSCT (range: 0.2-182.9), the median age at transplant was 59 years (range: 35-77) and 52% were male. In evaluated patients (n=109), TCL1A was positive by cytogenetics or FISH in 69%. As our recent analysis demonstrated significant differences in survival among specific subtypes of T-PLL, we evaluated outcomes in patients with CD4+CD8- T-PLL (n=90, 53%), CD4-CD8+ (n=17, 10%) T-PLL, and CD4+CD8+ T-PLL (n=52, 31%). 53% (87/164) had known nodal involvement at diagnosis identified by PET or CT scan and 45% (43/96) of known patients had minimal residual disease (MRD) at the time of transplant [defined as <5% T-PLL in marrow by flow, or +cytogenetics (e.g. TCL1A)] prior to alloSCT. At the time of alloSCT, 136 (80%) patients were in CR and 23 (14%) patients were in PR. Forty-nine (30%) had a myeloablative (MAC)conditioning regimen and 114 (70%) had a reduced intensity chemotherapy (RIC) conditioning regimen. Eighty (49%) patients had TBI as part of their regimen. The most common regimens were fludarabine (flu)/melphalan based regimens (n=44; 26.0%), flu/cyclophosphamide (cy) based regimens (n=33; 19.5%), flu/busulfan based regimens (n=22; 13.0%), flu/total body irradiation (TBI) (n=8; 4.7%), and cy/TBI (n=4; 2.4%). Across the whole cohort, the median OS and PFS post-alloSCT was 32.6 months (95% CI: 21.0-41.9) and 20.8 months (95% CI: 14.4-30.5) months while the 1-year cumulative incidences (CI) of NRM and relapse were 17% and 20%, respectively. The incidences of grade II-IV acute GVHD and cGVHD were 19% and 23%. There was no difference between patients with myeloablative conditioning (MAC) (n=49, 29%) when compared to patients that received reduced intensity conditioning (RIC) (n=114, 67%) in OS (33.1 vs 29.2; p=0.68) and PFS (20.2 vs 20.8; p=0.97). Patients that were MRD+ (n=31) had worse OS (22.2 vs 48.6; p=0.1) and PFS (14.1 vs 32.5; p=0.04) and higher rates of relapse (1-year relapse 20% vs 8%; p=0.08) than patients that were MRD- (n=50). PFS was improved in those who received alloSCT though only trended towards significance due to low numbers (HR 0.76, p=0.09). In subtype analysis, TCL1A+ T-PLL had significantly worse outcomes compared to TCL1A negative T-PLL. TCL1A+ disease had significantly worse OS (21.6 vs 63.1; p=0.01) and PFS (12.4 vs 50.7; p=0.01) compared to TCL1A-. Additionally, in TCL1A+ disease CI of NRM (24% vs 3%; p=0.02) and relapse (25% vs 12%; p=0.86) was higher vs TCL1A- PLL. CD4+CD8-, CD4-CD8+, and CD4+CD8+ disease had no difference in survival via either OS (28.0 vs 34.4 vs 21.0; p=0.17) or PFS (29.4 vs 23.5 vs 13.6; p=0.09) as well as no difference 1-year CI of NRM ( 11.6 vs 23.5 vs 26.2; p=0.35) and relapse (18.5 vs 23.5 vs 20.0; p=0.67).Conclusions: AlloSCT significantly improved outcomes for patients with T-PLL compared to those who did not proceed to alloSCT and remains he only curative therapy for those with T-PLL. OS, PFS, and CI relapse were significantly worse for patients with TCL1A+ subtype of T-PLL, or those with MRD positivity or PR prior to alloSCT. Novel strategies to decrease relapse such as post-alloSCT maintenance therapy to improve outcomes are urgently needed in these patients.