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Abstract Background The Alzheimer's disease (AD) Braak staging is a key framework for classifying tau pathology progression in AD based on histopathological post‐mortem brain examinations. However, adapting it to PET imaging can be challenging due to differences in tracer uptake patterns and binding properties, which affect sensitivity, specificity, and regional staging. This study compares Braak staging across four tau PET tracers: Flortaucipir, MK6240, PI2620, and RO948. Methods We assessed 90 participants across the AD spectrum (46 CU, 31 MCI, 13 dementia; mean age 66.1 ± 7.8) using Aβ PET and four tau PET tracers: (Flortaucipir, MK6240, PI2620, and RO948). Braak positivity was defined based on Aβ− CU individuals (mean +2.5 SD, SUVR). To evaluate systematic bias and agreement between tracers, we computed pairwise differences at corresponding Braak stage estimates and applied the Bland‐Altman method to assess mean bias and limits of agreement. Additionally, Tau PET Braak region trajectories were modeled as functions of Aβ burden (Centiloid scale) using the Lowess method. Results Braak stage trajectories as a function of Aβ differ depending on the tracer and the sequential order of abnormality is highly variable. For instance, while for MK6240, RO948 and PI2620, Braak I is the first region to became abnormal, for Flortaucipir the earliest region to became abnormal is Braak IV (Figure 1). This variable pattern of abnormality impacts in the concordance of Braak staging between tracers with the highest Braak staging agreement resulting in concordance levels of approximately 70%. The highest levels of agreement between tracers usually happen at Braak 0 or Braak IV‐V, with intermediate stages showing very low concordance (Figure 2). The Bland‐Altman analysis identified wide limits of agreement, suggesting high variability and high tracer‐specific differences (Figure 3). On the other hand, it also identified that mean differences between tracers were small, indicating minimal systematic bias. Conclusion These preliminary findings reveal discrepancies in Braak staging when comparing Flortaucipir, MK6240, PI2620 and RO948. These findings suggest that while the tracers provide comparable stages on average, they may not be fully interchangeable in individual cases.

Abstract Background Tau‐PET tracers have been used to monitor the progression of Alzheimer’s disease (AD). However, different tracers present distinct patterns of binding throughout the brain, challenging the harmonization of their findings. Leveraging the HEAD Study, the largest head‐to‐head study of tau‐PET tracers, we recently developed the Uniτ scale, which cross‐sectionally harmonizes Flortaucipir and MK6240 onto a universal tau‐PET measurement. Here, we provide a preliminary evaluation of the Uniτ scale’s longitudinal performance in HEAD and two independent cohorts. Methods We assessed 422 individuals across the AD spectrum with longitudinal tau‐PET from three cohorts: HEAD [13 cognitively unimpaired (CU), 9 cognitively impaired (CI) individuals, scanned head‐to‐head with Flortaucipir and MK6240], ADNI [74 CU, 208 CI, tracer: Flortaucipir], and TRIAD [72 CU, 46 CI, tracer: MK6240]. Standardized uptake ratios (SUVRs) were harmonized to Uniτ using the Uniτ Ecosystem ( unitau.app ). Braak I‐II and the Meta‐Temporal regions were used as regions of interest. Annual tau‐PET uptake change was calculated, and the effect size was defined as the mean annual change divided by its standard deviation. Results In HEAD, annual change in tau‐PET uptake in Braak I‐II across CU and CI was only detectable in MK6240 (Figure 1A). However, both tracers detected significant annual changes in the Meta‐Temporal ROI for CI (Figure 1B). In both ADNI (Flortaucipir) and TRIAD (MK6240), changes in tau‐PET uptake in Braak I‐II regions were not significant (Figures 2‐3A). However, across all cohorts, the Meta‐Temporal ROI consistently showed detectable annual tau‐PET increases—most pronounced among CI—leading to larger effect sizes than in Braak I‐II (Figures 1‐3B). The Uniτ harmonization did not fundamentally alter the pattern of the findings. However, in ADNI (Flortaucipir), Uniτ yielded a slightly higher effect size than SUVR in CU for both Braak I‐II and Meta‐Temporal regions. Conclusion In this large longitudinal sample, our findings confirm that Flortaucipir and MK6240 can detect tau PET changes over time likely associated with the progression of tau tangle pathology. While MK6240 appears to show greater progression in CU, both tracers progress similarly in CI. Our data also suggested that Uniτ harmonized tau PET measurements maintain the longitudinal characteristics of each tau PET tracer for use in clinical trials.

The treatment landscape for soft tissue sarcomas (STS) is evolving constantly. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for STS specific to surgical management and systemic therapy recommendations for various subtypes.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cervical Cancer provide diagnostic workup, staging, and various treatment recommendations for cervical cancer based on clinical and surgical staging. This selection from the NCCN Guidelines for cervical cancer specifically focuses on diagnosis and workup, principles of staging and surgery, and primary treatment recommendations for early-stage and advanced disease and provides a detailed overview of systemic therapy recommendations for cervical cancer.

PURPOSE Previous studies suggest that SPOP mutations result in increased sensitivity to androgen receptor pathway inhibitors (ARPIs) but are limited by lack of granular data. We hypothesize that SPOP mutations are associated with improved outcomes across the spectrum of advanced prostate cancer (PC). METHODS Using the real-world clinicogenomic Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort database, we analyzed outcomes based on SPOP mutation status. The primary end point was overall survival (OS) from the diagnosis of metastatic disease. Secondary end points included real-world progression-free survival (PFS) and PSA90 response. RESULTS Among 2,097 patients with metastatic PC, 5.5% (N = 115) had SPOP -mutated tumors. Compared with SPOP wild-type, patients with SPOP mutations were older at diagnosis (median 65 v 63 years; P = .001) and had higher (≥8) Gleason sum (68% v 54%; P = .02), higher incidence of lung metastasis (17% v 6%; P = .001), and increased frequency of intraductal features (13% v 5%; P < .001). SPOP mutations were associated with improved PSA90 response with first ARPI exposure in the castrate-resistant setting (60% v 40.6%; OR, 2.20 [95% CI, 1.15 to 4.19]; P = .02) but not in the castrate-sensitive setting (78.9% v 71.5%; OR, 1.49 [95% CI, 0.66 to 3.37]; P = .43). Median PFS with first ARPI did not differ in SPOP- mutated versus wild-type group in both the castrate-sensitive (24.2 v 19.2 months; hazard ratio [HR], 0.80 [95% CI, 0.49 to 1.32]; P = .39) and castrate-resistant settings (15.0 v 12.4 months; HR, 0.81 [95% CI, 0.58 to 1.12]; P = .20). In multivariable analysis, SPOP mutations were associated with improved OS (HR, 0.65, P = .02). CONCLUSION SPOP mutations were associated with longer OS despite the presence of aggressive clinical features. The distinct clinical and molecular features of SPOP -mutated PC support its consideration as a unique molecular subtype with prognostic implications.

Abstract Introduction: CTCLs are rare, heterogeneous non-Hodgkin lymphomas (NHL) with significant regional variability in treatment patterns. Prospective studies characterizing CTCL management, particularly in racially and ethnically diverse populations, remains limited. The LEO-MER multi-center prospective cohort study (NCT02736357) is designed to address the persistent disparities in outcomes research by enrolling historically underrepresented groups of patients diagnosed with lymphoma across the United States (US). Here, we present a real-world analysis of CTCL patients that reflects US academic practice, evaluating treatment patterns, as well as prognostic factors influencing survival outcomes. Methods: Patients aged ≥18 years with newly diagnosed CTCL were prospectively enrolled in either the University of Iowa/Mayo Clinic MER cohort (2002-2015) or the expanded LEO cohort (2015-2020), which included 8 US academic centers. Standardized protocols were used to abstract clinical, pathologic, treatment, and outcome data from medical records. ANOVA/Kruskal-Wallis and Fisher's/chi-square tests were used to compare patient distribution across demographic and clinical characteristics based on data distribution and sample size. Overall survival (OS) was calculated from diagnosis to death or last follow-up. Survival analyses employed Kaplan-Meier estimation supplemented by Cox proportional hazards modeling. Results: The LEO-MER cohort enrolled 223 CTCL patients (91 MER and 132 LEO). Subtypes included mycosis fungoides (MF, n=155, 69.5%), Sézary syndrome (SS, n=22, 9.9%), primary cutaneous anaplastic large-cell lymphoma (n=17, 7.6%), subcutaneous panniculitis-like T-cell lymphoma (n=11, 4.9%), cutaneous CD4+ small/medium T-cell lymphoproliferative-disorder (n=9, 4%), and other rarer CTCL subtypes (n=9, 4%). Among the MF/SS cohort, median age was 64 years (Range: 18-89 years), 58.2% (n=103) were male and race/ethnicity distribution included White (n=123, 69.5%), Black (n=29; 16.4%) and others/unknown (n=25; 14.1%). Stage distribution included 62.7% with early-stage (ES) MF (IA-IIA, n=111), 37.2% with advanced-stage (AS) MF (IIB-IVB, n=66). To complete diagnostic workup, T-cell receptor (TCR) testing was performed in 52.6% of skin biopsies (n=92) and 62.5% of blood samples (n=110), with clonal detection rates of 75% (69/92) in skin and 51.8% (57/110) in blood. Paired TCR matching between skin and blood samples was performed in 31.6% (n=56) of cases, demonstrating 53.6% (30/56) concordance. Blood flow cytometry data were reported in 80.1% (89/111) and 84.4% (56/66) of ES and AS MF cases, with T-cell population being detected in 7.2% (8/111) and 62.1% (41/66) of ES and AS cases. Nodal biopsies were obtained in 23.4% (n=41) of patients and clonality assessment was reported in 18.6% (33/177) of these cases. The MF/SS cohort's lifetime treatment exposure data (n=160) revealed topical skin-directed therapies alone (n=49, 31.8%) as the most common approach followed by lifetime exposure to topical skin-directed and systemic therapies (n=45, 29.2%) followed by multimodal exposure of topical skin-directed, radiation and systemic treatments (n=30, 19.5%). Only 5.6% of patients were enrolled in a clinical trial. First-line (1L) systemic regimens were predominantly a) immunomodulatory agents (n=47, 29.3%); including oral retinoid (n=20), extracorporeal photopheresis (n=18), interferon (n=9) followed by b) chemotherapy (n=30, 18.7%) and c) targeted therapies (n=17, 10.6%) including Brentuximab Vedotin (n=6), Romidepsin (n=5), Mogamulizumab (n=3), Vorinostat (n=2) and Pralatrexate (n=1). Multivariable analysis predicting 1L systemic treatment initiation demonstrated a significant association with presence of N2/N3 stage (N2/N3 vs N0/N1: Odds Ratio (OR): 5.45) and elevated LDH (OR: 5.30). At median follow-up of 91.1 months (mon), median OS was 122.3 mon (95% confidence interval 67.2-159.2 mon). In subset analyses, Black race (p=0.001) and SS (p=0.0001) were associated with worse OS outcomes. Conclusion: We present initial data from our prospective LEO-MER cohort, a large US-based multicenter consortia. Our findings demonstrate variability in both diagnostic staging and treatment approaches for MF/SS patients. The cohort demonstrated worse outcomes with high-risk disease and Black race/ethnicity. These findings warrant further study on the impact of underlying social determinant factors, given the variability noted in this population.

Abstract Background Nodal peripheral T-cell lymphomas (nPTCLs) are a challenging group of non-Hodgkin lymphomas that frequently recur after or are refractory to first line (1L) treatment. Chemotherapy options in the relapsed or refractory (R/R) setting are limited. The incorporation of non-cytotoxic agents including antibody drug conjugates, immune checkpoint inhibitors, epigenetic modifiers, and phosphatidylinositol 3-kinase inhibitors offers new therapeutic potential and possibly better outcomes. We report on outcomes for patients (pts) with R/R nPTCL enrolled in the multi-center LEO-MER prospective cohort study (NCT02736357) who received second line (2L) therapy. Methods Six hundred and three adult pts with newly diagnosed nPTCL were prospectively enrolled in the University of Iowa/Mayo Clinic MER observational cohort (2002-2015) or the expanded LEO cohort (2015-2020). Secondary overall survival (sOS) was calculated from date of 2L treatment initiation to date of death or last follow-up. Secondary event-free survival (sEFS) was calculated from date of 2Ltreatment initiation to disease progression, initiation of 3rd line therapy, or death from any cause. sEFS and sOS were evaluated using Cox model and Kaplan-Meier estimator. Log-rank test was used to test the significance of difference between groups. Pts with concomitant B-cell lymphomas were excluded from this analysis. Results Thus far, 169 pts with nPTCL initiating 2L therapy were evaluated. Of these, 75 (44.4%) had PTCL-NOS, 63 (37.3%) had angioimmunoblastic T-cell lymphoma (AITL, inclusive of nodal T-follicular helper cell lymphoma), 20 (11.8%) had ALK-negative anaplastic large cell lymphoma (ALCL), and 11 (6.5%) had ALK-positive ALCL. At 2L treatment initiation, the median age was 64 with 86.1% of pts having advanced stage disease. Of the 108 pts with available international prognostic index (IPI) scoring, 46.3% had an IPI of ≥3. Thirty-four (20.1%) pts had received a consolidative autologous stem cell transplant (ASCT) in the 1L. A total of 86 pts (50.1%) had primary refractory disease (partial response, stable or progressive disease as best response to 1L therapy), 45 (26.6%) experienced early relapsing disease within 6 months of 1L therapy, and 38 (22.5%) had relapsed disease &gt;6 months from 1L therapy. After a median follow-up of 7.1 years (yrs), median sOS was 1.52 yrs, and sEFS was 3.2 months (mos). There was no difference in sOS or sEFS regardless of timing of relapse. In keeping with other studies, ALK-positive ALCL pts had the best 5-year OS (70.1%) compared to other subgroups (ALK-negative ALCL 45.0%, AITL 30.4%; PTCL-NOS 21.3%). Lymphoma was the leading cause of death following 2L therapy, with a 2-year cumulative incidence of 49.2%. Eighty pts (47.3%) received only cytotoxic chemotherapy as second line (2L) therapy; ICE (41 (51.3%)) and gemcitabine-containing regimens were most common (14 (17.5%)). Seventy-five pts (44.4%) were treated with non-cytotoxic agents given as monotherapy or in combination with chemotherapy. The most common non-cytotoxic therapies were brentuximab vedotin (33 (44.0%)), romidepsin (17 (22.7%)) and immune checkpoint inhibitors (9 (12.0%)). Fourteen pts (8.3%) underwent palliative interventions involving radiation, steroids, or cyclosporine alone. Intent to proceed to transplant in the 2L was known in 158 pts (101 (63.9%) not intended, 57 (36.1% intended)). Following 2L treatment, 18 (10.7%) pts proceeded to consolidative ASCT and 10 (5.9%) to allogeneic transplant. Only 21 (12.9%) were treated on a clinical trial. Pts who received a non-cytotoxic agent had superior outcomes compared to pts receiving only chemotherapy; the median sOS was 30.4 mos (95% confidence interval [CI] 15.3, 53.52 mos) vs 11.7 mos ((95% CI 7.95,19.58); p=0.04; HR 0.67) and the median sEFS was 4.83 mos (95% CI 3.38, 10.09) vs 2.33 mos ((95% CI 1.71,3.02); p=0.02; HR=0.65). Conclusions We report here one of the largest prospective cohorts in R/R nPTCL. The LEO-MER cohort, despite its association with academic centers, shows poor outcomes regardless of refractory or relapsed disease, frequent inability to proceed to intended consolidative transplant, and low clinical trial participation in 2L, which corroborates findings from other registries (Jain 2025, Stuver 2019). Outcomes improved for pts treated with non-cytotoxic agents. Updated data including additional pts and subgroup analyses will be reported at the meeting.

Abstract Background Previous studies in aggressive B-cell lymphoma demonstrate that patients with shorter diagnosis-to-treatment intervals (DTI) represent those with higher risk disease. This suggests that patients enrolled in clinical trials may carry a selection bias as they often have longer DTI than patients in the general population. This has important implications for clinical research design and the generalizability of clinical trials in aggressive lymphomas. However, the prognostic implications of DTI have not been evaluated in peripheral T-cell lymphomas (PTCL). Therefore, we examined DTI and its association with clinical factors and outcomes in a prospective observational cohort of patients with PTCL from the United States within the LEO (Lymphoma Epidemiology and Outcomes) and MER (University of Iowa and Mayo Clinic Specialized Programs of Research Excellence Molecular Epidemiology Resource). Patients and Methods We evaluated patients enrolled to the MER (2002-2015) and LEO (2015-2020) cohorts with the following forms of PTCL: PTCL-not otherwise specified (PTCL-NOS, n=217), nodal T-follicular helper (TFH) cell lymphoma (nTFHL, n=153), anaplastic large cell lymphoma (ALCL), ALK positive (ALCL, ALK+, n=74), ALCL, ALK negative (ALCL, ALK-, n=95), enteropathy associated T-cell lymphoma (n=18), and monomorphic epitheliotropic intestinal T-cell lymphoma (n=2). Associations of DTI with clinical factors and outcomes were examined using Kaplan Meier and Cox models. Event free survival (EFS) was defined as the time from start of treatment to relapse/progression, start of 2nd line therapy, or death from any cause. Overall survival (OS) was defined as the time from start of treatment until death from any cause. DTI was defined as the number of days between the first diagnostic biopsy and the start of therapy. Patients who were initially observed or had DTI &gt; 100 days were excluded. Results In 559 patients (229 MER and 330 LEO), median age was 60, 34% had IPI&gt;2 and 71% were stage III/IV. 472 (84%) patients initially received anthracycline-based chemotherapy. Median DTI was 23 days (interquartile range (IQR): 12-39) and was similar in MER (21 days, IQR: 11-33) and LEO (25 days, IQR: 14-42). 168 (30%) patients had DTI 0-14 days, 178 (32%) 15-28 days, and 213 (38%) 29-100 days. Overall in the cohort, shorter DTI was associated with a worse 5-year OS (DTI 0-14 days: 43%; DTI 15-28 days: 53%; DTI 29-100 days: 58%, p&lt;0.001) and 5-year EFS (DTI 0-14 days: 31%; DTI 15-28 days: 39%; DTI 29-100 days: 45%, p&lt;0.001). In multivariable analyses, the association of DTI with outcomes remained consistent after adjusting for age and International Prognostic Index (IPI). Shorter DTI was strongly associated with adverse clinical factors, including elevated lactate dehydrogenase levels, poor performance status, B-symptoms, and higher IPI in both cohorts (all P &lt; .003). DTI was not associated with age, sex, or distance from the LEO/MER center (all p&gt;0.3). 6% patients with DTI of 0-14 days received 1L treatment on a clinical trial, compared to 11% with DTI 15-28 days and 13% with DTI 29-100 days, underscoring that patients with lower DTI may be underrepresented in clinical trials. When examining within PTCL subtypes, the association between short DTI (0-14 days) and inferior outcomes was most prominent in PTCL, NOS (OS HR=2.13, 95% CI: 1.52-2.94; EFS HR =1.49, 95% CI: 1.19-1.85). Associations between short DTI and outcomes were weaker in other subtypes: nTFHL (OS HR=1.28, 95% CI: 0.83-2.00; EFS HR =1.22, 95% CI: 0.82-1.81), ALCL, ALK-, (OS HR=1.30, 95% CI: 0.59-2.86; EFS HR =1.32, 95% CI: 0.68-2.56), ALCL, ALK+, (OS HR=1.05, 95% CI: 0.26-4.17; EFS HR =2.12, 95% CI: 0.84-5.26). Conclusion Shorter DTI is associated adverse prognostic clinical factors (LDH, stage, high IPI) and inferior EFS and OS in newly diagnosed PTCL. Patients with DTI ≤ 14 days, which represents approximately 1/3 patients with PTCL, may be underrepresented in clinical trials. Understanding of this selection bias should inform clinical trial design and interpretation. Future studies should consider strategies to minimize barriers to enrollment for patients with low DTI.

Abstract Introduction: Telomere biology disorders (TBDs) are caused by germline pathogenic or likely pathogenic variants in telomere maintenance genes and result in multisystem manifestations, including impaired bone health. Patients with TBDs experience reduced bone mineral density (BMD), avascular necrosis, and increased rates of fragility fractures. However, the underlying mechanisms of these bone complications remain poorly understood, and no TBD-specific treatments for bone health currently exist. Our objective was to characterize the clinical features, management, and outcomes of TBD-related bone health issues, including fractures and reduced BMD. Methods: We conducted a retrospective, multicenter, international cohort study using data from 232 patients with TBDs enrolled across 12 centers participating in the Clinical Care Consortium of Telomere-Associated Ailments. Medical records were reviewed for fracture history and BMD assessments by dual-energy X-ray absorptiometry (DXA). The primary endpoint was fracture incidence; secondary endpoints included BMD assessment and fracture management. Data were stratified by pediatric (≤18 years) and adult (&gt;18 years) age groups. Analyses were based on data availability; specific denominators are provided where applicable. Result: Data were available for 53 (23%) pediatric and 179 (77%) adult patients. TERT mutations were the most frequently identified variants in both groups (28% pediatric, 23% adult). Fractures occurred in 25% (13/53) of pediatric patients and 35% (62/178) of adults. In contrast, fractures are estimated to occur in 10-15% of the general pediatric population. The median age at first fracture was 8.2 years (range 2.5–17) in children and 29.2 years (range 18.3–66.9) in adults. Among those with fracture data (n=20 pediatric, n=22 adult), fragility fractures were more common in adults (57%) versus predominantly traumatic fractures in children (61%). Multiple fractures occurred in 65% of affected pediatric patients and 45% of affected adults. Fracture management also differed: non-surgical treatments were used in 60% of pediatric fractures (n=12/20) versus 36% (n=8/22) of adult fractures; surgical interventions were more common in adults (36%). The inheritance pattern (autosomal dominant versus recessive or X-linked) was not associated with fracture risk but the subset of patients with CTC1 mutations were associated with increased fracture risk (n=5 of 124 patients with fracture history, 4% vs n=2 of 247 patients with no fracture history, 0.8%; p=0.04). We also assessed whether vascular manifestations were associated with fracture risk comparing patients with and without fractures. Pulmonary arteriovenous malformations (AVMs) were significantly more common in patients with fractures (17%, 7/42) versus those without (5.4%, 6/112; p=0.04). No significant differences were found in rates of retinal vasculopathy or hemorrhage (13% vs 7.2%, p=0.23) or gastrointestinal bleeding (22% vs 16%, p=0.35). DXA data were available for 171 patients (22 pediatric, 149 adult). The median age at first DXA was 11.4 years (range 4–17.7) for children and 58.2 years (range 20.8–79.4) for adults. Among pediatric patients, the median lumbar spine Z-score was –1.2 (IQR –3.0 to –0.2, n=18), with 39% (7/18) showing a Z-score &lt; –2. Among adults, the median femoral neck T-score was –1.1 (IQR –1.7 to –0.5, n=118), with 21% (29/138) demonstrating T-scores &lt; –2, indicating low BMD. Conclusions: Fractures and reduced BMD are common in both pediatric and adult patients with TBDs, with a substantial burden of early-onset and recurrent fractures. Our findings underscore the importance of early bone health screening and surveillance in TBDs and suggest a possible link between vascular abnormalities and skeletal fragility in this population that requires further study.

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 &lt;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.