7058 Background: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin lymphoma. For decades, cytarabine-based regimens have been the cornerstone of MCL treatment, offering substantial efficacy but often at the cost of significant toxicity. More recently, non-cytarabine-based regimens, such as bendamustine combined with rituximab, have emerged as a promising alternative, demonstrating comparable efficacy with more favorable toxicity profile. This study aims to compare the clinical efficacy of cytarabine-based (Ara-C) versus non-cytarabine-based (non-Ara-C) regimens. Methods: We conducted a retrospective cohort study for patients diagnosed with MCL between 2010 and 2023 at Allegheny Health Network and Markey Cancer Center. Data pertaining to demographics, MIPIc, Lugano stage and treatments at induction were collected. Patients were divided into two groups based on whether they received cytarabine based regimen during induction (Ara-c) or not (non-Ara-c). Primary outcomes were overall survival (OS) measured from the time of diagnosis to the time of last follow up or death, and relapse free survival (RFS), calculated from the time of diagnosis to the time of relapse, persistent or progressive disease at the last day of follow up. Sensitivity analysis, with censoring on the time of autologous bone marrow transplant (ASCT) was done. RFS and OS were compared between the two groups after weighted propensity score matching (PSM). Results: We identified 223 patients diagnosed with MCL. The median age was 67.7 (IQ 60-74.5), Majority of patients were males (71%). The median MIPIc score was 8.1(IQR 7-9.5). 72 patients (31%) were in the Ara-c group while 151 patients (69%) were in the non-Ara-c group. The median follow-up of 5.6 years (0.95CI 4.91-6.32). Median OS was 13 years (0.95 CI 7.24-NR) and median RFS was 4.1 years (0.95 CI 3-4.96) for the entire cohort. Baseline comparison between the two groups is shown in table_1. After PSM, Median RFS for Ara-c group was 4.8 (IQR=1.8-16.2) yrs VS 3.6 (IQR=1.52-7) yrs for non-Ara-c group (P value 0.03). However, after censoring on ASCT, median RFS for Ara-c group was 4.7 (IQR 1.5-16.2) yrs VS 3.3 (IQR 1.5-6.9) yrs (P value 0.16). Median OS for Ara-c group was 16.2 yrs (IQR=4.3-16.2) vs 12.95 yrs (IQR=3.7-17.8) for non-Ara-c group (P value 0.5), which was the same after censoring on ASCT. Conclusions: In our cohort, cytarabine use in induction chemotherapy for MCL was associated with longer RFS and OS but it did not reach statistical significance. Larger scale studies are warranted to confirm these results. Of note, older and less fit patients received less cytarabine. Cytarabine Other P value Age 64 (57-69) 69 (63-77) 0.013 Eastern Cooperative group 0,1 96% 84% 0.05 MIPIc 7.56 (6.89-7.92) 8.28 (6.97-9.66) 0.01 Consolidation with ASCT 42% 13% <0.01

Introduction: Limited data compare total body irradiation (TBI)-based versus chemotherapy-based myeloablative conditioning (MAC) in haploidentical transplants. An EBMT study showed similar major transplant outcomes, but TBI was linked to a higher risk of severe chronic GVHD in multivariable analysis. Methods: We combined two CIBMTR datasets: one comparing myeloablative vs. reduced-intensity T-cell–replete haploidentical transplantation (PMID: 31582392), and the other evaluating optimal donor sources for African American patients with hematologic malignancies (PMID: 32649981). Both datasets included patients underwent haploidentical transplantation between 2008 and 2016. We excluded patients who received nonmyeloablative or reduced-intensity conditioning, and those received umbilical cord grafts. All patients received post-transplant cyclophosphamide, a calcineurin inhibitor, and mycophenolate mofetil for GVHD prophylaxis. Patients received ≥12 Gy TBI were classified as TBI-based MAC; all others receiving MAC were classified as chemotherapy-based (CT)-MAC. We calculated the cumulative incidence (CI) of relapse, non-relapse mortality (NRM), and grade II–IV acute GVHD up to 40 months post-transplant. CI of relapse was estimated using death as a competing risk, and CI of NRM was calculated using relapse as a competing risk. CI of acute and chronic GVHD was calculated using death as the competing risk. Both groups were matched on key confounders using inverse probability of treatment weighting (IPTW), including age, sex, KPS (>90 vs. ≤90), disease type (AML vs. ALL), disease risk (low, intermediate, high/very high), disease status at transplant (CR vs. refractory), transplant year (2008–2013 vs. 2013–2016), donor CMV status, HCT-CI (0, 1, 2, ≥3), and graft source (peripheral blood vs. bone marrow). All analyses were performed in R version 4.4.0. Results: A total of 629 patients were included. The median age was 45 years (range 18–70). Of these, 353 (56%) received TBI-based MAC and 276 (44%) received CT-based MAC. A total of 319 patients (52%) had a KPS ≥90, and 329 (52%) were male. Compared to the CT-based group, patients received TBI-based MAC were more likely to receive peripheral blood grafts (76% vs. 58%, P<0.01), have acute lymphoblastic leukemia (43% vs. 13%, P<0.01), and received transplant between 2013–2016 (89% vs. 77%, P<0.01). There were no significant differences between groups in disease risk, KPS, HCT-CI score, or disease status at transplant. Median follow-up was 24.6 months (95% CI, 24.3–25.1) overall, 24.4 months (95% CI, 24.1–25.0) in the TBI group, and 24.7 months (95% CI, 24.3–34.0) in the CT group. The CI of relapse was 38% in the TBI group versus 33% in the CT group (P=0.73). NRM was 19% for TBI versus 24% for CT (P=0.13). The incidence of grade II–IV acute GVHD and chronic GVHD were significantly higher in the TBI group VS CT group (36% vs. 21%, P<0.01 and 34% VS 25%, P value=0.03 respectively). After propensity score matching using IPTW, there was no significant difference in overall survival (OS) or relapse-free survival (RFS) between the TBI and CT groups. Median OS was not reached (NR) for the TBI group (95% CI, 23.3–NR) and 27.8 months for the CT group (95% CI, 17.4–60.0; P=0.15). Median RFS was NR for both groups, with 95% CI of 29.9–NR for TBI and 43.5–NR for CT (P=0.7). Subgroup analyses by disease risk (high/very high) and disease type (AML vs. ALL) also showed no differences in OS or RFS. Similarly, there were no significant differences in GVHD outcomes after matching. Median time to grade II–IV acute GVHD was 33.5 months (95% CI, 15.6–NR) in the TBI group versus 31.5 months (95% CI, 16.4–NR) in the CT group (Weighted P value=0.36). Median time to chronic GVHD was 15.8 months (95% CI, 9.87–NR) in the TBI group versus NR (95% CI, 10.5–NR) in the CT group (Weighted P value=0.95). Conclusion: In this combined CIBMTR analysis of patients undergoing T-cell–replete haploidentical transplantation, there were no significant differences in OS, RFS, or NRM between TBI-based and chemotherapy-based MAC. TBI-based MAC was associated with a higher incidence of grade II–IV acute GVHD and chronic GVHD. The observed increase in acute and chronic GVHD with TBI may be partially driven by a higher use of peripheral blood grafts in this group. Overall, both conditioning strategies appear to offer comparable long-term outcomes, with graft source and GVHD risk requiring careful consideration in regimen selection.

Introduction: Limited studies have evaluated the efficacy of different induction regimens in patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and data on outcomes by molecular subgroups remain sparse. In this single-institution retrospective study, we examined treatment responses and survival outcomes of AML-MRC patients, with analyses stratified by molecular and induction regimens. Methods: We retrospectively reviewed adult AML patients (≥18 years) diagnosed and treated at the Markey Cancer Center between January 2015 and February 2025. AML-MRC was defined per WHO 2016 classification. Demographic, clinical, laboratory, and pathologic data were abstracted from medical records. Treatment response was assessed using ELN 2022 criteria. Primary endpoints were complete remission (CR) or CR with incomplete hematologic recovery (CRi), relapse-free survival (RFS), and overall survival (OS). RFS and OS were estimated using the Kaplan–Meier method. Molecular mutations were categorized as follows: Epigenetic regulators: ASXL1, BCOR, EZH2, DNMT3A, TET2; RNA signaling pathway: CALR, CBL, FLT3, KRAS, NRAS, KIT, PTPN11, JAK; RNA splicing factors: SF3B1, SRSF2, U2AF1, ZRSF2 and Transcription factors: RUNX1, GATA. Induction therapies were grouped into 4:1- Cytarabine plus anthracycline (7+3) with or without targeted therapy; 2-Hypomethylating agent (HMA) plus venetoclax with or without targeted therapy; 3-Cladribine- or fludarabine-based regimens; 4-Low-dose cytarabine with or without HMA or other targeted therapies. To account for baseline differences in age and performance status, we performed propensity score matching (IPTW) by age, gender, and performance status. Outcomes were censored at the time of allogeneic stem cell transplant. Statistical analysis was performed using R version 4.4.0. Results: A total of 193 AML-MRC patients were included. The median age was 65 years (range 22–86), and 56% were male. Molecular analysis showed mutations in epigenetic pathways in 45% (n=71), IDH1/2 in 10% (n=15), TP53 in 19% (n=30), RNA signaling in 14% (n=22), RNA splicing in 6.4% (n=10), and transcription factors in 4.4% (n=7). One patient each had NPM1 and CEBPA mutations. Treatment induction included: HMA-Ven (n=91, 47%), cytarabine + anthracyclines (n=57, 30%), Vyxeos (n=25, 13%), CLIA-Ven (n=5, 3%), and low-dose cytarabine–based therapy (n=6, 3%). Patients receiving CLIA-Ven or 7+3 were younger (median 43 and 58 years, respectively) compared with HMA-Ven (69 years), Vyxeos (66 years), or low-dose cytarabine (78 years; p<0.01). Overall, 122 patients (60%) achieved CR/CRi after first- or second-line induction, while 40% were refractory after two lines. At median follow-up of 34 months (95% CI: 23.7–58), 71 patients (37%) relapsed. CR/CRi rates varied by regimen: 100% for CLIA-Ven, 70% for Vyxeos, 67% for cytarabine + anthracyclines, 58% for HMA-Ven, and 17% for low-dose cytarabine (p<0.01). No significant difference in CR rates was seen across molecular categories; notably, both patients with CEBPA and NPM1 mutations achieved CR. Median RFS was 12.2 months (95% CI: 11–18) and OS was 9.4 months (95% CI: 7.4–12.5). Thirty-four patients (18%) underwent allogeneic transplant, achieving improved outcomes: median RFS 18 months (95% CI: 12.4–NR; p=0.04) and OS 21 months (95% CI: 18.6–NR; p<0.01) compared with non-transplanted patients. After IPTW, comparing the three most common regimens (7+3, HMA-Ven and Vyxeos), no significant differences in RFS or OS were observed after censoring for transplant. The mRFS for 7+3, HMA-Ven and Vyxeos: 23 months (95% CI: 11–NA), 12 months (95% CI: 11–18), 8.8 months (95% CI: 6–NR); (p=0.44), respectively.The mOS for 7+3, HMA-Ven and Vyxeos: 8.7 months (95% CI: 6.1–20), 8.1 months (95% CI: 7.3–13), 11.3 months (95% CI: 6.5–NR); (p=0.56), respectively. Conclusion: Epigenetic mutations are highly enriched in AML-MRC. CLIA-Ven achieved the highest CR/CRi rates, followed by Vyxeos, 7+3, and HMA-Ven. However, after adjusting for age, gender, and performance status, no differences were observed in RFS or OS among 7+3, HMA-Ven, or Vyxeos. Allogeneic transplantation was associated with significant improvements in both RFS and OS, underscoring its critical role in the management of AML-MRC.

Abstract Background Median overall survival (mOS) in patients ≥60 years with newly diagnosed acute myeloid leukemia (AML) remains <10%, driven by adverse cytogenetics, high-risk mutations, and limited tolerance to intensive therapy. High-intensity induction chemotherapy-such as anthracycline with cytarabine (7+3), Vyxeos, or cladribine/idarubicin/cytarabine with venetoclax (CLIA-Ven)-remains the standard of care for medically fit patients. Hypomethylating agents with venetoclax (HMA+Ven) is preferred for older/unfit adults and increasingly used in younger patients ineligible for intensive therapy. However, real-world comparisons across age groups remain limited. We evaluated molecular features, treatment patterns, and outcomes in a large, single-institution cohort. Methods We performed retrospective analysis of 459 newly diagnosed AML patients (treated January 2015-February 2025), comparing those ≥60 vs. <60 years. EMR data included demographics, cytogenetics (karyotype, FISH), mutations, 30-gene NGS panel, treatment, and outcomes. Induction regimens were grouped as CLIA-Ven, 7+3 ± FLT3 inhibitors, Vyxeos, HMA-Ven, low-dose cytarabine (LDAC) ± Ven, or other. Mutations were classified by function: epigenetic (ASXL1, BCOR, EZH2, DNMT3A, TET2), RNA splicing (SF4B1, U2AF1, SRSF2, ZRSR2), transcription factor (RUNX1, GATA), signaling (CEBPA, CALR, CBL, FLT3, KRAS, NRAS, KIT, PTPN11, JAK), and IDH, STAG2, and NPM1. Statistical analysis was performed using R 4.4.0. Patients were censored at allogeneic stem cell transplant (SCT) for survival analysis. Primary endpoints were complete remission with or without count recovery (CR/CRi) and mOS, with subgroup analyses by age, cytogenetic risk, and SCT status. Results Of 459 patients, 237 (52%) were ≥60 and 222 (48%) were <60 years. Gender distribution was similar (58% vs. 54% male, p=0.4). Older patients more often had epigenetic (57% vs. 37%), TP53 (10% vs. 5%), and RNA splicing mutations (7.3% vs. 3.3%), with fewer signaling mutations (8% vs. 35%) (p<0.01 for all). Transcription factor mutations were similar (3.4% vs. 3.3%). ELN 2022 classification revealed more poor-risk disease in older patients (31% vs. 21%, p<0.01). Overall CR/CRi after first/second induction was significantly lower in older patients (60% vs. 84%, p<0.01). HMA+Ven was used more in the older cohort (54% vs. 15%, p<0.01). Relapsed/refractory disease was also higher in older patients (33.3% vs. 20%, p<0.01). SCT was performed less in older patients (13% vs. 37%, p<0.01). Among patients ≥60 years, CR/CRi rates varied by regimen: CLIA-Ven (100%, n=3), 7+3 (84%), Vyxeos (76%), HMA+Ven (62%), and LDAC (14%) (p<0.01). The mOS was 15.4 months (mo) (95% CI: 13.3–30) in patients <60 years vs. 8 mo (95% CI: 7.2–12) in those ≥60 years (p<0.01). Median relapse-free survival (mRFS) was also superior at 35 mo (95% CI: 22–NR) in older patients vs. 20 mo (95% CI: 14–32) in younger (p=0.001). Amid patients ≥60 years, the longest OS was with CLIA-Ven (mOS 14.3 mo, 95% CI: 6.3–NR), followed by HMA+Ven (11.3 mo, 95% CI: 7.7–14), Vyxeos (11.3 mo, 95% CI: 6.2–NR), 7+3 ± targeted therapy (8.7 mo, 95% CI: 6.3–22), and LDAC ± Ven (6.4 mo, 95% CI: 1.7–NR) (p <0.01). After propensity score matching (PSM) using inverse probability of treatment weighting (IPTW) to balance mutation profile and ELN risk, older patients had inferior mOS (8.8 mo, 95% CI: 7.3–NR) vs. 14.7 mo (95% CI: 11.8–25) in younger (p<0.01). The mRFS was 22 mo for younger (95% CI: 13–NR) vs. 10 mo for older patients (95% CI: 7.7–14). However, after adjusting for treatment regimen, OS and RFS differences by age were no longer significant: mOS 12.4 (95% CI: 10–19) vs. 11 mo (95% CI: 7.3–14), p=0.49; mRFS 14.6 (95% CI: 11–25) vs. 13.4 mo (95% CI: 9–25), p=0.27. Conclusion Older adults with AML often present with poor-risk genetics, receive low-intensity therapy, and have inferior outcomes. However, after adjusting for treatment intensity, age-related differences in OS and RFS diminished, suggesting outcomes are driven more by treatment selection and frailty than age alone. Subsets of older patients, especially those treated with CLIA-Ven or HMA+Ven, achieved meaningful responses, supporting individualized, risk-adapted therapy. SCT remains underutilized in older patients, where selected individuals can achieve durable remission. These findings confirm the prognostic impact of genomics and support risk-stratified therapy to improve outcomes in older adults with AML.

e18562 Background: Disease progression is the leading cause of allogeneic stem cell transplantation (allo-SCT) failure in acute myeloid leukemia (AML). Outcomes are influenced by patient, disease, donor, and transplant-related factors. This study utilized machine learning to identify risk factors for disease progression after allo-SCT in AML. Methods: We retrospectively reviewed adults (>18 years) who underwent their first allo-SCT for AML between January 2017 and June 2024. Patients without pretransplant molecular mutation or post-transplant chimerism data were excluded. Elastic Net machine learning was applied to identify risk factors for disease progression. Results: A total of 64 patients (median age: 55 years, range: 23–72; 54.7% male) were included. Fifteen patients (23%) had adverse-risk disease per ELN2022. The majority were in complete remission (CR) at the time of transplant (97%), with 44 (69%) in first complete remission (CR1). Donor types included HLA-matched unrelated (n=50), HLA-identical sibling (n=7), haploidentical (n=3), and HLA-mismatched unrelated (n=3). 34 (53.1%) patients received reduced-intensity conditioning (RIC), and 18 (28%) received post-transplant cyclophosphamide (PTCy) as part of GVHD prophylaxis. The median follow-up for surviving patients was 21.9 months (range: 1.0–101.2). Full donor chimerism at day 100 was achieved by 54 patients. During follow-up, 16 (25%) patients experienced disease progression, with a median time to progression of 21.9 months. Elastic Net analysis identified mixed chimerism at day 100 (HR 9.7), absence of PTCy (HR 1.5), HCT-CI >2 (HR 1.35), secondary AML (HR 2.04), DNMT3A mutation (HR 1.23), FLT3-ITD mutation (HR 1.47), and adverse ELN2022 risk (HR 2.47) as significant predictors of disease progression. Favorable factors included NPM1 mutation (HR 0.79) and the development of low-grade acute GVHD (HR 0.86). Conclusions: AI models improve risk stratification for disease progression after allo-SCT by analyzing multiple variables simultaneously. This approach enables personalized post-transplant strategies to enhance outcomes. Further validation in larger cohorts is warranted. Patient characteristics. Variable N (%age) Median Age At Transplant 55 (23-72) Gender Male 36 (56.2%) Female 28 (43.8%) Donor Type MUD 48 (79.9%) MRD 6 (10.1%) Haplo 3 (5%) MMRD 3 (5%) CMV Data (R vs D) Positive vs Positive, n (%) 21 (32.8%) Negative vs Negative, n (%) 12 (18.8%) Positive vs Negative, n (%) 30 (46.9%) Negative vs Positive, n (%) 1 (1.6%) Donor-recipient gender match Match 46 (76.6%) Mismatch 14 (23.4%) Full Chimerism at D100 54 (90%) Conditioning regimen MAC 30 (46.9%) RIC/Non-MAC 34 (53.1%) GVHD Prophylaxis PTCy 18 (30%) Others 42 (70%)

Abstract Background Relapsed or refractory acute myeloid leukemia (R/R AML) carries poor outcomes, with standard salvage regimens yielding complete remission (CR) rates of only 20–30% and median overall survival (OS) of less than 6 months. Venetoclax combined with cladribine, idarubicin, and cytarabine (CLIA-ven) has shown promising efficacy in newly diagnosed AML. Its role in the salvage setting, however, remains uncertain. Methods We retrospectively reviewed adult patients (≥18 years) with R/R AML treated with CLIA-ven at our institution between June 2023 and July 2025. AML was diagnosed per 2016 World Health Organization criteria, and risk stratification was performed according to European LeukemiaNet 2022. Measurable residual disease (MRD) was assessed by multicolor flow cytometry (sensitivity 0.02%). Outcomes included CR/CR with incomplete hematologic recovery (CRi), MRD negativity, relapse-free survival (RFS), and overall survival (OS). RFS and OS were estimated using the Kaplan–Meier method. Induction consisted of cladribine 5 mg/m² IV days 1–5, idarubicin 10 mg/m² days 1–3, cytarabine 1500 mg/m² days 1–5, and venetoclax 400 mg PO daily days 2-8. Following induction, up to five 28-day consolidation cycles (cladribine 5 mg/m² days 1–3, idarubicin 8 mg/m² days 1–2, cytarabine 1000 mg/m² days 1–3, and venetoclax 400 mg PO days 2–8) could be offered. All cycles were inpatient with TLS monitoring; venetoclax ramp-up was omitted. Venetoclax doses were reduced to 200 mg with fluconazole and 70 mg with posaconazole prophylaxis. Results Sixteen patients were treated. The median age was 46 years (range: 24–68); 75% were male. At diagnosis, 44% had adverse-risk, 44% intermediate-risk, and 12% favorable-risk AML. Fifty-six percent had de novo AML; the remainder had secondary AML (MDS 19%, MPN 19%, CMML 6%). Approximately 39% had extramedullary disease. Complex cytogenetics were present in 19%. Most commonly mutated genes included NRAS (25%), FLT3 (15%), WT1 (19%), JAK2 (19%), U2AF1 (13%), DNMT3A (13%), and TP53 (13%). Median prior therapy lines were 2 (range 1–5). 50% had prior venetoclax, 94% prior anthracycline, and 19% prior allogeneic transplant. Three patients had primary refractory disease. CLIA-ven was started a median of 7.7 months (range: 2.2 to 99 months) following the initial diagnosis with AML. The CR/CRi rate was 76%, with 38% achieving CR. Among 11 evaluable patients, 7 (64%) achieved MRD negativity. Six patients underwent CLIA-ven consolidation with a median of 2 cycles of consolidation received (range: 1-5). Three patients underwent allogeneic transplant and remain in remission. No treatment-related deaths occurred, and toxicities were manageable. At a median follow-up of 8.8 months (95% CI: 2.3–NR), 9 patients relapsed. The median RFS was 4.3 months (95% CI: 3.3–NR) and median OS 12.3 months (95% CI: 5.1–NR). The 6month OS was 62%. Conclusion CLIA-ven appears to be an effective and well-tolerated salvage regimen in a heavily pretreated cohort with relapsed/refractory AML, achieving high rates of remission with a substantial proportion achieving MRD negativity. While only a minority of patients proceeded to allogeneic transplant in this series, the regimen may provide an important option for achieving remission and facilitating transplant candidacy.

6557 Background: Allogeneic transplantation is the only potential cure for patients with myelodysplastic syndrome (MDS). It is unclear whether cytoreduction with hypomethylating agents (HMAs) prior to reduced intensity conditioning (RIC) transplantation in patients with 5–10% bone marrow blasts impact transplant outcomes. Methods: We utilized the publicly available CIBMTR dataset from the publication “Alternative Donor Transplantation for Myelodysplastic Syndrome: Haploidentical Relative and Matched Unrelated Donor” to evaluate the differences in relapse-free survival (RFS), transplant-related mortality (TRM), and overall survival (OS) between recipients and non-recipients of pretransplant HMAs among MDS patients undergoing RIC Allo-SCT. The two groups were matched on confounding variables, including donor type, blast percentage at diagnosis and at the time of transplant, age, sex, race, IPSS-R score, CMV donor status, conditioning regimen, time to transplant, and year of diagnosis. Matching was performed using the inverse probability of treatment weights (IPTW) method. Weighted Kaplan-Meier curves were used to evaluate OS, RFS, and TRM between the two groups. Additionally, a doubly robust Cox regression model was constructed to estimate hazard ratios (HR) for the effect of pretransplant HMA use on OS and RFS. Results: A total of 603 patients were included in our analysis. The median age was 67.1 years (IQR 63.1–70.5), and the median follow-up was 21.8 months (0.95 CI 13.1–NR). In the weighted data. The 0.75 quantile for RFS was 7.57 months (0.95 CI 6-NR months) for the non-HMA group versus 5.79 months (0.95 CI 4.14–6 months) for the HMA group (P = 0.027). Similarly, the 0.75 quantile for OS was 9.54 months (0.95 CI 7.96–NR) for the non-HMA group versus 5.79 months (0.95 CI 4.38–7.43 months) for the HMA group (P = 0.005). There was no significant difference in the incidence of acute or chronic GVHD or TRM. In doubly robust Cox regression model. Pretransplant HMA was associated with worse RFS and OS with a HR of 0.66 (0.95 CI 0.44-0.97, P value =0.035) and HR of 0.60 (0.95 CI 0.42-0.90, P value< 0.01) respectively. Conclusions: Pretransplant use of HMA in MDS patients with less than 10% bone marrow blasts is associated with worse RFS and OS following allogeneic SCT with RIC. Notably, this detrimental impact is most pronounced in patients with less than 5% blasts, raising critical questions about the role of pretransplant HMA in this low-risk subgroup and emphasizing the need for refined treatment strategies. Doubly robust (weighted) Cox-regression model on RFS. Variable Estimate Lower .95 CI Upper .95 CI P-Value No-Hypomethylating agents before Transplant (Reference=HMA pretransplant) 0.66 0.44 0.97 0.035 Sex (Reference=Male) 1.27 0.89 1.80 0.186 MUD VS Haploidentical 0.92 0.42 2.02 0.84 Poor cytogenetics (Reference=very good and good) 3.9 2.66 5.82 <0.01

IntroductionChimeric antigen receptor T (CAR-T) cell therapy has become widely used in patients with relapsed and refractory B-cell lymphomas and considered the standard of care in such patients. The success of CAR-T cell therapy depends on the number and fitness of the autologous T-cells used during the manufacturing phase. Patients who received bendamustine prior to CAR-T cell therapy may experience higher incidence of failure of CAR-T given its known lymphotoxic effects and thus toxic effects on circulating T-cells. Our study explores bendamustine effect on CAR-T cell therapy success.MethodsWe conducted a single-center retrospective analysis using patients with relapsed and refractory aggressive B-cell lymphoma who were treated with CAR-T cell therapy between August 2018 and December 2022. Demographic, clinical, laboratory, and pathologic data were obtained from clinical records. Frequency and incidence were compared using univariate logistic regression. Kaplan-Meier method and Cox model were used to compare overall survival (OS) and progression-free survival (PFS) analysis. PFS and OS were calculated from time of infusion.ResultsWe identified 46 patients with relapsed/refractory large B cell lymphoma for analysis. The average age of patients was 63, of which 29 (63%) were male and 17 (34%) were female. Most of the patients (82%) had ECOG 0-1 and 42 (91%) patients had at least 2 prior lines of therapy. As for bendamustine, 94% of patients received more than 2 cycles while 6% of patients received 2 or less cycles. Bendamustine exposure was further categorized into less than 1 year before CART (27% of patients) and more than one year before CART (73% of patients). The average follow up was comparable between groups (11 months vs 13 months). At 1 year, the PFS was 73% in patients not exposed to Bendamustine compared to 46% in patients exposed to Bendamustine (HR: 1.91; p=0.1). There was a trend towards a worse overall survival in the patients who received bendamustine (HR 1.49, p=0.37), however this was not statistically significant. Patients who received bendamustine had a 75% frequency of relapse vs 60% in the non-bendamustine arm (HR 2, p=0.31). There was no observed difference in incidence of cytokine release syndrome or Immune effector cell-associated neurotoxicity syndrome. Once subdivided further into patients who received bendamustine less than one year prior to CART therapy vs more than one year prior to CART therapy, there was no observed difference in the two groups with regards to OS, PFS, or frequency of relapse.ConclusionsBendamustine's lymphotoxic properties seem detrimental to CART cells. Our study suggests that patients who have been exposed to bendamustine (regardless of time to CART) had a worse progression free survival. Our study also suggests that there may be a trend toward an overall survival difference however more patients are necessary to validate this finding.

Introduction Chimeric antigen receptor (CAR)–T cell therapy is associated with cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). These immune-related toxicities can be severe or life-threatening. It is difficult to predict which patients will have these reactions. Some studies have tried to assess whether inflammatory biomarkers such as ferritin and interleukin-6 correlate to toxicity. Our study aims to assess whether cortisol as an independent biomarker has some predictive effect on incidence of CRS and ICANS. Methods We conducted a single-center retrospective analysis using patients with relapsed and refractory aggressive B-cell lymphoma who were treated with CART cell therapy between August 2018 and December 2022. Demographic, clinical, laboratory, and pathologic data were obtained from clinical records. CRS and ICANS were assessed daily using the CTCAE v 5. Fisher's exact tests were used for the test of associations among categorical variables. Pearson's Chi-square tests were used for analyzing incidence rate ratios of CRS and ICANS. Kaplan-Meier and log-rank tests were used to compare overall survival (OS) and progression-free survival (PFS) between different treatment exposures. PFS and OS were calculated from time of infusion. Results We identified 46 patients with relapsed/refractory large B cell lymphoma for analysis, of which 29 (63%) were male and 17 (34%) were female. The average age of patients was 63 (SD ±11) and most (82%) patients had ECOG 0-1. CART agents used were Tisagenleucel (31%), Axicabtagene ciloleucel (52%), and Lisocabtagene maraleucel (17%). The average follow up was 17 months. Most patients developed either a grade 1 or grade 2 CRS (33% and 37%, respectively), and only 3% of patients developed grade 3 or above. As for neurotoxicity, most patients (59%) did not develop ICANS, however of those who did, 19% were grade 3 and beyond. The average AM cortisol level prior to CART infusion was 12 ug/dL (AM cortisol reference range: 6-25 ug/dL). Patients with a baseline cortisol <12 ug/dL had a similar overall survival to those with a baseline cortisol >12 ug/dL (HR 0.82, p=0.7) with no difference in incidence of CRS (HR 0.63, p=0.27) and ICANS (HR 1.77, p=0.46). Patients with a CRP> 8 mg/L at baseline had a higher incidence of CRS (HR=2.46, p=0.04) than patients with CRP <8 mg/L. There was also a trend towards a worse overall survival in those with CRP >8 as compared to those <8 (HR 3.22, p=0.06). Lastly, there was no significant correlation observed between CRP and cortisol. Conclusion Inflammatory markers are monitored in patients who receive CART. Previous data suggest that higher baseline CRP and Ferritin levels predict for CRS and ICANS. Our data suggest that baseline cortisol level does not appear to have a similar effect. Additional studies analyzing trends in these inflammatory markers may provide more insight.

Introduction: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare neoplasm that usually affects older adults with a median age of 66. ALL or AML induction regimens have been used to treat BPCN for many years. Tagraxofusp received FDA approval in December 2018 after showing a 75% complete response rate in the upfront setting and 67% in the relapsed setting based on a noncomparative phase II clinical trial. There is a paucity of real-world data on its efficacy. Methods: We identified the patients with BPDCN using the Surveillance Epidemiology and Results Database (SEER) database between 2000 and 2021. We calculated each year's mortality incidence rate (MIR) by summing the number of deaths for patients diagnosed with BPDCN each year over their total follow-up time in months. Data was grouped by age categories, sex, race, and year of diagnosis. To accurately estimate the efficacy of Tagraxofusp on overall survival, we chose 1000 randomly selected acute myeloid leukemia patients from the SEER database and used them as a comparator group. AML data was grouped, and MIR was calculated similarly to the BPDCN dataset. Both data were combined. We used an interrupted time series model using the Non-linear mixed effect model package in R to evaluate the difference in MIR before and after 2019 (2015-2019 and from 2019-2021) using AML patients as a comparator group. The year 2019 was used because it is the year when Tagraxofusp was available in the market. . Survival probabilities were estimated using the Kaplan-Meier method, with differences assessed by the log-rank test. Results: We identified 638 patients with BPDCN in the SEER database between 2000-2021. Only 87 patients (13.6%) were diagnosed after 2019. The median age of the participants was 60 years old (IQR 35-73). 84% were males, and most were white (85%). The median survival was 25 months (0.95 CI 21-31 months). Median overall survival (OS) significantly decreased with age, with a median OS of 11 months (0.95 CI 9-14) and 24 months (0.95 CI 19-45) for those above the age of 70 and between 60-70 years old compared to 63 months (0.95 CI 18-113) for those between 50-60 years-old (P<0.01). There was no difference in median OS between White and non-White ethnic groups (25 months (0.95 CI 21-32) vs 19 months (0.95 CI 15-45), P= 0.79). Females tend to have higher median OS compared to males (37 months (0.95 CI 25-47) vs 23 months (095 CI 19-27) with a P value of 0.078. There was no difference in OS among patients with BPDCN diagnosed between 2010-2015,2015-2018 and 2019-2021, with a median OS of 18 months (0.95 CI 13-46), 23 months (0.95 CI 16-38), and 16 months (0.95 CI 9-24) (P=0.33). Similarly, there was no difference in OS across the same year groups among AML sample patients with a median OS of 7 months (0.95 CI 6-11), eight months (0.95 CI 6-10), and eight months (0.95 CI 6-12) (P=0.63). In the interrupted time series model that considers the randomly selected 1000 AML patients as a comparator group. patients who had BPDCN after 2019 had numerically lower absolute values of MIR compared to AML patients (-10.2%). However, the P value was not significant. Also, it was not significant for the trend post-Tagraxofusp approval (0.018, P=0.8). Conclusion In this interrupted time series analysis, we found that Tagraxofusp use was associated with a drop in MIR. However, this was not statistically significant. This could be due to limited size or due to non-superiority to other regimens used in the pre-Tagraxofusp era. Further research is needed to determine the efficacy of Tagraxofusp in the real-world.

Introduction: The is no clear consensus on the appropriate timing of allogeneic bone marrow transplant (Allo-SCT) for patients with Myelodysplastic syndrome (MDS). A study by Cutler et al showed improvement in life expectancy with early Allo-SCT for patients with intermediate-2 and high-risk IPSS scores but without clear guidance on the appropriate timing for Allo-SCT. Herein, we looked at the risk of disease recurrence (RFS) and overall survival (OS) among MDS patients who had Allo-SCT within 6 months Group (A), 6-12 months (Group B), and more than 12 months (Group C) from the time of diagnosis among different IPSS-R categories. Methods: We used the publicly available dataset from CIBMTR associated with the following publication, “Alternative donor transplantation for myelodysplastic syndromes: haploidentical relative and matched unrelated donors” by Mehta et, to evaluate the difference in outcomes among patients who had Allo-SCT early after diagnosis (within six months) (Group A) VS 6-12 months (Group B) and more than 12 months (Group C). The three groups were matched on age categories (40-50,50-60 and more than 60), sex, donor type (MUD VS Haploidentical), type of MDS (therapy-related VS non-therapy-related), Karnofscky score, HCT-CI score, conditioning regimen, race, cytogenetics, IPSS-R score, CMV status (both donor and recipient) and year of diagnosis using inverse probability of treatment weights. The difference in RFS and OS was calculated using a doubly robust Cox model. All statistical analysis was done using R. Results: A total of 604 patients were identified in the dataset. 66% were males. 383 (64%) were diagnosed from 2015-2017 and 220 (36%) from 2012-2014. 72.2% under 50 years old had an Allo-SCT within a year from diagnosis compared to 55.5% older than 60 (P-value= 0.039). 169 (28%), 198 (33%) and 236 (39%) patients had Allo-SCT within 6 months (Group A), 6-12 months (Group B) and more than 12 months (Group C). Appropriate balance was achieved after matching on the previously mentioned variables. An effective sample size of 108 (64%) in Group A, 155 (79%) in Group B and 158 (67%) in Group C were matched. In the matched dataset, 33.3% VS 33.2% VS 33.4% of Group A, B and C were older than 60 (P value=1). One-third of each group in the matched dataset had Allo-SCT from MUD (P value=1). One third of Group A, B and C after matching received HMA compared to 22% VS 27% VS 27% respectively before matching. The median time to relapse was not reached in each of the groups with a P value of 0.21. However, among high and very high IPSS-R group, the median time to relapse was 10 months for Group C (0.95 CI 5.59-NR) compared to NR (0.95 CI 7.6-NR) for Group B and NR for group A (0.95 CI 10.4-NR) with a P-value of 0.097. In the double-robust Cox model. Patients with high and very high IPSS scores and transplanted more than one year from the diagnosis (Group C) had a 2.75 risk of recurrence compared to those transplanted in less than one year (Group A and B) (P-value of 0.046 (HR=2.75, 0.95 CI 1.014-7.43)). Patients with intermediate and good risk groups had a similar risk of relapse regardless of the timing of Allo-SCT. This was translated into higher mortality among patients with high IPSS scores who were transplanted more than 12 months from the time of diagnosis (HR=2.66, 0.95 CI 1.01-6.98). Hypomethylating agents (HMA) before the transplant were associated with a 45% higher risk of relapse (P-value<0.01). However, there was no interaction between the HMA and the Groups with median time to recurrence NR for Group C , 24 months and 12 months for Groups B and A respectively with a P value=0.16. Conclusion: Among high and very high-risk MDS patients who have Allo-SCT with RIC. Delaying the transplant to more than a year from the diagnosis is associated with a higher risk of recurrence. This could be due to selection of resistant clone from multiple prior treatment.

BACKGROUND:The molecular architecture of acute myeloid leukemia (AML) is heterogeneous. Obesity has been identified as a risk factor for the development of AML. There remains a scarcity of data elucidating the specific genetic profile of AML in obese patients. METHODS:We conducted a review of adult patients treated at our institution for newly diagnosed AML from January 1, 2017, to January 1, 2023. Obesity is defined as BMI > 30 kg/m2. Demographic, clinical, laboratory, and pathologic data were collected retrospectively. The primary outcome of interest was the molecular features of obese compared to non-obese AML patients. The secondary outcome was overall survival (OS). Inverse probability of treatment weights (IPTW) used to balance both groups on several confounding variables. RESULTS:A total of 185 patients were included in the analysis. 90 (49%) were obese. Compared with non-obese patients, obese patients were younger and more likely to be females (55 vs. 63, p = 0.04, 55% vs. 38%, p value, p = 0.02, respectively). After matching on age, gender, and ethnicity, obese patients exhibit lower rates of total number of gene mutations (median 2.7 vs. 3.2, p = 0.05), significantly lower rates of mutations in transcriptional factor genes (15.7% vs. 33.2%, p = 0.01), and near-significant in spliceosome genes (12% vs. 22.3%, p = 0.08), and higher rates of NPM1 mutation (23.3% vs. 12.6%, p = 0.08). Median OS was not significantly different in the matched cohort. CONCLUSIONS:The molecular features of obese AML patients significantly differ from non-obese counterparts. These findings suggest distinct underlying mechanisms in leukemogenesis in obese patients.

Introduction: Several studies have shown the superiority of cytarabine when added to anthracyclines and cyclophosphamide-based regimens, such as the Nordic regimen, in achieving remission in patients with Mantle cell lymphoma (MCL). However, no randomized control trial proved the benefit of adding Cytarabine to Bendamustine. In this single-institution study, we retrospectively evaluated overall and relapse-free survival in both cohorts. Methods: We retrospectively collected demographic, clinical, and outcome data on patients diagnosed with MCL at the University of Kentucky from 2009 to 2021. Data was collected in RedCaps at the University of Kentucky. We divided our cohort into three groups: Group A received a Cytarabine induction regimen without Bendamustine, Group B received a Bendamustine regimen without Cytarabine, and Group C received neither Cytarabine nor Bendamustine in their first induction. The chi-square test and t-test are used for unadjusted binary and continuous variables, respectively, and the Gehan-Breslow test was used to compare the survival curves. We used inverse probability of treatment weights (IPTW) to match the three groups on the following confounding variables: age, sex, Ki-67, the presence of blastoid or pleomorphic variants, estimated GFR (<45, 45-60, >60), body mass index and TP 53 mutation and Mantle Cell Lymphoma international prognostic score (MIPI) using group C as the reference group. Overall survival (OS) and relapse-free survival (RFS) were compared in the weighted data. Results: We identified 92 patients with MCL in our institution from 2009-2023. The median age was 65.8 (IQR=58.8-71.2). The median MIPI score was 5 (IQR=3-8). 63% were males. Most patients (72%) had stage IV at diagnosis. We identified only seven patients with TP53 mutation; most patients (67%) had normal karyotypes. Thirty-eight patients (41%) received cytarabine as part of their induction regimen (Group A). In comparison, 30 (33%) received a Bendamustine-based regimen without cytarabine (Group B), and 24 patients (26%) received other upfront induction regimens (Group C). The median overall (OS) and relapse-free survival (RFS) for the total cohort was 87 months (0.95 CI 56.8-NR) and 85.5 months (0.95 CI 47-NR) respectively in the unadjusted analysis. Group B was older than Group A (70.5 VS 58.9, Pvalue=0.003). The median MIPI score was six for group B versus four for group A (P value<0.01). The median LDH was 308 in group B and 212 in group A (P value=0.18). 50% of Group A (19 patients) had consolidation with Autologous Stem Cell Transplant (ASCT), while only four patients (13%) of Group B had ASCT. Group A tends to have better OS compared to group B (Median OS NR VS 85 months (P value=0.068)) and median RFS of 104 months VS 51 months (P value of 0.049). Also, they were more likely to achieve CR following induction (38% VS 32%, P value=0.6). Appropriate balance was achieved after matching using IPTW. After matching, the mean age was 71 VS 66 VS 65 in Groups A, B, and C respectively. The mean MIPI was 5.7 VS 6.4 VS 5.9 for Groups A, B, and C, respectively. The median OS for group A was NR (0.95 CI 59.6-NR) and 85 months for group B (0.95 CI 44.2-86.56) with a P value of 0.23. Also, the Median RFS was NR in group B (0.95 CI 44.2 -NR) VS NR for group A (0.95 CI 103-NR) with a P value of 0.163. Conclusion: MCL patients who received Bendamustine without Cytarabine in their first induction have OS and RFS comparable to those treated with Cytarabine-based regimens. A larger study is needed to validate our findings and evaluate whether adding Cytarabine to Bendamustine could improve the outcomes among MCL patients.

"CLO24-086: The Effect of TBI-Based Conditioning Regimen on Recurrence and Transplant-Related Mortality Among Patients With Mantle Cell Lymphoma Who Received Autologous Bone Marrow Transplant" published on 05 Apr 2024 by National Comprehensive Cancer Network.

Aims: Acute myeloid leukemia (AML) represents 80% of the cases of acute leukemia in adults, and obesity has been found to be associated with an increased risk of developing AML. However, there is no data regarding the presenting clinical, cytogenetic, and molecular features of AML in obese patients. Methods: We retrospectively evaluated adult patients with newly diagnosed AML treated at our institution from January 2017 to January 2021. Patients with acute promyelocytic leukemia (APL), as well as those with secondary and therapy-related AML, were excluded. Patients with an available genetic profile obtained from next-generation sequencing (NGS) were included. Demographic, clinical, laboratory, and pathologic data were obtained from clinical records. Obesity was defined as a BMI > 30. A 97-gene panel was used for NGS analysis. Cytogenetic and molecular data, along with responses to treatments, were classified according to the European LeukemiaNet2022 (ELN) guidelines. Statistical analysis included the Mann-Whitney test for continuous variables, Fisher's exact test for categorical variables, and Kaplan-Meier survival curves for overall survival and relapse-free survival. Results: We identified 185 newly diagnosed de novo AML cases for analysis, of which 90 (49%) were classified as obese (Table). The median age at diagnosis was 60 (range, 20-91), and 84 (46%) were male. The most commonly mutated gene was DNMT3A (n=42, 23%), followed by IDH2 (n=36, 19%), and FLT3-ITD (n=33, 18%). Approximately 47% (n=79) of patients had adverse risk based on ELN2022 risk classification by genetics, and 40% (n=23) had adverse cytogenetic risk. The majority of patients were treated with intermediate or high-dose cytarabine-based regimens (n=128, 73%), and the rest with HMA plus venetoclax (n=29, 16%) and HMA alone (n=19, 11%). The median follow-up was 22 months (range, 1-71 months), and the estimated median overall survival (OS) was 21 months for the entire patient population. Within the follow-up, approximately half of the patients (n=90, 47%) died. Compared to non-obese patients, obese patients were younger at presentation (55 vs. 63, p=0.04) and consisted of more females (n=48 (55%) vs. n=36 (38%), p=0.02). Obese patients had a significantly lower number of mutations (p=0.01), particularly in spliceosome (n=12 (13%) vs. n=29 (31%), p=0.007) and transcription factor genes (n=17 (19%) vs. n=31 (33%), p=0.04). Obese patients were noted to have more NPM1 mutations (n=21 (23) vs. n=11 (11%), p=0.05) (Figure). According to ELN2022, obese patients were classified more favorably than non-obese patients (p=0.002). Patients were treated with similar regimens across the study populations, and obese patients' estimated OS was significantly longer than that of non-obese patients (44 vs. 13 months, p=0.02). The median follow-up was comparable in obese vs. non-obese patients, and within the follow-up, fewer obese patients died (n=36 (40%) vs. n=54 (57%), p=0.02). Conclusions: AML in obese patients appears to have distinct clinical and genetic characteristics compared to non-obese patients. This suggests that different underlying mechanisms may contribute to leukemogenesis in these two patient groups. Future studies should focus on elucidating the specific molecular pathways and mechanisms through which obesity influences AML development, which could pave the way for novel treatment approaches tailored to obese patients.

Immunohistochemical staining of Bcl2, cMyc, Ki67, and CD3 in DLBCL subtype representative tumor samples (same as Supplementary Figure S1). Note that AD091967 is positive for both Bcl2 and cMyc. Cases AB189717, AD550620, and AE575816 show high proliferation rates (80%, 80%, 60%) Scale bars represent 50 µm.

Hematoxylin and eosin (H&E), CD20, CD10, Bcl6, and MUM1 stainings in 4 non-GCB and 2 GCB cases representative for each DLBCL subtype. Bars, 50 µm.

Introduction The Appalachian region's cancer mortality rate is 10% higher than the national rate. Central Appalachia, which is predominantly in Kentucky, exceeds the national average by 35%. Appalachian Kentucky has higher mortality rates for prostate, lung, cervical, and head and neck cancers compared to non-Appalachian Kentucky. This can be attributed to health care disparities, environmental factors, and unique genomic characteristics of the tumors seen in the Appalachian population. Based on this, we hypothesized that patients with acute myeloid leukemia (AML) in Appalachian Kentucky would have worse outcomes and higher mutational burden compared to patients in non-Appalachian Kentucky. To test this hypothesis, we compared overall survival (OS) and frequency of molecular mutations between patients from Appalachian (ApK) and Non-Appalachian Kentucky (Non-ApK). Methods A single-center retrospective analysis was done utilizing the Kentucky Cancer Registry (KCR) to identify patients with De Novo AML from January 2015 to January 2021. Patients with available cytogenetic and somatic mutations profile from next-generation sequencing (NGS) were included. Demographic, clinical, laboratory, and pathologic data were obtained from clinical records. Statistical analysis was done using the Mann-Whitney U test for continuous variables and proportions were compared using Chi-square test. The Kaplan-Meier curves were used for overall survival. Results A total of 225 patients with de novo AML were identified. The median age at diagnosis was 61 (range, 21-86). The population was fairly distributed among males (52%) and females (48%). Approximately 56% (n=127) of patients were from ApK and 46% (n=98) were from non-ApK. Of the patients from ApK, approximately 22% (n=29) had favorable risk AML per the ELN 2022 classification, while 24% (n=30) had intermediate and 54% (n=68) had poor risk AML. This was not statistically different from the Non-ApK patients where 22% (n=22) had favorable, 21% (n=21) had intermediate, and 56% (n=55) of patients had poor risk AML (Table 1). The median number of clinically significant mutations were also similar between the two groups (p value = 0.47). The most commonly occurring somatic mutations were NPM1, DNMT3A and FLT3-ITD, which occurred at similar frequencies between the ApK and non-ApK cohorts. There was no difference in the median overall survival between the two cohorts (17 versus 22 months, p =0.47; 90% CI). Median OS and 1-year OS for the entire cohort were 21 months and 47.1%, respectively. Conclusions This study demonstrated that the outcomes of de novo AML is similar for patients from Appalachian versus Non-Appalachian Kentucky when treated at an Academic Medical Center. There were no statistically significant differences between ELN 2022 risk classification and mutational abnormalities tested between these two groups. This suggests that the biology in de novo AML is similar in both ApK and non-ApK patients.

Secondary malignancies including leukemia are an increasing concern in patients with prior primary malignancies treated with alkylating agents or topoisomerase II inhibitors. These can also be referred to as therapy-related leukemia. Therapy-related leukemia most commonly results in myelodysplastic syndrome or acute myeloid leukemia. The alkylating agent can cause chromosomal aberrations typically manifest as deletions in chromosome 11 or loss of part of complete loss of chromosomes 5 and 7. Conversely, acute lymphoblastic leukemia (ALL) has been described following maintenance therapy with immunomodulatory (IMiD) drugs pomalidomide, thalidomide, and lenalidomide. We present a case of a 71-year-old man with a history of multiple myeloma (MM) maintained on lenalidomide after stem cell transplant who presented with treatment-associated ALL. At time of leukemic presentation, chromosomal analysis showed a near-triploid clone consistent with masked double low hyplodiploidy which is associated with a poor prognosis. The patient had a deletion of the long arm of chromosome 5 which has been described in prior case reports with ALL secondary to lenalidomide therapy. There are explicit mechanisms in the literature, which have been attributed to development of ALL after exposure to thalidomide or lenalidomide. At time of submission, there are 20 cases described in the literature linking ALL to IMiD drugs. We describe a case and review the mechanisms of lenalidomide-associated ALL.

Acute leukemia in the elderly population remains a challenge with poor outcomes despite considering patient's age and performance status.