Hogan, William J.

Key Points The MAGIC algorithm probability, computed from 2 serum biomarkers, predicts mortality in all GVHD grades after 4 weeks of treatment. Dynamic changes in the MAGIC algorithm probability occur within all biomarker risk groups and can guide therapy.

Summary Tumour lysis syndrome (TLS) is a significant complication of haematologic malignancies and their management. The syndrome consists of laboratory abnormalities either alone (laboratory TLS) or with clinical sequelae including renal failure, seizures, and arrhythmias (clinical TLS). Clinical TLS is a predictor for worse overall morbidity and mortality in cancer patients, but can be prevented. Thus, accurate prognostication is critical to appropriate management of patients at risk for TLS, and incorporates both disease factors (tumour type and burden) and patient factors (baseline renal insufficiency or hyperuricaemia). Strategies to prevent TLS include hydration and allopurinol in low‐ and intermediate‐risk patients and rasburicase in high‐risk patients.

Abstract Background: Patients with hematological malignancies are at an increased risk for developing both primary and recurrent Clostridium difficile Infection (RCDI) along with complications such as toxic mega colon and treatment failure likely due to underlying immunosuppression and frequent use of broad spectrum antibiotics that lead to altered gut microbiome. Fecal Microbiota Transplantation (FMT) is an effective treatment for RCDI (Brandt et. al; 2012). However, experience in patients with hematologic malignancies is sparse and most clinical trials exclude these patients due to potential complications. We report the largest case series to date from a single institution evaluating the safety and efficacy of FMT for RCDI in patients with hematologic malignancies. Methods: After IRB approval, a database of 452 RCDI patients treated with FMT between August 2012 and June 2016 was reviewed to identify those with an underlying hematologic malignancy. Data regarding demographics, hematologic disease, C. difficile history, treatments, and outcomes were retrospectively abstracted from the electronic medical record. Results: Sixteen patients (median age 74 years; male 50%) with known hematologic malignancies underwent FMT during the study period. The underlying diagnoses are outlined in Table 1. Five patients had received hematopoietic cell transplantation (3 allogeneic and 2 autologous) prior to FMT. Patients had a median of 4.5 (range 2-9) CDI episodes before FMT, and 4 of them had severe/severe-complicated CDI at some stage. Prior treatments included a median of 3 (range 1-5) standard vancomycin/metronidazole courses, median of 2 (range 0-4) vancomycin taper courses, fidaxomicin in 3 patients, and chronic vancomycin suppression in one patient. Diarrheal symptoms were in remission in all but 3 patients in the week before FMT. FMT was performed via colonoscopy in all patients. At the time of FMT, hematologic malignancies were in complete remission in 9 patients, stable on active treatment in 4, stable off treatment in 2, and relapsed awaiting treatment in 1 patient. Median time from last anti-neoplastic treatment (n = 14) and from last neutropenia (n = 8) to FMT were 10 (range 0-301) and 9.5 (0-68) months, respectively. One patient with hairy cell leukemia was still neutropenic and on prophylactic oral trimethoprim/sulfamethoxazole at the time of FMT. Five patients were on active immunosuppressive medications, including prednisone (n = 2), methotrexate (n = 2), sirolimus (n =1), and cyclosporine (n =1) for related comorbidities at the time of FMT (Table 2). At last follow up (median 12, range 0-32 months), 6 patients had active/relapsed hematological disease, 6 had received additional antineoplastic treatments, and 7 had received additional antibiotics. RCDI developed in two (12%) patients at 8 and 22 months post FMT secondary to exposure to broad spectrum antimicrobials. These patients were successfully treated with a second FMT and with metronidazole, respectively. Severe adverse events included death in one patient that occurred 3 days post FMT due to unexpected cardiac arrest and was deemed unrelated to the procedure. Another patient developed community-acquired pneumonia 15 days post FMT and was treated successfully with oral azithromycin. Minor adverse events within the first two weeks post FMT were noted in 6 (38%) patients (self-limited diarrhea in 3, fecal urgency in 2, abdominal cramps in 2, and constipation in one patient) (Table 3). Only one patient had persistent diarrhea shortly after FMT, with the cause attributed to underlying Crohn's disease. No complications related to the colonoscopy procedure were noted. Conclusion: FMT appears to be a safe and effective therapeutic option for RCDI in patients with hematological malignancies. Considering very few adverse events and particularly no infectious complications in our series, we conclude that immunosuppression should not preclude the use of FMT for treatment of RCDI in this high risk population. These results need prospective validation. Disclosures No relevant conflicts of interest to declare.

Abstract Background : Momelotinib is a JAK1 and JAK2 inhibitor that is currently being evaluated in phase-3 clinical trials for the treatment of myelofibrosis (MF) (NCT01969838, NCT02101268). In a phase-1/2 clinical trial of patients with MF, the drug was shown to improve anemia, reduce spleen size and alleviate symptoms (Leukemia 2013;27:1322). In the current study, we considered 100 consecutive patients from the Mayo Clinic who received momelotinib therapy, in order to identify molecular and cytogenetic predictors of treatment response and survival from the time of study entry. Methods : The study patients constituted part of a phase-1/2 clinical trial (NCT00935987) using momelotinib in MF. Details of the protocol, including inclusion and exclusion criteria were previously published (Leukemia 2013;27:1322). Response was determined by the 2006 response criteria published by the IWG-MRT. Data analysis and interpretation was carried out independent of any influence from the sponsor. Results : 100 patients with MF (median age 66 years; 58% males) were treated at the Mayo Clinic between 11/20/09 and 11/10/10. MF type was primary in 64% of the patients and post-polycythemia vera/essential thrombocythemia in 36%. DIPSS-plus risk distribution was 63% high, 36% intermediate-2 and 1% intermediate-1. Red cell transfusion dependency was documented in 49% and palpable spleen size of >5 cm (median 19 cm) in 92%. All patients were annotated for JAK2/CALR/MPL mutations with respective frequencies of 73%, 16% and 7%. Frequencies for other mutations included 42% for ASXL1 (84 evaluable) and 18% for SRSF2(78 evaluable). All patients were evaluable for karyotype, which was unfavorable in 17%. Previous treatment included other JAK inhibitors in 21 patients, thalidomide/lenalidomide/pomalidomide in 31 and hydroxyurea or other cytoreductive agents in 55. Momelotinib was initiated at 100 mg/day in 3 patients, 150 mg/day in 21, 150 mg twice-daily in 20, 200 mg/day in 3, 300 mg/day in 47 and 400 mg/day in 6. The maximum momelotinib dose was 150 mg/day in 6 patients, 150 mg twice-daily in 20, 300 mg/day in 68 and 400 mg/day in 6. Treatment duration was <6 months in 12 patients, 6-12 months in 22, 12-24 months in 19 and >24 months in 47. Genetic correlates of response to momelotinib : Overall response rate was 57% and included no complete remissions (0%), one (1%) partial remission and 57 (57%) clinical improvements (CI). Response rates for spleen/liver and anemia were 43% (91 evaluable) and 44% (68 evaluable), respectively. Transfusion independency was achieved in 25 (51%) of 49 evaluable cases. Spleen/liver response rate was significantly affected by JAK2/CALR/MPL mutational status (34% vs 73% vs 60%, respectively, and 50% in triple-negative; p=0.04), CALR mutated vs unmutated status (73% vs 37%; p=0.009), and unmutated vs mutated ASXL1 (53% vs 29%; p=0.035). Furthermore, all 8 (100%) patients who were CALR+/ASXL1- responded vs 6 (25%) of 24 CALR-/ASXL1+ vs 3 (50%) of 6 CALR+/ASXL1+ vs 16 (43%) of 37 CALR-/ASXL1- patients (p=0.003). Spleen/liver response rates were not affected by SRSF2 mutations (p=0.93) or karyotype (p=0.41). Anemia response rate was not affected by JAK2/CALR/MPL (p=0.81), ASXL1 (p=0.16), SRSF2 (p=0.12) or CALR/ASXL1 (p=0.42) mutational status or karyotype (p=0.65). The number of informative cases for EZH2, IDH, SF3B1 and U2AF1mutations were not adequate enough to warrant similar analysis. Genetic correlates of survival from time of protocol entry : Median follow-up after the institution of protocol drug therapy was 35 months (range 1-49). During this period, 57 (57%) deaths and 12 (12%) leukemic transformations were documented. On multivariable analysis, shortened survival was predicted by the presence of ASXL1 (p=0.01; HR 2.1, 95% CI 1.2-3.8) or SRSF2 (0.01; HR 2.4, 95% CI 1.2-4.8) mutations and the absence of CALR mutations (p=0.03; HR 3.2, 95% CI 1.1-8.9). Karyotype was significant on univariate (p=0.01) but not in multivariable (p=0.6) analysis that included the aforementioned mutations. The prognostic relevance of each specific mutation was DIPSS-plus independent. Conclusions : We demonstrate significant associations between CALR and ASXL1 mutational status and spleen response to momelotinib therapy in MF. We also show that momelotinib therapy did not overcome the inferior survival associated with the presence of ASXL1 or SRSF2 mutations or the absence of CALR mutations. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Over 10,000 new cases of myelodysplastic syndrome (MDS) are diagnosed in the US annually (MA X, Cancer 2007). Hypomethylating agents (azacitidine and decitabine), immunomodulating drugs (lenalidomide) and erythropoietin stimulating agents (epoetin α and darbepoetin) have been approved for more than a decade for the treatment of MDS. However, changes in overall outcome after the approval of these treatments are unknown. We used the National Cancer Data Base (NCDB), a nationwide oncology registry covering 70% of the US cancer population to answer these questions. Methods: We identified patients with MDS diagnosed from 2004-2013 using ICD-O-3 codes 9980-9983 and 9985-99912. Overall survival (OS) was estimated using the Kaplan-Meier method. We compared OS using the log-rank test according to demographic subgroups (sex, age [<40, 41-65, and ≥65 years], race [White, Black, Native American, Asian/Pacific Islander, and other], and ethnicity) across years of diagnosis (Period 1: 2004-2006, Period 2: 2007-2009, and Period 3: 2010-2013). Results: i) Characteristics: There were 54,953 MDS patients in our study. The median age at diagnosis was 76 years (78.7% older than 65) and 44% were females. White race (88.9%) was the most common, followed by black (7%). Four percent were Hispanics. A third (30.8%) of all patients were treated in academic centers. Three quarters (75.8%) had either Medicaid or Medicare insurance. ii) MDS Subtypes: 5q Syndrome was seen in 2008 cases (3.7%) while the most common subtype was MDS-Unclassifiable (U) (55.6%). Therapy related MDS (t-MDS) was seen in 1125 cases (2%), however coding for t-MDS was discontinued in 2009. Refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD), and refractory anemia with excess blasts were seen in 9%, 7.6%, 6%, and15.6%, respectively. iii) OS: Compared to their counterparts, patients who were male, older, had a diagnosis of RAEB, covered by Medicare insurance, and treated at non-academic centers had the worse OS (all P <0.001). Across Periods 1-3, we did not see improvement in OS among demographic subgroups except for those who were <40 years old (P=0.03). Conclusions: In the past decade, the overall outcome of MDS did not improve despite the advent of new therapies. More than half of the cases were classified as MDS-U reflecting the difficulty of subtyping MDS based on World Health Organization classification. We found disparity in outcomes by demographics and type of treatment facility. This is the largest study of MDS outcome to-date and should help in understanding the gaps and areas that need future research. Figure Figure. Disclosures Al-Kali: Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding.

Abstract Background: Adult relapsed/refractory acute lymphoblastic leukemia/lymphoma (rALL) carries a very poor prognosis with limited options for effective salvage therapy. To date, there has been only a single retrospective report on the use of clofarabine in adult rALL demonstrating CR rate of 31% in this setting (Barba P et al. 2012). Aim: To evaluate the efficacy and toxicity of clofarabine based therapy in a relatively large cohort of adult rALL patients. Method: After IRB approval, a retrospective single institution study of all patients (pts) diagnosed with rALL treated with a clofarabine based regimen at Mayo Clinic between 2000 - 2014 was performed. Categorical variables were analyzed using Pearson's chi-squared test while continuous variables were analyzed using the Wilcoxon / Kruskal-Wallis test with P < 0.05 considered statistically significant. Survival estimates were calculated using Kaplan-Meier method and means were compared using log ranks. Results: Presenting features: We identified a total of 22 pts with a diagnosis of rALL who received clofarabine based therapy. 20 patients were evaluable and 2 were excluded (one received clofarabine as salvage for positive MRD and the other as systemic maintenance with CNS directed therapy for an isolated CNS relapse). Among evaluable pts, median age at time of Clofarabine based chemotherapy was 39 years (range 19-65) and 50% were males. Thirteen had B-ALL while 7 had T-ALL. Median leukocyte count was 6 x109 (0.2-28.7), hemoglobin 9.8 g/dL (7-12.9), platelet 65 x109 (12-493), peripheral blood blast 4% (0-88) and bone marrow blasts 80% (0-95) while five pts had extramedullary disease. Median number of prior regimens was 2 (1-7).. 8 (40%) pts were post allogeneic transplant Treatment and Response: 10 pts (50%) received clofarabine monotherapy, 7(35%) clofarabine and cytarabine, and 3 (15%) had clofarabine, etoposide and cyclophosphamide. Overall response rate (CR/CRi + PR) was 35%. Five (25%) achieved CR/CRi, and 2 achieved PR. Among those who achieved CR, 4 out 5 proceeded to further therapy; 2 to allogeneic stem cell transplant and two additional patients received donor lymphocyte infusion (DLI). One pt with PR also proceeded to allogeneic stem cell transplant. In comparative analysis, there were more males 6 (86%) vs 1(14%) in the responding arm (P = 0.014), otherwise the number of regimens prior to clofarabine, type of clofarabine regimen, transplant status, T vs B cell ALL, did not impact response. Median overall survival was 2.4 months (1.3-2.9) in non-responders vs. 12.8 months (3-27.4) in responders (P =0.0007) (Figure 1). All pts who proceeded to transplant or DLI relapsed with a median time to relapse of 6.4 (4.8-13.7) months. Toxicity: Rash/Hand Foot syndrome was observed in 3 pts (19%), Grade III-IV liver toxicity occurred in 4 (26%) with no permanent sequela. Opportunistic infection occurred in 3 pt (17%). Conclusion: Clofarabine based chemotherapy was a well-tolerated salvage regimen in heavily pretreated patients and was an effective bridge to definitive therapy in a significant proportion of cases. Prospective evaluation of these findings is warranted. Figure 1. Figure 1. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background: MDS is a clonal bone marrow disorder characterized by ineffective hematopoiesis with peripheral blood cytopenias and an increased risk for transformation to acute leukemia. Patients with MDS who have a history of prior exposure to chemotherapy and/or radiotherapy are called therapy-related MDS (t-MDS). We hereby describe our experience with this entity and compare it to our experience with de novo MDS patients. Aim: To study the differences of clinical outcome between t-MDS and de novo MDS patients. Method: A retrospective single institution study chart review of cases with MDS at Mayo Clinic Rochester between 1993- 2011 was performed. De novo MDS, t-MDS and leukemic transformation (LT) were defined according to the World Health Organization (WHO) classification (Swerdlow et al 2008). Prior exposures to chemotherapy, radiotherapy and/ or both were defined as t-MDS; while lack of any as de novo MDS. Appropriate IRB approval was obtained in accordance with the Helsinki declaration. Comparison between group medians was done using Wilcoxon test, comparison between values was done using contingency and One-way analyses (Means/Anova/Pooled t), while survival estimates were calculated using Kaplan-Meier curves JMP V10 Results: Out of 827 patients with MDS, 153 (19%) patients were t-MDS (group (Gr) 1) versus 674 (81%) (rest of patients, Gr 2). Out of the t-MDS, 79 (52%) pts had CTX, and 42 (27%) had XRT, and 32 (21%) pts had both CTX/XRT). Upon comparison between Gr 1 vs 2, statistical significant difference was seen in median age 69 vs 72 (p=0.01), Platelets 68 vs 114 x109(<p0.0001), and WBC 3.2 vs 3.6 x109(0.02), respectively. No significant statistical difference was found in median Hg 9.6 vs 9.7 gm/dL (p 0.6), peripheral blood (PB) blasts 0% in both groups, and bone marrow (BM) blasts 2% in both groups. IPSS was low, int-1, int-2, high in 16%, 40%, 34%, 9%in Gr 1 and 32%, 46%, 18%, 4% in Gr 2. IPSS-R was very low, low, int, high, very high in 9%, 24%, 18%, 20%, 28% in Gr 1 vs 18%, 36%, 20%, 16%, 10% in Gr 2. AML transformation (LT) was identical in both groups at 12%. Upon comparison between Gr 1 and 2, median time to AML transformation was 7.9 vs 13 months (p=0.08). Median overall survival (mOS) was shorter in Gr 1 vs 2 at 16 vs 34 months (P<0.0001). When analysis was limited to diploid cytogenetics, median OS was 63 vs 50 months, respectively (p=0.9). Both IPSS and IPSS-R were prognostic of mOS in t-MDS (p<0.0001). On multivariate analysis; age (<0.0001), IPSS-R (p<0.0001) and previous CTX and/ or XRT (P=0.02) were the only variables that affected mOS. Conclusion: T-MDS comprises a small portion of all MDS cases (19%). Median overall survival in the de novo MDS group was longer than t-MDS group; however this difference was not maintained in patients with diploid cytogenetics. Similarly, time to AML was longer in de novo MDS compared to t-MDS (although similar rates of incidence). All of age, IPSS-R and t-MDS did affect median OS on multivariate analysis. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background: Momelotinib is a JAK 1/2 inhibitor that is active in the treatment of myelofibrosis (MF); a previous phase 1/2 study included 100 consecutive patients from the Mayo Clinic (Leukemia. 2015;29:741). In the current long-term study of these 100 patients, we provide a cumulative account of short and long term efficacy and toxicity data, as well as survival analysis. Methods: The current study represents sponsor-independent analysis. The study patients are part of a larger (n=166) phase-1/2 momelotinib study (NCT00935987), which was conducted in two dose-escalation (100 mg-400 mg daily doses) and dose-confirmation (300 mg daily dose) phases. Adverse events (AEs) were monitored by Common Terminology Criteria for Adverse Events (Version 4.03) and responses by the International Working Group criteria (Blood. 2013;122:1395). All statistical analyses considered clinical and laboratory parameters obtained at the time of entry to study. Results: Baseline data: 100 patients with MF (median age 66 years; 58% males) were treated between 11/20/09 and 11/10/10; 64 patients had primary MF, 22 post-polycythemia vera MF and 14 post-essential thrombocythemia MF. 73 (73%) patients harbored JAK2 mutations, 16 (16%) CALR, 7 MPL and 4 were "triple-negative"; among the 16 CALR-mutated cases, 13 were classified as "type 1/type 1-like". DIPSS-plus risk distribution (JCO 2011;29:392) was 63% high, 36% intermediate-2 and 1% intermediate-1; 49% displayed red cell transfusion-dependency, 58% constitutional symptoms, 87% palpable splenomegaly >5 cm and 50% abnormal karyotype. 94 patients were screened for ASXL1 mutations with 41 (44%) mutated and 78 for SRSF2 mutations with 14 (18%) mutated. 21 (21%) patients were previously treated with another JAK inhibitor. Current disposition: All information was updated in July 2016. To-date, after a median follow-up of 3.2 years, 88 drug discontinuations, 70 deaths and 14 leukemic transformations have been documented; median follow-up for living patients was 5.7 years (range 5.1-6.4). Among the 30 patients who are currently alive, 12 remain on study and another 5 have received stem cell transplant. Toxicity data: After a median treatment duration of 1.7 years, "momelotinib related" grade 3 or 4 AEs included thrombocytopenia (34%), neutropenia (9%), anemia (5%), increased lipase (7%), increased ALT (4%), increased AST (2%), increased ALP (2%) and headaches (2%). In addition, noteworthy grade 1 or 2 AEs included peripheral neuropathy (PN) 47%, increased lipase (14%), increased amylase (17%), increased bilirubin (13%), increased AST (21%), increased ALT (19%), increased APTT (17%), headaches (13%), dizziness (22%), nausea (23%) and diarrhea (20%). Most of the AEs, except PN, were reversible. Efficacy data and predictors of response and relapse-free survival: Clinical improvement (CI) was documented in 57% of patients, anemia response in 44%, and spleen response in 43%. 51% of transfusion-dependent patients became transfusion independent. The majority of patients also had marked improvement in their symptoms. 46 (81%) of the 57 responding patients discontinued treatment after a median treatment duration of 2.3 years. ASXL1 mutations predicted inferior CI (p=0.03) whereas relapse-free survival was adversely affected by absence of type 1/type 1-like CALR (p=0.03) or presence of unfavorable karyotype (p=0.002); among the 11 responding patients currently still receiving the drug, all had favorable karyotype and 5 had type 1/type 1-like CALR mutations. Survival analysis and risk factors : Median survival, calculated from the time of study entry, was 3.2 years with 5-year survival rate of 32%. In multivariable analysis of genetic markers, absence of type 1/type 1-like CALR (HR 2.9, 95% CI 1.1-7.2) or presence of SRSF2 (2.9, 1.5-5.4) or ASXL1 (1.8, 1.1-3.2) mutations were independently predictive of shortened survival (Figure). Conclusions: Momelotinib therapy in MF provides effective palliation in terms of anemia, splenomegaly and constitutional symptoms. However, less than 20% of treated patients enjoy durable long-term benefit and almost half experience drug-related and mostly irreversible peripheral neuropathy. Long-term survival and durability of response were superior in patients with type 1/type 1-like CALR mutations and inferior in those with ASXL1/SRSF2 mutations or unfavorable karyotype. Figure Figure. Disclosures Al-Kali: Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding.

Introduction Novel high-risk groups have been identified in adult ALL, including secondary (sALL) and Philadelphia-like ALL (Ph-like, based on CRLF2, IgH, ABL2, JAK2 and other tyrosine kinase translocations), and those with minimal residual disease >0.1% (MRD+) after induction therapy. Novel targeted therapies are now routinely incorporated into 1st line regimens, including tyrosine kinase inhibitors (BCR-ABL1-pos), rituximab (CD20+) and blinatumomab (Blina) for MRD+. The impact of these novel high risk groups and therapies after alloHCT is unknown; therefore, we evaluated their impact on overall survival (OS), relapse rate (REL), non-relapse mortality (NRM) and acute and chronic GVHD. Methods We evaluated pts receiving 1st Allo-HCT for ALL at Mayo Clinic (Rochester, Phoenix, and Jacksonville) from 2008-2018 for outcomes of interest, specifically the impact of novel therapies and risk groups. Associations of patient factors with outcomes were examined using univariable (UVA) and multivariable (MVA) Cox proportional hazards regression models, where the cause-specific hazard of the given outcome was modeled to account for the competing risk of death. Results We identified 261 consecutive AlloHCT recipients during the study period. Median age at transplant was 48 years (18-72) and 147 (56.3%) were male. The median comorbidity (HCT-CI) score was 2 (0-8). 213 pts (81.6%) had B-lineage ALL, of which 85 (32.6%) were BCR-ABL-pos, 17 (6.5%) Ph-like (identified by FISH), 16 (6.1%) hypoploidy/near triploidy (Hy/Tri), and 67 (25.7%) pre-B ALL NOS. The remaining 48 (18.4%) had T-ALL. 30 pts (11.5%) had sALL (i.e. prior chemo/radiotherapy for another malignancy). HyperCVAD was the most common 1st line regimen (68.2%). 243 (93.1%) pts achieved Complete Remission (CR1) after induction therapy, and 203 (77.8%) were in CR1 at the time of alloHCT. Blina was administered for MRD+ in 14 pts (5.4%), and for relapsed/refractory ALL (R/R) in 13 (27% of R/R pts), 7 of whom received Blina as initial therapy for R/R. Donors were matched unrelated in 149 (57.1%), matched related in 98 (37.5%), and haploidentical in 14 (5.4%). Peripheral blood (PB) grafts were used in 233 (89.3%). 103 (54.5%) were donor:recipient (D:R) sex-matched, and 86 D:R mismatched [47 (24.9%) M:F; and 39 (20.6%) F:M]. Myeloablative conditioning was used for the majority (78.5%) mostly with Cy/TBI (60.5%). Standard GVHD prophylaxis regimens were used. Outcomes Median follow-up after transplant was 22.4 months (0.5-135), and 51 (19.5%) had REL. The 1, 2 and 5-year survival rates were 71.9%, 64.9%, and 54.1%, respectively (Figure 1). Acute GVHD developed in 144 (55.2%) and chronic GVHD in 100 (38.3%). Ph-like ALL, Blina for MRD+, Blina for R/R, sALL and CD20-pos had no independent impact on OS. In contrast, age>60, Hy/Tri, and >CR1 at alloHCT were associated with worse OS in UVA, however, in MVA only pre-B ALL NOS was associated with better OS. Female:male D:R status was associated with inferior OS. Blina for R/R disease was associated with increased risk of REL in UVA [HR 5.26 95% CI (1.33, 20.00), p=0.017], whereas other novel high risk groups had no impact on REL. In contrast, T-ALL, Hy/Tri and >CR1 at AlloHCT were associated with increased REL in UVA, but only T-ALL and Hy/Tri continued to predict for increased REL in MVA. Secondary ALL was associated with increased NRM in UVA [HR 1.96 95% CI (1.07, 3.57), p=0.028], whereas other novel high risk groups had no impact on NRM. In contrast, age>60, >CR1 at AlloHCT and D:R sex mismatch were associated with higher NRM in UVA, but only sex mismatch and >CR1 at AlloHCT were associated with higher NRM in MVA. TBI use was associated with higher risk of acute GvHD (p=0.008) and ATG use with lower risk chronic GVHD (p<0.001). Similarly non-PB grafts were associated with a lower risk of chronic GVHD (p=0.005). Results for OS, REL, NRM, acute and chronic GVHD analysis are shown in Table 1. Conclusion Novel high risk groups (CD20+, Ph-like and sALL) do not appear to adversely impact OS after alloHCT, although sALL was associated with increased risk of NRM. Interestingly, pre-B-ALL NOS appear to be associated with favorable OS. Novel targeted therapies also do not independently predict outcome, with the exception of Blina for R/R ALL which may be associated with REL after subsequent alloHCT (a subgroup for whom novel maintenance strategies should be explored). Our analysis highlights the importance of allo-HCT for novel high risk ALL subgroups. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Foran:Agios: Honoraria, Research Funding.