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Ionising radiation impacts many organ systems, each of which comprises a level of immunity to infectious disease. Bone marrow toxicity after radiation results in a predisposition to leukopenia and subsequent susceptibility to bacterial, viral, and fungal infections. Radiation-induced damage to mucosal, integumentary, and solid organ structures disrupts additional lines of innate defense. Over the past three decades, much progress has been made in effective antimicrobial prophylaxis, resulting in decreased infectious complications and improved survival. Vaccination schedules following myeloablative radiation have become highly regimented and treatment of overt infectious complications is largely standardised. In this article, we discuss consequences, prevention, and management of infections following exposure to ionising radiation.

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic neoplasm which results in clonal proliferation of abnormally differentiated hematopoietic cells. In this review, mechanisms contributing to myeloid leukemogenesis are summarized, highlighting aberrations of epigenetics, transcription factors, signal transduction, cell cycling, and the bone marrow microenvironment. The mechanisms contributing to AML are detailed to spotlight recent findings that convey clinical impact. The applications of current and prospective therapeutic targets are accentuated in addition to reviews of treatment paradigms stratified for each characteristic molecular lesion - with a focus on exploring novel treatment approaches and combinations to improve outcomes in AML.

Background: The addition of venetoclax to a hypomethylating agent (HMA) backbone has been shown to augment responses when compared to HMA monotherapy or to low-dose cytarabine in the treatment of acute myeloid leukemia (AML). The aim of this retrospective analysis was to characterize venetoclax-based regimens in both the first-line and relapsed/refractory settings to determine efficacy and safety outcomes. Patients & Methods: We retrospectively analyzed 74 patients treated with venetoclax in combination with decitabine, azacitidine, or low-dose cytarabine treated from June 2018 to December 2020. This analysis included 41 patients in the upfront setting and 33 patients in the relapsed/refractory setting. Baseline patient demographics were obtained alongside ECOG performance status at diagnosis, cytogenetics and molecular profiling, dates and doses of induction, toxicity, responses, MRD analysis, and allogeneic hematopoietic stem cell transplant (HSCT) outcomes. The event for calculating the overall survival was the date of death and patients were otherwise censored at the date of last contact. Results: In the upfront setting of 41 patients, 25 (61%) were male and 16 (39%) were female, the median age was 72 (range: 37 - 85), the median ECOG score was 2 (range: 0 - 3), and the median Charlson Comorbidity Index (CCI) score was 6 (range: 3 - 12). There were four patients with favorable-risk cytogenetics (9.8%), six (14.6%) with intermediate cytogenetics, and 29 (70.7%) with adverse cytogenetics. Two (4.9%) patients had cytogenetics unknown at diagnosis. Eight (19.5%) had mutations in TP53. Thirty-three (80.5%) received venetoclax with 5-day decitabine, one (2.4%) with 10-day decitabine, six (14.6%) with azacitidine, and one (2.4%) with low-dose cytarabine. In the entire cohort, 37 (90.2%) experienced at least one grade 1 non-hematological toxicity during induction. Non-hematological adverse events were infection (58.5%), neutropenic fever (53.7%), and acute kidney injury (26.8%). Six (14.6%) patients had tumor lysis syndrome defined by Cairo-Bishop criteria and all six were spontaneous rather than therapy-induced. One (2.4%) died within 30 days of induction, nine (22.0%) died within 60 days, and 29 (70.7%) had no death during induction. Three (7.3%) achieved CR and 13 (31.7%) achieved CRi for an ORR of 39.0%. Two patients (4.9%) went on to receive HSCT. The median OS was 416 days (13.7 months) in the intermediate category and 281 days (9.2 months) in the adverse category. In the relapsed/refractory setting, 20 (60.6%) were male and 13 (39.4%) were female. The median age was 63 (range: 23 - 76), the median ECOG score was 1 (range: 0 - 4), and the median CCI score was 5 (range: 2 - 11). At the time of initial diagnosis, two patients (6.1%) had favorable cytogenetics, three (9.1%) had intermediate cytogenetics, 27 (81.8%) had adverse cytogenetics, and one had unknown cytogenetics. Seven (21.2%) patients had a TP53 mutation at initial diagnosis. Twenty-five (75.8%) received venetoclax with 5-day decitabine, 6 (18.2%) with azacitidine, one (3.0%) with low-dose cytarabine, and one with an unknown duration of decitabine. Common non-hematological toxicities included 13 (39.4%) with infection, 11 (33.3%) with neutropenic fever, and 3 (9.1%) with acute kidney injury. Five patients (15.2%) achieved CR and 5 (15.2%) achieved CRi for an ORR of 30.3%. Four (12.1%) died within 30 days, 3 (9.1%) within 60 days, and 25 (75.8%) with no death during induction. The median OS was 251 days (8.25 months). Conclusion: The combination of venetoclax with decitabine, azacitidine, or low-dose cytarabine demonstrates an ORR of 39.0% in the upfront setting and the OS was 13.7 months and 9.2 months in the intermediate and adverse categories, respectively. The relapsed/refractory setting featured a shorter OS at 8.25 months and an ORR of 30.3%, which does not appear to be substantially different from historical data with HMA monotherapy in relapsed disease (mOS = 6.7 months). These findings raise the question regarding the benefit of venetoclax in the relapsed setting for selected patients. Additionally, our findings augment the small sample of available data on the utility of HMA/venetoclax, particularly in the treatment of relapsed disease, with recent retrospective data showing a CR/CRi rate of 24% and a mOS of 6.1 months. Prospective trial designs are needed to confirm these findings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Acute myeloid leukemia (AML) is an aggressive bone marrow cancer affecting 20,000 adults in the United States yearly. Five-year relative survival remains poor at 29.5%, though this has been steadily increasing. There are no known differences in diagnostic rates between racial and ethnic groups. Previous work has shown being African American is an independent predictor of poorer survival - particularly in impoverished areas and those with Medicaid. We aimed to identify potential racial disparities amongst our AML population - with special attention to insurance coverage, access to care, disease biology, regimen selection, toxicities, referral for allogeneic hematopoietic stem cell transplant (alloHSCT), and overall survival with non-Hispanic Whites as a control. Methods: This study is a retrospective analysis of patients diagnosed with AML and treated at Virginia Commonwealth University/Massey Cancer Center identified by our data analytics core from June 2018 to December 2020. Data were extracted and manually verified from the electronic medical record into an AML database instrument created in RedCap. Race was determined by self-report. Statistical analysis was performed using GraphPad Prism. Descriptive and inferential statistics were performed with comparisons between groups using an unpaired t-test with Welch's correction or with Fischer's exact test. Overall survival rates were evaluated using Kaplan-Meier analyses and compared using log-rank test. The event date was death and patients were otherwise censored at the date of last contact. Results: Our cohort consisted of 160 patients: 26.3% African Americans, 68.8% Whites, 1.9% Hispanic/Latinos, 1.9% other or declined to state, and 1.3% were unknown. To analyze the impact of minority populations, Hispanic/Latino and "other" categories were combined with African American into a "Non-White" cohort (N = 48) and compared to the "White" cohort (N = 110). There was no baseline difference in age (p= 0.212), Charleson Comorbidity Index (CCI) at presentation (p = 0.692), or ECOG status (p = 0.920) at presentation (Table 1). Assessment of disease biology, including European Leukemia Network risk stratification (p = 0.507), presence of complex karyotype (p = 0.366) and presence of TP53 mutations (p = 0.776) did not detect a statistically significant difference between the two groups (Table 1). Choice of intensive (vs non-intensive) induction based on physician's discretion was also similar (62.5% in non-White, 68.2% in Caucasians, p = 0.583). Toxicity analysis such as ICU during induction (p = 0.519) and death within 60 days of induction (p = 0.8) showed no difference between groups. In parameters assessing access to care, non-Whites were more likely than Whites to have either Medicaid or no insurance coverage, opposed to private insurance or Medicare (p = 0.0166). Despite this, there was no difference in overall survival assessed by log-rank test (p = 0.068) across all cytogenetic cohorts or with respect to the adverse risk cohort (p = 0.143), though the non-White cohort had a mOS of 286 days (9.4 months) compared to 764 days (25.1 months) in the White cohort. Rates of being lost to follow up were not different between the two groups (p = 0.34). However, rates of alloHSCT were approaching significance with p = 0.0528 favoring Caucasians. Discussion: Our data suggest similar disease biology at presentation amongst racial and ethnic groups, as well as similar comorbidities, performance status at diagnosis, and choice of induction regimen. As previous research has shown, our minority cohort was more likely to have no insurance or Medicaid than the Caucasian population. However, this did not lead to a statistically significant overall survival difference. Rates of alloHSCT were approaching statistical significance between the groups. This suggests that improving access to transplant might be one of the more effective tools for improving outcomes in this group. Additionally, demographics in the Richmond metro area demonstrate a population of 47% African American and 48% Whites, whereas our data showed 26% African Americans and 69% Whites, with no known strong racial predilection of AML based on SEER data (46% vs 54%, respectively). Thus, concern remains that there may be a significant number of patients with AML who either do not seek care, or present in a condition where treatment is no longer possible. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Sequencing and selection of salvage regimens for acute myeloid leukemia (AML) remains unclear. Venetoclax augmentation of a hypomethylating agent (HMA) backbone has joined the salvage armamentarium following impressive performance in the front-line setting. However, little is known about the outcomes with venetoclax in relapsed and refractory (R/R) AML. Survival and toxicity data remain scarce for venetoclax-based salvage, particularly when compared to intensive reinduction. This study characterizes outcomes between venetoclax-based salvage regimens and FLAG-IDA in the R/R setting. Patients & Methods: We retrospectively analyzed all patients with AML treated at Massey Cancer Center younger than 65 in the R/R setting with either FLAG-IDA (fludarabine, cytarabine, G-CSF, and idarubicin) or venetoclax in combination with decitabine, azacitidine, or low-dose cytarabine from June 2018 to December 2020. Baseline patient demographics and disease characteristics were obtained and recorded in RedCap. Statistical analyses using unpaired t-test with Welch's correction or the Mann-Whitney test, Fischer's exact test, and Kaplan-Meier survival analyses were computed and compared with log-rank tests using GraphPad Prism. The event for calculating the overall survival was the date of death with patients otherwise censored at the date of last contact. Results: Twenty-eight patients were identified meeting inclusion criteria: 19 underwent salvage with venetoclax-based regimens and 9 patients were treated with FLAG-IDA. Five patients (55.6%) in the FLAG-IDA cohort underwent salvage for refractory disease (primary induction failure), compared to only two (10.5%) in the venetoclax group, which was statistically significant (p = 0.019). The remaining patients in both cohorts were treated in the relapsed setting. There was no significant difference in sex (p = >0.999), ECOG performance status at diagnosis (p = 0.083), or Charlson Comorbidity Index (CCI) scores (p = 0.128). The median age of patients treated with FLAG-IDA was 39 (range: 24 - 62), the four most common molecular mutations in the FLAG-IDA cohort occurred at a frequency of 22.2% each: FLT3-ITD, NPM1, WT1, and biallelic CEBPA. Two patients (22.2%) had favorable cytogenetics at diagnosis, one (11.1%) had intermediate cytogenetics, five (55.6%) had adverse cytogenetics, and one was unknown. All were initially treated with a 7+3 backbone. The most common non-hematological toxicities were neutropenic fever (55.6%) and acute kidney injury (22.2%). Five (55.6%) achieved CR and one (11.1%) achieved CRi for an ORR of 66.7%. There were no deaths within 60 days of salvage. Five (55.6%) patients went on to receive allogeneic SCT. Median survival was not reached at a median follow-up of 430 days (14.1 months). In the venetoclax-based cohort of 19 patients, the median age was 58 (range: 23 - 65), At the time of initial diagnosis, the most common molecular aberrations were TP53 (26.3%), NPM1 (15.7%), followed by FLT3-TKD, RUNX1, and TET2 (10.5% each). Two (10.5%) patients had favorable cytogenetics at initial diagnosis, two (10.5%) had intermediate, 14 (73.7%) had adverse cytogenetics, and one patient had unknown cytogenetics. Seventeen (89.5%) patients were initially treated with 7+3, one (5.3%) was treated with azacitidine, and one (5.3%) was treated with CPX-351. The most common non-hematological toxicities were infection (42.1%), neutropenic fever (31.6%), and GI toxicity (15.8%). Two (10.5%) patients achieved CR and four (21.1%) achieved CRi for an ORR of 31.6%. There were 3 deaths in 30 days and 1 death within 60 days. Four (21.1%) went on to receive allogeneic SCT after venetoclax-based salvage. The median survival was 268 days (8.81 months) and was statistically significant from the FLAG-IDA cohort (p = 0.0029). Conclusion: Our results suggest the efficacy of FLAG-IDA compared to venetoclax-based regimens with respect to ORR, survival, toxicity, and progression to transplant in the R/R setting for presumable intensive induction candidates, as evidenced retrospectively by prior receipt of such regimens. These differences may be impacted by changes to disease biology between the relapsed and refractory settings and TP53 status. Larger prospective studies with separate analyses between the relapsed and refractory settings are needed to confirm these findings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Clonal diversity and evolution in acute myeloid leukemia (AML) are consequences of disease progression and play a pivotal role in the development of drug resistance and refractoriness to therapy. Much work has been done with characterizing clonal architecture in bulk tumors samples or single-cell DNA sequencing, but real-world data observing the impact of clonal evolution and responses to therapy remains scarce in the relapsed and refractory settings. Therefore, the purpose of this study was to analyze the impact of observed clonal evolution on survival. Patients & Methods: We retrospectively analyzed 81 patients with AML with relapsed or refractory disease from June 2018 to December 2020. Cytogenetic and molecular data were obtained at the time of diagnosis and the time of primary induction failure or relapse, when available. We identified a total of 24 patients that demonstrated evidence of clonal evolution following induction or salvage therapy. Baseline patient demographics were obtained, including cytogenetic risk and next-generation sequencing molecular profiling at diagnosis and throughout treatment alongside dates and types of induction regimens. We compared the survival of those with evidence of clonal evolution to matched groups without. The groups with and without clonal evolution were compared for baseline statistical differences using an unpaired t-test with Welch's correction and Kaplan-Meier survival analyses were computed and compared with log-rank tests using GraphPad Prism. The event for calculating the overall survival was the date of death with patients otherwise censored at the date of last contact. Results: Of the 24 patients with evidence of clonal evolution, we detected that evolution occurred in four (16.7%) patients at the time of primary induction failure (refractory to first induction), 19 (70.8%) at the time of first relapse, and 3 (12.5%) at the time of second relapse. The median age of patients with clonal evolution was 63 years (range: 23 - 74) with 17 (70.8%) males and 7 (29.2%) females. The most commonly occurring mutations were NPM1 (25.0%), FLT3-ITD (20.8%), and TP53 (20.8%). At the time of initial diagnosis, cytogenetic risk was favorable in one (4.2%), intermediate in 7 (29.2%), and adverse in 16 (66.7%). The majority (79.2%) of patients underwent first induction with 7+3 and 8 (33.3%) patients underwent allogenic SCT. At the time of clonal evolution and ignoring the adverse prognosis associated with relapse, one patient with favorable cytogenetics remained favorable, only one (14.3%) patient with intermediate cytogenetics shifted to adverse, and one (6.3%) patient in the adverse category shifted to intermediate by ELN criteria. Three (12.5%) patients out of 24 acquired FLT3-ITD and three (12.5%) acquired an additional cooperating mutation (NRAS, KRAS, or KIT) for a total of 25.0% acquiring a signaling pathway mutation. Out of 10 patients with either mutated TP53 or MLL, three (27.3%) acquired a cooperating mutation in FLT3 or RAS. We then compared the clonal evolution cohort with the 57 remaining relapsed/refractory patients without evidence of clonal evolution. There was no difference between the groups with respect to baseline characteristics, including age (p = 0.989), ECOG status at diagnosis (p = 0.4689), Charlson Comorbidity Index (CCI) score (p = 0.6454), or prior SCT (p = >0.999). The median overall survival (OS) of the clonal evolution group was 227 days and compared to 382 days in the non-evolution cohort (p = 0.843). Conclusion: We did not detect a significant OS difference between those with clonal evolution and those without. Independent of the adverse prognosis associated with relapsed or refractory disease, cytogenetic risk category appeared to remain the same with clonal evolution. Common trends during clonal evolution included acquisition of one or several cooperating mutations in FLT3 or RAS, both with and without the presence of mutated TP53 and MLL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: The optimal induction strategy for patients with acute myeloid leukemia (AML) older than 65 years remains unknown. The use of lower intensity therapies in this population has become routine. The inclusion of venetoclax to intensify a hypomethylating agent backbone has efficacy outcomes approaching those of anthracycline-based inductions in elderly adults. This retrospective analysis sought to compare venetoclax-based induction combinations to anthracycline-based regimens. Patients & Methods: We retrospectively analyzed all patients with AML older than 65 treated with 7+3 or liposomal daunorubicin and cytarabine (CPX-351) versus venetoclax with either decitabine or azacitidine from June 2018 to December 2020 at our institution. Patients were included in the analysis only if ECOG performance status prior to induction supported intensive induction (≤2). Baseline patient demographics, cytogenetic risk, molecular profiling (through next-generation sequencing), toxicity, responses, and MRD analysis were obtained. Kaplan-Meier curves were constructed using censoring at date of last contact for those that did not have a death event in the specified time period. Results: The intensive cohort included 28 patients, 15 (53.6%) males and 13 (46.4%) females. The median age at diagnosis was 69 (range: 65 - 76), the median ECOG score was 1, and the median CCI score was 6. The anthracycline in the 7+3 cohort was daunorubicin in 15 patients (53.6%) and idarubicin in 1 (3.6%) patient. This cohort also included 12 (42.9%) patients treated with CPX-351. Two (7.1%) patients had favorable cytogenetics, 6 (21.4%) had intermediate cytogenetics, and 20 (71.4%) had adverse cytogenetics. The most common non-hematological toxicities that Grade 1 or higher were neutropenic fever (85.7%), infection (71.4%), GI/hepatobiliary (42.9%), cardiovascular (35.7%), and acute kidney injury (32.1%). One (3.8%) of the 26 evaluable patients died within 30 days and one (3.8%) died within 60 days. Fourteen patients (50.0%) achieved CR and 3 (10.7%) achieved CRi for an ORR of 60.7%. Six of the 17 patients with CR or CRi were analyzed for MRD and two (33.3%) were MRD-negative. Six (21.4%) received an allogenic stem cell transplant (SCT). The median OS in the intensive cohort was not reached at a median follow-up of 711 days (23.4 months). The lower intensity cohort totaled 28 patients, 18 (64.3%) males and 10 (35.7%) females. The median age at diagnosis was 75 (range: 65 - 85), median ECOG score was 1, and the median CCI score was 6. There were no differences in ECOG score (p = 0.930), CCI (p = 0.195), or cytogenetic risk (p = 0.924) between the two groups. Venetoclax was given in combination with 5-day decitabine (78.6%) or azacitidine (21.4%). Of the 28 patients with evaluable cytogenetics, 2 (7.1%) were favorable, 5 (17.9%) were intermediate, and 19 (67.9%) were adverse. The most common non-hematological toxicities were infection (57.1%), neutropenic fever (50.0%), GI/hepatobiliary (28.5%), cardiovascular (25.0%), and acute kidney injury (21.4%). Of the 28 evaluable patients, one (3.6%) died within 30 days and 7 (25.0%) died within 60 days, though not statistically significant compared to the intensive group (p = 0.103). Two (7.1%) achieved CR and 12 (39.3%) achieved CRi for an ORR of 46.4%. Two of the 13 patients were evaluated for MRD and none were MRD-negative after induction. Two (7.1%) patients received allogeneic SCT. The median OS in the venetoclax cohort was 354 days (11.6 months), though no statistically significant difference was detected when compared to the intensive cohort (p = 0.0735). However, when the two cohorts were selected for adverse cytogenetic risk and compared, the median OS was not reached in the intensive group at a median follow-up of 636 days but was 91 days in the venetoclax group (p = 0.025). Conclusion: Elderly patients had superior responses and survival to intensive induction when compared to venetoclax-based strategies when analyzed with respect to cytogenetic risk. Additionally, though the rates of toxicities were higher in the intensive cohort, the mortality during induction appeared to be lower, but did not reach statistical significance. Our work indicates that careful selection of intensive induction candidates is warranted, as those who can tolerate intensive regimens may be undertreated by selecting a less-intensive therapeutic strategy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a poor prognosis in the adult population, despite recent advancements in treatment paradigm. Induction with the liposomal formulation of cytarabine and daunorubicin (CPX-351) which has been shown in phase III trials to improve the median overall survival (OS) compared to standard induction (9.6 versus 5.9 months, respectively) and is FDA approved for patients therapy related AML or AML with myelodysplasia-related changes. Hypomethylating agents (HMA) (azacitidine and decitabine) have recently garnered renewed attention in combination with the BCL-2 inhibitor venetoclax (VEN). Azacitidine with venetoclax demonstrated a median overall survival of 16.9 months in those that were deemed ineligible for intensive induction. While these trials were inherently different patient populations, in clinical practice, physicians must often choose between these two therapies in the frontline setting. Thus, we aimed to examine patient characteristics and respective outcomes with these two treatment approaches. Methods: This was a retrospective cohort studies of patients diagnosed with AML and treated at Virginia Commonwealth University/Massey Cancer Center as identified by our data analytics core between June of 2018 and December of 2020. Data was extracted and manually verified from the electronic medical record into an AML database instrument created in RedCap. Statistical analysis was then performed using GraphPad Prism. Descriptive analyses were conducted for demographics and baseline clinical characteristics, and OS rates were evaluated using Kaplan-Meier analyses and compared using log-rank test. Results: A total of 160 patients with AML were identified. Of those, 58 were treated with either HMA/VEN (N = 43) or CPX-351 (N = 15) in the frontline setting. Median age of patients treated with HMA/VEN was 72 (range: 37 - 85) compared to the median age of 69 (range: 44 - 72) for the CPX-351 group, which was statistically significant (p = 0.002). There was no statistical difference in other demographic characteristics such as sex (p = 0.380), race (p = 0.323), Charleston Comorbidity Index (p = 0.097), or ECOG score (p = 0.126). AML risk stratification based on molecular and cytogenetic data per ELN 2017 also did not differ between the two groups (p = 0.230), with both groups having numerically similar adverse-risk patients (86.7% in the CPX-351 cohort and 70.7% in the VEN cohort). Figure 1 demonstrates a Kaplan-Meier analysis, which revealed a median OS in the VEN group of 281 days (9.23 months) compared to a median OS in the CPX-351 group of 713 days (23.4 months), which was not significant (p = 0.109). Additionally, there was no difference in the OS when only the adverse cytogenetic categories were analyzed from each cohort (Figure 2, p = 0.058). There was one (6.7%) death within 30 days in the CPX-351 group and no deaths within 60 days, compared to one (2.3%) death within 30 days and 9 (20.9%) deaths within 60 days in the VEN group, which was not significantly different (p = 0.257). Allogeneic stem cell transplant was more common in the CPX-351 group (40%) than the VEN group (4.7%) (p = 0.0007). Conclusion : Although these regimens were intended for diverging populations of induction versus non-induction candidates, there is clinical overlap in physician discretion regarding both regimens. Our data shows similar baseline characteristics between these two groups, though the VEN cohort was slightly older. Our data demonstrated that in the CPX-351 cohort, the OS was longer, there appeared to be fewer deaths during induction, and more patients proceeded to transplant - though the former approached statistical significance, particularly when matched with adverse cytogenetic risk (p = 0.058). This argues for continued use of intensive regimen for those who are candidates, especially those in whom allogeneic hematopoietic stem cell transplant is being considered. Prospective studies between these regimens is warranted. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The azanucleotide decitabine is used in the treatment of acute myeloid leukemia (AML). Studies have shown conflicting results with 10-day regimens used in previously untreated AML patients. Additionally, there is little data on 10-day decitabine regimens in the relapsed setting. This study investigated outcomes of 108 adult patients with AML in the upfront and relapsed setting treated with a 10-day decitabine regimen. In the upfront group, the overall response rate (ORR, CR + CRi) was 36.1% and the median overall survival (OS) was 6.6 months, while the relapsed/refractory group had an ORR of 25% with an OS of 4.8 months. When analyzed with respect to cytogenetics, the upfront group featured an ORR of 28.1% with an OS of 9.4 months in the intermediate cytogenetic cohort compared to a 40.5% ORR and an OS of 5.4 months in the unfavorable cytogenetic cohort. An analysis of the relapsed/refractory group demonstrated an ORR of 26.3% with an OS of 7.9 months for intermediate cytogenetics versus 25.0% with an OS of 1.8 months in the unfavorable cohort. While these response rates are similar to previously published data, the median OS appears shorter.