Diagnosis Of t-AML Research Articles

Clinical outcome of therapy-related acute myeloid leukemia patients. Real-life experience in a University Hospital and a Cancer Center in France.

t-AML occurs after a primary malignancy treatment and retains a poor prognosis. To determine the impact of primary malignancies, therapeutic strategies, and prognostic factors on clinical outcomes of t-AML. A total of 112 adult patients were included in this study. Fifty-Five patients received intensive chemotherapy (IC), 33 non-IC, and 24 best supportive care. At t-AML diagnosis, 42% and 44% of patients presented an unfavorable karyotype and unfavorable 2010 ELN risk profile, respectively. Among treated patients (n = 88), 43 (49%) achieved complete remission: four out of 33 (12%) and 39 out of 55 (71%) in non-IC and IC groups, respectively. With a median follow-up of 5.5 months, the median overall survival (OS) and disease-free survival (DFS) for the whole population were 9 months and 6.3 months, respectively, and for the 88 treated patients 13.5 months and 8.2 months, respectively. Univariate analysis on OS and DFS showed a significant impact of high white blood cells (WBC) and blast counts at diagnosis, unfavorable karyotype and ELN classification. Multivariate analysis showed a negative impact of WBC count at diagnosis and a positive impact of chemotherapy on OS and DFS in the whole population. It also showed a negative impact of previous auto-HCT and high WBC count on OS and DFS and of IC on OS in treated patients which disappeared when we considered only confounding variables (age, previous cancers, marrow blasts, and 2010 ELN classification). In a pair-matched analysis comparing IC treated t-AML with de novo AML, there was no difference of OS and DFS between the two populations. We showed, in this study that t-AML patients with unfavorable features represented almost half of the population. Best outcomes obtained in patients receiving IC must be balanced by known confounding variables and should be improved by using new innovative agents and therapeutic strategies.

Risk of Therapy-Related Acute Myeloid Leukemia (t-AML) in Cancer Patients Treated with Chemotherapy with or without Radiotherapy: A National Population-Based Cohort Study Using SEER Registry

Background: Therapy-related AML (t-AML) is a rare and fatal complication in cancer patients (pts) previously treated with chemotherapy (CTX) and radiotherapy (RT). The risk of t-AML has evolved over time mostly due to advances in cancer therapeutics. In this study, we provide a comprehensive analysis on the risk of t-AML over a 40-year period in cancer patients treated with CTX with or without RT in the US. Methods: Eligible pts for this study were identified from nine Surveillance, Epidemiology, and End Results Program (SEER 9) registries and included those between the ages of 18 and 84 years who were diagnosed with any first primary malignancy (other than CML) between 1975-2018 and received initial course of treatment with CTX. All AML cases that occurred at least one year after the first diagnosis of a primary malignancy were included as t-AML as per the World Health Organization classification. All malignancies were identified based on International Classification of Disease for Oncology, 3rd edition (ICD-O-3) morphology and topography codes. Subjects were followed until t-AML diagnosis, attained age of 85 years, death, loss to follow up, or end of study (December 31, 2018). Standardized incidence ratios (SIRs) were calculated as the ratio of the observed-to-expected (O/E) number of AML using SEER*Stat. The expected number of AML was computed from age-, race-, sex-, and calendar year-specific incidence rates of AML from the general SEER population, multiplied by the appropriate person-years at risk. We calculated exact 95% confidence intervals (CI) about the SIRs. We also computed the excess absolute risk (EAR) to estimate the number of excess cancers beyond that expected per 10,000 persons per year. We conducted Poisson regression analyses comparing excess relative risks (ERR) with initial RT, using CTX alone as the reference. Results: Among 1,030,380 pts initially treated with CTX for first primary malignancy, we identified 2,081 t-AML cases with a 4.76 fold increased risk of AML (SIR; 95% CI, 4.55-4.96) compared to the general population and an excess of 3.94 cases per 10,000 person-years (Table 1). We focused our analysis on first primary malignancies with at least 100 t-AML cases, which included cancers of the lung, breast, ovaries, Hodgkin Lymphoma (HL), Non-Hodgkin Lymphoma (NHL), and myeloma. t-AML risks were particularly high (six- to twenty-fold higher than general population) in the first 5 years following these primary cancer diagnoses, then declined substantially with increasing latency. Long-term risk (≥10 years) of t-AML remained significantly elevated in pts with all these primary cancers except for lung cancer and the risk was highest in pts with myeloma (SIR = 13.74; 95% CI, 8.27-21.46). Additionally, we assessed the risk of t-AML with and without RT in addition to CTX (Table 2). Pts were more likely to develop t-AML if they were treated with both RT and CTX for lung cancer (ERR 1.85, 95%CI, 1.24-2.78), breast cancer (ERR 1.36, 95%CI, 1.13-1.65), and ovarian cancer (ERR 1.70, 95%CI, 0.83-3.47) compared to pts who were treated with CTX alone. When analyzed by different calendar periods of diagnosis, the risk of t-AML in pts with HL, NHL and myeloma was lower following combined modality compared to chemotherapy alone in recent time periods (1997-2007, 2008-2018) compared to earlier years of diagnosis. We also identified trends of t-AML risk over time, displayed in 11-year intervals from 1975-2018 (Table 2). Ptrend was calculated using annual SIRs over the study period. In patients who received CTX for their first primary malignancy, irrespective of RT, we found that t-AML risk has significantly declined after CTX for lung cancer (Ptrend < 0.001), HL (Ptrend = 0.003), and myeloma (Ptrend = 0.001). Over the same period, the risk of t-AML increased in breast cancer (Ptrend < 0.001) and NHL (Ptrend < 0.001). Conclusions: In our study spanning the past 40 years, we observed the risk of t-AML trending down for lung cancer, HL, and myeloma while increasing for breast cancer and NHL. A notable finding was increasing risk of t-AML with increasing latency in myeloma. Of interest, the risk of t-AML with combined modality regimens (CTX and RT) in recent time periods is lower than chemotherapy alone for HL, NHL and myeloma. Based on these observations, it is imperative to analyze the impact of newer therapies on the risk of t-AML, which will greatly benefit risk-benefit counseling of pts at individual level. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P508: REAL LIFE EXPERIENCE USING FRONT-LINE CPX-351 FOR THERAPY-RELATED AND AML-MRC: RESULTS FROM THE SPANISH PETHEMA REGISTRY.

Background: Acute Myeloid Leukemias arising after cytotoxic therapy (t-AML) or with myelodysplasia-related changes (AML-MRC) share adverse risk features and poor outcomes after standard 3 + 7 chemotherapy. In a randomized clinical trial, CPX-351 has shown superior overall survival (OS) compared to standard anthracycline-cytarabine schedule in these AML subtypes. Aims: to evaluate the effectiveness of CPX-351 treatment in a real-world setting. Methods: adult t-AML and AML-MRC patients who have been treated upfront with CPX-351 in 35 Spanish centers between 2018 and 2021. All patients were included in the PETHEMA registry (NCT02606825). Primary end-point was OS. Secondary end points were complete remission with or without hematological recovery (CR/CRi), proportion of minimal residual negativity (MRD), rate of allogeneic hematopoietic stem cell transplant (HSCT) and safety. Results: CPX-351 was administered to 74 patients as first induction chemotherapy. Median age was 67 (63-71) years, with 40% (30/74) of female patients. ECOG performance status score was 0-1 in 85% (53/62) patients. A diagnosis of t-AML was present in 30% (22/74) patients. Hypomethylating agents were used for MDS or CMML phase in 15%. Hematopoietic Transplant Comorbidity Index was low, intermediate and high in 14% (10/74), 43% (32/74) and 43% (32/74) patients. ELN17 risk classification was favourable, intermediate, adverse and indeterminate in 9% (7/74), 38% (28/74), 46% (34/74) and 5% (4/74). CR/CRi was obtained in 43% (32/74) patients after first cycle with CPX-351. Three additional patients achieved Morphological Leukemia Free Status. A second induction with CPX-351 was administered in 5 patients with 100% CR (CR/CRi after 2 cycles 37/74, 50%). MRD was evaluated in 97% (36/37) of CR/CRi patients, being low (<0.1%) in 47% (17/36) of them. In univariate analysis, no factor was associated with response. However, 71% (5/7) response rate was observed in the favourable ELN17 genetic risk group compared to 48% (32/67) in the non-favourable. HSCT was performed in 27% (20/74) patients, in 1st CR/CRi in 70% (14/20), MLFS in 15% (3/20) and active disease in 10% (2/20). With median follow up of 11.9 months (7.2-23.6) from HSCT, median OS was not reached (95% CI 9.5-NR months (Figure). In univariate analysis no factors were significantly associated with OS after HSCT. Median time to absolute neutrophil count ≥0.5 x109/L and platelets ≥50 x109/L were 30.5 (25-35) and 30 (26-39) days, respectively. Deaths within the first 30 days after induction occurred in 12% (9/74) patients. Causes of early death: infection in 5 patients, haemorrhage in 3 and respiratory failure in 1. With 6.1 (1.8-14) months of median follow up, median OS was 10.5 (6.9-NR) months, with significant differences between HSCT and non-HSCT patients [NR, (95% CI: 12.7-NR), vs. 6 months, (95% CI: 4-NR), P<0.001]. In univariate analysis, factors associated with lower OS were non-favourable ELN17 [8.9 vs 23.5, P=0.04]; ECOG≥2 [0.7 vs 12., P=0.002]; age ≥65 [7.9 vs NR, P=0.007] and male [6.6 vs NR, P= 0.007]. In multivariate analysis, age above 65 years [HR 1.6, P<0.001], male [HR -0.9, P=0.02] and ECOG≥2 [HR 1.9, P<0.001] were associated with OS. Image:Summary/Conclusion: Our real-life cohort was comparable to the target population of the pivotal trial including patients diagnosed with sAML (t-AML, AML-MRC and ELN17 high risk AML), obtaining similar outcomes than the CPX-351 phase 3 trial arm. To optimize treatment outcomes CPX-351 should be preferably offered to t-AML and AML-MRC patients who are suitable for HSCT.

P513: CPX-351 TREATMENT FOR ACUTE MYELOID LEUKEMIA IN ENGLAND: REAL-WORLD OUTCOMES IN ADULTS AGED &lt;60 YEARS VERSUS ≥60 YEARS

Background: CPX-351 (Vyxeos® liposomal) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. Since 2018, NICE and the EMA have recommended the use of CPX-351 for adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) due to prior myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) or de novo AML with myelodysplasia-related cytogenetic changes. Aims: To compare the characteristics and overall survival (OS) of younger (18–60 years) versus older (≥60 years) adults with AML who were treated with CPX-351 in England. Methods: This retrospective study utilized the Cancer Analysis System database available through England’s National Cancer Registration and Analysis Service. A diagnosis of t-AML or AML-MRC between 01/01/2013 and 31/03/2021 was determined either directly using International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes or indirectly using nonspecific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS/CMML (AML-MRC). OS was estimated from the diagnosis date or landmarked from the hematopoietic cell transplantation (HCT) date. Results: Overall, 211 patients with AML received CPX-351; their median (IQR) age was 65 (59, 70) years, 133 (63%) were male, 187 (89%) were White, 87 (41%) had secondary AML (t-AML or prior MDS/CMML), 33 (16%) had other AML-MRC, and 91 (43%) had unspecified de novo AML. Of the 60 (28%) patients aged <60 years, 12 were aged 18–44 years and 48 were aged 45–59 years. Of the 151 (72%) patients aged ≥60 years, 97 were aged 60–69 years and 54 were aged ≥70 years. The cutoff date for OS was 31/08/2021, with a median (IQR) follow-up of 11.3 (4.7, 20.1) months. The estimated median OS (95% CI) was 12.9 (10.5, 17.5) months overall, 18.5 (11.0, not estimable) months for adults aged <60 years, and 11.2 (8.5, 15.9) months for adults aged ≥60 years, with 2-year survival of 35%, 44%, and 32%, respectively (Figure). Early mortality at 30 days was 6% overall, 3% for adults aged <60 years, and 7% for adults aged ≥60 years. Among adults aged <60 years, HCT was reported for 29/60 (48%) patients, including 29/50 (58%) with ≥3 months of follow-up. Among adults aged ≥60 years, HCT was reported for 55/151 (36%) patients, including 55/115 (48%) with ≥3 months of follow-up. When landmarked from the HCT date, median OS was not reached in either age group (Figure). In a treatment patterns analysis, after receiving CPX-351, 14/60 (23%) adults aged <60 years and 63/151 (42%) aged ≥60 years died without salvage therapy, and 19/60 (32%) adults aged <60 years and 37/151 (25%) aged ≥60 years were alive without receiving subsequent therapy by the end of the study period. The most common salvage therapy after CPX-351 was FLAG-based chemotherapy (aged <60 years: n=12/60; aged ≥60 years: n=17/151). Image:Summary/Conclusion: This study provides real-world survival outcomes in younger and older adults with AML who were treated with CPX-351 in England. These results suggest CPX-351 is an effective treatment for patients with AML aged <60 and ≥60 years in a real-world setting that bridged many patients to HCT, with promising post-HCT outcomes.

Therapy-Related Acute Myeloid Leukemia (t-AML) and the Advantage of Intensive Chemotherapy: Real-Life Analysis from Two Regional French Centers

Rational: Patients with t-AML are those previously treated for primary malignancy and are categorized with poor prognosis. t-AML treatment options include intensive chemotherapy (IC), hypomethylating agents (HMA) or low dose cytarabine (LDC). However, survival remains poor and allogeneic hematopoietic cell transplantation (Allo-HCT) could lead to better outcomes. The aim of this analysis is to assess the outcome of all consecutive t-AML pts from two regional centers in France, based on treatment intensity, and to identify prognostic factors.Patients and Methods: between January 2006 and December 2019, 112 adult pts diagnosed with t-AML occurring after treatment of solid tumors (ST; n=72), hematologic malignancies (HM; n=34) or autoimmune diseases (AID; n=6). Pts received chemotherapy and/or radiotherapy or high dose chemotherapy followed by autologous hematopoietic cell transplantation (Auto-HCT) in some. All eligible t-AML pts received intensive chemotherapy (IC, n=55) with the combination of anthracycline and cytarabine in 48 pts and CPX-351 in 7 pts. Unfit pts received non-IC (9 LDC, 24 HMA). The third study group (24 pts) received best supportive care (BSC). Fifteen pts underwent HSCT in first CR.Statistical analysis: We performed a descriptive analysis of the baseline characteristics and each treatment group was compared with a Kruskal-Wallis test and a Pearson's Chi-square test. Survival curves (Kaplan-Meier method) were compared with a log-rank test. Univariate and multivariate analyses on survival, relapse and NRM were done using Cox regression, Gray test, Fine & Gray regression. The bilateral level of significance was set at 5%. All analyses and graphics were made under the R program (v3.5.1). A pair-matched control analysis with de novo AML was performed only on pts who received IC matched for age, cytogenetics and ELN 2010 classification.Results: A total of 112 t-AML pts were identified, 56 were males (50%) with a median age of 68 yrs (19-87) at t-AML diagnosis. Before t-AML, 72 pts had ST (64.5%), 34 HM (30.5%) and 6 AID (5%). Forty-six pts (41%) received chemotherapy alone for their primary cancer, 17 (15%) radiotherapy alone, 49 (44%) radio chemotherapy, 17 (15%) auto-HCT and 6 (5%) long-term methotrexate for AID. Median interval from treatment of previous ST or HM to t-AML diagnosis was 4.7 years in ST, 6.6 years in HM and 21 years in AID (p=0.03). At t-AML diagnosis, 42% of pts presented an unfavorable karyotype and 44% an unfavorable ELN 2010 classification. Regarding molecular alterations, FLT3-ITD, FLT3-TKD, NPM1 and IDH1/2 mutations were observed in 6.9, 2.3, 11.5 and 2.3% of pts respectively. MECOM1 was overexpressed in 25.5% of cases. Among treated pts (n=88), 43 pts (49%) achieved CR: 4 from 33 (12%) in non-IC pts (3 in HMA and 1 in LDC) and 39 from 55 (71%) in IC pts. Fifteen pts (17%) underwent Allo-HCT with a median interval between AML diagnosis and Allo-HCT of 4.7 mo (2.6-17.5). The best response after transplantation was CR in 10 pts; at the last follow up, 4 pts are alive (3 in CR and 1 in relapse) and 11 died (5 from relapse, 5 from TRM causes and 1 from another subsequent malignancy). Overall, with a median follow up of 5.5 mo (0-144), the median OS and DFS were 9 mo (5.9-13.5) and 6.3 mo (5.3-10.3) respectively (Figure). There was a significant difference between the 3 treatment groups concerning OS (p<0.001) and DFS (p<0.001) with a significant difference in OS between IC and non-IC groups (p=0.02). In the 88 treated t-AML pts, with a median follow up of 8.2 mo (0.3-144), the median OS was 13.5 mo (10.3-19.6) and the median DFS was 8.2 mo (7-13.7). Multivariate analysis for total and treated populations showed no impact of all variables related to previous malignancies except for auto-HCT pre-t-AML (significant negative impact on OS, DFS, NRM), WBC at t-AML diagnosis (negative impact on OS, DFS) and chemotherapy (positive in total population on OS, DFS, NRM and negative impact of IC on OS and NRM in treated pts) . In IC treated pts, we showed, in a pair-matched analysis with de novo AML, no difference in term of OS and DFS due to a significant higher CI of NRM (p=0.045) at 24 mo (40% in t-AML versus 27.4% for de novo AML) and a lower CI of relapse (NS) at 24 mo (33% in t-AML versus 47.6% for de novo AML).Conclusion: The prognosis of t-AML remains poor and our study showed the advantage of using intensive chemotherapy whenever possible and, in comparison with de-novo AML, a higher NRM and a lower incidence relapse. [Display omitted] DisclosuresNicolini: Sun Pharma Ltd.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kartos Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses, Research Funding; Incyte Biosciences: Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; BMS: Honoraria.

Clinical Outcome of t-AML with Respect to Genetic Abnormalities and Treatment Intensity - Single Center Analysis over the Past Two Decades

Background: Therapy-related acute myeloid leukemia (t-AML) represents emerging challenge of the modern oncology as a life-threatening complication of cytotoxic therapy. Disease characterises poor prognosis and presence of adverse cytogenetic and genetic abnormalities.The goal of the study: Clinical outcome of t-AML patients with respect to genetic changes and treatment intensity.Patients and methods: Retrospective analysis of all consecutive AML patients treated in years 2000-2021 in one hematological center was performed. Diagnosis of t-AML was established according to WHO 2016 criteria. Overall survival (OS) and progression free survival (PFS) was defined to evaluate treatment outcomes only within t-AML patients undergoing intensive treatment (standard induction/consolidation; allogeneic cell transplantation (alloHCT) if eligible).Results: Among 743 AML patients 60 (8.1%) were diagnosed as t-AML (38 woman) with median age 57 years. Solid tumors (ST) preceded t-AML in 63.3%, hematological neoplasms (HN) in 36.7%. Majority of t-AML was preceded by breast cancer (30.0%), Hodgkin Lymphoma (11.7%), non-Hodgkin Lymphoma (10.0%) and ovarian cancer (10.0%). Median latency time for ST and HN subgroups was 5 vs 7 years respectively (P = .036). Previous cytotoxic therapy consisted of chemotherapy, radiotherapy or combination in 56.6%, 18.3% and 25.0% (autologous cell transplantation was performed in 54.5% of HN).Cytogenetic and molecular biology analysis was performed in 44 and 27 of t-AML respectively. Cytogenetic abnormalities, complex karyotype and normal karyotype occurred in 78.9%, 28.9% and 15.8% patients. KMT2A, RUNX1-RUNX1T1 and PML-RARA rearrangement was found in 21.1%, 18.4% and 7.9% of t-AML. FLT3-ITD, FLT-TKD, NPM1 and C-KIT DNA sequence variant occurred as follows: 14.8%, 7.4%, 3.7% and 3.7% correspondingly. Three pathogenic TP53 DNA sequence variants were detected in t-AML patients: c.711G>A, c.704A>G and c.989T>C (analysis performed on 20 t-AML patients). According ELN2017 genetic risk stratification patients were classified as adverse, intermediate and favorable in 51.4%, 35.1% and 13.5% respectively.Intensive treatment was implemented in 48 patients including alloHCT in 23 of them. Median OS and PFS was 15 and 8 months respectively for whole treated group. Median OS in t-AML undergoing intensive chemotherapy only vs alloHCT was 7 vs 47 months (P = .0025) with 12-year OS after alloHCT- 21.1% (Fig.1A). Among therapy-related acute promyelocytic leukemia (t-APL) patients median OS was not reached, without alloHCT. Median OS was higher for t-AML patients younger than 65 years than older ones: 20 vs 13 months respectively (P = .048) (Fig.1B). Among t-AML median OS in subgroup with adverse ELN 2017 vs intermediate and favorable ELN 2017 was 15 vs 40 months (P = .037) with 5-years OS 8.2% vs 41.0% (Fig.1C). In multivariate Cox proportional hazard regression model alloHCT was the only factor significantly influencing OS (HR = 0.16, 95% CI = 0.05-0.56, P = .004).All patients with TP53 mutations were intensively treated, one patient underwent alloHCT. 66.6% of patients had complex karyotype and any co-occuring DNA sequence variant was detected. Importantly, c.704A>G and c.989T>C TP53 DNA sequence variants were not previously described in AML according Catalogue of Somatic Mutations In Cancer database. Median OS in t-AML with TP53 mutation vs without was 4 vs 7 months (P = .398) (Fig.1D).Conslusions: Our study brings detailed analysis of clinical outcome of t-AML. Patients with t-AML undergoing intensive treatment, younger than 65 years and with t-APL have significantly higher OS rates. On the contrary t-AML patients classified as adverse genetic ELN2017 subgroup have poorer OS rates. Treatment strategy in t-AML should rely on performing alloHCT possibly soon. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Real-World Study of CPX-351 Treatment Outcomes for Acute Myeloid Leukemia (AML) in England

Introduction: CPX-351 (US: Vyxeos ®; Europe: Vyxeos ® Liposomal) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. Since November 2018, the National Institute for Health and Care Excellence (NICE) has recommended its use for adults with newly diagnosed, therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) due to either prior myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) or de novo AML with myelodysplasia-related cytogenetic changes. The key aims of this study were to utilize the Cancer Analysis System (CAS) database available through the National Cancer Registration and Analysis Service (NCRAS) to describe the demographics and clinical characteristics of adults with AML in England who have received CPX-351, as well as to estimate overall survival (OS) and survival within stratifications of interest.Methods: The NCRAS systematically collects and curates population-level data about cancer diagnoses, treatments, and outcomes across England. Adults (aged ≥18 years) diagnosed with AML and treated with CPX-351 were included in this study. A diagnosis of t-AML or AML-MRC between January 2013 and March 2020 was determined either directly using International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes or indirectly using non-specific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with either prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS or CMML (AML-MRC; other AML-MRC subtypes could not be specifically identified and are included within the de novo AML subgroup). OS was measured from the date of diagnosis; a separate analysis of OS landmarked from the date of hematopoietic cell transplant (HCT) was also performed. Within this preliminary analysis, no OS adjustments have been made to account for any COVID-19-related deaths.Results: A total of 172 patients with AML who were treated with CPX-351 were identified: 37 (22%) had t-AML, 57 (33%) had AML-MRC, and 78 (45%) had de novo AML. At diagnosis, the mean (standard deviation) age was 62.8 years (10.1), with 49/172 (28%) patients aged <60 years; 66% of patients were male; 87% were white; and most had an Eastern Cooperative Oncology Group performance status of 0 or 1 (68%). Six (3%) patients had received azacitidine treatment for a prior malignancy. To date, 43/172 (25%) patients had undergone HCT overall, including 43/97 (44%) patients with ≥3 months of follow-up.The cut-off date for OS was December 31, 2020, giving a median (interquartile range) follow-up of 11.2 months (3.6, 16.9). Overall, 91 patients had died, with an estimated median OS (95% confidence interval [CI]) of 16.6 months (11.0, not estimable) and probability of survival (95% CI) at 1 and 2 years of 0.54 (0.47, 0.62) and 0.39 (0.30, 0.50), respectively (Figure 1). Early mortality rates were 7% at 30 days and 15% at 60 days. When OS was landmarked from the date of HCT, median OS was not reached, with a probability of survival (95% CI) at 1 year of 0.74 (0.62, 0.89; Figure 2). When stratified by age, estimated median OS (95% CI) was not reached for patients aged <60 years and 12.8 months (8.9, 17.6) for patients aged ≥60 years. In a treatment patterns analysis that evaluated second-line treatments after CPX-351, 68 patients died without salvage therapy and 64 were alive without receiving subsequent therapy by the end of the study period. The most common salvage treatments were fludarabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor (FLAG-Ida; n = 15), daunorubicin plus cytarabine (DA)-based therapy (n = 6), and azacitidine alone (n = 7). Of the 43 patients who received an HCT, 6 (14%) underwent HCT following salvage therapy.Conclusions: This is the largest study to date examining the real-world outcomes for patients with AML who were treated with CPX-351. The estimated median OS of 16.6 months is consistent with reported real-world outcomes for CPX-351 in French and Italian studies. Median OS has not been reached in patients aged <60 years or when landmarked from the date of HCT. Once the CAS database has been updated, these analyses will be repeated to increase follow-up and patient numbers and to determine the impact of COVID-19 on OS following CPX-351 treatment. [Display omitted] DisclosuresLegg: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Doubleday: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Reich: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Lambova: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Medalla: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.

AML-248: Clinico-Pathological Profile of Therapy-Related Acute Myeloid Leukemia

<h3>Context:</h3> Secondary acute myeloid leukemia (sAML) may arise from a previous clonal disorder of hematopoiesis, usually from myelodysplastic syndrome, chronic myeloproliferative neoplasm, or as a complication in patients receiving chemotherapy or radiotherapy for a primary malignancy, including hematological and non-hematological/solid malignancies (therapy-related AML [t-AML]). Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. It is associated with specific clinical features with a uniformly poor prognosis. <h3>Objective:</h3> To study patients of t-AML with respect to clinical presentation, laboratory parameters (including flow cytometry immunophenotyping), cytogenetic and molecular studies, and clinical outcome. <h3>Design:</h3> This study was a retrospective analysis of patients of t-AML from January 2011 to December 2019. <h3>Patients:</h3> The patients underwent a detailed hematological work up: peripheral blood smear, bone marrow examination along with flow cytometric immunophenotyping, and karyotyping and molecular studies (NPM1, FLT3ITD/TKD, BCR/ABL, PML/RARA, INV16, AML-ETO). Outcomes of the patients were also reviewed. <h3>Results:</h3> A total of 20 cases of therapy-related AML were diagnosed in patients treated for various malignancies of the breast (9 cases), prostate (3 cases), and pancreas (2 cases), as well as lymphomas (NHL: 4 cases and HL: 2 cases). There were 7 males and 13 females (M:F: 1:1.85) with a median age of 63 years (range 35–82 years). Median latency period to t-AML was 3.5 years (range 0.5–11.0 years). Median haemoglobin was 72.5 g/L (61–151 g/L), WBC count 3.7× 10⁹/L (1.02–169.1×10⁹/L), platelet count 40 × 10⁹/L (12–257 ×10⁹/L, peripheral blood and bone marrow blast percentage 48% (5-98%) and 76% (20–98%), respectively. AML with monocytic differentiation was the most common morphological and flow cytometric subtype (50% cases). Complex karyotype was seen in 50% cases. Molecular studies for NPM, FLT3ITD/TKD, PML/RARA, AML-ETO, and INV16 showed 8 cases with NPM1 positivity and 4 case with FLT3ITD positivity. Only 4 patients (20%) achieved complete remission but relapsed within 1 year of duration. Ten patients succumbed to their disease, the majority within 1 year of t-AML diagnosis. <h3>Conclusion:</h3> The study highlights the development of therapy-related AML following chemotherapy and/or radiotherapy as an important therapy-related complication. The latency period and clinical manifestations may differ depending on the type of cytotoxic drug, cumulative dose, and dose intensity. A close hematological follow-up should always be done for an accurate and timely diagnosis.

Predictors of outcomes of therapy-related acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

Background/ObjectiveExisting literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in therapy-related acute myeloid leukemia (t-AML) is confounded by the inclusion of patients with secondary AML and t-MDS. We aim to report our 20-year experience of HSCT in t-AML. MethodsWe retrospectively reviewed patients with t-AML who underwent HSCT. Patients were analyzed for prior malignancy, therapy, time to diagnosis of t-AML, transplant details, relapse-free survival (RFS), overall survival (OS), and predictors of outcomes. ResultsIn total, 68 patients (59.9% female; median age, 56.5 years) underwent HSCT. Acute and chronic graft-versus-host disease (GVHD) occurred in 39 (57.4%) and 23 (33.8%) patients, respectively. Cumulative incidence of relapse, nonrelapse mortality, RFS, and OS at 2 years were 17.9%, 34.5%, 47.6%, and 49.3%, respectively. Significant predictors of reduced OS were presence of 11q23 rearrangement (hazard ratio [HR], 3.24), using induction regimens other than FLAG-Ida or 7 + 3 (HR, 3.65), haploidentical donors (HR, 3.48), Eastern Cooperative Oncology Group performance status 2 or higher (HR, 5.83), and using cyclosporine A–methotrexate as GVHD prophylaxis (HR, 2.41). A significant decrement in survival was seen with an increasing number of any of these prognostic factors. ConclusionOutcomes of t-AML are satisfactory after allo-HSCT. Patients with t-AML with good-risk karyotypes, good performance status, having HLA-matched donors, and receiving intensive induction regimens have better outcomes after HSCT.

Therapy Related Acute Myeloid Leukemia in Solid Tumors: Two Pediatric Case Reports and Review of the Literature

Introduction: Therapy-related acute myeloid leukemia is devastating late effects in solid tumors. The most frequent and lethal secondary malignancy is secondary acute myeloid leukemia t-AML. t-AML is a sequel of specific chemotherapeutic agents, specifically alkylating agents, and topoisomerase II inhibitors, commonly used in treating solid tumors. t-AML is relatively rare with a poor prognosis. Case reports: We are reporting two cases of t-AML. Case 1: A 13-year-old girl presented with left hand swelling in 2014. Biopsy confirmed the diagnosis as Ewing sarcoma. She started a chemotherapy regimen that contained alkylating agents and epipodophyllotoxins. In 2017, local recurrence occurred, and she received salvage chemotherapy (ifosfamide, carboplatin, and etoposide) followed by amputation of the left 4th finger. In 2020, she had a second local recurrence with unexplained prolonged neutropenia. Diagnosis of t-AML was confirmed by bone marrow aspiration. Case 2: A 5-years-old boy presented with an abdominal mass in July 2006. It was diagnosed as rhabdomyosarcoma and treated with alkylating agents. He showed a good response to the treatment initially. In September 2007, prolonged pancytopenia, neutropenia, and thrombocytopenia occurred. Diagnosis of t-AML was confirmed by bone marrow aspiration as it showed mild dysplastic, moderate marrow fibrosis. Conclusion: t-AML is of growing interest to the pediatric oncologist and requires further studies to develop pathways for leukemogenesis. We discussed two cases to highlight the importance of designing treatment regimens for solid tumors associated with t-AML.

Potential Predictors of Induction Failure and Complete Remission Duration in FLT3-ITD Mutated Acute Myeloid Leukemia

Potential Predictors of Induction Failure and Complete Remission Duration in FLT3-ITD Mutated Acute Myeloid Leukemia

Acute Myeloid Leukemia Following Gynecologic Cancer in the Era of Platinum-Based Chemotherapy.

The aim of the present study was to estimate the risk of therapy-related acute myeloid leukemia (t-AML) in patients with gynecologic malignancies receiving chemotherapy using a population-based database. The National Cancer Institute's Surveillance, Epidemiology, and End Results database was accessed, and a cohort of women diagnosed with a primary ovarian, uterine, or cervical malignancy between January 1, 1992, and December 31, 2014, who received chemotherapy was selected. Those who subsequently developed AML were identified. Standardized incidence ratio (SIR) with 95% confidence intervals (CIs) and excess risk (ER) per 10,000 persons were calculated. Median overall survival of women with t-AML was calculated following generation of Kaplan-Meier curves. We identified 60,130 women who met the inclusion criteria; 56.4%, 19.4%, and 24.2% were diagnosed with ovarian, cervical, and uterine cancer, respectively. A total of 79 patients (0.13%) developed t-AML. The calculated SIR was 4.41 (95% CI, 3.49-5.50). For women with ovarian, cervical, and uterine cancer, the SIRs were 4.25 (95% CI, 3.13-5.66), 5.33 (95% CI, 2.92-8.95), and 4.26, (95% CI, 2.52-6.73), respectively. The highest risk was observed among women younger than 50 years (SIR, 11.69; 95% CI, 7.56-17.25). Median interval between gynecologic cancer and t-AML diagnosis was 40 months (range, 3-218 months), whereas median OS following the diagnosis of t-AML was 4 months (95% CI, 1.52-6.48 months). Therapy-related AML following chemotherapy treatment for a gynecologic malignancy is a very rare late treatment-related event associated with a poor prognosis.

Therapy-related acute myeloid leukemia following treatment for cancer in childhood: A population-based registry study.

Therapy-related acute myeloid leukemia (t-AML) is defined as AML that develops after exposure to cytotoxic chemotherapy and/or radiation therapy. There is a paucity of available literature, particularly in regard to t-AML following childhood cancer. Our aim was to describe the risk of t-AML among children treated for other cancers and their subsequent survival. We utilized data from the population-based Australian Childhood Cancer Registry to examine all childhood patients (<15 years at diagnosis) treated with chemotherapy and/or radiotherapy for cancers other than AML who received a subsequent diagnosis of AML between 1983 and 2014. Standardized incidence ratios (SIRs) were calculated to approximate the relative risk of being diagnosed with AML compared to the general population. Estimates of 5-year observed survival were obtained using the Kaplan-Meier method, with differences determined by the log-rank test. Fifty-eight of 11,753 patients in the study cohort (0.5%) were diagnosed with t-AML, an almost 50-fold higher risk than expected (SIR=45.6, 95% confidence interval [CI]=35.3-59.0). Five-year observed survival from the date of t-AML diagnosis was 31.2% (95% CI=19.6-43.5%). A significant survival advantage was found for patients who underwent hematopoietic stem cell transplantation (HSCT) following diagnosis of t-AML, with a 5-year survival of 52.4% (29.7-70.9%) compared to 5.7% (0.4-22.6%) for those who did not have HSCT (P<0.001). Although rare, t-AML is an important potential late effect of childhood cancer therapy. Prognosis is generally poor, with HSCT offering some survival benefit.

Therapy-related Acute Myeloid Leukemia After the Treatment of Primary Solid Cancer in Children: A Single-center Experience.

Therapy-related acute myeloid leukemia (t-AML) has a dismal prognosis and is one of the most frequent second malignant neoplasms which could be encountered by pediatric oncologists. Between October 2000 and September 2016, 16 patients who had primary solid tumors were diagnosed with t-AML at the Seoul National University Children's Hospital. The median patient age at the time of diagnosis of their primary solid tumors was 9.6 years (range, 0.1 to 15.4 y), and that of t-AML was 14.0 years (range, 4.7 to 23.9 y). The median latency period from the end of the primary tumor treatment to the initial diagnosis of t-AML was 29 months (range, 6 to 130 mo). Twelve patients achieved complete remission. Of them, only 7 patients underwent hematopoietic stem cell transplantation (HSCT). The 3-year overall survival (OS) rates and event-free survival rates were 33.7±12.2% and 26.9±11.5% respectively. The patients who underwent HSCT showed favorable 5-year OS rates (57.1±18.7%), whereas the 5-year OS rates of those who did not undergo HSCT was 0%. This study demonstrates that an achievement of complete remission and a subsequent HSCT can be the optimal solution for the treatment of t-AML, and this strategy showed acceptable outcomes.

Characteristics and Outcomes of Older Patients with Secondary AML According to Treatment Approach

BACKGROUND: Advanced age, AML arising from an antecedent hematologic disorder (AHD), and therapy-related AML (t-AML) are well established risk factors associated with poor outcome in AML. This subgroup of AML has been associated with lower rates of complete remission (CR) and shorter disease-free survival compared with de novo AML in younger patients (pts), when using standard therapy. Developing newer strategies to improve outcomes in this subgroup of pts is therefore a critical unmet need. Establishing baseline metrics from which to evaluate newer approaches is important. We sought to review our own experience with pts treated with different therapies at our institution to establish this baseline.METHODS: We retrospectively reviewed pts aged 60-75 years with newly diagnosed AML treated at our institution from 1990-2015 with one or more of the following characteristics: history of prior MDS, CMML, MPN, or aplastic anemia, the diagnosis of t-AML, or AML with karyotypic abnormalities characteristic of MDS as defined by the WHO. The pts were grouped into 5 study cohorts based on their treatment regimen: 1) High-dose Ara-C based intensive chemotherapy (HiDAC), 2) Hypomethylating agents (HMA)/HMA combinations, 3) Low-dose Ara-C combinations (LDAC), 4) Liposomal Ara-C:Daunorubicin (CPX-351), and 5) Other investigational agents (INV). Pts’ karyotypes were divided into 4 categories: adverse karyotype (complex: defined by >2 chromosomal abnormalities, Del 5/5q, Del 7/7q, 11q, 3q abnormality); diploid karyotype, intermediate karyotype (karyotype other than adverse or diploid); and unknown/not available. Endpoints included complete response (CR) rate/CR with low platelets (CRp) and 8-week mortality rates. Both univariate and multivariate analyses were performed to examine the relationships between disease characteristics and outcomes (CR, Overall survival).RESULTS: We evaluated a total of 931 pts with newly diagnosed AML meeting these criteria of age and secondary AML (s-AML). The baseline characteristics of pts in each group are summarized in table 1. The median age was 68 (60-75) years. Most pt characteristics were well balanced across the 5 treatment groups. Karyotyping was performed in 89% of the pts: 57.5% belonged to adverse risk profile and 31% belonged to intermediate risk profile (excluding diploid). The overall CR/CRp rates for the entire group was 39.5%. CR/CRp rates were lower in the HMA (36%) and INV (16%) groups compared to HiDAC (46%), CPX (45%) and LDAC (43%). Eight week mortality rate for the entire group was 20%: HiDAC (23%), HMA (12%), CPX (10%), LDAC (19%), and INV (27%). The median OS for the entire group was 6 months and by each treatment regimen is shown in Figure 1. There was a significant difference in OS between the 5 treatment groups. Pts receiving less intensive regimens [HMA + LDAC] had a superior median OS compared to those receiving HiDAC-based regimens (6.9 vs. 5.4; P=0.002, Figure 2). There was no difference in median survival in pts treated with CPX compared with conventional lower-intensity approaches (HMA + LDAC) (p=0.75). In the multivariate analysis, age >70yrs, adverse karyotype, and prior treatment for AHD were associated with a decreased OS. Similarly, use of HMA/INV treatment, adverse/intermediate risk karyotype, history of prior treatment for AHD were associated with lower CR rates.CONCLUSIONS: The outcomes of older pts with newly diagnosed s-AML are poor and reflective of their advanced age and poor-risk karyotype. Various treatment approaches have been attempted to improve outcomes. Lower-intensity approaches such as HMA and LDAC-based regimens have response rates similar to HiDAC regimens, but are associated with lower early mortality and improved overall survival. While the investigational liposomal formulation CPX-351was associated with favorable CR rates and low early mortality, the median OS was similar to pts treated with low intensity therapy. The unsatisfactory outcomes using other investigational agents in the INV group underscores the need for more effective therapies for these patients. [Display omitted] [Display omitted] [Display omitted] DisclosuresKantarjian:BMS, Pfizer, Amgen, Novartis: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. DiNardo:Celgene: Research Funding; Abbvie: Research Funding; Novartis: Other: advisory board, Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Agios: Other: advisory board, Research Funding. Jain:Celgene: Research Funding; Infinity: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Novimmune: Consultancy, Honoraria; Incyte: Research Funding; Abbvie: Research Funding; Novartis: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Seattle Genetics: Research Funding. Wierda:Acerta: Research Funding; Novartis: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Genentech: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

Therapy-related acute myeloid leukemia following treatment of lymphoid malignancies.

Therapy-related acute myeloid leukemia (t-AML) is a heterogeneous entity most frequently related to breast cancer or lymphoproliferative diseases (LD). Population-based studies have reported an increased risk of t-AML after treatment of lymphomas. The aim of this study was to describe the characteristics and outcome of 80 consecutive cases of t-AML following treatment of LD. t-AML accounted for 2.3% of all AML cases, occurred 60 months after LD diagnosis, and were characterized by a high frequency of FAB M6 AML and poor-risk cytogenetic abnormalities. Time to t-AML diagnosis was influenced by patient age, type of LD, and treatment. Among the 48 t-AML patients treated with intensive chemotherapy, median overall survival (OS) was 7.7 months compared to 26.1 months in de novo, 4.2 months in post-myeloproliferative neoplasm, 9.4 months in post-myelodysplastic syndrome, 8.6 months in post-chronic myelomonocytic leukemia AML, 13.4 months in t-AML secondary to the treatment of solid cancer, and 14.7 months in breast cancer only. OS of post-LD t-AML patients was significantly influenced by age, performance status, myelodysplastic syndrome prior to LD/t-AML, and treatment regimen for LD. Thus, t-AML following lymphoid malignancies treatment should be considered as very high-risk secondary AML. New treatment strategies in patients with LD/t-AML are needed urgently.

Prognostic Implication of Therapy-Related Acute Myeloid Leukemia after Comparative Analysis with De Novo acute Myeloid Leukemia

Background: Therapy-related acute myeloid leukemia (t-AML) is regarded as a complication after cytotoxic chemotherapy and/or radiation therapy, and also considered to have a poor survival outcome compared to de novo AML. We still have a question whether t-AML itself indicates a poor prognosis or whether the inferior outcome results from the association with such an adverse characteristics including cytogenetic risk or age or underlying malignancies.Methods: In this single center retrospective study, 1825 patients (median 46 years old [range, 17-92]) with variable karyotypes were enrolled from 2002 to 2013. Fifty-four (3.0%) patients had previous malignancies or autoimmune diseases, and all of them were treated with radiation or toxic chemotherapy before diagnosis of t-AML with a median duration of 36.3 months (range, 2.9-280.5). We analyzed clinical outcomes compared to 1771 de novo AML patients who were not related with any toxic therapies before.Results: Among 54 t-AML patients, 42 (77.8%) was in remission of prior malignant disease and 8 were in stable disease and 4 were in relapsed disease. In t-AML subgroup, median age was older (50 vs. 46 years old, p =0.119), leukocyte and bone marrow blast counts were significantly lower than de novo AML subgroup. There were more female patients in t-AML subgroup (70.3% vs. 45.4%, P =0.003). Among 38 female t-AML patients, 13 (34.2%) patients had breast cancer, 10 patients had hematological malignancies (i.e. APL in 5, lymphoma in 3, multiple myeloma in 2), and 8 (21.1%) had gynecological malignancies (i.e. ovarian and cervical cancer etc.). One or more chromosomal abnormalities (82.6% vs. 68.3%, P =0.015) and more adverse-risk karyotypes (41.2% vs. 20.0%, p<.001) were in t-AML subgroup. Especially, t-AML had more 5 or 7 chromosomal abnormalities (7.8% vs. 2.0%, P =.004) and complex karyotypes (27.5% vs. 7.6%, p<.001) which also included abnormal 5 or 7 chromosomes. Smaller number of t-AML patients received induction chemotherapy (74.1% vs. 87.6%, P =0.006) and early death rate was higher in t-AML group (22.2% vs. 13.7%, P =.083). After median follow-up of 70 months (range: 5.6-165.0), t-AML showed inferior 5-year overall survival (OS) compared to de novo AML (23.8% vs. 39.0%, p <.001). The result was more significant in intermediate to poor-risk group (9.2% vs. 30.0%, p<.001), but it was similar in favorable-risk group (75.0% VS. 62.8%, P =.532). In treated cohort, however, remission rate (70.0% vs. 79.3%, p =.149) and relapse rate (28.8% vs. 35.9%, p =.544) was not different, and multivariate analysis showed t-AML did not affect OS (HR=1.25, P =.185), while age >50 years old (HR=1.48, p<.001), hematopoietic cell transplantation (HCT, HR=0.37, p<.001), favorable-risk karyotype (HR=0.48, p<.001), and post-induction remission status (HR=0.26, p<.001) did. Five-year OS of t-AML patients treated with HCT (n=16) was 50.0%, and for intermediate to poor-risk subgroup treated with HCT, 5-year OS was 33.3%.Conclusion: In this study, t-AML was related with a larger proportion of adverse-risk karyotype, and many patients could not start induction chemotherapy due to old age, and remained prior malignant disease, which might result in poor survival outcome. On the other hand, response to induction chemotherapy of t-AML was similar with de novo AML consistent with a recent report (Kayser et al. Blood 2011). Therefore, if previous malignancy is in remission or in stable disease, aggressive treatment strategy using HCT may overcome poor survival outcome of t-AML. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Outcomes of Autologous Transplantation for Treatment-Related AML and MDS in Previously Treated Multiple Myeloma Patients (pts)

Introduction:Therapy related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) are significant long-term complications of MM treatment. We have treated pts on standard therapy protocols including TT2, TT3, TT4 and TT5. These protocols include an induction, tandem melphalan-based ASCT and consolidation, followed by three years of maintenance. As a part of the protocols, multiple bone marrow examinations including metaphase cytogenetics are performed at regular intervals, giving us the unique opportunity to examine the development of t-MDS/t-AML and understand the efficacy of subsequent treatment. Here we investigate the outcome of t-AML and t-MDS treated with autologous stem cell transplantation (ASCT) in MM patients.Materials and Methods, Results:During the period between 1998 to 2015, a total of 1558 pts were treated for MM with standard therapy protocols. We identified 68 pts out of 1558 who developed t-AML + t-MDS. Thirty-one had a confirmed diagnosis of t-AML, and thirty-seven had a diagnosis of t-MDS. The median age at diagnosis was 60 years (range 45-76). The median time from diagnosis MM of t-AML and t-MDS was 66 months (range, 9.6-155.4) and 63 months (range, 8-130), respectively. Baseline cytogenetics were as follows: complex cytogenetics in 34 pts out of 68, del(7) in 24 pts, del(5) in 17 pts, and del(17p) in 5 pts.Eighteen out of thirty-one t-AML pts were treated with ASCT. The remaining 13 pts did not receive ASCT. The treatment related mortality (TRM) at day100 (D100) in the ASCT group was 33% (6/18 pts). Neutrophil and platelet engraftment was achieved in all 18 pts by D21. Complete remission was achieved in 50% (9 out of 18) of pts. When we compared pts who received ASCT to those who were treated with chemotherapy only, the median overall survival (OS) was 11.28 months after ASCT vs 1.32 months without ASCT (p < 0.05). Nineteen out of thirty seven t-MDS pts were treated with ASCT. When we compared pts who received ASCT to chemotherapy only for t-MDS, there was no difference in survival between the groups. A mortality rate of 47% (9/19) was recorded at D200 after transplantation due to severe infections and lack of engraftment.Conclusion:t-AML and t-MDS treatment is a significant therapeutic challenge for the elderly, who often have poor risk cytogenetic markers, significant comorbidities and a compromised performance status. In our case series of post MM therapy t-AML, ASCT prolonged survival. In contrast, there was no change in survival of t-MDS pts, most likely due to high rate of infectious complications seen in this group. To our knowledge, this is the first analysis suggesting a survival benefit from ASCT in treating t-AML. Although the numbers in our study are small, we recommend that ASCT can be safely considered for t-AML patients who are physically fit, have autologous stem cells in storage and are overseen by a good supportive care team. These results need to be validated in large prospective studies. DisclosuresAtrash:University of Arkansas for Medical Sciences: Employment. Barlogie:Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; European School of Haematology- International Conference on Multiple Myeloma: Other: Travel Stipend; ComtecMed- World Congress on Controversies in Hematology: Other: Travel Stipend; International Workshop on Waldenström's Macroglobulinemia: Other: Travel Stipend; Dana Farber Cancer Institute: Other: Travel Stipend; Multiple Myeloma Research Foundation: Other: Travel Stipend; Myeloma Health, LLC: Patents & Royalties: Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC. Zangari:Onyx: Research Funding; Novartis: Research Funding; Millennium: Research Funding; University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Bailey:University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Heuck:Celgene: Consultancy; Janssen: Other: Advisory Board; Millenium: Other: Advisory Board; Foundation Medicine: Honoraria; University of Arkansas for Medical Sciences: Employment. Morgan:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; Weismann Institute: Honoraria; CancerNet: Honoraria; University of Arkansas for Medical Sciences: Employment; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jethava:University of Arkansas for Medical Sciences: Employment.

Therapy-related acute myeloid leukemia following radioactive iodine treatment for thyroid cancer.

Therapy-related acute myeloid leukemia (t-AML) associated with radioiodine treatment (RAI) is emerging as an important clinical entity with the rise in incidence of thyroid cancer. We conducted an electronic search of MEDLINE and EMBASE, and also searched reference lists of articles and abstracts from conference proceedings for case reports and review articles on t-AML following radioiodine therapy. A total of 37 patients with acute myeloid neoplasms following radioiodine treatment were analyzed. The median RAI dose was 324 mCi, and median age was 47.5 years with M/F ratio of 1:3. Latency period was 1-4 years, and the median time from RAI exposure to diagnosis of t-AML was 2.9 years. FAB M2 and M3 were the two most common t-AML subtypes reported. Seventy-one percent of the cases that reported cytogenetic abnormalities were classified as unfavorable. The most commonly reported abnormalities were del 5q and t(15:17). Survival outcomes were not reported due to lack of patient-level data. T-AML following radioiodine therapy for thyroid cancer appears to have a shorter latency period than other types of t-AML, which is an important consideration for post-therapy surveillance. Reporting of cases and outcomes will help provide data for further research. Identifying biomarkers that help risk-stratify patients prior to therapy and specific genetic-guided therapies may help improve outcomes.

Therapy-related acute myeloid leukemia in patients with lymphoma: A report of four cases and review of the literature.

Due to advances in the treatment of lymphoma, the remission and overall survival rates for this disease have improved in recent years. However, the incidence of therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) has increased. In order to further the understanding of the mechanisms of t-MDS/AML and reduce its incidence, the present study reports 4 cases of t-AML following treatment for lymphoma. The 4 patients presented aggressive forms of lymphoma in stage III/IV, and 3 were diagnosed with non-Hodgkin's lymphoma. All patients had previously undergone chemotherapy containing alkylating agents and/or topoisomerase II inhibitors. The latency period between the time of primary diagnosis and occurrence of t-AML ranged from 15 to 42 months. At the time of diagnosis of t-AML, 3 of the 4 patients presented pancytopenia, whilst the remaining patient exhibited leukocytosis. The majority of the patients succumbed to their disease within 1 year of t-AML diagnosis, with the exception of the patient in case 3, who survived following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The present cases indicate that an advanced stage of disease at the time of primary diagnosis, prior exposure to radiotherapy, and administration of ≥4 regimens and ≥8 cycles of chemotherapy may be risk factors for the development of t-AML. Based on the present findings and a review of the literature, we propose that allo-HSCT should be recommended for patients at high risk of developing t-AML. In addition, chimeric antigen receptor T-cell immunotherapy may constitute a novel type of immunotherapy for the treatment of cancer, particularly for cases of relapsed and refractory lymphoma or leukemia.