Double minute chromosomes in acute myeloid leukemia and myelodysplastic syndromes are associated with complex karyotype, monosomal karyotype, TP53 deletion, and TP53 mutations

Abstract Introduction Higher-risk myelodysplastic syndromes (MDS) progress to secondary acute myeloid leukemia (sAML) within months. Treatment with azacitidine (AZA) has been shown to prolong survival and delay progression to sAML. TP53 mutations are found in MDS with abnormal chromosome 5 or complex karyotype and are associated with poor prognosis. In particular, TP53 mutations confer resistance to lenalidomide in low-risk MDS with del(5q). However, whether TP53 mutations also influence response to AZA is unclear. Therefore, we analyzed the prevalence of TP53 mutations in a cohort of 100 patients with higher-risk MDS or sAML treated with AZA and correlated this to outcome. Patients and Methods 100 cases of higher risk MDS (IPSS INT-2 or High, n= 53), MDS/MPN (n= 8) or sAML (≥ 20% marrow blasts, n= 39) were included who had received at least one complete cycle of AZA (75 mg/m2 d1-7 q28) and for whom a bone marrow biopsy was available before the start of treatment. Presence of TP53 mutations was determined by immunohistochemistry [Iwasaki et al, Pathol Int 2008; Jädersten et al, JCO 2011; Kulasekararaj et al, Br J Haematol 2013]. Staining was defined as positive if ≥5% of CD34+ cells showed strong nuclear staining. In addition, 37 randomly selected cases were confirmed by sensitive next-generation amplicon deep-sequencing, demonstrating good correlation between both methods. Response to AZA was determined using IWG2006 criteria. Kaplan-Meier curves were estimated from the first day of AZA treatment with the log-rank test to determine significance. Patients who subsequently underwent allogeneic transplantation were censored at that date. Results Thirty-five patients (35%) had TP53 mutations. Both TP53 positive and negative cohorts were balanced in age (median 71 years) and number of administered AZA cycles (median 5/4, TP53 positive/negative, respectively). Of the TP53 positive patients, 68% had higher-risk MDS, 6% had MDS/MPN and 26% had sAML. Significantly more patients diagnosed with sAML had unmutated TP53 (46%, p=0.046). With regard to cytogenetics, only 23% of patients with TP53 mutations showed a good risk karyotype (KT) according to IPSS cytogenetic risk classification whereas 74% were diagnosed with poor risk KT. A closer look at the TP53 positive patients with poor risk cytogenetics revealed involvement of chromosome 5 aberrations in 77% compared to 33% in wild-type TP53 patients (p < 0.001). Of all 100 patients a total of 18 fulfilled the criteria for monosomal KT and 14 of these harbored TP53 mutations (77%, p < 0.001). There was no difference in pretreatment absolute neutrophil count or hemoglobin value in patients with or without TP53 mutations. The pretreatment median platelet count in TP53 mutated patients was significantly higher than in patients with wild-type TP53 (90 G/l vs. 43 G/l, respectively, p=0.021). The overall response rate (ORR) for patients with and without TP53 mutations treated with AZA was 74% (26/35) and 68% (44/65), respectively (n.s.). Quality of response did not show any differences between cohorts. However, hematologic improvement was significantly more frequent in patients with MDS and TP53 mutations than in MDS with wild-type TP53 (46% vs. 14%, p=0.015). Patients with complex KT and TP53 mutations responded as well as patients with wild-type TP53 to treatment with AZA (ORR 65% versus 53%, respectively, n.s.). Regarding the subgroup of patients with any kind of chromosome 5 abnormality within the complex KT group, there was a better ORR to AZA but no statistical significance between those with TP53 mutations compared to those with wild-type TP53 (75% vs. 43%, respectively). A similar result with respect to ORR was seen in the subgroup of patients with monosomal KT and the presence or absence TP53 mutations (ORR: 64% vs. 25%, respectively, n.s.). The median OS of the total cohort was 288 days, with a median OS of 212 days for TP53 positive patients and 353 days for TP53 negative patients (p = 0.731). Conclusion TP53 mutations in higher-risk MDS and sAML are frequent and predominantly associated with complex karyotype involving chromosome 5 abnormalities. In our cohort of 100 patients treated with AZA, the presence of TP53 mutations did not negatively impact on response to epigenetic therapy. However, although this analysis was not created for survival assessment it confirms the very poor survival for higher-risk MDS and sAML patients with TP53 mutations, in spite of response to AZA. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Germing:Celgene: Honoraria, Research Funding. Platzbecker:Celgene Corp: Honoraria. Götze:Celgene Corp: Honoraria.

Download Full-text

Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia

Annals of Hematology ◽

10.1007/s00277-020-04082-7 ◽

2020 ◽

Vol 99 (7) ◽

pp. 1551-1560

Author(s):

Heiko Becker ◽

Dietmar Pfeifer ◽

Gabriele Ihorst ◽

Milena Pantic ◽

Julius Wehrle ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Tp53 Mutations ◽

Monosomal Karyotype ◽

Acute Myeloid

Download Full-text

Validation of Monosomal Karyotype Based Model In the Risk Stratification of Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v116.21.2745.2745 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2745-2745

Author(s):

Murtadha K. Al-Khabori ◽

Karen Yee ◽

Vikas Gupta ◽

Aaron Schimmer ◽

Andre Schuh ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Risk Stratification ◽

Induction Chemotherapy ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Structural Abnormality ◽

Complex Karyotype ◽

Poor Risk ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 2745 Background: The influence of cytogenetic abnormalities on the prognosis of acute myeloid leukemia (AML) has been well-documented; however, the relative impact of certain miscellaneous abnormalities remains controversial. Recently, monosomal karyotype-based risk stratification has been shown to further discriminate the prognosis within the poor-risk karyotype group (Breems et al. JCO 2008), but this finding requires further validation. Methods: We retrospectively reviewed 779 consecutive adult AML patients treated with standard induction chemotherapy, consisting of daunorubicin plus cytarabine (3+7), at our institution from 1998–2008. After excluding patients with favourable risk, normal, missing or failed karyotype, 290 patients remained and were included in the analysis. Results: The baseline characteristics of these 290 patients were as follows: median age 59 y (range 18–81), male 181, prior malignancy 110, median white cell count (WBC) 7.6 × 10^9/L (range 0–246). The karyotypic features included single monosomy in 42, 2 or more monosomies in 51, and non-monosomy structural and numerical abnormalities in 197 patients. Of the 290, 116 (40 %) had three or more abnormalities (complex karyotype, CK). A total of 141 patients (49 %) achieved complete remission (CR) with 3+7 induction chemotherapy. Sixty-four patients received allogeneic stem cell transplantation in CR. The median overall survival (OS) for all patients was 12 months (95% CI: 10–14 months). The median OS was 10 (95% CI: 6–18), 7 (95% CI: 6–10) and 14 months (95% CI: 12–16) in the single monosomy, 2+ monosomy and non-monosomy groups, respectively (p < 0.0001 by log-rank test comparing the three groups). Among the patients containing at least one monosomy, the OS was not significantly different between the CK and non-CK groups (p = 0.08 by log rank). Similarly, in the non-monosomy structural abnormality group, the OS was not significantly different between the CK and non-CK groups (p = 0.2). Conclusions: Our results provide validation for the monosomal karyotype-based risk stratification for AML, indicating that patients with at least one monosomy have an inferior OS compared to other poor-risk non-monosomy groups. Within each of the monosomy and non-monosomy groups, the presence of a complex karyotype does not significantly influence the OS. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

The Influence of Monosomal Karyotype On Survival in Patients with Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Survey On Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v118.21.158.158 ◽

2011 ◽

Vol 118 (21) ◽

pp. 158-158 ◽

Cited By ~ 1

Author(s):

Angelique V.M. Brands-Nijenhuis ◽

Myriam Labopin ◽

Harry C. Schouten ◽

Liisa Volin ◽

Gérard Socié ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Complex Karyotype ◽

Hematopoietic Stem ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 158 Introduction: Monosomal karyotype (MK) has been shown to be associated with a very poor prognosis in AML patients (Breems, 2008). Whether allogeneic hematopoietic stem cell transplantation (alloHSCT) performed in an early phase can overcome the adverse prognosis in this cytogenetic patient category is currently unknown. To address this issue we performed a retrospective analysis on data from the registry of the EBMT among patients with primary AML who underwent alloHSCT in CR1. Patients and methods: A total of 4119 patients with primary AML and known cytogenetic abnormalities at diagnosis that underwent alloHSCT in CR1 were included in the analysis. Survival curves were calculated with Kaplan-Meier method. Log rank test and Cox regression analysis were used to determine statistical significance. Results: Median follow-up was 24 months (range 2–374). Overall, 171 patients (4.2%) fulfilled criteria for MK and 297 patients (7.2%) for complex karyotype (CK), with 115 patients fulfilling both conditions (MK and CK). Both the presence of a MK (2-yr OS: 35.5% versus 63.2%, p<0.0001) and CK (2-yr OS: 48.8% versus 61.9%, p<0.0001) were associated with a poorer outcome when compared with the remaining cytogenetics subtypes. Given the significant overlap between both categories, we further analyzed their prognostic impact after defining four subgroups of patients: MK but not CK (56 patients; MK+CK-), no MK but CK (180 patients; MK-CK+), MK and CK (115 patients; MK+CK+), and patients without either MK or CK (MK-CK-). Outcome of the MK-CK- subgroup did not differ according to cytogenetics. Patients harboring a MK, regardless concomitant presence of a CK, presented with a poorer OS after alloHSCT (2-yr OS: 31.7–43.0% versus 61.1%, p<0.0001). On the contrary patients with a CK but not MK showed a similar outcome than MK-CK- (2-yr OS: 61.1% versus 63.3%, p=0.170). Moreover, multivariate analysis confirmed the independent negative impact of MK (HR:1.90, range 1.5–2.4; p<0.0001) together with age, interval diagnosis-transplant, AML subtype, WBC at diagnosis, T-cell depletion, number of induction cycles and use of TBI during conditioning, whereas the presence of a CK did not retain its negative prognostic value. Conclusion: These results indicate that MK is a better indicator for poor outcome than CK after alloHSCT in patients with primary AML in CR1. Nonetheless, the potential curative role of alloHSCT for a subset of patients with MK should be further investigated. Reference: DA Breems, WLJ van Putten, GE de Greef, SL van Zelderen-Bhola, KBJ Gerssen-Schoorl, CHM Mellink, A Nieuwint et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 2008;26(29):4791–7. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

TP53 Alterations in Acute Myeloid Leukemia with Complex Karyotype Correlate with Specific Copy Number Alterations, Monosomal Karyotype, and Dismal Outcome,

Blood ◽

10.1182/blood.v118.21.3558.3558 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3558-3558 ◽

Cited By ~ 3

Author(s):

Frank G. Rücker ◽

Richard F. Schlenk ◽

Lars Bullinger ◽

Sabine Kayser ◽

Veronica Teleanu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Copy Number ◽

Myeloid Leukemia ◽

Multivariable Analysis ◽

Complex Karyotype ◽

Copy Number Alterations ◽

Free Survival ◽

Genomic Complexity ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 3558 Acute myeloid leukemia with complex karyotype (CK-AML, CK+) is defined as ≥3 acquired chromosome abnormalities in the absence of recurrent genetic abnormalities (WHO 2008). CK-AML account for 10–15% of all AML and are characterized by a dismal outcome. To delineate prognostic markers in this unfavorable subgroup, we performed integrative analysis using genomic profiling (array-comparative genomic hybridization [CGH] and/or single-nucleotide polymorphism [SNP] analysis), as well as TP53 mutation screening in 234 CK-AML. TP53 mutations were found in 141/234 (60%) CK-AML comprising 130 missense, 21 insertion/deletion, nine nonsense, and eight splice site mutations; genomic losses of TP53 were identified in 94/234 (40%). Combining these data, TP53 alterations were detected in 70% of patients, and at least 66% of these exhibited biallelic alterations. TP53 alterations (loss and/or mutation in TP53) were characterized by a higher degree of genomic complexity, as measured by total number of copy number alterations per case (mean±SD 14.30±9.41 versus 6.16±5.53, P <.0001), and by the association with specific genomic alterations, that is, monosomy 3 or losses of 3q (-3/3q-) (P=.002), -5/5q- (P<.0001), -7/7q- (P=.001), -16/16q- (P<.0001), -18/18q- (P=.001), and -20/20q- (P=.004); gains of chromosome 1 or 1p (+1/+1p) (P=.001), +11/+11q (P=.0002), +13/+13q (P =.02), and +19/+19p (P =.04); and amplifications in 11q13∼25 [amp(11)(q13∼25)]. The recently described cytogenetic category “monosomal karyotype” (MK), defined as two or more autosomal monosomies or one single autosomal monosomy in the presence of structural abnormalities, for which a prognostic impact could be demonstrated even in CK-AML, was correlated with TP53 alterations (P <.0001). Clinically, TP53altered CK-AML patients were older (median age, 61 versus 54 years, P =.002), had lower bone marrow (BM) blast counts (median 65% versus 78%, P=. 04), and had lower complete remission (CR) rates (28% versus 50%, P =.01). For multivariable analysis, a conditional model was used with an age cut point at 60 years to address the different treatment intensities applied in the different age cohorts. In this model the only significant factors for CR achievement were TP53altered (OR, 0.55; 95%-CI, 0.30 to 1.00; P =.05) and age (OR for a 10 years difference, 0.67; 95%-CI, 0.52 to 0.87; P =.003). TP53 altered predicted for inferior survival; the 3-year estimated survival rates for CK+/TP53altered and CK+/TP53unaltered patients were as follows: event-free survival (EFS), 1% versus 13% (log-rank, P =.0007); relapse-free survival (RFS), 7% versus 30% (P =.01); and overall survival (OS), 3% versus 28% (P <.0001), respectively. Other variables predicting for inferior OS in univariable analyses were age and MK. Among the cohort of CK+/MK+ AML, TP53altered patients had a significantly worse OS (P =.0004). Multivariable analysis (stratified for age at cut point of 60 years) revealed TP53altered (HR, 2.43; 95%-CI, 1.56 to 3.77; P =.0001), logarithm of WBC (HR, 1.62; 95%-CI 1.17 to 2.26; P =.004), and age (HR for 10 years difference, 1.26; 95%-CI, 1.01 to 1.56, P =.04), but not MK as significant variables for OS. In addition, explorative subset analysis suggested that allogeneic hematopoietic stem-cell transplantation in first CR which was performed in 30 CK-AML did not impact outcome in TP53altered CK-AML. In summary, TP53 is the most frequently known altered gene in CK-AML. TP53 alterations are associated with older age, genomic complexity, specific DNA copy number alterations, MK, and dismal outcome. In multivariable analysis, TP53 alteration is the most important prognostic factor in CK-AML, outweighing all other variables, including the MK category. TP53 mutational status should be assessed in clinical trials investigating novel agents in order to identify compounds that may be effective in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Patients with Monosomal Karyotype in Acute Myeloid Leukemia Is Prognostically Worse Than with Complex Karyotype

Blood ◽

10.1182/blood.v118.21.4735.4735 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4735-4735

Author(s):

Liu Xiaoli ◽

Xu Na ◽

DU Qingfeng ◽

Xu Dan ◽

Meng Fanyi ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Confidence Interval ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Disease Free Survival ◽

Structural Abnormality ◽

Complex Karyotype ◽

Significant Difference ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 4735 Purpose: Monosomal karyotype (MK) refers to the presence of two or more distinct autosomal monosomies or a single monosomy associated with a structural abnormality. To analyze the prognosis of cytogenetic components of a complex karyotype or Monosomal Karyotype in acute myeloid leukemia (AML) except acute promyelocytic leukemia(APL). Patients and Methods:Cytogenetics and overall survival (OS), Disease free survival(DFS) were analyzed in 551 AML patients age 14 to 60 years in our center.Results: There ware 235 patiets with cytogenetic abnormalities, 25 cases with inv(16)(p13.1q22) or t(16;16)(p13.1;q22),and 63 cases with t(8;21); 31 cases (13.2%)met the criteria for MK and 39 cases (16.6%) had a complex karyotype without monosomies. OS was significantly inferior in patients with MK compared with those with a complex karyotype without monosomies (P<0.01;HR 1.85,95% confidence interval(95%CI),0.95-2.81). There was no difference between MK cases with complex karyotype cases in DFS (P>0.05□GHR 3.42,95% confidence interval(95%CI),2.96-6.70). There was significant difference in regardless of whether OS or DFS between MK+ patients with MK− patients (P<0.01). Conclusion: MK was one of independent risk factor in AML patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Prognostic Value of Monosomal Karyotype in Patients with Primary Acute Myeloid Leukemia On Behalf of Spanish CETLAM Group.

Blood ◽

10.1182/blood.v114.22.1003.1003 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1003-1003 ◽

Cited By ~ 3

Author(s):

Isabel Granada ◽

Salut Brunet ◽

Montserrat Hoyos ◽

Dolors Costa ◽

Anna Aventín ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Conflicts Of Interest ◽

Treatment Strategies ◽

Disease Free Survival ◽

Prognostic Impact ◽

Complex Karyotype ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 1003 Poster Board I-25 Introduction: Recently, the cooperative group HOVON-SAKK has refined the prognostic impact of cytogenetic abnormalities in acute myeloid leukemia (AML) by introducing the concept of monosomal karyotype (MK). This consists of ≥ 2 autosomal monosomies or one autosomal monosomy in addition to a structural alteration. In their experience, MK would explain the poor prognosis of AML with a complex karyotype. Objective: To investigate the prognostic impact of MK in patients with primary (de novo) AML enrolled in the Spanish CETLAM group protocols (AML 94/99/03). Also, to determine whether considering MK added predictive value to the cytogenetic classification of the Medical Research Council (MRC). Methods: Retrospective analysis of data from 1149 AML patients. Chromosomal formula was centrally reviewed with karyotypes being classified by the presence of MK and allocated into the MRC risk categories. Complete remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were calculated. Results: The karyotype was assessable in 904 (79%) of the 1149 cases. In 145 of the 904 cases (16%), abnormalities involving CBF gene were detected and in 437 (48%) the karyotype was normal (NK). In 253 (28%) additional patients the karyotype was not monosomal; of them, 61 (24%) belonged to the unfavorable MRC with 17 cases harboring a complex karyotype ≥ 5 abnormalities, 7 cases with rearrangements 3q, 13 cases with -7, 9 cases with 5q abnormalities and 16 cases with t(6;9)). The remaining 69 (7.7%) patients had a MK; of them, 59 (85.5%) were from the unfavorable MRC category and included 43 cases with complex karyotype ≥ 5 abnormalities, 6 cases with rearrangements 3q, 5 cases with -7, 5 cases with alterations of 5q). The following table summarizes the results in terms of CR rate, DFS and OS: Conclusions: The addition of MK to the MRC cytogenetic classification refines the prognostic prediction. In our series, the dismal outcome of patients with MK is confirmed; these patients had worse prognosis than those with adverse cytogenetics without MK. Alternative treatment strategies are mandatory for MK+ patients. Supported in part by grants: GR1-01075, ECO07/90065, PI080672 and RD06/0020/0101. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Prognostic Implication of Chromosome 17 Abnormalities in the Context of Monosomal Karyotype (MK) in Patients with Acute Myeloid Leukemia (AML) and Complex Cytogenetics

Blood ◽

10.1182/blood.v118.21.1495.1495 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1495-1495

Author(s):

Aziz Nazha ◽

Vijaya R Bhatt ◽

Graciela Nogueras-Gonzalez ◽

Tapan Kadia ◽

Jorge E. Cortes ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Chromosome 17 ◽

Cancer Center ◽

Poor Performance Status ◽

Complex Karyotype ◽

The Impact ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 1495 Background: Monosomal karyotype (MK) is a stronger indicator of dismal clinical outcome than complex karyotype alone among patients with acute myeloid leukemia (AML) (J Clin Oncol 26: 4791–4797). We previously reported that Chromosome 17 abnormalities are associated with worse overall and relapse free survival among patients with AML and complex karyotype (ASH 2009, Borthakur et al #1501). Objectives: To investigate the impact of chromosome 17 abnormalities on the overall survival (OS) and eventfree survival (EFS) in AML patients (pts) with complex cytogenetics after monosomal karyotype is taken into account. Patients and Method: We conducted a review of 1086 pts with newly diagnosed AML treated at MD Anderson Cancer Center between January 1998 and December 2007. Four hundred eighty-three pts had complex cytogenetics defined by the presence ≥ 3 unrelated cytogenetic abnormalities and 37 patients were excluded from the final analysis because of poor performance status (≥ 3 ECOG) at presentation, a population least likely to be offered therapy. Monosomal karyotype (MK+) was defined as presence of at least an autosomal monosomy and a structural chromosomal abnormality or at least two autosomal monosomies. Cox proportional hazards regression was used to model the association between potential prognostic factors and survival (OS and EFS). The Kaplan-Meier product limit method was used to estimate the median time to death or event. Statistical analysis was performed using STATA/SE version 11.2 statistical software (Stata Corp. LP, College Station, TX). Result: Of the 446 pts with complex cytogenetics, 342 (76.7%) pts had MK and 183 (41.0%) pts had chromosome 17 abnormalities (Ch17+). The median age for the entire cohort was 64 years (range: 13–86). One hundred eighty-one (40.6%) pts achieved complete remission (CR/CRp) after induction chemotherapy, 173 (38.8%) pts had resistant disease and 89 (19.9%) had early death. Median OS among pts with MK+ was 4.7 months compared with 8.4 months in MK- patients (Hazard ratio [HR]: 1.37, 95%CI: 1.09–1.72, p=0.006) and was 4.4 months among pts with Ch17+ compared with 6.7 months for Ch17- (HR: 1.28, 95%CI: 1.05–1.55, p=0.014) (Fig.1). Within the group of patients with MK+, additional presence of Ch17 abnormalities was associated with worse OS (HR: 1.23, 95%CI: 1.00, 1.53, p=0.046).On multivariate analysis age, high WBC and MK+ (HR: 1.47, 95%CI: 1.17–1.85, p=0.001) were the variables associated with shorter OS to the exclusion of Ch17+. On the other hand age, higher WBC and Ch17+ (HR: 1.25, 95%CI: 1.04–1.50, p=0.019) were the variables that correlated to shorter EFS to the exclusion of MK+. Conclusion: Among patients with AML and complex cytogenetics, monosomal karyotype is associated with poor outcomes. Additional presence of chromosome 17 abnormalities further worsen outcome in this particularly poor-risk patients with AML. Disclosures: No relevant conflicts of interest to declare.

Download Full-text