The Prognostic Impact of the Revised IPSS Cytogenetic Scoring System for Patients with MDS Allows a Risk-Stratification for Patients with MDS-Derived Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1715-1715
Author(s):  
Friedrich Stölzel ◽  
Michael Kramer ◽  
Brigitte Mohr ◽  
Martin Wermke ◽  
Martin Bornhäuser ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Scoring System ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Poor Risk ◽  
The Impact ◽  
Acute Myeloid

Abstract Abstract 1715 Besides cytopenias and the medullary blast count, cytogenetic risk groups (good vs. intermediate vs. poor) according to IPSS are of main prognostic relevance for overall survival (OS) in patients with myelodysplastic syndrome (MDS). Recently, the revised IPSS (rIPSS) was introduced involving 5 (very good vs. good vs. intermediate vs. poor vs. very poor) instead of 3 cytogenetic risk groups, which better predict disease progression to MDS-derived acute myeloid leukemia (mdsAML) and OS of MDS patients receiving supportive care only. We analyzed the impact of the rIPSS-based cytogenetic scoring systems on the outcome of patients with AML undergoing intensive chemotherapy within the AML96, AML2003, and AML60+ trials of the Study Alliance Leukemia (SAL). This was done in an intention to compare its general prognostic influence as well as between patients with mdsAML and those with a de novo disease (dnAML). A total of 258 patients (median age 63 years, range 24 – 82) with mdsAML were identified and 258 patients with dnAML were matched with regards to age, gender, clinical trial, induction and consolidation therapy, respectively. Distributions of the cytogenetics in both groups according to MRC, IPSS and rIPSS score are shown in Table 1. Expectedly, the MRC cytogenetic scoring system revealed a stratification into two risk groups for patients with mdsAML with intermediate (3-year OS 27%) and adverse (3-year OS 10%), p=.004, and stratification into three groups for dnAML with favorable (3-year OS 50%), intermediate (3-year OS 32%) and adverse (3-year OS 10%), p=.001. When using the new rIPSS, this allowed a stratification of mdsAML patients with a 3-year OS of 28% for good+intermediate, 12% for poor, and 2% for very poor, p<.001, compared to 28% for good, 22% for intermediate, and 7% for poor risk cytogenetics according to the IPSS, p=.002. Importantly, the rIPSS allowed for a refined subdivision of patients within the poor and very poor group. By applying the rIPSS in dnAML patients we observed a 3-year OS of 34% for good+intermediate, 22% for poor, and 11% for very poor, p<.001, compared to 37% for good, 23% for intermediate, and 19% for poor risk cytogenetics according to the IPSS, p=.028. In conclusion, the rIPSS and IPSS-based classifications are feasible for prognostic risk stratification of patients with both dnAML and mdsAML. Interestingly, the rIPSS-based good and intermediate risk groups do not separate patients in both groups sufficiently. Furthermore, the rIPSS as compared to the current MRC-based cytogenetic scoring system allowed for a more concise distribution of mdsAML patients with the detection of a very poor (rIPSS) risk group with a dismal outcome. Table 1. dnAML, n=258 (%) mdsAML, n=258 (%) Cytogenetics MRC AML Good 16 (7) 0 Intermediate 210 (81) 179 (69) Poor 32 (12) 79 (31) Cytogenetics IPSS Good 158 (61) 121 (47) Intermediate 59 (23) 79 (31) Poor 41 (16) 58 (22) Cytogenetics rIPSS Very good 0 0 Good 167 (65) 131 (51) Intermediate 47 (18) 53 (20) Poor 18 (7) 34 (13) Very poor 26 (10) 40 (15) Disclosures: Platzbecker: Novartis: Consultancy; Celgene: Consultancy; GlaxoSmithKline: Consultancy; Amgen: Consultancy.

Clinical Implications of Reticulin Fibrosis of Bone Marrow in De Novo Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2585-2585
Author(s):  
Tzung-Chih Tang ◽  
Hung Chang ◽  
Chien-Feng Sun ◽  
Lee-Yung Shih ◽  
Po Dunn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Recovery Duration ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Abstract 2585 Background: Microenvironment of bone marrow (BM) plays an important role to support proliferation, renewal and differentiation of hematopoietic stem cells. Whether the stroma of BM affects leukemic cells with the same manner, or impacts on the prognosis in leukemia patients, has not been fully investigated. Previous studies have described that increased reticulin content in the BM is associated with poor outcome in patients with acute lymphoblastic leukemia, chronic myeloid leukemia and primary myelofibrosis, but there is no cohort study to determine the clinical correlation between degree of reticulin fibrosis of BM and acute myeloid leukemia (AML). To investigate prognostic impact of reticulin fibrosis on de novo AML, 881 patients diagnosed between Jun 1999 to Dec 2011 in Chang Gung Memorial Hospital and treated with anthracycline-containing induction chemotherapy were retrospectively reviewed. Patients and methods: According to the grading of reticulin content in the bone marrow, we categorized the 881 patients into four groups: A. BM easily aspirated without biopsy, n = 698; B. Reticulin grade 0, n = 99; C. Reticulin grade 1–2, n = 51; D. Reticulin grade 3–4, n = 33. The induction failure (IF) rate after treatment with induction chemotherapy, the recovery duration of absolute neutrophil count (ANC) greater than 0.5 × 109/L in patients who achieved the first complete remission, the overall survival (OS) and relapse-free survival (RFS) in four groups were analyzed. Based on the cytogenetic or molecular features, 648 of the patients were stratified into unfavorable, intermediate and favorable risk groups, and the clinical significance of reticulin fibrosis of BM were also examined for various risk groups. Results: Of the 881 patients, the patients in group D had a statistically higher IF rate (P = 0.0108) and longer ANC recovery duration (P = 0.0008). But the OS and RFS between four groups were not significantly different (P = 0.5146 and 0.3853, respectively). After risk stratified by cytogenetic and molecular analysis, increased reticulin content of BM (group C or D) had an adverse impact on OS in the intermediate and favorable risk groups (P = 0.006 and 0.0215, respectively). Conclusion: Reticulin content of BM influences the IF rate and myeloid recovery for the patients of de novo AML, and affects OS in patients with intermediate or favorable risk factors. Disclosures: No relevant conflicts of interest to declare.

WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5222-5231 ◽  
Author(s):  
Hsin-An Hou ◽  
Tai-Chung Huang ◽  
Liang-In Lin ◽  
Chieh-Yu Liu ◽  
Chien-Yuan Chen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Scoring System ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Normal Karyotype ◽  
Poor Prognostic Factor ◽  
Disease Evolution ◽  
Wt1 Mutation ◽  
The Impact ◽  
Acute Myeloid

Abstract The impact of WT1 mutations in acute myeloid leukemia (AML) is not completely settled. We aimed to determine the clinical implication of WT1 mutation in 470 de novo non-M3 AML patients and its stability during the clinical course. WT1 mutations were identified in 6.8% of total patients and 8.3% of younger patients with normal karyotype (CN-AML). The WT1 mutation was closely associated with younger age (P < .001), French-American-British M6 subtype (P = .006), and t(7;11)(p15;p15) (P = .003). Multivariate analysis demonstrated that the WT1 mutation was an independent poor prognostic factor for overall survival and relapse-free survival among total patients and the CN-AML group. A scoring system incorporating WT1 mutation, NPM1/FLT3-ITD, CEBPA mutations, and age into survival analysis proved to be very useful to stratify CN-AML patients into different prognostic groups (P < .001). Sequential analyses were performed on 133 patients. WT1 mutations disappeared at complete remission in all WT1-mutated patients studied. At relapse, 3 of the 16 WT1-mutated patients who had paired samples lost the mutation and 2 acquired additional mutations, whereas 3 of 110 WT1-wild patients acquired novel mutations. In conclusion, WT1 mutations are correlated with poor prognosis in AML patients. The mutation status may be changed in some patients during AML progression.

Prognostic Impact of Specific Chromosomal Aberrations in a Large Group of Pediatric Patients With Acute Myeloid Leukemia Treated Uniformly According to Trial AML-BFM 98

2010 ◽  
Vol 28 (16) ◽  
pp. 2682-2689 ◽  
Author(s):  
Christine von Neuhoff ◽  
Dirk Reinhardt ◽  
Annette Sander ◽  
Martin Zimmermann ◽  
Jutta Bradtke ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Chromosomal Aberrations ◽  
Myeloid Leukemia ◽  
Prognostic Impact ◽  
Monosomy 7 ◽  
Large Group ◽  
Cytogenetic Data ◽  
The Impact ◽  
Acute Myeloid

Purpose Because cytogenetic data are essential for risk stratification of childhood acute myeloid leukemia (AML), the impact of chromosomal aberrations is crucial. Patients and Methods Data of a large group of patients younger than 18 years treated according to study AML–Berlin-Frankfurt-Münster (BFM) 98 (n = 454), including their cytogenetics, were analyzed. Results The favorable outcome in the subgroups of patients with t(8;21), inv(16), and t(15;17), with an overall survival of 91% (SE, 4%), 92% (SE, 6%), and 87% (SE, 5%), respectively, was confirmed. Within this group, the 5-year probability of event-free survival (pEFS) of all 17 children with t(8;21) and additional aberrations apart from del(9q) or −X/−Y was 100%. As expected, the cytogenetic finding of a complex karyotype (n = 35; pEFS, 33%; SE, 8%) or a monosomy 7 (n = 12; pEFS, 17%; SE, 11%) was associated with a poor outcome. Compared with remaining patients with cytogenetic data (pEFS, 48%; SE, 2%), prognosis in patients with an MLL rearrangement (n = 91) was inferior (pEFS, 34%; SE, 5%; P = .0005). Particularly, children with t(9;11) and additional aberrations (n = 13; pEFS, 31%; SE, 14%) and MLL rearrangements other than t(9;11) and t(11;19) (n = 41; pEFS, 24%; SE, 7%) had an unfavorable outcome. Nine patients with aberrations in 12p showed an adverse prognosis (pEFS, 11%; SE, 10%). The outcome of patients with aberrations of chromosome 5 (n = 13) was better than expected (pEFS, 50%; SE, 13%). Conclusion Because the prognostic value of rare recurrent chromosomal aberrations still has to be elucidated, these data will contribute to future risk stratification for the treatment of pediatric AML.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

scholarly journals Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4188-4198 ◽  
Author(s):  
Sebastian Schwind ◽  
Guido Marcucci ◽  
Jessica Kohlschmidt ◽  
Michael D. Radmacher ◽  
Krzysztof Mrózek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Hox Genes ◽  
De Novo ◽  
Prognostic Significance ◽  
The Impact ◽  
Favorable Group ◽  
Acute Myeloid

AbstractLow MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene–embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.

scholarly journals Prospective Identification of Acute Myeloid Leukemia Patients Who Benefit from Gene-Expression Based Risk Stratification

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1397-1397
Author(s):  
Diego Chacon ◽  
Ali Braytee ◽  
Yizhou Huang ◽  
Julie Thoms ◽  
Shruthi Subramanian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Genetic Risk ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Risk Groups ◽  
High Fidelity ◽  
Improve Outcome ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a highly heterogeneous malignancy and risk stratification based on genetic and clinical variables is standard practice. However, current models incorporating these factors accurately predict clinical outcomes for only 64-80% of patients and fail to provide clear treatment guidelines for patients with intermediate genetic risk. A plethora of prognostic gene expression signatures (PGES) have been proposed to improve outcome predictions but none of these have entered routine clinical practice and their role remains uncertain. Methods: To clarify clinical utility, we performed a systematic evaluation of eight highly-cited PGES i.e. Marcucci-7, Ng-17, Li-24, Herold-29, Eppert-LSCR-48, Metzeler-86, Eppert-HSCR-105, and Bullinger-133. We investigated their constituent genes, methodological frameworks and prognostic performance in four cohorts of non-FAB M3 AML patients (n= 1175). All patients received intensive anthracycline and cytarabine based chemotherapy and were part of studies conducted in the United States of America (TCGA), the Netherlands (HOVON) and Germany (AMLCG). Results: There was a minimal overlap of individual genes and component pathways between different PGES and their performance was inconsistent when applied across different patient cohorts. Concerningly, different PGES often assigned the same patient into opposing adverse- or favorable- risk groups (Figure 1A: Rand index analysis; RI=1 if all patients were assigned to equal risk groups and RI =0 if all patients were assigned to different risk groups). Differences in the underlying methodological framework of different PGES and the molecular heterogeneity between AMLs contributed to these low-fidelity risk assignments. However, all PGES consistently assigned a significant subset of patients into the same adverse- or favorable-risk groups (40%-70%; Figure 1B: Principal component analysis of the gene components from the eight tested PGES). These patients shared intrinsic and measurable transcriptome characteristics (Figure 1C: Hierarchical cluster analysis of the differentially expressed genes) and could be prospectively identified using a high-fidelity prediction algorithm (FPA). In the training set (i.e. from the HOVON), the FPA achieved an accuracy of ~80% (10-fold cross-validation) and an AUC of 0.79 (receiver-operating characteristics). High-fidelity patients were dichotomized into adverse- or favorable- risk groups with significant differences in overall survival (OS) by all eight PGES (Figure 1D) and low-fidelity patients by two of the eight PGES (Figure 1E). In the three independent test sets (i.e. form the TCGA and AMLCG), patients with predicted high-fidelity were consistently dichotomized into the same adverse- or favorable- risk groups with significant differences in OS by all eight PGES. However, in-line with our previous analysis, patients with predicted low-fidelity were dichotomized into opposing adverse- or favorable- risk groups by the eight tested PGES. Conclusion: With appropriate patient selection, existing PGES improve outcome predictions and could guide treatment recommendations for patients without accurate genetic risk predictions (~18-25%) and for those with intermediate genetic risk (~32-35%). Figure 1 Disclosures Hiddemann: Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Bayer: Research Funding; Vector Therapeutics: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Metzeler:Celgene: Honoraria, Research Funding; Otsuka: Honoraria; Daiichi Sankyo: Honoraria. Pimanda:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Beck:Gilead: Research Funding.

scholarly journals Survival and Prognostic Factors in Adults Acute Myeloid Leukemia: A Retrospective Analysis of 119 Cases

2013 ◽  
Vol 1 (2) ◽  
pp. 70-73
Author(s):  
Alina M Gridjac ◽  
Cristian Daniel Pirlog ◽  
Anca Simona Bojan
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Risk Groups ◽  
Developed Countries ◽  
Risk Level ◽  
Secondary Aml ◽  
Cytogenetic Testing ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a malignant disease with significant identified prognostic factors. Therefore our aim was to develop an Assessment Scheme of Prognosis in AML based on prognostic factors. In some counties, such as Romania or other less-highly developed countries, this scheme would be beneficial particularly when cytogenetic testing is unavailable or time-intensive. Methods: We analyzed 119 adult patients with AML during a five year-period from a single-center in Romania. We retrospectively collected and analyzed data with Epi Info and Excel using patient medical records. Results: According to age, the group A1 (<60 years) had a 40 months survival, in contrast with the group B1 (≥60 years) with a survival of 19 months (p=0,0063). The group A2 (secondary AML) survived 15 months, whereas the group B2 (AML de novo) survived 40 months (p=0.0021). Additionally, the group A3 (mild comorbidities) achieved a 40 months survival, the group B3 (moderate comorbidities) survived 19 months, whereas the group C3 (severe comorbidities) survived 7 months (p=0,0059). According to WBC and blast number, the group A4 (high levels) had a 25 months survival, whereas the group B4 (low levels) survived 40 months (p=0,0057). Conclusion: The prognostic factors studied are useful to identify the risk level of AML disease for each patient at diagnosis. We developed an assessment scheme of prognosis with three risk groups according to age, secondary AML, comorbidity, WBC and blasts and cytogenetic examination.

The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2137-2145 ◽  
Author(s):  
Sabine Kayser ◽  
Konstanze Döhner ◽  
Jürgen Krauter ◽  
Claus-Henning Köhne ◽  
Heinz A. Horst ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Topoisomerase Ii ◽  
De Novo ◽  
Negative Impact ◽  
Primary Malignancy ◽  
De Novo Aml ◽  
The Impact ◽  
Acute Myeloid

Abstract To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P < .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P < .0001); t-AML patients had NPM1 mutations (P < .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P < .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.

Impact of Pretransplant Cytogenetics and Marrow Remission Status on Outcome of Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Stem Cell Transplantation Conditioned with Busulfan and Fludarabine

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 341-341
Author(s):  
Ebru Koca ◽  
Rima M Saliba ◽  
Marcos De Lima ◽  
Uday Popat ◽  
Partow Kebriaei ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Scoring System ◽  
Myeloid Leukemia ◽  
Remission Status ◽  
The Impact ◽  
Acute Myeloid

Abstract BACKGROUND: The purpose of this study was to determine the impact of cytogenetics and remission status on outcome of allogeneic stem cell transplantation (alloSCT) conditioned with busulfan and fludarabine based regimens for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: We retrospectively collected data on all consecutive patients (pts) who received busulfan and fludarabine with alloSCT at MD Anderson Cancer Center for AML and MDS between January 2001 and December 2007. All pts received busulfan and fludarabine in myeloablative (busulfan 130 mg/m2 for 4 days and fludarabine 40 mg/m2 for 4 days) or reduced intensity doses. ATG was added to the regimen for unrelated and mismatched related donor transplants. Pts in first complete remission (CR) or advanced CR (2nd or 3rd CR) and also pts with morphologic remission but platelet count &lt;100,000/mcl (termed “marrow remission”) were included. Pts were divided into subgroups according to cytogenetic abnormalities based on the MRC, SWOG, CALGB, and the recently described Dana-Farber (DF) categorization systems. Cox’s regression analysis was used to evaluate the impact of the prognostic factors on overall survival (OS), progression free survival (PFS) and non-relapse mortality (NRM). The cumulative incidence of NRM was estimated considering progression of disease as a competing risk. RESULTS: 215 pts were included in the analysis with a median age 47 (range 13–69). Four pts were less than 18 years old and 117 (54%) were older than 45 years. Diagnoses were AML (n=176), MDS (n=14) and AML evolving from MDS (n=25). Disease status at alloSCT was; first CR (n=111), advanced CR (n=65) and marrow remission (n=39). Donors were matched related (n= 114), matched unrelated (n=86), 1 antigen mismatched related (n=7), or 1 antigen mismatched unrelated (n=6). Stem cell source was bone marrow (n=84) or peripheral blood (n=131). Median follow-up time of surviving pts was 36 months (range 1.6–85). The 3 years actuarial probabilities of OS and PFS were 59% and 51%, respectively. The 3 years cumulative incidence of NRM was 22%. On univariate analysis, adverse cytogenetics according to the DF scoring system (but not the MRC, SWOG and CALGB classifications) was associated with a significantly lower OS (HR=1.8, P=0.03) and PFS (HR=1.7, P=0.02). Three year PFSs for pts in CR with favorable, intermediate or adverse cytogenetics were 58%, 56% and 49%, respectively (Figure 1). In addition, pts in marrow remission compared to those who were in first or advanced CR with full platelet recovery prior to transplant had a significantly poorer OS (41 vs 63 % at 3 yrs, HR=2.1, P=0.01), and PFS (33 vs 55% at 3 yrs, HR=1.9, P=0.01). Outcomes were comparable for pts in first and advanced CR (Figure 2). AML evolving from MDS was a significant adverse risk factor for OS (HR=1.9, P=0.04) but not for PFS (HR=1.6, P=0.08). On multivariate analysis, pts had the highest mortality rate if they had both a marrow remission and adverse cytogenetics, classified according to the DF system (HR (OS)=3.4, P&lt;0.001; and HR (PFS)=3.2, P&lt;0.001). A diagnosis of AML evolving from MDS remained as a significant adverse factor for OS on multivariate analysis (HR=2.1; P=0.01). Significant adverse prognostic factors for NRM on univariate and multivariate analysis included alloSCT later than one year after diagnosis (HR=2; P= 0.02) and AML evolving from MDS (HR=2.6; P=0.01). There was no impact of cytogenetics on the rate of NRM. CONCLUSION: Cytogenetic characteristics and remission status before alloSCT correlate with transplantation outcome in MDS or AML pts conditioned with busulfan and fludarabine. This regimen with alloSCT produced improved outcomes compared to published results with standard chemotherapy for pts in the intermediate and high risk cytogenetic groups. Figure 1. PFS by DF cytogenetic scoring system for patients in first and advanced CR. Figure 1. PFS by DF cytogenetic scoring system for patients in first and advanced CR. Figure 2. PFS by remission status prior to transplant. Figure 2. PFS by remission status prior to transplant.

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