Long-Term Prognosis of Acute Myeloid Leukemia According to the New Genetic Risk Classification of the European LeukemiaNet Recommendations: Evaluation of the Proposed Reporting System

2011 ◽  
Vol 29 (20) ◽  
pp. 2758-2765 ◽  
Author(s):  
Christoph Röllig ◽  
Martin Bornhäuser ◽  
Christian Thiede ◽  
Franziska Taube ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Reporting System ◽  
Young Patients ◽  
Risk Classification ◽  
Rank Test ◽  
Kaplan Meier ◽  
Heterogenous Group ◽  
Long Term Prognosis ◽  
Acute Myeloid

Purpose The current European LeukemiaNet (ELN) recommendations for acute myeloid leukemia (AML) propose a new risk reporting system, integrating molecular and cytogenetic factors and subdividing the large heterogenous group of intermediate-risk patients into intermediate-I (IR-I) and intermediate-II (IR-II). We assessed the prognostic value of the new risk classification in a large cohort of patients. Patients and Methods Complete data for classification were available for 1,557 of 1,862 patients treated in the AML96 trial. Patients were assigned to the proposed genetic groups from the ELN recommendations, and survival analyses were performed using the Kaplan-Meier method and log-rank test for significance testing. Results The median age of all patients was 67 years. With a median follow-up of 8.3 years, significant differences between all risk categories were observed in patients age ≤ 60 years regarding the time to relapse, relapse-free survival, and overall survival (OS). Patients in the IR-II group had a better prognosis than patients in the IR-I group. The median OS times in young patients with favorable risk (FR), IR-I, IR-II, and adverse risk (AR) were 5.3, 1.1, 1.6, and 0.5 years, respectively. Separate analyses in the age group older than 60 years revealed significant differences between FR, AR, and IR as a whole, but not between IR-I and IR-II. Conclusion In younger patients with AML, the ELN classification seems to be the best available framework for prognostic estimations to date. Caution is advised concerning its use for prospective treatment allocation before it has been prospectively validated. In elderly patients, alternative prognostic factors are desirable for further risk stratification of IR.

Effect of induction intensity on survival in patients with acute myeloid leukemia.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19004-e19004
Author(s):  
Kieran Sahasrabudhe ◽  
Melanie Rebechi ◽  
Ying Huang ◽  
Gregory Behbehani ◽  
Bhavana Bhatnagar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Rank Test ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Kaplan Meier ◽  
To Receive ◽  
Acute Myeloid

e19004 Background: Acute Myeloid Leukemia (AML) has traditionally been treated frontline with intensive induction chemotherapy in patients fit enough for this treatment. The FDA has approved several oral targeted therapies for AML in recent years. The survival impact of these agents vs induction chemotherapy is unknown. Methods: In this single-center, retrospective study, patients diagnosed with AML from 2015-2020 were included if they received treatment with either high intensity chemotherapy (HiC) or lower intensity targeted therapy (LITT). HiC was defined as a regimen containing cytarabine + anthracycline given on a “7+3” based schedule. Patients treated with liposomal cytarabine-daunorubicin were excluded. LITT was defined as venetoclax, gilteritinib, enasidenib, or ivosidenib alone or in combination with a hypomethylating agent. Patients fell into four groups: HiC only, LITT only, HiC followed by LITT, and LITT followed by HiC with assignment censored at transplant. Overall survival (OS) was estimated using Kaplan-Meier method and patients receiving any HiC vs LITT only were compared using log-rank test. Results: A total of 332 patients were included: 177 received HiC only, 116 LITT only, 32 HiC before LITT, and 7 LITT before HiC. Baseline characteristics and OS data are outlined in the table. The any HiC group had a lower median age and more patients with WBC >10 K/µL at diagnosis, as well as more patients receiving allogeneic hematopoietic cell transplant (HCT). OS was superior in the any HiC group vs LITT only group. Receipt of any HiC remained predictive of OS after adjusting for age (HR 0.65, 95% CI 0.44-0.96, p = 0.03); however, was no longer predictive of OS after adjusting for age and receipt of HCT. Conclusions: While HiC was associated with superior OS compared to LITT only treatment in univariable analysis, the survival benefit was no longer apparent after adjusting for age and receipt of HCT. The results suggest that intensity of AML treatment is less impactful on prognosis than ability to receive HCT. Differences in age were likely confounded by clinical trial eligibility and prescribing information specifically affecting patients receiving LITT. In the era of LITT, prospective randomized studies of intensity of AML therapy, particularly in non-favorable risk disease, are imperative to striking a balance between toxicity and cure for patients of all ages.[Table: see text]

scholarly journals Acute Megakaryocytic Leukemia (AMegL) Is Associated with Inferior Outcomes Relative to Other Acute Myeloid Leukemia (AML) Morphologies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2285-2285
Author(s):  
Smith Giri ◽  
Michael G Martin ◽  
Ranjan Pathak ◽  
Bojia Li ◽  
Philippe E Prouet
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Rank Test ◽  
P Value ◽  
Survival Curves ◽  
Kaplan Meier ◽  
Acute Megakaryocytic Leukemia ◽  
Acute Myeloid

Abstract Introduction: Acute Megakaryocytic Leukemia (AMegL) is a rare subtype of Acute Myeloid Leukemia (AML) resulting from uncontrolled proliferation of megakaryoblasts. Due to its rarity it is unclear if AMegL morphology is independently associated with outcomes in AML. Methods: We used the Surveillance, Epidemiology and End Results (SEER) 18 database to identify adult patients with AML diagnosed between 1991-2011 using the appropriate International Classification of Disease (ICD-O-3) histology codes. Cases of APL (M3) were excluded. Kaplan Meier Survival curves were generated to compare survival statistics between AMegL subtype and the rest of AML types. Multivariate analysis was done using Cox Linear Proportional Hazard Regression model. Statistical analysis was done using Statistical Package of Social Sciences (SPSS) version 21.0 (IBM Corporation, Armonk, NY). Results: Of 45,564 cases of AML identified, 304 (0.7%) belonged to the AMegL subtype. The median ages were 69 (range 18-111), and 67.5 (range 18-92) years, respectively (p value 0.08); the proportion of males were 54.3% and 59.2% respectively (p value 0.09), the median year of diagnosis was 2004 in AMegL versus 2002 in other AML. Whites comprised 82.6% and 84.7% respectively. The 5 year overall survival rates were 17.5% and 10.6% respectively. Kaplan Meier Survival curves showed significantly inferior survival for AMegL relative to other AML cases (p value of log rank test 0.01). On multivariate analysis AMegL was as an independent predictor of increased mortality (adjusted RR 1.23, 95% CI 1.09-1.38, p value <0.01), after adjusting for age of diagnosis, sex, race and year of diagnosis. This remained significant after removing core binding factor leukemia cases from the analysis (RR 1.21; 95% CI 1.07-1.36, p value <0.01) Conclusion: AMegL is a rare subtype of AML which is associated with significantly worse survival in comparison to other AML subtypes. We recommend that the National Comprehensive Cancer Network (NCCN) consider adding AMegL morphology to the list of adverse prognostic factors and as a reason to consider allogeneic stem cell transplantation. Table 1: Multivariate Analysis showing the independent predictors of survival in the study population. Variable RR 95% CI of RR P value Lower Upper AML M7 type 1.229 1.092 1.383 0.001 Race - White - American Indian/Alaska Native - Asian or Pacific Islander - Black 1.0 1.166 0.957 1.112 0.994 0.919 1.070 1.366 0.996 1.156 0.06 0.03 <0.01 Age at diagnosis 1.035 1.034 1.036 <0.01 Year of Diagnosis 0.985 0.983 0.987 <0.01 Male Sex 1.040 1.019 1.061 <0.01 Disclosures No relevant conflicts of interest to declare.

scholarly journals Chemotherapy Cannot Replace Transplantation in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5186-5186
Author(s):  
Xiaoyu Li ◽  
Baoan Chen ◽  
Jian Cheng ◽  
Min Lin ◽  
Xiaoping Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Univariate Analysis ◽  
Individual Therapy ◽  
Rank Test ◽  
Kaplan Meier ◽  
One Year ◽  
Acute Myeloid

Abstract Abstract Text: Objective: The mortality rate of refractory/relapsed acute myeloid leukemia (AML) is very high with poor prognostic. Three are still no standard treatments for these patients nowadays. Our research compared the treatment effect between patients with chemotherapy and transplantation. Method: A retrospective research of 45 patients with refractory/relapsed AML was performed in our center. We analyzed the clinical features including gender, age, classification of AML, performance status (PS), complete remission (CR) duration, cytogenetic and molecular abnormities. Survival analyses were made by using the Kaplan Meier method and took the Log - rank test. Results: The mean survival time of the 45 patients with refractory/relapsed AML was (36.25¡À8.40) months and the median follow up was (9¡À2.58) months. The one year and two years overall survival rate was (40.6¡À7.5)% and (23.7¡À7.0)%. Univariate analysis results demonstrated that age¡Ý60 years and failing to undergo HSCT after relapse had poor influence on OS. Conclusion: Performance of HSCT after relapse can improve the prognosis through the single center study. HSCT is still the effective salvage therapy for patients with refractory/relapsed AML. Our research is benefit for individual therapy and can be applied to improve the survival. Disclosures No relevant conflicts of interest to declare.

Identification of Distinct inv(16) Subclasses in Adult Acute Myeloid Leukemia Based on Gene Expression Profiling.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2037-2037
Author(s):  
Lars Bullinger ◽  
Claudia Scholl ◽  
Eric Bair ◽  
Konstanze Dohner ◽  
Stefan Frohling ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Target Genes ◽  
Expression Patterns ◽  
Rank Test ◽  
Survival Times ◽  
Strong Trend ◽  
Candidate Target ◽  
Acute Myeloid

Abstract Recurrent cytogenetic aberrations have been shown to constitute markers of diagnostic and prognostic value in acute myeloid leukemia (AML). However, even within the well-defined cytogenetic AML subgroup with an inv(16) we see substantial biological and clinical heterogeneity which is not fully reflected by the current classification system. To better characterize this cytogenetic group on the molecular level we profiled gene expression in a series of adult AML patients (n=26) with inv(16) using 42k cDNA microarrays. By unsupervised hierarchical clustering we observed that samples with inv(16) separated primarily into two different subgroups. These showed no significant differences regarding known risk factors like age, WBC, LDH, etc. However, these newly defined inv(16)-subgroups were characterized by distinct clinical behavior. There was a strong trend towards unfavorable outcome with shorter overall survival times in one group (P=0.09, log rank test). Since the primary translocation/inversion events themselves are not sufficient for leukemogenesis, distinct patterns of gene expression found within each of these cytogenetic groups may suggest alternative cooperating mutations and deregulated pathways leading to transformation. Therefore, we performed a supervised analysis to determine the characteristic gene expression patterns underlying the cluster-defined subgroups. This Significance Analysis of Microarrays (SAM) method identified 260 genes significantly differentially expressed between the two newly defined inv(16)-subgroups (false discovery rate = 0.002). High expression levels of JUN, JUNB, JUND, FOS and FOSB characterized the first inv(16) subgroup (having less favorable prognosis). FOS gene family members can dimerize with proteins of the JUN family, forming the transcription factor complex AP-1 which has been implicated in the regulation of cell proliferation, differentiation, and transformation. Among the second subgroup, the proto-oncogene ETS1,displayed elevated expression, possibly resulting from aberrant MEK/ERK pathway activation as these cases also showed an over-expression of MAP3K1 and MAP3K2. In conclusion, both supervised and unsupervised methods provide numerous insights into the pathogenesis of AML with inv(16), identifying clinically significant patterns of gene expression, as well as candidate target genes involved in leukemogenesis.

Acute GVHD May Play a Role in Preventing Relapse Following Reduced Intensity Allografts for Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1807-1807
Author(s):  
Leslie Andritsos ◽  
Kristan Augustin ◽  
Ravi Vij ◽  
John F. DiPersio ◽  
Steven M. Devine
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Initial Period ◽  
Single Agent ◽  
Unrelated Donor ◽  
Kaplan Meier ◽  
Full Intensity ◽  
Reduced Intensity ◽  
Acute Myeloid

Abstract The role of reduced intensity allografting in the treatment of patients (pts) with acute myeloid leukemia (AML) and the role that graft versus host disease (GVHD) plays in preventing relapse in this setting is unclear. While more pts may survive the initial period following allografting in comparison to those receiving full intensity transplants, the risk of relapse may be greater, particularly in those not in remission at the time of transplantation. Here we report the results of allogeneic transplants following a reduced intensity conditioning (RIC) regimen given to 158 consecutive pts with AML. All were all conditioned with an identical regimen containing Cyclophosphamide at 120mg/kg iv over 2 days (days −3 and −2) followed by a single dose of total body irradiation at 550cGy on day −1. HLA-identical (HLA-ID) siblings donated cytokine mobilized peripheral blood (PB) to 68 recipients and unrelated donor (UD) bone marrow (BM) was used for 90 patients. GVHD prophylaxis consisted of single agent cyclosporine (CSP) for recipients of HLA-ID allografts and CSP, methotrexate, and methylprednisolone in recipients of UD BM. The median age of recipients was 44 years (range 6–70), with 74 males and 84 females. 43 pts were in CR1, 47 in CR2 or 3, and 68 had relapsed or refractory disease. The majority of UD BM recipients were serologically identical with their donors at 6/6 antigens. There were no graft failures in either group.The median follow-up in survivors was long at 1903 days (range 938–2757). Overall survival (OS) was evaluated in relation to the development of any grade of acute GVHD. There were no significant differences in the incidence of grade 2–4 (30+/− 6%) or grade 3–4 (7+/−3%) acute GVHD in the HLA-ID PB or UD BM groups. Since OS was not significantly different between CR1 and CR2 pts, the results were pooled. The Kaplan-Meier (KM) estimate of 3 year OS in UD BM pts in CR was 45+/−9% in those with no acute GVHD compared to only 25+/−10% with any grade of acute GVHD (p=0.24). In recipients of HLA-ID PB who were in CR, 3 yr OS was 39+/−12% without acute GVHD and interestingly, 54+/−10% with acute GVHD. UD BM recipients not in remission at the time of transplant had dismal outcomes with or without acute GVHD, with less than 5% OS. No recipients of HLA-ID PB with active disease at the time of transplant remained alive if they did not develop acute GVHD versus 19+/−10% if they did (p=0.17).These data obtained in a large group of homogeneously treated pts suggest that acute GVHD may play an important role in preventing relapse after RIC and HLA-ID sibling PB transplantation. Following UD BM, acute GVHD appears to adversely affect OS. RIC should not be proposed in the unrelated donor setting if pts with AML are not in remission. Future efforts aimed at harnessing graft versus leukemia effects in the HLA-ID setting following RIC may lead to improvements in OS and are clearly warranted.

Gene Expression Profiling Identifies Distinct Subclasses in Core Binding Factor Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 673-673
Author(s):  
Lars Bullinger ◽  
Stephan Kurz ◽  
Konstanze Dohner ◽  
Claudia Scholl ◽  
Stefan Frohling ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Expression Patterns ◽  
The Other ◽  
Rank Test ◽  
Core Binding Factor ◽  
Log Rank Test ◽  
Binding Factor ◽  
Acute Myeloid

Abstract Recurrent cytogenetic aberrations have been shown to constitute markers of diagnostic and prognostic value in acute myeloid leukemia (AML). However, even within well-defined cytogenetic AML subgroups with an inv(16) or a t(8;21) we see substantial biological and clinical heterogeneity which is not fully reflected by the current classification system. Therefore, we profiled gene expression in a large series of adult AML patients with core binding factor (CBF) leukemia [inv(16) n=55, t(8;21) n=38] using a whole genome DNA microarray platform in order to better characterize this disease on the molecular level. By unsupervised hierarchical clustering based on 8556 filtered genes we observed that our CBF leukemia samples separated primarily into three different subgroups. While two of the subgroups were characterized by inv(16) and t(8;21) cases, respectively, the third subgroup contained a mixture of both cytogenetic groups. There was no obvious correlation with known secondary aberrations or molecular marker like FLT3-ITD, NRAS and KIT mutations between the cases in the mixed subgroup and the others. However, the newly defined inv(16)/t(8;21)-subgroup (n=35) was characterized by distinct clinical behavior with shorter overall survival times (P=0.029; log rank test) compared to the other two groups. Unsupervised analyses within the inv(16) and t(8;21) cases also revealed corresponding inv(16) and t(8;21) subgroups with a strong trend towards inferior outcome (P=0.11 and P=0.09, respectively; log rank test). Since the primary translocation/inversion events themselves are not sufficient for leukemogenesis, distinct patterns of gene expression found within each of these cytogenetic groups may suggest alternative cooperating mutations and deregulated pathways leading to transformation. Therefore, we performed a supervised analysis to determine the characteristic gene expression patterns underlying the cluster-defined subgroups. We identified 528 genes significantly differentially expressed between the newly defined inv(16)/t(8;21)-subgroup and the other CBF cases (significance analysis of microarrays, false discovery rate &lt; 0.001). Potential candidates for cooperating pathways characterizing the mixed inv(16)/t(8;21)-subgroup included e.g. AVO3, a member of the mTOR pathway, oncogene homologs like LYN and BRAF, as well as FOXO1A and IL6ST which have been previously identified to correlate with outcome in AML (Bullinger et al., N Engl J Med350:1605, 2004). In conclusion, while the observed signatures remain to be validated for their functional relevance, both supervised and unsupervised methods provide numerous insights into the pathogenesis of CBF AML, identifying clinically significant patterns of gene expression, as well as candidate target genes involved in leukemogenesis.

Expression of CD56 Is an Independent Prognostic Factor to Predict Relapse in Acute Myeloid Leukemia with t(8;21): Results of Japan Adult Leukemia Study Group (JALSG) AML97 Protocol.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2511-2511
Author(s):  
Noriyoshi Iriyama ◽  
Yoshihiro Hatta ◽  
Jin Takeuchi ◽  
Yoshiaki Ogawa ◽  
Shigeki Ohtake ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Univariate Analysis ◽  
Rank Test ◽  
Hematopoietic Stem ◽  
Wbc Count ◽  
Adverse Factor ◽  
Acute Myeloid

Abstract Abstract 2511 Background: Although prognosis of acute myeloid leukemia (AML) with t(8;21) is better than other types of AML, outcome of the patients has not been satisfied. Previously, aberrant antigen expression has been reported as risk factor for AML with t(8;21). However, in the reported series, number of cases was not large enough and chemotherapy regimens were variable. We investigated the association of prognosis and several biomarkers including immunophenotype, WBC count, age, and performance status for large number of AML patients with t(8;21) uniformly treated in JALSG AML97 regimen. Patients and Methods: Seven hundred eighty-nine eligible AML patients were evaluated for the multicenter JALSG AML97 study. Adult patients with de novo AML except for APL, ages 15–64 years, were registered consecutively from 103 institutions that participated in JALSG from December 1997 to July 2001. One hundred forty-four patients with AML with t(8;21) were analyzed in this study with a median 1205 days of observation term from diagnosis. Complete remission (CR), relapse-free survival (RFS), and overall survival (OS) rates were analyzed by Fisher's exact test and log-rank test. Factors that would affect clinical outcome were analyzed by multivariate Cox proportional hazard regression model. Results: AML with t(8;21) frequently expressed CD19, CD34, and CD56 compared to other subtypes of AML. CD11b was rarely expressed. Expression of CD19 favorably affected on CR rate (96% in CD19 positive and 87% in negative patients, p<0.05). Univariate analysis showed WBC>20×109/L, CD19 negativity, and CD56 positivity were adverse factors for RFS. CD56 expression was the only independent adverse factor for RFS by multivariate analysis (73.7% in CD56 negative and 48.2% in CD56 positive patients at 3 yrs) although its expression did not affect on OS. There was no difference of age, sex, WBC count, presence or absence of Auer rod, performance status, or CD15 expression between CD56 positive and negative cases. Expression of CD19 was more common in CD56 negative patients (50% in CD56 negative and 30.6% in CD56 positive patients, p<0.05). Conclusions: We demonstrated that the expression of CD56 was a distinctive adverse factor in a large number of AML patients with t(8;21) treated with JALSG AML97 regimen. CD56 positive AML patients with t(8;21) are possible candidates for hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Survival and Prognosis of Chinese Patients with Post-Polycythemia Vera Myelofibrosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1607-1607
Author(s):  
Jie Bai ◽  
Yuan Zhou ◽  
Lei Zhang ◽  
Mengyao Sheng ◽  
Rong Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Platelet Count ◽  
Polycythemia Vera ◽  
Myeloid Leukemia ◽  
Jak2v617f Mutation ◽  
Chinese Patients ◽  
Kaplan Meier ◽  
Wbc Count ◽  
Acute Myeloid

Abstract Objective: Polycythemia vera (PV) is a chronic progressive myeloproliferative neoplasm (MPN) characterized by pancytosis, especially the overproduction of red blood cells (RBCs), which is often associated with thrombocytosis and leukocytosis. Post-polycythemia vera myelofibrosis (post-PV MF) is a critical hematologic evolution of PV. Up to 20% of patients with PV evolves into life-threatening myelofibrosis. The current study aims to determine the possible risk factors for the occurrence and prognosis of post-PV MF in Chinese patients with PV. Molecular genetic tests for JAK2V617F and Exon12 of JAK2 are highly informative in the progression of patients with PV. Recently, ASXL1 mutation has been proposed as a prognostic marker for risk stratification in patients with primary myelofibrosis (PMF). We, thus, evaluated the prognostic significance of JAK2V617F allele burden (V617F %) and the concomitant of JAK2 activating mutation and ASXL1 loss of function in the evolution of PV. Methods: The clinical characteristics of a large cohort of 590 PV Chinese patients were evaluated retrospectively to determine the possible risk factors for the occurrence and prognosis of post-PV MF in Chinese patients with PV. The existence of JAK2V617F mutation in mononuclear cells of PV patients was detected at diagnosis with nested allele-specific PCR. The mutation in Exon12 of JAK2 and ASXL1 were determined by Sanger sequencing, and V617F % were analyzed by Taqman Real-time PCR. Results: We have found that the 10-, 15-, and 20-year overall survival (OS) of PV was 89.3%, 75.9%, and 65%. The incidence of thrombosis, post-PV MF and acute myeloid leukemia (AML) was 75.0/1000 (95% CI: 66.3-83.9), 24.1/1000 (95% CI: 19.7-28.4), and 3.0/1000 (95% CI: 1.5-4.5) person/year, respectively. Up to 19.83% of PV patients (117 of 590) developed post-PV MF. The incidence of 10-, 15-, and 20-year post-PV MF transformation was 19.3%, 33.7%, and 49.3%, respectively. OS was much lower in patients with post-PV MF compared that in the general Chinese population matched by age, sex, and calendar year. Multivariate analyses revealed that splenomegaly, WBC count >13 x 109 /L, and platelet count >550 x 109/L were independently associated with post-PV MF transformation. In the 117 patients with post-PV MF, 13 developed acute myeloid leukemia (AML), and the 5-year leukemia-free survival after diagnosis of post-PV MF was 87.4%. The results of multivariate Cox regression analysis showed that platelet count <100 × 109/L and patient age >65 years were independent risk factors for disease transformation into AML in patients with post-PV MF. Of the 346 patients with PV screened for JAK2V617F mutation, 273 patients were found to carry the JAK2V617F allele. The V617F % was examined in 104 patients with adequate DNA samples, and the median V617F% was 81.9% and 32.5% for patients with and without post-PV MF, respectively (p < 0.001). Kaplan-Meier analysis showed that myelofibrosis-free-surviva (MFS) was significantly reduced in PV patients with V617F % ≥50% compared with patients with V617F % <50% or no JAK2V617F mutation. Thirteen patients were found to carry ASXL1 mutation among 95 patients screened ASXL1 mutation, and all of these 95 patients were divided into four groups based on V617F% and the status of ASXL1 mutation: V617F % ≥50% with mutant ASXL1 (n=12), V617F % ≥50% with wt ASXL1 (n=48); V617F %<50% with mutant ASXL1 (n=1), and V617F %<50% with wt ASXL1 (n=32). By Kaplan-Meier analysis across all four groups, patients with both V617F % ≥50% and ASXL1 mutation had the worst MFS rates, with a 5-year MFS rate of 75.0%. Conclusion: PV has a higher incidence of progression to post-PV MF in Chinese patients. The risk factors for post-PV MF transformation included WBC count >13 x 109/L, platelet count >550×109/L and splenomegaly at diagnosis of PV. Anemia (Hg <100 g/L) and age >65 years at diagnosis of post-PV MF were identified as significant risk factors for poor survival of patients with post-PV MF. MFS was significantly lower in patients with V617F % ≥50% than in patients with V617F % <50%, and patients carried both V617F % ≥50% and ASXL1 mutation had the worst MFS rate. Disclosures No relevant conflicts of interest to declare.

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