AML-M4: Role of Eosinophilia and Cytogenetics on Treatment Response and Survival. The GIMEMA Experience.

Abstract Background: The acute myeloid leukemia (AML)-M4 subtype is frequently associated to eosinophilia and/or to the cytogenetic alteration inv(16)/t(16;16). The presence of these features is generally associated with good prognosis, but the studies concerning their exact role are hampered by the low number of cases. We retrospectively analyzed patients with AML-M4 enrolled in two consecutive GIMEMA studies to assess the influence of eosinophilia and of the inv(16) cytogenetic abnormality on the prognosis of acute myelomonocytic leukemia (M4) and acute myelomonocytic leukemia with abnormal eosinophils (M4eos). Setting: A retrospective study, conducted over 9 years in patients affected by AML, admitted to 35 Italian hematological divisions. Patients and methods: Between December 1993 and December 2002, 1686 patients aged over 15 years with a diagnosis of AML were admitted to the EORTC-GIMEMA AML10 and AML 99p trials; of these, 400 patients (355 M4 and 45 M4Eo) were studied. The diagnosis of M4 and M4eos was first established at each institution and subsequently centrally reviewed at the time of study entry. The following parameters were evaluated: morphology, immunophenotype, cytogenetics performed at the onset of the disease, complete remission achievement and duration, overall survival (OS) and event-free survival (EFS) from AML diagnosis. Patients with M4eo were younger and more frequently associated with inv(16) compared to M4. Cytogenetic analisis failed or was not carried out in 40% of cases, while it was successfully analyzed in 240 cases; inv(16) was found in 17% of them. Results: Concerning the probability of obtaining a CR after standard treatment, at univariate analysis M4Eo had a non significant advantage compared to M4, while presence of inv(16) was significantly correlated to a higher CR probability; multivariate analysis showed a significant advantage only of M4Eo+ inv(16) compared to M4-without eosinophilia and without inv(16). DFS was not different in univariate analysis between patients carrying or not inv(16), while a borderline advantage of M4Eo was observed with respect of M4, not confirmed at multivariate analysis. OS curves showed at univariate analysis a significant advantage both of the presence of eosinophilia (P=0.004) and of inv(16) (P=0.01); at multivariate analysis, patients with M4Eo+ inv(16) had a highly significant advantage compared to M4 without eosinophilia and without inv(16) (P=0.004), but also compared to M4+ inv(16) (P=0.045), and M4Eo-without inv(16) (P=0.076). Conclusions: AML-M4 with or without eosinophilia represent 23.7% of AML. The presence of eosinophilia and of inv(16)/t(16;16) can be both considered favorable prognostic factors; however, only the association of both features allows a highly significant advantage in terms of CR and OS.

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Treatment of Chronic Myelomonocytic Leukemia with 5-Azacytidine: Case Reports

Case Reports in Hematology ◽

10.1155/2012/369086 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Peter Rohon ◽

Jana Vondrakova ◽

Anna Jonasova ◽

Milena Holzerova ◽

Marie Jarosova ◽

...

Keyword(s):

Myeloid Leukemia ◽

Case Reports ◽

Quality Adjusted Life Year ◽

Chronic Myelomonocytic Leukemia ◽

Epigenetic Therapy ◽

Event Free Survival ◽

Free Survival ◽

Future Studies ◽

Myelomonocytic Leukemia ◽

Quality Adjusted Life

Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA) is common in the management of specific subtypes of myelodysplastic syndrome (MDS), but there are only few studies in chronic myelomonocytic leukemia (CMML) patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML) after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT), but in the control bone marrow aspirate (before ASCT) a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy.

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IDH1 mutations are detected in 6.6% of 1414 AML patients and are associated with intermediate risk karyotype and unfavorable prognosis in adults younger than 60 years and unmutated NPM1 status

Blood ◽

10.1182/blood-2010-02-267955 ◽

2010 ◽

Vol 116 (25) ◽

pp. 5486-5496 ◽

Cited By ~ 130

Author(s):

Susanne Schnittger ◽

Claudia Haferlach ◽

Madlen Ulke ◽

Tamara Alpermann ◽

Wolfgang Kern ◽

...

Keyword(s):

Myeloid Leukemia ◽

Cumulative Risk ◽

Intermediate Risk ◽

Age Group ◽

Event Free Survival ◽

Free Survival ◽

Idh1 Mutations ◽

French American British ◽

Acute Myeloid

Abstract Mutations in the IDH1 gene at position R132 coding for the enzyme cytosolic isocitrate dehydrogenase are known in glioma and have recently been detected also in acute myeloid leukemia (AML). These mutations result in an accumulation of α-ketoglutarate to R (2)-2-hydroxyglutarate (2HG). To further clarify the role of this mutation in AML, we have analyzed IDH1R132 in 1414 AML patients. We detected IDH1R132 mutations in 93 of 1414 patients (6.6%) with a clear prevalence in intermediate risk karyotype group (10.4%, P < .001). Although IDH1R132 mutations can incidentally occur together with all other molecular markers, there were strong associations with NPM1 mutations (14.2% vs 5.4% in NPM1wt, P < .001) and MLL-PTD (18.2% vs 7.0% in MLLwt, P = .020). IDH1-mutated cases more often had AML without maturation/French-American-British M1 (P < .001), an immature immunophenotype, and female sex (8.7% vs 4.7% in male, P = .003) compared with IDH1wt cases. Prognosis was adversely affected by IDH1 mutations with trend for shorter overall survival (P = .110), a shorter event-free survival (P < .003) and a higher cumulative risk for relapse (P = .001). IDH1 mutations were of independent prognostic relevance for event-free survival (P = .039) especially in the age group < 60 years (P = .028). In conclusion, these data show that IDH1R132 may significantly add information regarding characterization and prognostication in AML.

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Acute Myeloid Leukemia Treatment Outcomes: First Report from Single Center Retrospective Study in Kazakhstan

10.21203/rs.3.rs-757253/v1 ◽

2021 ◽

Author(s):

Jamilya Saparbay ◽

Gulnara Kulkayeva ◽

Vadim Kemaykin ◽

Aset Kuttymuratov ◽

Zhanna Burlaka ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Good Prognosis ◽

Event Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Acute Myeloid

Abstract Acute myeloid leukemia (AML) is the most common hematological malignancy in adults. In the last decade, internationally approved AML treatment guidelines, including hematopoietic stem cell transplantation are widely used in Kazakhstan. The categorization of acute myeloid leukemia was done according to the French-American British classification. The prognosis of patients at the time of diagnosis was determined by cytogenetic tests following the guidelines of the European LeukemiaNet. The overall survival and event-free survival were analyzed using the Kaplan-Meier method, and hazard ratios were defined with Cox regression. Totally 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The mean age was 38.3 years. We have found the correlation between ethnicity, cytogenetic group, white blood cell count, and treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group with a good prognosis compared with intermediate and poor prognosis. The median survival time in the group with a good prognosis was 43 months, 23 months in the intermediate group (p=0.7), and 12 months in the poor prognosis group (p=0.016). There was a significantly longer OS for the group of patients who received hematopoietic stem cell transplantation (HSCT), 52 months versus 10 months in the group who received chemotherapy only, p-value < 0.0001. Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated with patient survival. Our study data were consistent with previous reports.

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Sorafenib Versus Placebo in Addition to Standard Therapy in Younger Patients with Newly Diagnosed Acute Myeloid Leukemia: Results from 267 Patients Treated in the Randomized Placebo-Controlled SAL-Soraml Trial

Blood ◽

10.1182/blood.v124.21.6.6 ◽

2014 ◽

Vol 124 (21) ◽

pp. 6-6 ◽

Cited By ~ 30

Author(s):

Christoph Röllig ◽

Carsten Müller-Tidow ◽

Andreas Hüttmann ◽

Richard Noppeney ◽

Volker Kunzmann ◽

...

Keyword(s):

Myeloid Leukemia ◽

Standard Treatment ◽

Healthcare Research ◽

Newly Diagnosed ◽

Event Free Survival ◽

Bleeding Events ◽

Sorafenib Treatment ◽

Free Survival ◽

Risk Patients ◽

Double Blinded

Abstract Background: Sorafenib is a multi-kinase inhibitor with activity against several oncogenic kinases that may play a role in the pathogenesis of acute myeloid leukemia (AML). In-vitro data and results from non-randomized clinical trials suggest that sorafenib might be an effective drug for the treatment of AML. We present the results of the randomized placebo-controlled SORAML trial testing sorafenib versus placebo as add-on to standard induction and consolidation treatment in AML patients ≤60 years. Patients and Methods: Between March 2009 and October 2011, 276 patients from 25 centers were enrolled in the SORAML trial (NCT00893373). The main eligibility criteria were newly diagnosed AML, age from 18 to 60 years and suitability for intensive therapy. The treatment plan for all patients included two cycles of induction with DA (daunorubicin 60 mg/m2 days 3-5 plus cytarabine 100 mg/m2 cont. inf. days 1-7), followed by three cycles of high-dose cytarabine consolidation (3 g/m2 b.i.d. days 1, 3, 5). Patients without response after DA I received second induction with HAM (cytarabine 3 g/m2 b.i.d. days 1-3 plus mitoxantrone 10 mg/m2 days 3-5). Allogeneic stem cell transplantation was scheduled for all intermediate-risk patients in first complete remission with a sibling donor and for all high-risk patients with a matched related or unrelated donor. At study inclusion, patients were randomized to receive either sorafenib (800 mg/day) or placebo as add-on to standard treatment in a double blinded fashion. Block randomization at a ratio of 1:1 was performed within cytogenetic and molecular risk strata, allocation was concealed and treatment was double blinded. Study medication was given on days 10-19 of DA I+II or HAM, from day 8 of each consolidation until 3 days before the start of the next consolidation and as maintenance for 12 months after the end of consolidation. The primary endpoint of the trial was event-free survival (EFS) with an event being defined as either failure to achieve a complete remission (CR) after induction, relapse or death. Secondary endpoints were relapse-free survival (RFS), overall survival (OS), CR rate and incidence of adverse events (AE). We present the results of the final analysis of the primary endpoint EFS (intent to treat) after the occurrence of 134 events. Results: Out of 276 enrolled patients, 267 received study treatment, 134 in the sorafenib arm and 133 in the placebo arm. Demographic and disease characteristics were equally distributed between the two arms; the incidence of FLT3-ITD was 17%. The median cumulative dose of administered study medication was similar in both arms. The CR rates were 59% versus 60% in the placebo versus sorafenib arm (p=0.764). After a median observation time of 36 months, the median EFS was 9.2 months in the placebo arm and 20.5 months in the sorafenib arm, corresponding to a 3-year EFS of 22% versus 40% (p=0.013). Median RFS after standard treatment plus placebo was 23 months and not yet reached after sorafenib treatment, corresponding to a 3-year RFS of 38% and 56%, respectively (p=0.017). The median OS had not been reached in either arm; the 3-year OS was 56% with placebo versus 63% with sorafenib (p=0.382). In 46 FLT3-ITD positive patients, no difference in EFS, but a trend for prolonged RFS and OS in favor of sorafenib was observed. The most common reported AEs Grade ≥3 were fever (40%), infections (22%) and bleeding events (2%). The risk for fever, bleeding events and hand-foot syndrome was significantly higher in the sorafenib arm while the incidence of all other AEs showed no significant differences. Conclusions: In younger AML patients, the addition of sorafenib to standard chemotherapy in a sequential manner is feasible and associated with antileukemic efficacy. We observed a higher incidence of infections and bleeding events under sorafenib. Whereas OS in both treatment arms was similar, sorafenib treatment resulted in a significantly prolonged EFS and RFS. Figure 1: Event-free survival Figure 1:. Event-free survival Disclosures Off Label Use: sorafenib for treatment of aml. Serve:Bayer HealthCare: Research Funding. Ehninger:Bayer HealthCare: Research Funding.

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High miR-93 Expression Predicts Good Prognosis in Acute Myeloid Leukemia

10.21203/rs.3.rs-32079/v2 ◽

2021 ◽

Author(s):

Yan Liu ◽

Longzhen Cui ◽

Lin Fu

Keyword(s):

Myeloid Leukemia ◽

Prognostic Significance ◽

Good Prognosis ◽

The Cancer Genome Atlas ◽

Hematopoietic Stem ◽

Free Survival ◽

Prognostic Effect ◽

Cancer Genome Atlas ◽

Gastric Cancer Patients

Abstract Background: Overexpression of microRNA-93 (miR-93) predicted worse outcome in non-small cell lung cancer (NSCLC) and gastric cancer patients, yet the prognostic role of miR-93 in AML is still unclear.Methods: To further verify the prognostic significance of miR-93, the Cancer Genome Atlas database (TCGA) was screened and 161 AML patients with miR-93 expression information were included in our study.Results: Compared with the patients who received chemotherapy alone with lower miR-93 expression, those with higher miR-93 expression had significantly longer event-free survival (EFS) and overall survival (OS) (all P < 0.05). Moreover, the expression levels of miR-93 was no association with either EFS or OS in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Multivariate analysis confirmed that high miR-93 expression was an independent favorable factor for EFS and OS in AML patients only receiving chemotherapy (all P < 0.05).Conclusion: our study proved that high miR-93 expression could predict favorable prognosis in AML, but its prognostic effect could be overcome by allo-HSCT.

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A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome

Blood ◽

10.1182/blood-2007-11-124602 ◽

2008 ◽

Vol 112 (5) ◽

pp. 1638-1645 ◽

Cited By ~ 166

Author(s):

Stefan Faderl ◽

Farhad Ravandi ◽

Xuelin Huang ◽

Guillermo Garcia-Manero ◽

Alessandra Ferrajoli ◽

...

Keyword(s):

Older Patients ◽

Myeloid Leukemia ◽

Low Dose ◽

Response Rate ◽

Randomized Study ◽

Event Free Survival ◽

Front Line ◽

Free Survival ◽

Low Dose Cytarabine

AbstractWe previously reported the feasibility of clofarabine and cytarabine combinations in AML. Questions remain as to (1) the therapeutic advantage of this combination and (2) the role of lower doses of clofarabine and cytarabine in older patients. We have conducted an adaptively randomized study of lower-dose clofarabine with or without low-dose cytarabine in previously untreated patients with AML aged 60 years and older. Patients received 30 mg/m2 clofarabine intravenously daily for 5 days with or without 20 mg/m2 cytarabine subcutaneously daily for 14 days as induction. Consolidation consisted of 3 days of clofarabine with or without 7 days of cytarabine. Seventy patients were enrolled. The median age was 71 years (range, 60-83 years). Sixteen patients received clofarabine and 54 the combination. Overall, 56% achieved complete remission (CR). CR rate was significantly higher with the combination (63% vs 31%; P = .025). Induction mortality was 19% with the combination versus 31% with clofarabine alone (P = .276). The combination showed better event-free survival (7.1 months vs 1.7 months; P = .04), but not overall survival (11.4 months vs 5.8 months; P = .1). Clofarabine plus low-dose cytarabine has a higher response rate than clofarabine alone with comparable toxicity. This trial is registered at www.clinicaltrials.gov as no. NCT00088218.

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Gfi1 As a Novel Prognostic Marker and Tumor Suppressor In Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v122.21.2516.2516 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2516-2516

Author(s):

Judith Hönes ◽

Lacramioara Botezatu ◽

Amos Zeller ◽

Lars C. Michel ◽

Christian Thiede ◽

...

Keyword(s):

Stem Cells ◽

Myeloid Leukemia ◽

Complete Loss ◽

Expression Level ◽

Event Free Survival ◽

Free Survival ◽

Blast Cells ◽

Different Levels ◽

Lower Expression

Abstract The differentiation of hematopoietic stem cells to mature cells is essential for the function of the hematopoietic system. Disturbance of this process can lead to the emergence of Acute Myeloid Leukemia (AML). AML is characterized by an accumulation of immature, malignant blasts, which disturb the function of the “normal” hematopoietic cells. The differentiation to myeloid cells is regulated among others by transcription factors. Growth factor independence 1 (GFI1) is such a hematopoietic transcription factor regulating the differentiation of myeloid cells. We sought to investigate whether different Gfi1 levels are causative for emergence of AML and how different levels of Gfi1 might influence the prognosis of patients. Using published expression array data, we observed that Gfi1 is expressed at a lower expression level in blast cells and in leukemic stem cells compared to the control non-malignant cells and stem cells. We then correlated Gfi1 expression level in blast cells of patients from different centers in with the event free survival. In Essen and Dresden (Germany), low expression levels in blast cells were (n=39) associated with an inferior prognosis (EFS 9 months for low expression compared to 42 months; p=0.0095). We confirmed our observation with an independent cohort from Rotterdam and Nijmegen. Patients with low Gfi1 expression (n=32) had an inferior event free survival (9 months) compared to patients with higher Gfi1 levels (n=144; 17 months; p=0.02). To further investigate how different levels of Gfi1 might influence initiation and progression of leukemia, we used mice expressing Gfi1 at different levels, i.e. Gfi1 deficient mice (Gfi1KO), mice heterozygous for Gfi1 (Gfi1 het) or mice expressing Gfi1 only at 20% of normal Gfi1 expression levels (Gfi1KD). We used different murine AML models to examine the role of Gfi1 in AML development. First we crossed these mice with Nup98HoxD13 mice that recapitulate MDS disease course. We observed that knockdown of Gfi1 (Gfi1KD n=15, P=0.05) and heterozygosity of Gfi1 (Gfi1 het) (n=12) accelerated AML development and were associated with higher blast cell number compared to Gfi1 wt mice (n=16). Interestingly, complete loss of Gfi1 (Gfi1KO, n=16) inhibited leukemia development. To confirm our findings, we used an independent approach. It has been shown previously that enforced retroviral expression of certain onco-fusion proteins such as MLL-AF9 or AML1-ETO9a or proteins such as MN1 can cause AML in mice. To this end we transduced lineage negative (Lin-) cells from the different mouse strains with retroviruses overexpressing these different proteins and plated the Lin-cells in methycellulose media. Similar to above, transduced Gfi1 KD cells generated more colonies and proliferated at higher levels than wt or Gfi1 KO cells (ranging between 1,5 to 4 fold KD compared to wt, depending on oncofusionprotein or oncogene, p=0.05). We also transplanted these cells into lethally irradiated mice. Again, mice transplanted with MLL-AF9 transduced Gfi1 KD cells (n=6) developed leukemia faster than mice transplanted with transduced wt (n=8; p= 0.05). We hypothesized that if lower expression of Gfi1 promotes leukemia formation, then overexpression of Gfi1 should inhibit leukemia formation. To this end we transduced Lin neg cells simultaneously with retroviruses overexpressing either MLL-AF9 or AMLETO9a and either Gfi1 or an empty vector. The cells were then plated in methycellulose and cells overexpressing Gfi1 generated fewer colonies (between 3-5 fold less, depending on oncogene, p=0.01) than cells transduced with an empty control vector. Thus, up to now our data suggests that decreased levels of Gfi1 influence prognosis of AML development and are involved in the pathogenesis of AML. On a molecular level, we found that knock-down and complete loss of Gfi1 leads to deregulation of genes in AML development such as HoxA9. However, whereas Gfi1KD cells show a normal response to apoptotic events, complete loss of Gfi1 is associated with a very high level of spontaneous apoptosis, possibly explaining why knock-down but not complete loss of Gfi1 accelerates AML development. In summary we demonstrate that Gfi1 plays a crucial role in AML development depending on the expression level, which in turn might explain the role of Gfi1 in human AML. Disclosures: No relevant conflicts of interest to declare.

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High miR-93 Expression Predicts Good Prognosis in Acute Myeloid Leukemia

10.21203/rs.3.rs-32079/v1 ◽

2020 ◽

Author(s):

Yan Liu ◽

Zhiheng Cheng ◽

Longzhen Cui ◽

Yifan Pang ◽

Yifeng Dai ◽

...

Keyword(s):

Myeloid Leukemia ◽

Prognostic Significance ◽

Good Prognosis ◽

The Cancer Genome Atlas ◽

Hematopoietic Stem ◽

Free Survival ◽

Prognostic Effect ◽

Cancer Genome Atlas ◽

Gastric Cancer Patients

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First report from a single center retrospective study in Kazakhstan on acute myeloid leukemia treatment outcomes

Scientific Reports ◽

10.1038/s41598-021-03559-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

G. U. Kulkayeva ◽

V. M. Kemaykin ◽

A. M. Kuttymuratov ◽

Z. I. Burlaka ◽

J. Z. Saparbay ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Good Prognosis ◽

Event Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Acute Myeloid

AbstractAcute myeloid leukemia (AML) is the most common hematological malignancy in adults. In the last decade, internationally approved AML treatment guidelines, including hematopoietic stem cell transplantation are widely used in Kazakhstan. The categorization of acute myeloid leukemia was done according to the French-American British classification. The prognosis of patients at the time of diagnosis was determined by cytogenetic tests following the guidelines of the European LeukemiaNet. The overall survival and event-free survival were analyzed using the Kaplan–Meier method, and hazard ratios were defined with Cox regression. In total, 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The mean age was 38.3 years. We found a correlation between ethnicity, cytogenetic group, white blood cell count, and treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group with a good prognosis compared with intermediate and poor prognosis. The median survival time in the group with a good prognosis was 43 months, 23 months in the intermediate group (p = 0.7), and 12 months in the poor prognosis group (p = 0.016). There was a significantly longer OS for the group of patients who received hematopoietic stem cell transplantation (HSCT), 52 months versus 10 months in the group who received chemotherapy only, p-value < 0.0001. Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated with patient survival. Our study data were consistent with the most recent studies, available in the literature adjusted for the population in question.

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Quantification of VEGF Isoforms and VEGFR Transcripts by qRT-PCR and Their Significance in Acute Myeloid Leukemia

The International Journal of Biological Markers ◽

10.1177/172460080902400104 ◽

2009 ◽

Vol 24 (1) ◽

pp. 22-31 ◽

Cited By ~ 10

Author(s):

Samia Mourah ◽

Raphaël Porcher ◽

Géraldine Lescaille ◽

Philippe Rousselot ◽

Marie-Pierre Podgorniak ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Prognostic Impact ◽

Mrna Levels ◽

Event Free Survival ◽

Free Survival ◽

The Impact ◽

Acute Myeloid

Vascular endothelial growth factor (VEGF) and its receptors are known to play an important role in normal and pathological hematopoiesis but the prognostic impact of VEGF isoform transcripts in acute myeloid leukemia (AML) has not been addressed. We conducted a single-institution prospective study to analyze the impact of these angiogenic factors and the expression of their receptors on the survival of adult patients newly diagnosed with AML. We investigated the levels of VEGF transcript isoforms VEGF121, -145, -165, -189 and -206 and their receptors, VEGFR-1 and VEGFR-2, using quantitative reverse transcriptase polymerase chain reaction assays in peripheral blood mononuclear cells (PBMCs) of 67 consecutive AML patients at diagnosis. VEGF total protein was measured for comparison with mRNA levels in PBMCs. The VEGF121 splice variant transcript in AML PBMCs was significantly higher than in the normal controls. VEGF transcripts were quantified in all samples while its protein was detected in 42/67 (63%) of AML samples. High levels of VEGF121, VEGF165 transcripts and VEGF protein in AML were significantly related to a worse prognosis when analyzing overall survival (p<0.0001, p=0.019 and p=0.012, respectively) or event-free survival (p<0.0001, p=0.010 and p=0.047) using univariate analysis. In multivariable analysis only VEGF121 expression remained an independent prognostic factor for either event-free survival or overall survival [aHR=8.83 (3.48–22.4), p<0.0001, and aHR=9.52 (3.41–26.6), p<0.0001]. No prognostic value was observed for the other isoforms and the two receptors. Our findings show that the level of VEGF121 mRNA in circulating cells from AML patients is a strong independent prognostic parameter, which could be useful in the management of unselected AML patients.

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