IPSS Independent Prognostic Value of Plasma CXCL10, IL-7 and IL-6 Levels in De Novo Myelodysplastic Syndromes,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3795-3795
Author(s):  
Animesh Pardanani ◽  
Christy Finke ◽  
Terra L Lasho ◽  
Aref Al-Kali ◽  
Kebede Begna ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
Plasma Levels ◽  
Prognostic Value ◽  
De Novo ◽  
Primary Myelofibrosis ◽  
Plasma Cytokine ◽  
Plasma Cytokines ◽  
Normal Mean

Abstract Abstract 3795 Recent studies suggest a powerful prognostic value for plasma cytokine levels in primary myelofibrosis (IL-2R, IL-8, IL-12, IL-15 and CXCL10) and large cell lymphoma (IL-2R, IL-8, IL-10, IL-12, CXCL9 and CXCL10). In order to examine the possibility of a similar phenomenon in myelodysplastic syndromes (MDS), we used multiplex ELISA to measure 30 plasma cytokines in 78 patients with primary MDS. Compared to normal controls (n =35), the levels of 19 cytokines were significantly altered. Multivariable analysis identified increased levels of CXCL10 (p<0.01), IL-7 (p=0.02) and IL-6 (p=0.07) as predictors of shortened survival; the survival association remained significant when the Cox model was adjusted for the international prognostic scoring system (IPSS), age, transfusion-need or thrombocytopenia. MDS patients with normal plasma levels of CXCL10, IL-7 and IL-6 lived significantly longer (median survival 76 months) than those with elevated levels of at least one of the three cytokines (median survival 25 months) (p<0.01). Increased levels of IL-6 were associated with inferior leukemia-free survival, independent of other prognostic factors (p=0.01). Comparison of plasma cytokines between MDS (n =78) and primary myelofibrosis (n =127) revealed a significantly different pattern of abnormalities. These observations reinforce the concept of distinct and prognostically-relevant plasma cytokine signatures in hematologic malignancies.Figure:Survival data for 78 patients with de novo myelodysplastic syndrome (MDS) stratified based on plasma levels of CXCL10, IL-7 and IL-6: (i) normal levels of all 3 cytokines (top curve), or (ii) increased (> 3 standard deviations of the normal mean level) level(s) of one or more of the aforementioned cytokines (bottom curve) (p=0.002).Figure:. Survival data for 78 patients with de novo myelodysplastic syndrome (MDS) stratified based on plasma levels of CXCL10, IL-7 and IL-6: (i) normal levels of all 3 cytokines (top curve), or (ii) increased (> 3 standard deviations of the normal mean level) level(s) of one or more of the aforementioned cytokines (bottom curve) (p=0.002). Disclosures: No relevant conflicts of interest to declare.

Prognostic Significance of Serial Determinations of LDH Levels in Primary (De Novo) Myelodysplastic Syndromes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4828-4828
Author(s):  
Friedrich Wimazal ◽  
Wolfgang R. Sperr ◽  
Anja Vales ◽  
Michael Kundi ◽  
Alexandra Boehm ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lactate Dehydrogenase ◽  
Disease Progression ◽  
Myelodysplastic Syndromes ◽  
Prognostic Value ◽  
De Novo ◽  
Prognostic Significance ◽  
Bone Marrow Examination ◽  
Probability Of Survival

Abstract An increased lactate dehydrogenase (LDH) level at diagnosis is associated with a reduced probability of survival and an enhanced risk of AML development in primary (de novo) myelodysplastic syndromes (MDS). However, so far, little is known about the prognostic value of an increase in LDH levels during the follow up in these patients. We have serially determined LDH levels in 221 patients (102 males, 119 females) with de novo MDS (median age 70 years; FAB-types: RA, n=62; RARS, n=46; RAEB, n=48; RAEBT, n=36; CMML, n=29), and examined the prognostic value of LDH as a follow-up parameter. Confirming previous data, an elevated LDH level at diagnosis was found to be associated with a significantly increased probability of AML evolution and a significantly decreased probability of survival (p&lt;0.05). In the follow up, an increase in LDH (from normal to elevated) was found to be associated with progression of MDS and AML evolution in most cases. Moreover, in those patients who progressed to AML, LDH levels were found to be significantly higher in the two three-months-periods preceding progression compared to the two initial three-months-periods examined (p&lt;0.005). In most patients, the increase in LDH was accompanied or followed by other signs of disease progression, such as the occurrence of thrombocytopenia or an increase in blasts. Together, our data show that LDH can be employed as a prognostic follow-up variable in patients with MDS. In those patients in whom an increase in LDH is noted, a thorough re-evaluation of the progression-status of the disease including a bone marrow examination should be considered.

IPSS-Independent Cytogenetic Risk Categorization in Primary Myelofibrosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2909-2909 ◽  
Author(s):  
Kebede Hussein ◽  
Animesh D. Pardanani ◽  
Daniel van Dyke ◽  
Curtis A. Hanson ◽  
Ayalew Tefferi
Keyword(s):  
Median Survival ◽  
Prognostic Value ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Multivariable Analysis ◽  
Primary Myelofibrosis ◽  
Rank Test ◽  
International Prognostic Scoring System ◽  
Cytogenetic Abnormalities ◽  
Risk Categorization

Abstract Abstract 2909 Poster Board II-885 Background: Previous studies have identified sole abnormalities of del(20q) and del(13q) as prognostically favorable cytogenetic markers in primary myelofibrosis (PMF) (Tefferi et al. BJH 2001;113:763). A more recent study (Tam et al. Blood 2009;113:4171) confirmed these findings and suggested additional cytogenetic markers of prognosis. In the current study with larger numbers of informative patients studied at time of diagnosis, we wanted to validate these observations and examine the prognostic interaction between cytogenetic risk categorization and the International Prognostic Scoring System (IPSS). Methods: Patients with cytogenetic information at diagnosis were selected from the Mayo Clinic database of WHO-defined PMF. Specific cytogenetic categories were considered only in the presence of at least 5 informative patients; otherwise, they were included in the category of “other cytogenetic abnormalities”. Follow-up information was updated in July, 2009. Survival curves were prepared by the Kaplan-Meier method and compared by the log-rank test. Cox regression model was used for multivariable analysis. Results: 200 patients were studied (median age, 62 years; 63% males). The IPSS risk distributions were low in 66 patients, intermediate (int)-1 in 64, int-2 in 44 and high in 26. Cytogenetic findings at diagnosis were abnormal in 83 (42%) patients and included sole del(20q) in 21, complex (i.e. 3 or more abnormalities) in 13, sole del(13q) in 8, sole +8 in 7, sole +9 in 6, and other abnormalities in 28 patients. Median survivals in low, int-1, int-2 and high IPSS risk groups were 188, 71, 47 and 26 months, respectively (p < 0.0001). Median survival in patients with sole +9 was not reached and in those with sole del(13q), sole del(20q), normal karyotype, complex abnormalities and sole +8 was 112, 108, 80, 37 and 27 months, respectively, while it was 46 months for patients with other cytogenetic abnormalities (p = 0.01). Accordingly, sole abnormalities of +9, del(20q) and del(13q) were categorized as being favorable (n = 35) and complex abnormalities and sole +8 as unfavorable (n = 20); the respective median survivals were 112 and 34 months (p=0.002; Figure). Multivariable analysis confirmed the IPSS-independent prognostic value of cytogenetic risk categorization and the intra-IPSS risk prognostic distinction was most apparent in the int-1 group: median survival was 35 and 81 months in the presence of unfavorable or favorable cytogenetic markers, respectively (p=0.0009; Figure). Conclusion: The current study identifies sole +9, along with del(13q) and del(20q), as favorable and sole +8, along with complex abnormalities, as unfavorable cytogenetic markers of prognosis in PMF. Cytogenetic risk categorization in PMF has an IPSS-independent prognostic value that is important in patient selection for specific therapy. Disclosures: No relevant conflicts of interest to declare.

Prognostic value of U2AF1 mutant in patients with de novo myelodysplastic syndromes: a meta-analysis

2019 ◽  
Vol 98 (12) ◽  
pp. 2629-2639 ◽  
Author(s):  
Huifang Wang ◽  
Nanchen Zhang ◽  
Xia Wu ◽  
Xue Zheng ◽  
Yantao Ling ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Prognostic Value ◽  
De Novo ◽  
Meta Analysis

A Comparative Analysis of Outcomes in Primary Myelodysplastic Syndrome (MDS) and Therapy-Related MDS Reveals Two Subgroups with Differing Risk Profiles: Implications for the Application of a Prognostic Classification.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2532-2532 ◽  
Author(s):  
Caroline Alvares ◽  
Sue Ashley ◽  
Radovan Saso ◽  
Gita Patel ◽  
Amrana Qureshi ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Myelodysplastic Syndrome ◽  
Median Survival ◽  
De Novo ◽  
Performance Status ◽  
Intensive Treatment ◽  
Primary Group ◽  
Risk Profiles ◽  
Widespread Application ◽  
Therapeutic Decisions

Abstract Myelodysplastic syndrome is a heterogenous clonal disorder stemming from an insult at the progenitor cell level. The development of an International Prognostic Scoring System (IPSS) based on bone marrow blast percentage, degree of cytopenia and karyotype has allowed the widespread application of the IPSS to guide therapy in patients with MDS. To date, there are no reports distinguishing primary MDS from therapy related MDS (t-MDS) in terms of outcomes within a treatment algorithm. We performed a comparative analysis of patients with primary MDS and t-MDS, to ascertain whether both groups have similar risk profiles and outcomes within a defined treatment protocol. Between 1995 and 2005, 95 patients were diagnosed with MDS at our centre with an average follow-up of 6 years. In total, 50 patients presented in a de novo setting of which 41 received intensive therapy and 9 patients received non-intensive treatment. Of the 45 patients diagnosed with t-MDS, 25 received intensive treatment and 20 patients were managed non-intensively. Therapeutic decisions were based on ECOG performance status and cytogenetic risk group. Demographic analysis of primary and t-MDS patients showed no significant differences when comparing age, sex, degree of presentation cytopenia, or median IPSS score (IPSS 2.0 for primary MDS and 1.5 for t-MDS, p=0.4). In the primary MDS group, 32 patients had an IPSS of ≥1.5 (INT-2/high risk MDS) compared to 27 patients in the t-MDS group. There were 18 patients with primary MDS and 18 patients with t-MDS in the INT-1/low risk category (IPSS ≤1.0). Cytogenetic analysis of primary MDS and t-MDS patients showed a greater frequency of complex karyotypes and chromosome 7 abnormalities in t-MDS patients. A normal karyotype was commoner in the primary group (19:6 patients respectively). The median overall survival (OS) was 25 months for primary MDS patients and 16 months for the t-MDS group (p=0.1). On multivariate analysis, WBC and blast percentage were independent predictors of OS in primary MDS patients (p&lt;0.001, p=0.02). Using a WBC cut-off of 4.0, the median survival was 46 months if WBC &lt;4.0 and 11 months if WBC ≥ 4.0 (p=0.003). IPSS score was not a significant prognostic parameter for this group. In t-MDS patients, Hb, platelets and IPSS score were all independent predictors of OS (p=0.05, p=0.04, p=0.009). WBC was not significant. This group had a median survival of 21 months if IPSS ≤1.0 and 10 months if IPSS &gt;1.0, p=0.02). Remission rates were higher in primary MDS (86%) compared to t-MDS patients (68%) within the intensively treated arm (81% versus 39% for whole group, respectively). However, this did not translate into a better relapse free survival for primary MDS patients (p=0.9). Univariate analysis using binary logistic regression did not identify any factors that predicted response in the primary group. Age was a significant predictive factor for likelihood of response in the t-MDS group (p=0.008). These findings suggest that prognostic systems may need to be refined in MDS for patients presenting with de novo or therapy related disease. Adjustment for performance status may additionally contribute to risk based therapeutic protocols. According to our results, primary MDS may be more chemosensitive than t-MDS but if responses are obtained in t-MDS patients, they are maintained at a similar rate to primary MDS.

scholarly journals Prognostic value of SRSF2 mutations in patients with de novo myelodysplastic syndromes: A meta-analysis

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0185053 ◽  
Author(s):  
Xue Zheng ◽  
Zhi Zhan ◽  
Duolan Naren ◽  
Jing Li ◽  
Tianyou Yan ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Prognostic Value ◽  
De Novo ◽  
Meta Analysis

scholarly journals Refined chromosome analysis as an independent prognostic indicator in de novo myelodysplastic syndromes

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1721-1730
Author(s):  
JJ Yunis ◽  
RE Rydell ◽  
MM Oken ◽  
MA Arnesen ◽  
MG Mayer ◽  
...  
Keyword(s):  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
De Novo ◽  
Chromosome Analysis ◽  
Prognostic Indicator ◽  
Partial Loss ◽  
Monosomy 7 ◽  
Single Chromosome ◽  
Wide Range ◽  
First Time

In a study of 56 consecutive adult patients with de novo myelodysplastic syndromes (MDS), all cases were successfully analyzed with two refined chromosome banding techniques. Most patients (44 of 56, 79%) were found to have a chromosome defect. The majority of these patients had a recurrent loss of chromosomal material rather than a reciprocal translocation or inversion, as commonly found in acute leukemia. The three largest chromosomal categories found were associated with a wide range of survival. Twelve patients (21%) had normal chromosomes, a stable clinical course, and long survival (median follow-up time of 49 months, with all patients alive). Nine patients had in common a single chromosome defect resulting in either monosomy 7 or deletion 7q. They had a median survival of 12 months, and four died of acute nonlymphocytic leukemia (ANLL). Of 12 patients with complex defects, 11 had a complete or partial loss of a chromosome 5 and a complete or partial loss of the long arm of a chromosome 7 or 20. They had a poor median survival of four months, and six patients died of ANLL. Although the French-American-British (FAB) classification was also found to have some prognostic value, FAB subgroups were chromosomally heterogeneous and showed less dramatic differences in median survival than the larger chromosomal subgroups. We have shown, for the first time, that a refined chromosomal analysis is an independent prognostic indicator in de novo MDS and may be helpful in establishing therapeutic approaches in this difficult group of heterogeneous disorders.

Comprehensive Plasma Cytokine Profiling in Polycythemia Vera: Comparison with Myelofibrosis and Clinical Correlates,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3850-3850 ◽  
Author(s):  
Rakhee Vaidya ◽  
Nanna Sulai ◽  
Shaina A Rozell ◽  
Sania S Raza ◽  
Sameer Parikh ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Plasma Cytokine ◽  
Clinical Correlates ◽  
Gm Csf ◽  
Tnf Α ◽  
Plasma Cytokines ◽  
Ifn Γ ◽  
One Year ◽  
Normal Controls ◽  
Time Point

Abstract Abstract 3850 Background: We have recently shown that primary myelofibrosis (PMF) was associated with increased plasma levels of IL-1b/IL-1RA/IL-2R/IL-6/IL-8/IL-10/IL-12/IL-13/IL-15/TNF-α/G-CSF/INF-α/MIP-1α/MIP-1b/HGF/IP-10/MIG/MCP-1/VEGF in PMF (J Clin Oncol 2011; 29: 1356). In addition, increased levels of IL-8, IL-2R, IL-12, IL-15 and IP-10 were independently associated with inferior survival. In the current study, we focused on the plasma cytokine profile in polycythemia vera (PV) and examined how it compares with PMF or in a cohort of PV patients whose samples were collected during follow-up. We also looked for phenotypic and prognostic correlates. Methods: Study inclusion for patients with PV required availability of archived plasma within one year of diagnosis. Samples from PV patients seen at different points post-diagnosis were also collected, in order to compare their cytokine profile with that of patients whose samples were collected within one year of diagnosis. Standard procedures were followed to centrifuge peripheral blood samples at 4°C and store aliquots at −80°C. Concentrations of 30 plasma cytokines/chemokines were analyzed in duplicates using Multiplex Bead-based Luminex Technology (Invitrogen, Carlsbad, CA, USA): IL-1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, EGF, eotaxin, FGF-b, GM-CSF, G-CSF, HGF, IFN-α, IFN-γ, IP-10, MCP-1, MIG, MIP-1α, MIP-1β, RANTES, TNF-α, and VEGF. Measurements were performed on a Luminex 200 analyzer (Luminex Corporation, Austin, TX, USA) and resulting data were evaluated using STarStation Software Version 2.3 (Luminex Corporation, Austin, TX, USA). Results I: Plasma cytokines in PV (n=36 for samples collected within one year of diagnosis and n=40 for samples collected beyond that time point) vs. PMF (n=92) vs. normal controls (n=35) There was no significant difference between the three groups in the plasma levels of the following cytokines: IL-1β, IL-2, IL-4, EGF, and IL-17. PV and normal controls had similar levels of IL-2R, IL-5, FGF-b, and TNF-α; all four cytokines were elevated in PMF. The levels of the following cytokines were equally increased in PV and PMF: IL-1RA, IL-7, HGF, MIG, and VEGF. The following cytokines were also elevated in both PMF and PV but predominantly so in PV (MIP-1α) or PMF (IL-6, IL-8, IL-12, IL-13, IL-15, MIP-1β, IP-10, and MCP-1). Eotaxin and GM-CSF were elevated in PV but not PMF. Compared to normal controls, significantly lower levels were noted for IL-10 in PV and IFN-α and IFN-γ for PMF. IFN-α and IFN-γ levels were both elevated in PV. Comparison of PV samples collected within one year of diagnosis (n =36) vs. those collected beyond that time point (n =40) showed significantly increased levels of IL-8 (p=0.0005) and borderline significant increases in IP-10 (p=0.09) and IL-2R (p=0.09). Results II: Clinical correlates of plasma cytokines in PV Among the above-listed cytokines that were abnormally increased or decreased in PV, significant correlations were seen with sex (IP-10 and GM-CSF), age (IP-10, eotaxin), platelet count (MIG), hemoglobin level (IL-6), arterial thrombosis (IFN-γ, IL-1RA, VEGF, MIP-1α), and abnormal karyotype (IL-13, MIP-1α). None of the cytokines correlated with leukocyte count, venous thrombosis, pruritus or microvascular symptoms. The following, treated as continuous variables, were associated with inferior survival: IL-7, HGF, IFN-α, MCP-1, GM-CSF and IL-10 (p<0.05 for all). The number of events and sample size were too small to perform multivariable analysis. Conclusions: Plasma cytokine levels in PV are markedly abnormal and show both similarities and differences with PMF; the similarities became more pronounced in patients whose samples were examined at later stages of their disease. The current study suggests prognostic implications that warrant validation in a larger number of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1364-1372 ◽  
Author(s):  
SD Michels ◽  
RW McKenna ◽  
DC Arthur ◽  
RD Brunning
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Poor Response ◽  
Significant Difference ◽  
Multiple Cell ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French- American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy. The myelodysplastic phase, with or without evolution to acute leukemia, is a highly lethal disease with a median survival comparable to that of the patients who present with AML.

scholarly journals Refined chromosome analysis as an independent prognostic indicator in de novo myelodysplastic syndromes

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1721-1730 ◽  
Author(s):  
JJ Yunis ◽  
RE Rydell ◽  
MM Oken ◽  
MA Arnesen ◽  
MG Mayer ◽  
...  
Keyword(s):  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
De Novo ◽  
Chromosome Analysis ◽  
Prognostic Indicator ◽  
Partial Loss ◽  
Monosomy 7 ◽  
Single Chromosome ◽  
Wide Range ◽  
First Time

Abstract In a study of 56 consecutive adult patients with de novo myelodysplastic syndromes (MDS), all cases were successfully analyzed with two refined chromosome banding techniques. Most patients (44 of 56, 79%) were found to have a chromosome defect. The majority of these patients had a recurrent loss of chromosomal material rather than a reciprocal translocation or inversion, as commonly found in acute leukemia. The three largest chromosomal categories found were associated with a wide range of survival. Twelve patients (21%) had normal chromosomes, a stable clinical course, and long survival (median follow-up time of 49 months, with all patients alive). Nine patients had in common a single chromosome defect resulting in either monosomy 7 or deletion 7q. They had a median survival of 12 months, and four died of acute nonlymphocytic leukemia (ANLL). Of 12 patients with complex defects, 11 had a complete or partial loss of a chromosome 5 and a complete or partial loss of the long arm of a chromosome 7 or 20. They had a poor median survival of four months, and six patients died of ANLL. Although the French-American-British (FAB) classification was also found to have some prognostic value, FAB subgroups were chromosomally heterogeneous and showed less dramatic differences in median survival than the larger chromosomal subgroups. We have shown, for the first time, that a refined chromosomal analysis is an independent prognostic indicator in de novo MDS and may be helpful in establishing therapeutic approaches in this difficult group of heterogeneous disorders.

scholarly journals Clinical Features and Prognostic Assessment in 233 Patients with Therapy-Related Myelodysplastic Syndromes: The IPSS-R Is a Powerful Predictor of Outcome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4636-4636
Author(s):  
Meritxell Nomdedeu ◽  
Xavier Calvo ◽  
Arturo Pereira ◽  
Dolors Costa ◽  
Carmen Pedro ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Clinical Features ◽  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
De Novo ◽  
Prognostic Score ◽  
Rank Test ◽  
Combined Modality Treatment ◽  
Log Rank Test

Abstract Background Therapy-related Myelodysplastic Syndromes (t-MDS) are those MDS occurring after cytotoxic and/or radiation therapy administered for a prior neoplastic or non-neoplastic disorder. Their prognosis is generally very poor. The commonly used risk prognostic models for MDS (IPSS and IPSS-R) are not validated in this entity as they were developed after the exclusion of therapy-related cases (Greenberg et al. Blood 1997; Greenberg et al. Blood 2012). Aims The main aims of this study are: a) to report clinical findings and overall survival on 233 patients with t-MDS, and to compare them with a large series of de novo cases; b) to test if IPSS-R is applicable to t-MDS patients. Patients and methods The study is based on the Spanish Registry for MDS, a retrospective database that includes more than 10000 cases. The investigators were asked to fill in a questionnaire regarding prior disease (PD) and prior therapy in those cases reported to be t-MDS. Herein are described the clinical features and overall survival of the first 233 cases with the required information, and compared with patients with de novo MDS from a single center series (n=725). Log Rank test was applied to asses IPSS-R in t-MDS group. Results The 233 reported patients were diagnosed between January 1993 and February 2014. The series includes 104 women (44,6%) and 129 men (55,4%). One hundred and two patients (43.9%) had a primary hematologic malignancy, 119 (51%) had a solid tumor, and 12 (5.1%) received cytotoxic therapy for autoimmune disorders. Ninety eight patients (42.6%) received only chemotherapy (CT), 45 (19.6%) received only radiotherapy (RT), 44 (19.1%) received combined modality treatment (CMT), and 43 (18.6%) received an autologous stem cell transplantation (ASCT). The median time of latency between PD and diagnosis in t-MDS group was 4.56 years (range: 0.03-29.63) in patients previously treated with CT or CMT, significantly lower than the observed after RT (8.54; range 0.83-23.02) or ASCT (8.64; range 2.87-28.32) groups (p=0.023 and p<0.0001, respectively). Median age, hemoglobin concentration, platelet count and absolute neutrophil count at diagnosis were significantly lower in t-MDS compared with de novo MDS, while bone marrow blast cell count was significantly higher. A higher proportion of high risk karyotypes (intermediate, poor and very poor categories of R-IPSS for cytogenetics) in t-MDS than in de novo MDS was observed (45.5% versus 25.6% respectively, p<0.0001). Within t-MDS cases, those patients who had received CT, CMT or ASCT also presented a higher proportion of high risk karyotypes compared with t-MDS after RT (52.1 vs 24.1% respectively, p=0.006). There was a significantly shorter median overall survival in patients treated with CT/CMT or ASCT in comparison with de novo patients or t-MDS patients treated with RT (14.88 versus 25.06 versus 47.18 months, respectively (log rank test < 0, 0001). In contrast, no difference between de novo and t-MDS after RT was found (median survival 53.6 months vs. 47.17 months, respectively, n.s). These findings are in concordance with previously published data (Nardi et al, JCO 2012) suggesting that some t-MDS after RT may not be truly t-MDS, but just coincidental. The IPSS-R prognostic score could separate t-MDS patients into five risk groups in terms of overall survival, with a median survival of 76.68 months, 38.73 months, 16.59 months, 13.3 months and 6.37 months, respectively (p<0.0001; Figure 1). A shorter overall survival for each category was found in t-MDS in comparison with de novo MDS, reaching statistical significance in the intermediate and high risk category and showing a trend towards significance in the very low and low risk categories (Figure 2). Conclusions In conclusion, our data supports the notion that t-MDS may contain entities with heterogeneous prognosis due to a diverse biological basis. The capacity of the IPSS-R for separating good prognostic from bad prognostic cases shown in this study could be very useful in the clinical setting in order to offer risk-adapted treatments to patients, although the development of a specific prognostic score for these entities would be needed. <![if !vml]><![endif]> Disclosures No relevant conflicts of interest to declare.

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