Myelodysplastic syndromes with 20q deletion: incidence, prognostic value and impact on response to azacitidine of ASXL1 chromosomal deletion and genetic mutations

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<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<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.

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Prognostic value of lactate dehydrogenase activity in myelodysplastic syndromes

Leukemia Research ◽

10.1016/s0145-2126(00)00140-5 ◽

2001 ◽

Vol 25 (4) ◽

pp. 287-294 ◽

Cited By ~ 23

Author(s):

Friedrich Wimazal ◽

Wolfgang R Sperr ◽

Michael Kundi ◽

Petra Meidlinger ◽

Christa Fonatsch ◽

...

Keyword(s):

Lactate Dehydrogenase ◽

Dehydrogenase Activity ◽

Myelodysplastic Syndromes ◽

Prognostic Value ◽

Lactate Dehydrogenase Activity

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The prognostic value of maturation-associated phenotypic abnormalities in myelodysplastic syndromes

Leukemia Research ◽

10.1016/j.leukres.2007.06.014 ◽

2008 ◽

Vol 32 (2) ◽

pp. 211-213 ◽

Cited By ~ 13

Author(s):

I. Lorand-Metze ◽

S.M.V. Califani ◽

E. Ribeiro ◽

C.S.P. Lima ◽

K. Metze

Keyword(s):

Myelodysplastic Syndromes ◽

Prognostic Value

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The prognostic value of circulating myeloblasts in patients with myelodysplastic syndromes

Annals of Hematology ◽

10.1007/s00277-017-3186-4 ◽

2017 ◽

Vol 97 (2) ◽

pp. 247-254 ◽

Cited By ~ 4

Author(s):

Vu H. Duong ◽

Eric Padron ◽

Najla H. Al Ali ◽

Jeffrey E. Lancet ◽

Jeff Hall ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Prognostic Value

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Early platelet count kinetics has prognostic value in lower-risk myelodysplastic syndromes

Blood Advances ◽

10.1182/bloodadvances.2018020495 ◽

2018 ◽

Vol 2 (16) ◽

pp. 2079-2089 ◽

Cited By ~ 3

Author(s):

Raphael Itzykson ◽

Simon Crouch ◽

Erica Travaglino ◽

Alex Smith ◽

Argiris Symeonidis ◽

...

Keyword(s):

Platelet Count ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Prognostic Value ◽

Key Points

Key Points A drop in platelet count >25% relative to baseline at 6 months from diagnosis predicts inferior outcome in lower-risk MDS. Platelet drop combined with RBC-TD at 6 months provides an inexpensive and validated classifier of outcome in lower-risk MDS.

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Bone marrow fibrosis in patients with primary myelodysplastic syndromes has prognostic value using current therapies and new risk stratification systems

Modern Pathology ◽

10.1038/modpathol.2013.187 ◽

2013 ◽

Vol 27 (5) ◽

pp. 681-689 ◽

Cited By ~ 25

Author(s):

Bin Fu ◽

Jesse M Jaso ◽

Rachel L Sargent ◽

Maitrayee Goswami ◽

Srdan Verstovsek ◽

...

Keyword(s):

Bone Marrow ◽

Risk Stratification ◽

Myelodysplastic Syndromes ◽

Prognostic Value ◽

Bone Marrow Fibrosis ◽

Current Therapies ◽

Marrow Fibrosis

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

Blood ◽

10.1182/blood.v118.21.3795.3795 ◽

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.

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