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

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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Relationship of Treatment-Related Cytopenias and Response to Lenalidomide in Patients With Lower-Risk Myelodysplastic Syndromes

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.5770 ◽

2008 ◽

Vol 26 (36) ◽

pp. 5943-5949 ◽

Cited By ~ 86

Author(s):

Mikkael A. Sekeres ◽

Jaroslaw P. Maciejewski ◽

Aristotle A.N. Giagounidis ◽

Kenton Wride ◽

Robert Knight ◽

...

Keyword(s):

Platelet Count ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Multivariate Analyses ◽

Surrogate Marker ◽

Two Phase ◽

Transfusion Independence ◽

Response Predictors ◽

Phase Ii Studies ◽

Risk Patients

PurposePatients with myelodysplastic syndromes (MDS) often require treatment with growth factors (GFs) or non-GF therapies. One non-GF drug, lenalidomide, is particularly effective at achieving transfusion independence (TI) in patients with lower-risk MDS with the del(5q) cytogenetic abnormality. However, approximately half of del(5q) patients and one quarter of non–del(5q) patients treated with lenalidomide experience significant cytopenias. Lenalidomide-induced cytopenias occurring early in treatment may serve as a surrogate marker of clonal suppression and, therefore, may be predictive of a TI response.Patients and MethodsWe analyzed 362 low-risk, transfusion-dependent patients with MDS, with or without the del(5q) abnormality, enrolled in two phase II studies (MDS-003 and MDS-002) to determine whether treatment-related cytopenias are correlated with lenalidomide response. Cytopenias were assessed during the first 8 weeks of therapy, and response was defined as TI; response predictors were explored in univariate and multivariate analyses.ResultsAmong patients with del(5q), 70% of those whose platelet count decreased by ≥ 50% achieved TI, as compared with 42% of those whose platelet count remained stable or declined by less than 50% (P = .01). Among patients without baseline neutropenia, 82% of those whose absolute neutrophil count (ANC) decreased by ≥ 75% achieved TI, as compared with 51% whose ANC remained stable or decreased by less than 75% (P = .02). These relationships were consistent in multivariate analyses. No relationship between the development of cytopenias and response could be established for lower-risk patients with MDS without del(5q).ConclusionThese findings support the hypothesis that a direct cytotoxic effect of lenalidomide specific to the del(5q) clone may be indicative of a TI response.

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Additional Prognostic Value of Bone Marrow Histology in Patients Subclassified According to the International Prognostic Scoring System for Myelodysplastic Syndromes

Journal of Clinical Oncology ◽

10.1200/jco.2003.04.182 ◽

2003 ◽

Vol 21 (2) ◽

pp. 273-282 ◽

Cited By ~ 51

Author(s):

E. Verburgh ◽

R. Achten ◽

B. Maes ◽

A. Hagemeijer ◽

M. Boogaerts ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndromes ◽

Scoring System ◽

Lower Risk ◽

Prognostic Value ◽

Predictive Power ◽

Intensive Therapy ◽

International Prognostic Scoring System ◽

Prognostic System ◽

Bone Marrow Histology

Purpose: The most recent and powerful prognostic instrument established for myelodysplastic syndromes (MDS) is the International Prognostic Scoring System (IPSS), which is primarily based on medullary blast cell count, number of cytopenias, and cytogenetics. Although this prognostic system has substantial predictive power in MDS, further refinement is necessary, especially as far as lower-risk patients are concerned. Histologic parameters, which have long proved to be associated with outcome, are promising candidates to improve the prognostic accuracy of the IPSS. Therefore, we assessed the additional predictive power of the presence of abnormally localized immature precursors (ALIPs) and CD34 immunoreactivity in bone marrow (BM) biopsies of MDS patients. Patients and Methods: Cytogenetic, morphologic, and clinical data of 184 MDS patients, all from a single institution, were collected, with special emphasis on the determinants of the IPSS score. BM biopsies of 173 patients were analyzed for the presence of ALIP, and CD34 immunoreactivity was assessable in 119 patients. Forty-nine patients received intensive therapy. Results: The presence of ALIP and CD34 immunoreactivity significantly improved the prognostic value of the IPSS, with respect to overall as well as leukemia-free survival, in particular within the lower-risk categories. In contrast to the IPSS, both histologic parameters also were predictive of outcome within the group of intensively treated MDS patients. Conclusion: Our data confirm the importance of histopathologic evaluation in MDS and indicate that determining the presence of ALIP and an increase in CD34 immunostaining in addition to the IPSS score could lead to an improved prognostic subcategorization of MDS patients.

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Report on outcomes of hypomethylating therapy for analyzing prognostic value of Revised International Prognostic Scoring System for patients with lower-risk myelodysplastic syndromes

Annals of Hematology ◽

10.1007/s00277-016-2759-y ◽

2016 ◽

Vol 95 (11) ◽

pp. 1795-1804

Author(s):

Yoo Jin Lee ◽

Sung Woo Park ◽

In Hee Lee ◽

Jae Sook Ahn ◽

Hyeoung Joon Kim ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Scoring System ◽

Lower Risk ◽

Prognostic Value ◽

International Prognostic Scoring System

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Comparing the prognostic value of risk stratifying models for patients with lower-risk myelodysplastic syndromes: Is one model better?

American Journal of Hematology ◽

10.1002/ajh.24173 ◽

2015 ◽

Vol 90 (11) ◽

pp. 1036-1040 ◽

Cited By ~ 17

Author(s):

Amer M. Zeidan ◽

Mikkael A. Sekeres ◽

Xiao-Feng Wang ◽

Najla Al Ali ◽

Guillermo Garcia-Manero ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Lower Risk ◽

Prognostic Value

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Correction to: The prognostic value of serum erythropoietin in patients with lower-risk myelodysplastic syndromes: a review of the literature and expert opinion

Annals of Hematology ◽

10.1007/s00277-019-03874-w ◽

2019 ◽

Vol 99 (1) ◽

pp. 21-21

Author(s):

Sophie Park ◽

Charikleia Kelaidi ◽

Mathieu Meunier ◽

Nicole Casadevall ◽

Aaron T. Gerds ◽

...

Keyword(s):

Open Access ◽

Expert Opinion ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Prognostic Value ◽

Final Decision ◽

Review Of The Literature ◽

Serum Erythropoietin

This article was originally published without an Open Access but due to the authors final decision to opt for Open Choice this correction was created.

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Mutational hierarchies in myelodysplastic syndromes dynamically adapt and evolve upon therapy response and failure

Blood ◽

10.1182/blood-2015-11-679167 ◽

2016 ◽

Vol 128 (9) ◽

pp. 1246-1259 ◽

Cited By ~ 69

Author(s):

Maximilian Mossner ◽

Johann-Christoph Jann ◽

Janina Wittig ◽

Florian Nolte ◽

Stephanie Fey ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Therapeutic Intervention ◽

Lower Risk ◽

Therapy Response ◽

Molecular Heterogeneity ◽

Independent Evolution ◽

Key Points ◽

Complex Patterns

Key Points Mutational trajectories are defined by complex patterns of molecular heterogeneity in MDS, including lower-risk cases. Therapeutic intervention dynamically reshapes mutational patterns often resulting in branched or independent evolution of MDS clones.

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