Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R

Porta, Matteo Giovanni Della; Alessandrino, Emilio Paolo; Bacigalupo, Andrea; Lint, Maria Teresa Van; Malcovati, Luca; Pascutto, Cristiana; Falda, Michele; Bernardi, Massimo; Onida, Francesco; Guidi, Stefano; Iori, Anna Paola; Cerretti, Raffaella; Marenco, Paola; Pioltelli, Pietro; Angelucci, Emanuele; Oneto, Rosi; Ripamonti, Francesco; Bernasconi, Paolo; Bosi, Alberto; Cazzola, Mario; Rambaldi, Alessandro

doi:10.1182/blood-2013-12-542720

Cited by 162 publications

(74 citation statements)

References 36 publications

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“…Similar to our findings, recent reports also suggested that patients with MK+ also have increased risk of relapse with increased mortality post transplant 14,15 . The Spanish Registry for MDS 16 reported a strong association of MK with complex karyotype and suggested that it is the complexity of the karyotype (ie, number of chromosomal abnormalities) that is prognostic for worse outcomes in MDS.…”

Section: Discussionsupporting

confidence: 92%

Cytogenetics, Donor Type, and Use of Hypomethylating Agents in Myelodysplastic Syndrome with Allogeneic Stem Cell Transplantation

Oran

Kongtim

Popat

et al. 2014

Biology of Blood and Marrow Transplantation

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We investigated the impact of patient and disease characteristics including cytogenetics, previous therapy and depth of response on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) on myelodysplastic syndrome (MDS). We analyzed 256 MDS patients transplanted from a matched related (n = 133) or matched unrelated (n=123) donor after 2001. Of 256, 78 (30.5%) did not receive cytoreductive therapy before HSCT; 40 (15.6%) received chemotherapy (chemo), 122 (47.7%) hypomethylating agents (HMA) and 16 (6.2%) both (chemo+HMA). Disease status at HSCT defined by International Working Criteria was complete remission (CR) in 46 (18%) patients. There were significant differences between therapy groups: There were more therapy-related MDS and the use of MRD in the untreated group. The chemo group had higher serum ferritin levels at HSCT. Patients were older and had more high-risk disease by revised international prognostic scoring (r-IPSS) in the HMA group. Despite those differences, transplant outcomes were similar in patients who were untreated and who received cytoreductive therapy prior to HSCT. Three-year EFS was 44.2%, 30.6%, 34.2% and 32.8% for untreated, chemo, HMA and chemo+HMA groups respectively (p=0.5). Multivariate analyses revealed that older age (HR=1.3, p=0.001); high-risk histologic subtypes including refractory anemia with excess blasts (HR=1.5, p=0.05) and chronic myelomonocytic leukemia (HR=2.1, p=0.03); high risk cytogenetics with MK (HR=4.0, p<0.0001) and high serum ferritin level at HSCT (HR=1.8, p=0.002) were poor prognostic factors for EFS. Bone marrow blast count 5% or higher at HSCT (HR=1.6, p=0.01) and MK (HR=4.2, p<0.0001) were the only prognostic factor for increased relapse incidence after HSCT. Patients with MK represented a poor prognostic group with 3-year LFS of 11.4% and RI of (RI) of 60.9%. In this analysis, various therapy approaches prior to HSCT did not lead to different transplant outcomes. Cytogenetics defined by MK was able to identify a very poor prognostic group that innovative transplant approaches to improve outcomes are urgently needed.

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Section: Discussionsupporting

confidence: 92%

Cytogenetics, Donor Type, and Use of Hypomethylating Agents in Myelodysplastic Syndrome with Allogeneic Stem Cell Transplantation

Oran

Kongtim

Popat

et al. 2014

Biology of Blood and Marrow Transplantation

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“…Cytogenetically poor-risk group appeared with higher rate of relapse reflecting lower OS probability and mortality in GITMO co-operative study [123,163].…”

Section: Resultsmentioning

confidence: 89%

Mutations of myelodysplastic syndromes (MDS): An update

Ganguly

Kadam

2016

Mutation Research/Reviews in Mutation Research

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“…The model has been validated by several groups and was extended to and validated in treated patients and at times other than at diagnosis (31-37). Furthermore, the IPSS-R was shown to be an improvement over the IPSS as a classification method for predicting outcomes after standard or reduced-intensity allogeneic haematopoietic cell transplant (38). Additionally, the IWG-PM database was recently evaluated to address the potential attrition of prognostic power from the time of diagnosis, which has been a problematic issue for all prognostic scoring systems (39).…”

Section: Current Mds Prognostic Scoring Systems and Risk Modelsmentioning

confidence: 99%

MDS prognostic scoring systems – Past, present, and future

Jonas

Greenberg

2015

Best Practice & Research Clinical Haematology

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The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid haemopathies characterized by defective differentiation of hematopoietic cells and expansion of the abnormal clone. This leads to the bone marrow failure with resulting peripheral blood cytopenias and evolution to or toward acute myeloid leukaemia that characterise MDS clinically. The clinical heterogeneity of MDS has led several groups to analyse patient and clinical characteristics to develop prognostic scoring systems yielding estimates of overall and leukaemia-free survival to guide clinical decision-making. These models have evolved over time as our understanding of the pathogenesis, natural history, and treatment of MDS has improved. Rapid advances in flow cytometric analysis, adjuncts to standard metaphase cytogenetics, and gene mutation analysis are revolutionizing our understanding of MDS pathogenesis and prognosis. Despite the existence of multiple well-validated prognostic scoring systems, further needed refinements of current models with these new sources of prognostic data are described.

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Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R

Abstract: Key Points Disease relapse is a common cause of failure of allogeneic hematopoietic stem cell transplantation in patients with advanced MDS. High IPSS-R prognostic risk category and monosomal karyotype are independent predictors of relapse after allogeneic transplantation in MDS.

Cited by 162 publications

References 36 publications

Cytogenetics, Donor Type, and Use of Hypomethylating Agents in Myelodysplastic Syndrome with Allogeneic Stem Cell Transplantation

Cytogenetics, Donor Type, and Use of Hypomethylating Agents in Myelodysplastic Syndrome with Allogeneic Stem Cell Transplantation

Mutations of myelodysplastic syndromes (MDS): An update

MDS prognostic scoring systems – Past, present, and future

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