Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet

Malcovati, Luca; Hellström‐Lindberg, Eva; Bowen, David; Adès, Lionel; Čermák, Jaroslav; Cañizo, Consuelo del; Porta, Matteo Giovanni Della; Fenaux, Pierre; Gattermann, Norbert; Germing, Ulrich; Jansen, Joop H.; Mittelman, Moshe; Mufti, Ghulam J.; Platzbecker, Uwe; Sanz, Guillermo; Selleslag, Dominik; Skov-Holm, Mette; Stauder, Reinhard; Symeonidis, Argiris; Loosdrecht, Arjan A. van de; Witte, Théo de; Cazzola, Mario

doi:10.1182/blood-2013-03-492884

Cited by 570 publications

(579 citation statements)

References 262 publications

(97 reference statements)

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“…As observed in numerous previous studies, 23,[51][52][53][54][55][56] OS was found to be slightly lower in patients ⩾ 55 years without reaching any statistical significance in uni-and multivariate analysis. However, of greater clinical interest is that (1) the documented difference was so small that neither univariate nor multivariate analysis could reveal a significant impact of patient age on OS; and (2) stable plateaus for OS were reached for both subgroups, suggesting potential cure rates of 50% for younger and 42% for elderly patients (cf.…”

Section: Discussionsupporting

confidence: 59%

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

Heinzelmann

Bethge²,

Beelen

et al. 2016

Bone Marrow Transplant

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Allogeneic hematopoietic cell transplantation (HCT) offers the chance of cure for patients with non-transformed follicular lymphoma (FL), but is associated with the risk of non-relapse mortality (NRM). The aim of this study was to identify subgroups of FL patients who benefit from HCT. The European Society for Blood and Marrow Transplantation (EBMT) Minimum-Essential-A Data of 146 consecutive patients who received HCT for FL between 1998 and 2008 were extracted from the database of the German Registry 'DRST'. Diagnosis of FL was verified by contact with the reference pathologists. Estimated 1-, 2-and 5-year overall survivals (OS) were 67%, 60% and 53%, respectively. Day 100 NRM was 15%. Thirteen out of 33 patients (40%) with treatment-refractory disease (RD) at the time of transplantation survived long term. Univariate statistical analysis suggested limited chronic GvHD, donor age ⩽ 42 years and TBI-based conditioning in treatment refractory patients to correlate with favorable OS. Independent prognostic factors for OS were treatmentsensitive disease and limited chronic GvHD for the whole cohort, and additionally TBI-based conditioning for the treatment refractory subgroup. In contrast, patient age ⩾ 55 years had no impact on outcome. Thus, HCT for FL is associated with acceptable NRM, and offers a substantial chance of cure for patients with RD or advanced age. Donors ⩽ 42 years should be preferred if available.

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Section: Discussionsupporting

confidence: 59%

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

Heinzelmann

Bethge²,

Beelen

et al. 2016

Bone Marrow Transplant

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“…Guidelines on ICT in MDS are often included in guidelines on MDS treatment in general. For example, the European LeukemiaNet Guideline on the diagnosis and treatment of primary MDS in adults includes a short segment on ICT [45], suggesting that this treatment should be considered in transfusion-dependent patients with RA, RARS, or MDS with isolated 5q deletion and a serum ferritin level higher than 1000 ng/mL after approximately 25 units of red cells. In addition, MDS patients who are potential candidates for allo-SCT can be considered for appropriate iron chelation therapy prior to the conditioning regimen for transplantation.…”

Section: Treatment Of Iron Overload In Patients With Mdsmentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

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“…1 The authors provide encouraging data from both a leukemic mouse model and a single CML-AP patient, corroborating mechanistic studies suggesting that KPT-330 efficacy relies on targeting abundantly expressed XPO1, followed by the reactivation of protein phosphatase 2A (PP2A). N ormal cellular homeostasis depends on the cell's ability to compartmentalize proteins within specific subcellular compartments.…”

mentioning

confidence: 53%