Konference: 2013 18th Congress of the European Hematology Association - účast ČR

Kategorie: Myelodysplastický syndrom

Téma: Myelodysplastic syndromes - Clinical

Číslo abstraktu: P748

Autoři: Anna M. Aalbers; Vincent H.J. Van der Velden, PhD; Ayami Yoshimi-Nöllke ; Alexandra Fischer, R.N.; Peter Noellke; MD Christian Michel Zwaan, PhD; MD Irith Baumann; H.Berna Beverloo, PhD; Prof. MD Michael Dworzak; Prof. MD Henrik Hasle; Prof. MD Franco Locatelli, PhD; MD Barbara De Moerloose; Prof. MD Brigitte M. Schlegelberger; MD Markus Schmugge (Schmugge-Liner); prof. MUDr. Jan Starý, DrSc.; MD Marco Zecca; Dr. Anton W. (Ton) Langerak ; MD Jacques J.M. van Dongen, PhD; Prof. MD Rob Pieters, PhD; Prof. MD Charlotte M. Niemeyer, PhD; MD Marry M. van den Heuvel-Eibrink, PhD


Minor paroxysmal nocturnal hemoglobinuria (PNH) clones are frequently present in adults with myelodysplastic syndrome (MDS) and are predictive of response to immunosuppressive therapy (IST) in some studies. We recently reported that in refractory cytopenia of childhood (RCC), the most common subtype of childhood MDS, IST might be effective. Data on the frequency and clinical correlates of PNH clones in RCC are lacking, and the value of the presence of a PNH clone as response predictor to IST in RCC is unknown.


In a prospective multicenter study of the European Working Group of MDS in Childhood (EWOG-MDS), we determined the clinical relevance of PNH clones in RCC.


87 previously untreated primary RCC patients, diagnosed between June 2005 and December 2011, were evaluated for the presence of PNH clones. Diagnosis of RCC was based on WHO criteria for pediatric MDS and confirmed by central review of bone marrow morphology and histology. Peripheral blood was analyzed by high-sensitivity flow cytometry, defining PNH-type granulocytes as CD24-FLAER- and PNH-type erythrocytes as CD55-CD59-. Patients were considered PNH positive when a GPI-deficient population larger than 0.01% in the erythroid and/or a population larger than 0.03% in the granulocytic lineage were present. Of 87 RCC patients, 28 hypocellular patients were subsequently treated with IST, consisting of horse- or rabbit-ATG and CsA.


The median age of included patients was 10.2 years (range: 1-18 years). Bone marrow was hypocellular in 84% of patients; cytogenetic analysis was normal in 85%, monosomy 7 was present in 7%, and other cytogenetic aberrations in 8%. PNH clones were detected in 36 of 87 (41%) RCC patients at diagnosis. Median clone sizes were 0.06% (range: 0.01-58%) in erythrocytes and 0.9% (range: 0.03-86%) in granulocytes. PNH positive patients, compared to PNH negative patients, were significantly older (median: 12.7 versus 7.5 years, P=0.005), had lower leukocyte counts (median: 2.7 versus 3.3 x 109/L, P=0.029), lower platelet counts (median: 20 versus 44.5 x 109/L, P=0.008), lower hemoglobin levels (median: 7.7 versus 9.5 g/dL, P=0.006), tended to have a higher MCV (above the 97th percentile in 81 versus 62% of patients, P=0.073), and were more often HLADR15 positive (42% versus 21%, P=0.051). Hypocellular RCC patients with a PNH clone >0.1% were more likely to respond to IST than PNH negative patients (7 of 8 (88%) versus 8 of 20 (40%) patients responded at six months, respectively, P=0.038) and tended to have a better event-free survival. PNH clone size remained relatively stable in sequentially followed patients, both in patients under a watch-and-wait strategy, and in patients treated with IST, independent of response.

Summary / Conclusion: We conclude that PNH clones are frequently present in RCC, predict response to IST, and might indicate an immune-mediated pathophysiology in at least a subset of RCC patients.

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Keywords: Immunosuppressive therapy, MDS, Pediatric, PNH

Abstrakta v časopise Haematologica 2013, Suppl1

Online Program 

Datum přednesení příspěvku: 15. 6. 2013