Therapy with low‐dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG‐MDS study group

Abstract

Low-dose azacitidine is efficient and safe in the therapy of malignant myeloid disorders in adults but data in children are lacking. We present a retrospective analysis of 24 children and young adults with myelodysplastic syndrome (MDS) who received azacitidine at the time of first diagnosis or relapse after allotransplant (2 children were treated with azacitidine both initially and for relapse). Diagnoses were refractory cytopenia of childhood (N = 4), advanced primary MDS (N = 9) and secondary MDS (N = 11). The median duration of treatment was four cycles. Azacitidine was well tolerated, but cytopenias led to dose reduction in five cases. Treatment was discontinued in one child because of impaired renal function. Sixteen MDS patients were treated with azacitidine at first diagnosis. One complete clinical remission was observed and one child showed complete marrow remission; six children experienced stable disease with haematological improvement. Ten children received azacitidine for relapsed MDS after transplant: of these, seven experienced stable disease for 2-30 cycles (median 3), including one patient with haematological improvement for seven cycles. In summary, azacitidine is effective in some children with MDS and appears to be a non-toxic option in palliative situations to prolong survival.

Response to treatment with azacitidine in children with advanced myelodysplastic syndrome prior to hematopoietic stem cell transplantation

“…37 Our findings are consistent with a recent report of good tolerability of AZA in 24 children and young adults with different types of MDS and MDR-AML. 29 There was a trend towards higher bone marrow blast percentages at presentation in patients treated with AZA. A bias towards treating physicians favoring therapy with AZA in patients with higher blast counts at presentation cannot be completely excluded.…”

“…28 The European Working Group of Myelodysplastic Syndromes in Childhood recently reported their experience with AZA in MDS and MDR-AML. 29 Their retrospective analysis comprised a heterogeneous group of children with low-grade MDS (refractory cytopenia of childhood), advanced MDS, secondary MDS, MDR-AML, and relapsed disease after HSCT. Among the seven patients with RAEB/-T in this report, only one was declared alive in remission at 24 months of follow-up; the remaining 6/7 patients died after 1-6 months.…”

Epigenetic Combination Therapy for Children With Secondary Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) and Concurrent Solid Tumor Relapse

“…One retrospective study showed that low-dose azacitidine for children and adolescents with MDS was safe and effective as a non-toxic option to prolong life in the palliative context [28]. Furthermore, a pilot study of 13 pediatric patients investigating the use of vorinostat and decitabine followed by a standard cytotoxic re-induction chemotherapy regimen for relapsed/refractory B-acute lymphoblastic leukemia (B-ALL) showed that the regimen was tolerable and demonstrated clinical benefit with an overall response rate of 46.2% (complete and partial response) [15].…”

Azacitidine as a bridge to allogeneic hematopoietic cell transplantation in a pediatric patient with Fanconi anemia and acute myeloid leukemia

“…As epigenetic changes including aberrant DNA methylation and gene silencing play an important role in the pathogenesis of AML, inhibitors such as azacitidine and decitabine have been successfully used in adult patients to treat AML and MDS without major side effects . Further, while azacitidine has been used in conjunction with DLI as salvage therapy for treatment of relapse post‐HCT in adult patients, these agents have been used only infrequently in pediatric patients . Recent studies have reported the use of fludarabine‐based regimens in patients with FA and AML for disease reduction prior to HCT .…”