Azacitidine in the Treatment of Pediatric Therapy-related Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

We herein present a case of pediatric therapy-related myelodysplastic syndrome (t-MDS) with complex karyotype who was treated with azacitidine (AZA) for AML1-EVI1 fusion transcript as minimal residual disease after allogeneic hematopoietic stem cell transplantation (HSCT). The patient was started on AZA 41 days after the HSCT without having achieved complete remission. After 9 cycles of AZA, the AML1-EVI1 fusion transcript disappeared, and there was no manifestation of graft versus host disease during AZA treatment. Preemptive AZA treatment for minimal residual disease has an acceptable safety profile and appears to be an effective strategy for preventing or substantially delaying hematological relapse in pediatric patients with high-risk myelodysplastic syndrome after HSCT.

Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation

“…Table 1 summarizes the publications regarding the use of Aza as salvage treatment for relapse after allo-SCT: until now a total of 601 patients with AML, MDS and other related myeloid malignancies have been published with varying schedules and dosages of Aza. These included 3 prospective, non-randomized trials and the majority of patients reported retrospectively [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Furthermore, Aza was the first treatment of relapse and combined with DLI in some of these patients, while other patients had previously received other salvage therapies or did not receive DLI.…”

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

“…25 In a single case report, AZA was shown to induce complete remission in a child with treatment-related MDS and signs of early relapse after HSCT, however, long-term follow-up was not reported. 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.…”

Hypomethylating agents after allogeneic blood stem cell transplantation

“…Together with the experience from the early retrospective reports this prospective trial demonstrated that the combination of Aza and DLI was safe and effective in patients with AML or MDS who relapse after allo-SCT. Overall, as indicated in Table 1, a total of 215 patients with AML, MDS and other related myeloid malignancies had been reported in the literature until 2015 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)23,25). Treatment schedules and dosages of Aza varied between these reports.…”