Bridging to transplant with azacitidine in juvenile myelomonocytic leukemia: a retrospective analysis of the EWOG-MDS study group

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Busulfan-fludarabine- or treosulfan-fludarabine-based myeloablative conditioning for children with thalassemia major

Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients' life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfan-fludarabine-based and treosulfan-fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan-fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan-fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3-95.1%) after busulfan-fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7-96.6%) after treosulfan-fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function

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

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

Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile myelomonocytic leukemia increasingly receive novel agents in phase I-II clinical trials as pre-transplant therapy or therapy for relapse after transplantation. However, response criteria or definitions of outcome for standardized evaluation of treatment effect in patients with juvenile myelomonocytic leukemia are currently lacking. Here we propose criteria to evaluate the response to the non-transplant therapy and definitions of remission status after hematopoietic stem cell transplantation. For the evaluation of non-transplant therapy, we defined 6 clinical variables (white blood cell count, platelet count, hematopoietic precursors and blasts in peripheral blood, bone marrow blast percentage, spleen size and extramedullary disease) and 3 genetic variables (cytogenetic, molecular and chimerism response) which serve to describe the heterogeneous picture of response to therapy in each individual case. It is hoped that these criteria will facilitate the comparison of results between clinical trials in juvenile myelomonocytic leukemia