Successful treatment of multi-hit TP53-mutated myelodysplastic syndromes with erythroid predominance using allogeneic stem cell transplantation and ruxolitinib

TL;DR

A patient with a severe blood disorder achieved remission using a combination of stem cell transplantation and ruxolitinib, offering a potential new treatment strategy.

Contribution

This case demonstrates successful treatment of TP53-mutated MDS with ruxolitinib and allogeneic stem cell transplantation.

Findings

The patient achieved hematological complete remission after treatment with ruxolitinib and stem cell transplantation.

Remission persisted for 8 months without relapse despite residual disease post-transplant.

The combination therapy shows promise for TP53-mutated MDS and AEL with complex karyotype.

Abstract

TP53-mutated myelodysplastic syndrome (MDS) and acute erythroid leukemia (AEL) with complex karyotype have a very poor prognosis. The upregulation of the JAK-STAT pathway has been implicated in their pathogenesis, and inhibition of this pathway has shown promising disease control in preclinical models. Here, we report a case of refractory multi-hit TP53-mutated MDS with erythroid predominance on the verge of transitioning to AEL, which achieved hematological complete remission following allogeneic stem cell transplantation and ruxolitinib initiation. The patient exhibited chemoresistance to multiple regimens, including cytarabine with daunorubicin, high-dose cytarabine, and venetoclax with azacitidine. Despite the presence of residual disease post-transplant, complete remission was achieved two months after ruxolitinib initiation and tacrolimus tapering. At the 8-month follow-up, remission persists without evidence of relapse. This case highlights the potential of combining graft-versus-leukemia effects with ruxolitinib as a therapeutic strategy for TP53-mutated MDS/AEL. Further studies are warranted to evaluate the efficacy and safety of this strategy in a broader clinical setting.

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