Repeated courses of sequential venetoclax and donor lymphocyte infusions in a patient with relapsed high-risk myelodysplasia following allogeneic stem cell transplantation: a case report.

BACKGROUND

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potentially curative therapy in patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, a considerable proportion of patients experience post-transplant relapse, a condition associated with relevant morbidity and an overall dismal prognosis. In this context, the administration of donor lymphocyte infusion (DLI) has been historically used to exploit the graft-versus-leukemia (GvL) effect of allo-HSCT. More recently, hypomethylating agents (HMAs) and venetoclax (VEN), a combination used in first-line/relapsed AML, has also been applied, alone or in association with DLI, for post-transplant relapses, with some encouraging results. Despite several reports showing the feasibility and efficacy of the HMA-VEN combination, the long-term outcome is still poor and the management of AML relapse following allo-HSCT remains unsatisfactory. Thus far, the ideal treatment has not been defined.

CASE DESCRIPTION: We report here the successful treatment of a patient with high-risk MDS and relapse onset following allo-HSCT. The patient was started on salvage treatment with azacitidine (AZA) and low-dose VEN. Surprisingly, bone marrow cellularity was restored, with rapid improvement of the hematological parameters and recovery of full chimerism as well after a single initial course of AZA/VEN. Two additional courses of AZA/VEN supplemented with DLI were delivered, and then the patient was placed on a maintenance treatment with the sequence of VEN single agent tightly followed by DLI. Six courses of combined VEN/DLI were delivered at 3-month intervals. This innovative strategy proved to be effective in terms of disease control, absence of infectious complications, and quality of life. The patient is presently alive and well in continuous complete remission (CR) 24 months since disease recurrence. The details of his recent clinical history are reported here.

CONCLUSION

Recurrent courses of VEN in combination with DLI may be exploited for CR maintenance in patients with MDS/AML managed for disease recurrence after allo-HSCT.