Table 1.

Treatment options for relapsed MDS and donor cell MDS after allogeneic hematopoietic stem cell transplantation

Treatment Option	Primary Indication	Advantages	Disadvantages	Reference
Hypomethylating agents Azacitidine Decitabine	De novo MDS	Survival benefit with azacitidine in de novo disease Delays progression to AML Likely less TRM and side effects compared to other treatment options	Reduced efficacy in t-MDS Survival benefit unclear in high-risk and t-MDS Main anticipated toxicity is cytopenia, which may be worse after alloHSCT No known data in donor cell MDS One case report of CR in relapsed AML post-transplant for MDS	(70–72, 95)
Donor Lymphocyte Infusion	Relapsed primary disease	Reduced risk of GVHD with original donor	No anticipated GVL effect with original donor Limited efficacy for post-transplant relapsed MDS No known data in setting of t-MDS. Transient hematologic response seen in 1 case of donor cell MDS	(45, 81)
Second Allogeneic Stem Cell Transplant	Relapsed disease or graft failure	Curative option	High risk of TRM No anticipated GVL effect with original donor Risk of GVHD, especially with new donor	(35, 94, 96)
Chemotherapy	De novo or t-MDS	Standard of care for upfront therapy in low-risk disease	Low remission rates for t-MDS Transplant may be required for cure No survival benefit with intensive chemotherapy in advanced disease Anticipated side effects No known data in post-transplant setting	(22, 23, (84)
Autologous Stem Cell Rescue	De novo or t-MDS	Curative option Reduced risk of TRM in comparison to alloHSCT	Increased risk of relapse No GVL	(87, 88)
Lenalidomide	MDS with 5q-deletion	May reduce cytopenias and transfusion requirements	Unclear benefit in t-MDS No known data in donor-cell MDS or post alloHSCT	(90, 91)

Abbreviations: AML: acute myelogenous leukemia; DCL: donor cell leukemia; GVHD: graft-versus-host disease; GVL: graft-versus-leukemia; alloHSCT: allogeneic hematopoietic stem cell transplantation; TRM: treatment-related mortality