Certain patients with inborn errors of immunity have defects in DNA damage response, predisposing them to malignancy. Subsequent cancer therapy may require substantial attenuation given defective DNA repair; however, this carries risk of incomplete disease control. We describe a 5-year-old boy with peripheral T-Cell lymphoma with ataxia-telangiectasia (A-T). After incomplete chemotherapeutic response, he underwent allogenic hematopoietic cell transplantation (allo-HCT) with an attenuated preparative regimen, but developed graft rejection and relapse. Following remission with salvage chemotherapy, second allo-HCT with reduced intensity conditioning (RIC) resulted in minimal toxicity and short-term disease control. HCT with RIC can be considered in patients with A-T.