Single Agent Gemtuzumab Ozogamicin (Mylotarg) Can Induce Hematologic Remissions in Patients with Refractory Acute Myelogenous Leukemia (AML) Relapse Following Allogeneic Stem Cell Transplantation but May Precipitate Acute Graft-Versus-Host Disease (GVHD).

Relapse following allogeneic transplantation in the absence of GVHD is usually treated by withdrawing immunosuppressive therapy followed by donor lymphocytes infusions for the induction Graft-versus-Leukemia (GVL) effects. However, if this fails to result in graft-vs-leukemia effects, the prognosis for such patients is usually very poor. Re-induction therapy seldom has an effect on such patients, and the morbidity from full induction is substantial.

Patients: We retrospectively studied five patients with AML, who relapsed following allogeneic stem cell transplantation (SCT). Three patients had their transplant from HLA-identical siblings, and two from matched unrelated donors (URD). Both patients with URD transplant had a one HLA class I antigen mismatch.

Treatment Plan: After withdrawing the immunosuppressive therapy, no signs of GVHD was noted in any of the patients. All patients were then treated with Mylotarg 9 mg/M2 on days 1 and 14. All five patients received both doses. Three patients did not respond and died of progressive leukemia. Two patients achieved complete remission as documented by BM biopsy. One patient who had a one antigen mismatch URD SCT and who had evidence of skin and liver GVHD prior to the relapse, remains in remission without any evidence of GVHD, and off immunosuppressive therapy (day +327 post-BMT). The second patient, who never had GVHD prior to relapse, developed aGVHD of the skin and liver one months after Mylotarg therapy. Despite intensive immunosuppressive therapy, he continued with progressive GVHD of the skin and liver died of GVHD on day +224 post-SCT with no signs of recurrent leukemia.

Conclusions: Gemtuzumab Ozogamicin is effective in inducing hematologic remissions in refractory AML patients who relapse following allogeneic SCT. Mylotarg may precipitate aGVHD and we hypothesize that secondary inflammatory reactions following the cytolytic effects of the immunotoxin may be involved in the induction of GVHD. Caution should be exercised if this treatment is to be combined with donor lymphocyte infusions. Prospective studies are warranted to evaluate the role of Mylotarg in treatment patients in relapse following allo-HSCT and its effect on precipitating GVHD.