Abstract
Background: The treatment for acute myeloid leukemia patients with relapse after stem cell transplantation is limited to dose reduction of immunosuppressive agents, donor leukocyte infusion (DLI), and a second transplantation. The prognosis of such patient is very poor if these therapies cannot be tolerated or are unsuccessful. Gentuzumab ozogamicin(GO) is an antibody targeted chemotherapy consisting of a humanized anti-CD33 monoclonal antibody linked to calicheamycin. The CD33 antigen is expressed on most AML cells and myeloid progenitor cells, but is not expressed on lymphocytes which play an important role in GVL effect. Therefore, GO can potentially eradicate AML cells without harming these lymphocytes.
Patients: We retrospectively studied 9 patients with AML, who relapsed following allogeneic stem cell transplantation (SCT) and had difficulty tolerating DLI. Their donor sources included one 6/6 HLA-matched sibling bone marrow cells, four 6/6 HLA-matched unrelated bone marrow stem cells, and four 4/6 HLA-matched unrelated cord blood. The status of leukemia at SCT was 1st complete remission (CR) in one patient, 2nd CR in one patient, and active disease in seven patients. Treatment protocol: GO was administered at 6 mg/m2 for 2 doses separated by 2 weeks. Treatment was initially performed at morphological relapse but after April 2006 patients received treatment at molecular relapse. The molecular relapse was diagnosed by the quantitative expression of WT1 (Wilms tumor gene). (
Results: Five patients were treated at morphological relapse (group A) and four patients were treated at molecular relapse (group B). Eight received both doses of GO. The period from SCT to relapse ranged from 36 days to 193 days (median: 85 days). The period from SCT to GO administration ranged from 54 days to 229 days (median: 98 days). Seven of 9 patients achieved a remission (3/5 in group A, 4/4 in group B). Three CR patients in group A relapsed (day 48, 95, and 106, respectively). All of the patients in group A died within 447 days. (at 42 days, 131 days, 158 days, 173 days and 447 days, respectively, after GO). Two of the 4 patients in group B relapsed, one on day 300 and one on day 350. One patient died in CR from multiple organ failure following CMV infection; the fourth patient is still in CR. Three patients in group B are alive at 276 days, 410 days, and 443 days. Three patients developed infusion-related fever, one patients nausea. All patients developed grade 4 neutropenia and thrombocytopenia. Febrile neutropenia was observed in four patients. Five patients developed elevation of ALT, grade 3 in 1 patient and grade 1 in 4 patients. Three patients developed grade 1 hyperbilirubinemia. Only one patient developed reversible VOD. VOD occurred on thirteenth day after the administration of GO. The period between SCT and GO administration was 77 days.
Conclusion: The administration of GO is effective in inducing remission in relapsed AML patients after SCT. The ability of GO therapy to induce durable response may possibly be enhanced by early therapeutic intervention before the onset of hematologic relapse. This approach is feasible and well tolerated with minimal toxicity. Additional studies in a large group of patients will be required to adequately assess the safety and efficacy of this approach.
Author notes
Disclosure: No relevant conflicts of interest to declare.
