Gemtuzumab Ozogamicin as Induction Therapy Followed by Post-Remission Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia
Authors: Kim Heeje , Eom Ki-Seong , Cho Byung-Sik , Lee Jong-Wook , Min Woo-Sung , Kim Chun-Choo 
Published: April 2020

Abstract
Previously, we reported the effectiveness and safety of combining gemtuzumab ozogamicin (GO) with our center’s modified standard induction chemotherapy (IC) in elderly patients with untreated acute myelogenous leukemia (eAML)(Eom et al., Eur J Haematol2007;79:398–404). However, little is known about the impact of GO IC on hematopoietic stem cell transplantation (HSCT) and no study in this setting has been published. We hypothesized that GO IC could have beneficial effects on HSCT in eAML. On day 1, GO was administered at a dose of 6 mg/m2 as a single 2-h intravenous infusion. Following GO, a modified schedule of our center’s standard IC consisting of idarubicin (12 mg/m2/d, days 2–4) and N4-behenoyl-1-β-arabinofuranosyl cytosine (300 mg/m2/d, days 2–6) was given. All patients in complete remission (CR) received 1 or 2 cycles of consolidation chemotherapy depending on whether they were to undergo autologous or allogeneic HSCT. Patients with HLA-matched sibling donors received one course of consolidation chemotherapy, which consisted of 4~5 d of modified FLANG (fludarabine, cytosine arabinoside, mitoxantrone, and G-CSF) or a short repeated schedule of 4d of GO IC, and then proceeded to autologous or reduced intensity conditioning (RIC) HSCT. The preparative regimens for allogeneic transplants consisted of fludarabine (30 mg/m2/d, days–6 to –2) and busulfan (3.2 mg/kg/d, days–5 and –4) intravenously, or total body irradiation (1200 cGY fractionated, days–7 to –5), cytosine arabinoside (1.5 g/m2 bid, days–4 to –2) and melphalan (100 mg/m2/d, day–1) intravenously for autologous HSCT. In an allogeneic setting, cyclosporine and a short course of methotrexate were used to prevent graft-versus-host disease. Subcutaneous granulocyte colony-stimulating factor (G-CSF) was started on day +3 (autologous) or day +7 (allogeneic) and continued until the absolute neutrophil count reached 0.5 × 109/L on three consecutive days. Fifty-six elderly patients diagnosed as de novo AML have received GO IC since June 2005, and CR was achieved in 42 patients (75%). Sixteen of the patients were enrolled in a setting of HSCT: 10 patients were categorized as intermediate-risk and the others as high-risk cytogenetically. There were 6 men and 10 women with a median age of 61 years (range 56–66 years). All were in CR (CR1=15, CR2=1) pretransplant and the median follow-up duration was 21 months (range 13–34). Of these, seven patients underwent autologous HSCT and four patients are alive in CR. The cause of death for all three patients was relapse. Five and four patients received RIC HSCT from HLA-matched sibling and unrelated donors, respectively, and six patients are alive in CR. The causes of death include one case of relapse and two nonrelapse transplant-related deaths, including one case of severe acute GvHD. The estimated 3-year overall survival and event-free survival rates were 60 and 53%, respectively. Despite the limited numbers, GO IC induced CR with good efficacy and enabled HSCT with no critical sequelae for elderly patients. Our results suggest that elderly patients with AML have a better chance when undergoing HSCT and a better outcome using GO IC.