TY - JOUR T1 - A Phase I study of gemtuzumab ozogamicin (GO) in combination with busulfan and cyclophosphamide (Bu/Cy) and allogeneic stem cell transplantation in children with poor-risk CD33+ AML: a new targeted immunochemotherapy myeloablative conditioning (MAC) regimen. AU - Satwani,Prakash, AU - Bhatia,Monica, AU - Garvin,James H,Jr AU - George,Diane, AU - Dela Cruz,Filemon, AU - Le Gall,John, AU - Jin,Zhezhen, AU - Schwartz,Joseph, AU - Duffy,Deirdre, AU - van de Ven,Carmella, AU - Foley,Sandra, AU - Hawks,Ria, AU - Morris,Erin, AU - Baxter-Lowe,Lee Ann, AU - Cairo,Mitchell S, Y1 - 2011/11/09/ PY - 2011/06/14/received PY - 2011/11/01/accepted PY - 2011/11/15/entrez PY - 2011/11/15/pubmed PY - 2012/5/9/medline SP - 324 EP - 9 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 18 IS - 2 N2 - Children with high-risk acute myelogenous leukemia (AML) (induction failure [IF], refractory relapse [RR], third complete remission [CR3]) have dismal outcomes. Over 80% of AML patients express CD33, a target of gemtuzumab ozogamicin (GO). GO is an active drug in childhood AML but has not been studied in a myeloablative conditioning regimen. We sought to determine the safety of GO in combination with busulfan/cyclophosphamide (Bu/Cy) conditioning before allogeneic hematopoietic stem cell transplantation (alloSCT). GO was administered on day -14 at doses of 3.0, 4.5, 6.0, and 7.5 mg/m(2), busulfan on days -7, -6, -5, -4 (12.8-16.0 mg/kg), and cyclophosphamide on days -3 and -2 (60 mg/kg/day). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. We enrolled 12 patients: 8 IF, 3 RR, 1 CR3; median age: 3 years (1-17); median follow-up: 1379 days (939-2305). Nine received umbilical cord blood (UCB), 2 matched unrelated donors (MUDs) and 1 HLA-matched sibling donor: 3 patients each at GO doses of 3.0, 4.5, 6.0, or 7.5 mg/m(2). No dose-limiting toxicities secondary to GO were observed. Day 100 treatment-related mortality (TRM) was 0%. Myeloid and platelet engraftment was observed in 92% and 75% of patients at median day 22 (12-40) and 42 (21-164), respectively. Median day +30 donor chimerism was 99% (85%-100%). The probability of grade II-IV acute graft-versus-host disease (aGVHD) was 42% and chronic GVHD (cGVHD) was 28%. One-year overall survival (OS) and event-free survival (EFS) was 50% (95% confidence interval [CI], 20.8-73.6). GO combined with Bu/Cy regimen followed by alloSCT is well tolerated in children with poor-risk AML. GO at 7.5 mg/m(2) in combination with Bu/Cy is currently being tested in a phase II study. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/22079471/A_Phase_I_study_of_gemtuzumab_ozogamicin__GO__in_combination_with_busulfan_and_cyclophosphamide__Bu/Cy__and_allogeneic_stem_cell_transplantation_in_children_with_poor_risk_CD33+_AML:_a_new_targeted_immunochemotherapy_myeloablative_conditioning__MAC__regimen_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(11)00476-9 DB - PRIME DP - Unbound Medicine ER -