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
Autor: | James Garvin, R. Hawks, Erin Morris, John Le Gall, Carmella van de Ven, Zhezhen Jin, Filemon Dela Cruz, D. George, Sandra Foley, Mitchell S. Cairo, Deirdre Duffy, Prakash Satwani, Lee Ann Baxter-Lowe, Joseph Schwartz, Monica Bhatia |
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Rok vydání: | 2012 |
Předmět: |
Male
Transplantation Conditioning medicine.medical_treatment Sialic Acid Binding Ig-like Lectin 3 Graft vs Host Disease Hematopoietic stem cell transplantation Gastroenterology Pediatrics MAC Regimen AML Risk Factors Gemtuzumab ozogamicin Child Hematopoietic Stem Cell Transplantation Hematology Gemtuzumab Tissue Donors Survival Rate Leukemia Myeloid Acute Child Preschool Female Immunosuppressive Agents medicine.drug medicine.medical_specialty Adolescent Cyclophosphamide Antigens Differentiation Myelomonocytic Antineoplastic Agents Antibodies Monoclonal Humanized Disease-Free Survival Tacrolimus Antigens CD Conditioning regimen Internal medicine medicine Humans Transplantation Homologous Busulfan Transplantation business.industry Siblings Infant Mycophenolic Acid Myeloablative Agonists Surgery Allogeneic stem cell transplantation Regimen Aminoglycosides business Follow-Up Studies |
Zdroj: | Biology of Blood and Marrow Transplantation. 18(2):324-329 |
ISSN: | 1083-8791 |
DOI: | 10.1016/j.bbmt.2011.11.007 |
Popis: | 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. |
Databáze: | OpenAIRE |
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