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
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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