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Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia.
Clin Cancer Res. 2005 Oct 01; 11(19 Pt 2):7164s-7170s.CC

Abstract

PURPOSE

Myeloablative allogeneic stem cell transplantation (SCT) has been successful in the treatment of childhood acute myeloid leukemia (AML), but may be associated with significant toxicity and recurrent disease. Reduced-intensity allogeneic SCT may offer a less toxic approach to patients with AML. Targeted immunotherapy with gemtuzumab ozogamicin has been shown to be safe, well tolerated in children, and, as a single agent, gemtuzumab ozogamicin has induced responses in 30% of patients with recurrent CD33+ AML. There are no safety data with gemtuzumab ozogamicin post allogeneic SCT in children. Therefore, we explored the feasibility and toxicity of targeted immunotherapy following reduced-intensity allogeneic SCT in children with CD33+ AML.

EXPERIMENTAL DESIGN

Eight patients with CD33+ AML received a reduced-intensity allogeneic SCT following fludarabine 30 mg/m2 for 6 days and busulfan 3.2 mg/kg (<4 years, 4 mg/kg/d) for 2 days. Donor sources included six 6/6 HLA-matched related peripheral blood stem cells, one 6/6 sibling cord blood, and one 4/6 unrelated cord blood.

RESULTS

Day 30 and day 60 donor chimerisms in seven of eight evaluable patients were 96 +/- 2% (n = 7) and 94 +/- 3% (n = 6), respectively. Five of six patients (too early for one patient) received two doses of gemtuzumab ozogamicin and one patient received only one dose. After each dose, all patients developed grade 4 neutropenia, with recovery on median days 16 and 13, respectively, after dose 1 and dose 2. Grade 4 thrombocytopenia was only observed in 2 of 11 gemtuzumab ozogamicin courses. No patients have developed dose-limiting toxicity secondary to gemtuzumab ozogamicin.

CONCLUSIONS

The administration of gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with average risk AML is feasible and well tolerated with minimal toxicity. The maximal tolerated dose has yet to be determined for gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with CD33+ AML. Additional studies in a larger group of patients will be required to adequately assess the safety of this approach.

Authors+Show Affiliations

Department of Pediatrics, Columbia University, New York, New York 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16203817

Citation

Roman, Elizabeth, et al. "Preliminary Results of the Safety of Immunotherapy With Gemtuzumab Ozogamicin Following Reduced Intensity Allogeneic Stem Cell Transplant in Children With CD33+ Acute Myeloid Leukemia." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 19 Pt 2, 2005, 7164s-7170s.
Roman E, Cooney E, Harrison L, et al. Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia. Clin Cancer Res. 2005;11(19 Pt 2):7164s-7170s.
Roman, E., Cooney, E., Harrison, L., Militano, O., Wolownik, K., Hawks, R., Foley, S., Satwani, P., Unal, E., Bhatia, M., Bradley, B., Del Toro, G., George, D., Garvin, J., van de Ven, C., & Cairo, M. S. (2005). Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(19 Pt 2), 7164s-7170s.
Roman E, et al. Preliminary Results of the Safety of Immunotherapy With Gemtuzumab Ozogamicin Following Reduced Intensity Allogeneic Stem Cell Transplant in Children With CD33+ Acute Myeloid Leukemia. Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7164s-7170s. PubMed PMID: 16203817.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia. AU - Roman,Elizabeth, AU - Cooney,Erin, AU - Harrison,Lauren, AU - Militano,Olga, AU - Wolownik,Karen, AU - Hawks,Ria, AU - Foley,Sandi, AU - Satwani,Prakash, AU - Unal,Elif, AU - Bhatia,Monica, AU - Bradley,Brigid, AU - Del Toro,Gustavo, AU - George,Diane, AU - Garvin,James, AU - van de Ven,Carmella, AU - Cairo,Mitchell S, PY - 2005/10/6/pubmed PY - 2006/2/24/medline PY - 2005/10/6/entrez SP - 7164s EP - 7170s JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 11 IS - 19 Pt 2 N2 - PURPOSE: Myeloablative allogeneic stem cell transplantation (SCT) has been successful in the treatment of childhood acute myeloid leukemia (AML), but may be associated with significant toxicity and recurrent disease. Reduced-intensity allogeneic SCT may offer a less toxic approach to patients with AML. Targeted immunotherapy with gemtuzumab ozogamicin has been shown to be safe, well tolerated in children, and, as a single agent, gemtuzumab ozogamicin has induced responses in 30% of patients with recurrent CD33+ AML. There are no safety data with gemtuzumab ozogamicin post allogeneic SCT in children. Therefore, we explored the feasibility and toxicity of targeted immunotherapy following reduced-intensity allogeneic SCT in children with CD33+ AML. EXPERIMENTAL DESIGN: Eight patients with CD33+ AML received a reduced-intensity allogeneic SCT following fludarabine 30 mg/m2 for 6 days and busulfan 3.2 mg/kg (<4 years, 4 mg/kg/d) for 2 days. Donor sources included six 6/6 HLA-matched related peripheral blood stem cells, one 6/6 sibling cord blood, and one 4/6 unrelated cord blood. RESULTS: Day 30 and day 60 donor chimerisms in seven of eight evaluable patients were 96 +/- 2% (n = 7) and 94 +/- 3% (n = 6), respectively. Five of six patients (too early for one patient) received two doses of gemtuzumab ozogamicin and one patient received only one dose. After each dose, all patients developed grade 4 neutropenia, with recovery on median days 16 and 13, respectively, after dose 1 and dose 2. Grade 4 thrombocytopenia was only observed in 2 of 11 gemtuzumab ozogamicin courses. No patients have developed dose-limiting toxicity secondary to gemtuzumab ozogamicin. CONCLUSIONS: The administration of gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with average risk AML is feasible and well tolerated with minimal toxicity. The maximal tolerated dose has yet to be determined for gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with CD33+ AML. Additional studies in a larger group of patients will be required to adequately assess the safety of this approach. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/16203817/Preliminary_results_of_the_safety_of_immunotherapy_with_gemtuzumab_ozogamicin_following_reduced_intensity_allogeneic_stem_cell_transplant_in_children_with_CD33+_acute_myeloid_leukemia_ DB - PRIME DP - Unbound Medicine ER -