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Busulfan, fludarabine, and alemtuzumab as a reduced toxicity regimen for children with malignant and nonmalignant diseases improves engraftment and graft-versus-host disease without delaying immune reconstitution.
Biol Blood Marrow Transplant. 2012 Nov; 18(11):1656-63.BB

Abstract

For children receiving allogeneic hematopoietic stem cell transplants (HSCTs), the toxicity of the conditioning regimen and graft failure remain challenges. We previously reported that targeted i.v. busulfan, fludarabine, and rabbit anti-thymocyte globulin (rATG) decreased toxicity but had a graft failure rate of 21%. To improve the engraftment rate, we replaced ATG with alemtuzumab, a monoclonal Ab targeting CD52. Thirty-five children with malignant and nonmalignant diseases were enrolled in this phase II prospective study. Twelve children had HLA-matched related donors (MRDs), 16 had 10 of 10, and 7 had 9 of 10 HLA allele-matched unrelated donors (MUDs). Thirty-one of 34 evaluable patients (91%) achieved a durable engraftment. All 3 patients who rejected had a nonmalignant disease and received a MUD transplantation (2 mismatched at 1 antigen). Three patients died of a transplantation-related complication (9% ± 5.2%). Seven patients had disease relapse or progression, 2 of whom died. At a median follow-up of 35 months (range, 15-85 months), the event-free survival (EFS) was 61% ± 9.0% and the overall survival (OS) was 78% ± 7.5%. The median time to neutrophil recovery, B cell, and T cell reconstitution were 16 days, 3 months, and 6 months, respectively. At 1 year, the median donor chimerism in whole blood, CD3, CD14/15, and CD19 subsets were 97%, 87%, 100%, and 99%, respectively. Six patients (17% ± 6.6%) developed acute graft-versus-host disease (aGVHD), only 2 of which were >grade II. Two patients (8% ± 5.4%) progressed to chronic GVHD (cGVHD). These results suggest that replacement of rATG with alemtuzumab may improve engraftment as well as decrease cGVHD rates without resulting in delays in immune reconstitution.

Authors+Show Affiliations

Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article

Language

eng

PubMed ID

22609040

Citation

Law, Jason, et al. "Busulfan, Fludarabine, and Alemtuzumab as a Reduced Toxicity Regimen for Children With Malignant and Nonmalignant Diseases Improves Engraftment and Graft-versus-host Disease Without Delaying Immune Reconstitution." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 18, no. 11, 2012, pp. 1656-63.
Law J, Cowan MJ, Dvorak CC, et al. Busulfan, fludarabine, and alemtuzumab as a reduced toxicity regimen for children with malignant and nonmalignant diseases improves engraftment and graft-versus-host disease without delaying immune reconstitution. Biol Blood Marrow Transplant. 2012;18(11):1656-63.
Law, J., Cowan, M. J., Dvorak, C. C., Musick, L., Long-Boyle, J. R., Baxter-Lowe, L. A., & Horn, B. (2012). Busulfan, fludarabine, and alemtuzumab as a reduced toxicity regimen for children with malignant and nonmalignant diseases improves engraftment and graft-versus-host disease without delaying immune reconstitution. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 18(11), 1656-63. https://doi.org/10.1016/j.bbmt.2012.05.006
Law J, et al. Busulfan, Fludarabine, and Alemtuzumab as a Reduced Toxicity Regimen for Children With Malignant and Nonmalignant Diseases Improves Engraftment and Graft-versus-host Disease Without Delaying Immune Reconstitution. Biol Blood Marrow Transplant. 2012;18(11):1656-63. PubMed PMID: 22609040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Busulfan, fludarabine, and alemtuzumab as a reduced toxicity regimen for children with malignant and nonmalignant diseases improves engraftment and graft-versus-host disease without delaying immune reconstitution. AU - Law,Jason, AU - Cowan,Morton J, AU - Dvorak,Christopher C, AU - Musick,Lisa, AU - Long-Boyle,Janel R, AU - Baxter-Lowe,Lee Ann, AU - Horn,Biljana, Y1 - 2012/05/15/ PY - 2012/02/19/received PY - 2012/05/10/accepted PY - 2012/5/22/entrez PY - 2012/5/23/pubmed PY - 2013/5/4/medline SP - 1656 EP - 63 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 - 11 N2 - For children receiving allogeneic hematopoietic stem cell transplants (HSCTs), the toxicity of the conditioning regimen and graft failure remain challenges. We previously reported that targeted i.v. busulfan, fludarabine, and rabbit anti-thymocyte globulin (rATG) decreased toxicity but had a graft failure rate of 21%. To improve the engraftment rate, we replaced ATG with alemtuzumab, a monoclonal Ab targeting CD52. Thirty-five children with malignant and nonmalignant diseases were enrolled in this phase II prospective study. Twelve children had HLA-matched related donors (MRDs), 16 had 10 of 10, and 7 had 9 of 10 HLA allele-matched unrelated donors (MUDs). Thirty-one of 34 evaluable patients (91%) achieved a durable engraftment. All 3 patients who rejected had a nonmalignant disease and received a MUD transplantation (2 mismatched at 1 antigen). Three patients died of a transplantation-related complication (9% ± 5.2%). Seven patients had disease relapse or progression, 2 of whom died. At a median follow-up of 35 months (range, 15-85 months), the event-free survival (EFS) was 61% ± 9.0% and the overall survival (OS) was 78% ± 7.5%. The median time to neutrophil recovery, B cell, and T cell reconstitution were 16 days, 3 months, and 6 months, respectively. At 1 year, the median donor chimerism in whole blood, CD3, CD14/15, and CD19 subsets were 97%, 87%, 100%, and 99%, respectively. Six patients (17% ± 6.6%) developed acute graft-versus-host disease (aGVHD), only 2 of which were >grade II. Two patients (8% ± 5.4%) progressed to chronic GVHD (cGVHD). These results suggest that replacement of rATG with alemtuzumab may improve engraftment as well as decrease cGVHD rates without resulting in delays in immune reconstitution. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/22609040/Busulfan_fludarabine_and_alemtuzumab_as_a_reduced_toxicity_regimen_for_children_with_malignant_and_nonmalignant_diseases_improves_engraftment_and_graft_versus_host_disease_without_delaying_immune_reconstitution_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(12)00196-6 DB - PRIME DP - Unbound Medicine ER -