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Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients.
Clin Cancer Res. 2001 Aug; 7(8):2254-62.CC

Abstract

PURPOSE

A fludarabine-based "nonmyeloablative" preparative regimen was investigated in 42 patients with hematological malignancies receiving hematopoietic stem cell grafts from unrelated volunteer donors.

EXPERIMENTAL DESIGN

Recipient conditioning consisted of fludarabine 30 mg/m(2) on days -6 to -2 and i.v. busulfan 3.3 mg/kg on days -6 to -5. Antithymocyte globuline was added at 2.5 mg/kg i.v. on days -5 to -2. The patients were grafted with bone marrow (n = 13) or peripheral blood stem cells either unmanipulated (n = 20) or CD34+ selected (n = 9). Graft-versus-host disease prophylaxis was performed with cyclosporine A (CsA, n = 12), CsA/methotrexate (n = 12), or CsA/mycophenolate mofetil (n = 18).

RESULTS

With a median follow-up of 13 months (range, 5-26 months), the actuarial disease-free survival is 64% and 38% for patients with lymphoid malignancies and standard-risk leukemia compared with only 14% for patients with high-risk disease. The main cause of treatment failure was relapse of disease in high-risk patients (n = 14). An increased incidence of primary (n = 1) or secondary graft-failure (n = 8) was observed (21%). Chimerism analysis of CD56+/CD3--sorted natural killer (NK) cells, available in 10 patients, showed an impaired increase of donor NK cell chimerism between day 10 and 30 after transplantation in three of four patients with graft failure, whereas the percentage of donor NK cells surpassed 75% in all of the six patients with stable engraftment.

CONCLUSIONS

Unrelated transplants after dose-reduced conditioning are associated with a higher risk of graft-failure. Pretransplant host immunosuppression has to be optimized to overcome resistance to grafts from unrelated donors after nonmyeloablative conditioning therapy.

Authors+Show Affiliations

Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. bornhaeuser@oncocenter.deNo 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, Non-U.S. Gov't

Language

eng

PubMed ID

11489799

Citation

Bornhäuser, M, et al. "Dose-reduced Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated Donors in 42 Patients." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 7, no. 8, 2001, pp. 2254-62.
Bornhäuser M, Thiede C, Platzbecker U, et al. Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. Clin Cancer Res. 2001;7(8):2254-62.
Bornhäuser, M., Thiede, C., Platzbecker, U., Jenke, A., Helwig, A., Plettig, R., Freiberg-Richter, J., Röllig, C., Geissler, G., Lutterbeck, K., Oelschlagel, U., & Ehninger, G. (2001). Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 7(8), 2254-62.
Bornhäuser M, et al. Dose-reduced Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated Donors in 42 Patients. Clin Cancer Res. 2001;7(8):2254-62. PubMed PMID: 11489799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. AU - Bornhäuser,M, AU - Thiede,C, AU - Platzbecker,U, AU - Jenke,A, AU - Helwig,A, AU - Plettig,R, AU - Freiberg-Richter,J, AU - Röllig,C, AU - Geissler,G, AU - Lutterbeck,K, AU - Oelschlagel,U, AU - Ehninger,G, PY - 2001/8/8/pubmed PY - 2001/10/19/medline PY - 2001/8/8/entrez SP - 2254 EP - 62 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 7 IS - 8 N2 - PURPOSE: A fludarabine-based "nonmyeloablative" preparative regimen was investigated in 42 patients with hematological malignancies receiving hematopoietic stem cell grafts from unrelated volunteer donors. EXPERIMENTAL DESIGN: Recipient conditioning consisted of fludarabine 30 mg/m(2) on days -6 to -2 and i.v. busulfan 3.3 mg/kg on days -6 to -5. Antithymocyte globuline was added at 2.5 mg/kg i.v. on days -5 to -2. The patients were grafted with bone marrow (n = 13) or peripheral blood stem cells either unmanipulated (n = 20) or CD34+ selected (n = 9). Graft-versus-host disease prophylaxis was performed with cyclosporine A (CsA, n = 12), CsA/methotrexate (n = 12), or CsA/mycophenolate mofetil (n = 18). RESULTS: With a median follow-up of 13 months (range, 5-26 months), the actuarial disease-free survival is 64% and 38% for patients with lymphoid malignancies and standard-risk leukemia compared with only 14% for patients with high-risk disease. The main cause of treatment failure was relapse of disease in high-risk patients (n = 14). An increased incidence of primary (n = 1) or secondary graft-failure (n = 8) was observed (21%). Chimerism analysis of CD56+/CD3--sorted natural killer (NK) cells, available in 10 patients, showed an impaired increase of donor NK cell chimerism between day 10 and 30 after transplantation in three of four patients with graft failure, whereas the percentage of donor NK cells surpassed 75% in all of the six patients with stable engraftment. CONCLUSIONS: Unrelated transplants after dose-reduced conditioning are associated with a higher risk of graft-failure. Pretransplant host immunosuppression has to be optimized to overcome resistance to grafts from unrelated donors after nonmyeloablative conditioning therapy. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/11489799/Dose_reduced_conditioning_and_allogeneic_hematopoietic_stem_cell_transplantation_from_unrelated_donors_in_42_patients_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11489799 DB - PRIME DP - Unbound Medicine ER -