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Hematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin.
Biol Blood Marrow Transplant. 2009 Jan; 15(1):61-72.BB

Abstract

To extend the use of allogeneic hematopoietic cell transplantation (HCT) to patients without an HLA-matched donor, we investigated HCT from a related donor with 1 fully mismatched HLA-haplotype after conditioning with busulfan in reduced-dose, fludarabine, and antithymocyte globulin. Hematopoietic cells were collected from the donors via leukapheresis after mobilization and infused without further manipulation. Cyclosporin and methotrexate were administered for graft-versus-host disease (GVHD) prophylaxis. Posttransplant engraftment, GVHD, and transplantation-related mortality (TRM) were recorded. Thirty-one patients (age range: 16-69 years) with high-risk acute leukemia/myelodysplastic syndrome (n = 25) or bone marrow failure (n = 6) were enrolled. The donors were either mothers (n = 14), offspring (n = 9), or siblings (n = 8) of these patients. Excluding 3 patients who died or relapsed with leukemia within 3 weeks after HCT, all the remaining 28 patients engrafted with neutrophils (>500/microL) at a median of 16.5 days. Twenty-two of 24 evaluated patients achieved complete donor chimerism (> or =95%) 2 weeks after HCT and none experienced graft failure subsequently. The cumulative incidences of grade 2-4 acute GVHD (aGVHD) and moderate-severe chronic GVHD (cGVHD) were 19% (95% confidence interval [CI], 9%-40%) and 20% (95% CI, 10%-41%), respectively. After a median follow-up of 18.2 months (range: 6.3-52.1), 18 patients remained alive (53%). Four patients died without recurrence/progression of underlying diseases giving a TRM of 13% (95% CI, 5%-33%). HCT from an HLA-mismatched family member is feasible without ex vivo T cell depletion when reduced-intensity conditioning containing anti-hymocyte globulin is performed.

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Authors+Show Affiliations

Lee KH
Hematology Section, Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea. khlee2@amc.seoul.kr
Lee JH
No affiliation info available
Lee JH
No affiliation info available
Kim DY
No affiliation info available
Kim SH
No affiliation info available
Shin HJ
No affiliation info available
Lee YS
No affiliation info available
Kang YA
No affiliation info available
Seol M
No affiliation info available
Ryu SG
No affiliation info available

MeSH

AdolescentAdultAgedAntilymphocyte SerumBusulfanFamilyFemaleGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHistocompatibilityHistocompatibility TestingHumansLymphocyte DepletionMaleMiddle AgedSurvival AnalysisT-LymphocytesTissue DonorsTransplantation ConditioningTreatment OutcomeVidarabineYoung Adult

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

19135944

Clinical Trial Links

Donor-specific Allogeneic Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia (ALL)

Citation

Lee, Kyoo-Hyung, et al. "Hematopoietic Cell Transplantation From an HLA-mismatched Familial Donor Is Feasible Without Ex vivo-T Cell Depletion After Reduced-intensity Conditioning With Busulfan, Fludarabine, and Antithymocyte Globulin." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 15, no. 1, 2009, pp. 61-72.
Lee KH, Lee JH, Lee JH, et al. Hematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin. Biol Blood Marrow Transplant. 2009;15(1):61-72.
Lee, K. H., Lee, J. H., Lee, J. H., Kim, D. Y., Kim, S. H., Shin, H. J., Lee, Y. S., Kang, Y. A., Seol, M., & Ryu, S. G. (2009). Hematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 15(1), 61-72. https://doi.org/10.1016/j.bbmt.2008.10.025
Lee KH, et al. Hematopoietic Cell Transplantation From an HLA-mismatched Familial Donor Is Feasible Without Ex vivo-T Cell Depletion After Reduced-intensity Conditioning With Busulfan, Fludarabine, and Antithymocyte Globulin. Biol Blood Marrow Transplant. 2009;15(1):61-72. PubMed PMID: 19135944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin. AU - Lee,Kyoo-Hyung, AU - Lee,Je-Hwan, AU - Lee,Jung-Hee, AU - Kim,Dae-Young, AU - Kim,Se-Hyung, AU - Shin,Ho-Jin, AU - Lee,Young-Shin, AU - Kang,Young-Ah, AU - Seol,Miee, AU - Ryu,Sung-Gil, PY - 2008/09/08/received PY - 2008/10/28/accepted PY - 2009/1/13/entrez PY - 2009/1/13/pubmed PY - 2009/2/28/medline SP - 61 EP - 72 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 15 IS - 1 N2 - To extend the use of allogeneic hematopoietic cell transplantation (HCT) to patients without an HLA-matched donor, we investigated HCT from a related donor with 1 fully mismatched HLA-haplotype after conditioning with busulfan in reduced-dose, fludarabine, and antithymocyte globulin. Hematopoietic cells were collected from the donors via leukapheresis after mobilization and infused without further manipulation. Cyclosporin and methotrexate were administered for graft-versus-host disease (GVHD) prophylaxis. Posttransplant engraftment, GVHD, and transplantation-related mortality (TRM) were recorded. Thirty-one patients (age range: 16-69 years) with high-risk acute leukemia/myelodysplastic syndrome (n = 25) or bone marrow failure (n = 6) were enrolled. The donors were either mothers (n = 14), offspring (n = 9), or siblings (n = 8) of these patients. Excluding 3 patients who died or relapsed with leukemia within 3 weeks after HCT, all the remaining 28 patients engrafted with neutrophils (>500/microL) at a median of 16.5 days. Twenty-two of 24 evaluated patients achieved complete donor chimerism (> or =95%) 2 weeks after HCT and none experienced graft failure subsequently. The cumulative incidences of grade 2-4 acute GVHD (aGVHD) and moderate-severe chronic GVHD (cGVHD) were 19% (95% confidence interval [CI], 9%-40%) and 20% (95% CI, 10%-41%), respectively. After a median follow-up of 18.2 months (range: 6.3-52.1), 18 patients remained alive (53%). Four patients died without recurrence/progression of underlying diseases giving a TRM of 13% (95% CI, 5%-33%). HCT from an HLA-mismatched family member is feasible without ex vivo T cell depletion when reduced-intensity conditioning containing anti-hymocyte globulin is performed. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/19135944/Hematopoietic_cell_transplantation_from_an_HLA_mismatched_familial_donor_is_feasible_without_ex_vivo_T_cell_depletion_after_reduced_intensity_conditioning_with_busulfan_fludarabine_and_antithymocyte_globulin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(08)00474-6 DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓9]

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