Successful Engraftment of T-Cell–Depleted Haploidentical “Three-Loci” Incompatible Transplants in Leukemia Patients by Addition of Recombinant Human Granulocyte Colony-Stimulating Factor–Mobilized Peripheral Blood Progenitor Cells to Bone Marrow Inoculum

Patients who undergo transplantation with haploidentical “three-loci” mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both...

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Published in:Blood 1994-12, Vol.84 (11), p.3948-3955
Main Authors: Aversa, Franco, Tabilio, Antonio, Terenzi, Adelmo, Velardi, Andrea, Falzetti, Franca, Giannoni, Claudia, lacucci, Roberta, Zei, Tiziana, Martelli, Maria Paola, Gambelunghe, Cesare, Rossetti, Massimo, Caputo, Pierfranco, Latini, Paolo, Aristei, Cynthia, Raymondi, Carlo, Reisner, Yair, Martelli, Massimo F.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Biological and medical sciences
Bone Marrow Transplantation - adverse effects
Bone Marrow Transplantation - mortality
Bone Marrow Transplantation - pathology
Bone marrow, stem cells transplantation. Graft versus host reaction
Child
Female
Graft Survival
Graft vs Host Disease - mortality
Graft vs Host Disease - prevention & control
Granulocyte Colony-Stimulating Factor - pharmacology
Haplotypes
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cells - drug effects
Histocompatibility
Host vs Graft Reaction
Humans
Leukemia - pathology
Leukemia - therapy
Lymphocyte Depletion
Male
Medical sciences
Middle Aged
Recombinant Proteins - pharmacology
T-Lymphocytes
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Transplantation, Homologous
Treatment Outcome
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Summary:Patients who undergo transplantation with haploidentical “three-loci” mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both immune rejection and stem cell competition in murine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplants of a combination of BM with recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells from HLA-haploidentical “three-loci” incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the final inoculum was sevenfold to 10-fold greater than that found in BM alone. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E-rosetting technique. The conditioning regimen included total body irradiation in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and myeloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died from grade IV acute GVHD. There were no other cases of GVHD ≥grade II. Nine patients died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplantation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V84.11.3948.bloodjournal84113948