title: Influence of CD34 cell selection on the incidence of mixed chimaerism and minimal residual disease after allogeneic unrelated donor transplantation.
abstract: Marrow transplantation from unrelated donors has been linked with an increased risk of graft-versus-host disease (GVHD). In an attempt to lower the risk of acute GVHD we used CD34 marrow cell selection for T cell depletion. Since T cell depletion has been linked to an increased risk of relapse and an increased risk of marrow failure, we used PCR amplification of minisatellite sequences to investigate donor cell engraftment and RT-PCR amplification of recurrent chromosomal translocations to investigate the residual disease post-transplant. Twenty-three patients who underwent BMT after positive selection of the CD34-positive cell population were studied. Results were then compared with those of 37 patients who underwent transplantation with unmanipulated marrow graft. Among the 23 patients who received CD34+ selected cell grafts, seven (30%) had evidence of full donor engraftment, 14 had evidence of residual recipient cells (61%), one had a non-take, and one autologous bone marrow recovery. Analysis of the chimaerism status post-transplant in 36 patients who received unmanipulated marrow grafts showed that 31 patients (86%) had evidence of full donor engraftment. The difference in the incidence of mixed chimaerism profile between patients who received unmanipulated marrow graft and those receiving CD34+ selected cell grafts was statistically significant (P< 0.01). Nine patients who received CD34+ selected cell grafts could be analysed for the presence of minimal residual disease post-transplant (one with t(9;22) acute lymphoblastic leukaemia and eight with CML). In the patient transplanted for a Ph-positive acute leukaemia, and in two out of the eight patients with CML, the search fora fusion transcript was consistently negative after transplantation. Among the six patients with evidence of residual disease, three patients also had a mixed chimaerism profile and were given donor lymphocyte infusions. Minimal residual disease study was performed post-transplant in 16 patients who received unmanipulated marrow grafts. In 10 of 14 patients with CML, and in two patients with acute leukaemia the search for a fusion transcript was consistently negative after transplantation. The difference in the incidence of minimal residual disease between patients who received an unmanipulated marrow graft and those receiving CD34+ selected cell grafts was not statistically significantly significant, but numbers of patients included in this analysis are still few. In conclusion, our study highlights the strong influence of graft manipulation on the incidence of mixed chimaerism after transplantation from an unrelated donor.
authors.affiliation: Service d'Hématologie-Greffe de Moelle and Unité de Recherche sur la Biologie des Cellules Souches, Hôpital Saint Louis, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Socié
authors.forename: J M
authors.initials: JM
authors.lastname: Cayuela
authors.forename: B
authors.initials: B
authors.lastname: Raynal
authors.forename: H
authors.initials: H
authors.lastname: Esperou
authors.forename: X
authors.initials: X
authors.lastname: Fund
authors.forename: C
authors.initials: C
authors.lastname: Raffoux
authors.forename: A
authors.initials: A
authors.lastname: Devergie
authors.forename: P
authors.initials: P
authors.lastname: Ribaud
authors.forename: J P
authors.initials: JP
authors.lastname: Marolleau
authors.forename: N
authors.initials: N
authors.lastname: Parquet
authors.forename: F
authors.initials: F
authors.lastname: Sigaux
authors.forename: O
authors.initials: O
authors.lastname: Brison
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: C107844:AML1-ETO fusion protein, human; D018952:Antigens, CD34; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016044:Fusion Proteins, bcr-abl