Increased incidence of EBV-associated lymphoproliferative disorders after allogeneic stem cell transplantation from matched unrelated donors due to a change of T cell depletion technique.
Here, the influence of T vs T and B cell depletion on the incidence of EBV-associated lymphoproliferative disorder (EBV-LPD) after bone marrow transplantation (BMT) from a matched unrelated donor (MUD) is analyzed. From 1982 to 1997 the soy bean agglutinin/sheep red blood cell (SBA/SRBC) method was used for T cell depletion. This technique is well established, but the use of SRBC has a risk of transmitting prions or viruses. Therefore, a new T cell depletion method was introduced, using CD2 and CD3 monoclonal antibodies (CD2/3 method) instead of SRBC. Unfortunately, this led to an unexpected high number of EBV-LPDs in patients receiving transplants from MUDs. SBA depletion was reintroduced and combined with the CD2/3 method (SBA/CD2/3) in this patient population, later replaced by B cell-specific (CD19 and CD22) antibodies (CD3/19/22 method). The number of T (x 10(5)/kg) and B (x 10(5)/kg) cells in the graft was 1.5 +/- 0.8 and 2 +/- 1 (T/B ratio 0.75), 2.2 +/- 2.0 and 41 +/- 21 (ratio 0.055), 5.0 +/- 0.0 and 2 +/- 1 (ratio 2.5), 2.5 +/- 1.2 and 10 +/- 6 (ratio 0.25) using the SBA/SRBC, CD2/3, SBA/CD2/3 and CD3/19/22 techniques, respectively. When B cell depletion was performed (SBA/SRBC, SBA/CD2/3, CD3/19/22) four out of 31 patients (13%) receiving a BMT from a MUD developed an EBV-LPD. Without B cell depletion (CD2/3) this occurred in five out of seven patients (71%) (P < 0.05). A T/B cell ratio in the graft of > or = 0.25 seems sufficient to significantly reduce the incidence of EBV-LPD after BMT from MUDs.
Meijer
E
E
Department of Hematology, University Medical Centre, Utrecht, The Netherlands.
Slaper-Cortenbach
I C M
IC
Thijsen
S F T
SF
Dekker
A W
AW
Verdonck
L F
LF
D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology; D018801:CD2 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D020031:Epstein-Barr Virus Infections / Q000209:etiology* / Q000276:immunology; D004912:Erythrocytes; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006650:Histocompatibility Testing; D006801:Humans; D037102:Lectins; D008212:Lymphocyte Depletion / Q000009:adverse effects* / Q000379:methods; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D037121:Plant Lectins; D012756:Sheep; D051918:Sialic Acid Binding Ig-like Lectin 2; D030262:Soybean Proteins; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous; D010835:Phytohemagglutinins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D037102:Lectins; D037121:Plant Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D030262:Soybean Proteins; C497867:CD22 protein, human; C028824:soybean lectin; D010835:Phytohemagglutinins