Anti-B-cell monoclonal antibodies in the treatment of severe B-cell lymphoproliferative syndrome following bone marrow and organ transplantation.
BACKGROUND
The B-cell lymphoproliferative syndrome is an infrequent life-threatening complication of marrow or organ transplantation that is the consequence of profound immunosuppression. The results of treatment have been disappointing, although a small number of patients have been cured by chemoradiotherapy or antiviral agents after a reduction in the dosage of immunosuppressive therapy. We report here the results of treating this disorder with anti-B-cell antibodies.


METHODS
Twenty-six patients in whom aggressive B-cell lymphoproliferative syndrome developed after bone marrow (n = 14) or organ (n = 12) transplantation received 0.2 mg of CD21-specific and of CD24-specific antibodies per kilogram of body weight for 10 consecutive days in an open, prospective, multicenter trial.


RESULTS
The treatment was well tolerated. All patients had transient neutropenia, apparently because the CD24 molecule is also expressed on granulocytes. The treatment was ineffective in seven patients with monoclonal B-cell proliferation. In contrast, 16 patients with oligoclonal B-cell proliferation had complete remission. Systemic remission also occurred in two other patients with oligoclonal proliferation who had central nervous system involvement, although they subsequently died because of progression of the central nervous system disease. In one patient who died early, clonality was not determined. Of the 16 patients who had complete remission, 2 with persistent immunodeficiency due to graft (marrow) rejection or acute graft-versus-host disease had a relapse, and the 1 with graft-versus-host disease subsequently died. Eleven patients were alive and disease-free after a median follow-up of 35 months (5 of 14 marrow recipients and 6 of 12 organ recipients). Four other patients in complete remission died of unrelated causes 4 to 12 months after treatment.


CONCLUSIONS
Intravenous administration of anti-B-cell antibodies may be effective in controlling diffuse, severe, oligoclonal B-cell proliferation not involving the central nervous system.
Fischer
A
A
Unité 132, INSERM, Hôpital des Enfants-Malades, Paris, France.
Blanche
S
S
Le Bidois
J
J
Bordigoni
P
P
Garnier
J L
JL
Niaudet
P
P
Morinet
F
F
Le Deist
F
F
Fischer
A M
AM
Griscelli
C
C
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016026:Bone Marrow Transplantation; D051927:CD24 Antigen; D015815:Cell Adhesion Molecules; D002648:Child; D002675:Child, Preschool; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000150:complications; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007223:Infant; D007275:Injections, Intravenous; D037102:Lectins; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins; D008875:Middle Aged; D016377:Organ Transplantation; D011183:Postoperative Complications / Q000628:therapy; D051918:Sialic Acid Binding Ig-like Lectin 2
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D051927:CD24 Antigen; C497889:CD24 protein, human; D015815:Cell Adhesion Molecules; D037102:Lectins; D008562:Membrane Glycoproteins; D051918:Sialic Acid Binding Ig-like Lectin 2