Anti-B-cell monoclonal antibody treatment of severe posttransplant B-lymphoproliferative disorder: prognostic factors and long-term outcome.
B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus-transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic approaches using chemotherapy or antiviral drugs have limited effects on survival. Adoptive immunotherapy with donor T-cell infusions has given promising results in BMT recipients. We previously reported that administration of two monoclonal anti-B-cell antibodies (anti-CD21 and anti-CD24) could contribute to the control of oligoclonal BLPD. Here we report the long-term results of treatment with these monoclonal anti-B-cell antibodies for cases of severe BLPD. In an open multicenter trial, 58 patients in whom aggressive B-cell lymphoproliferative disorder developed after BMT (n = 27) or organ (n = 31) transplantation received 0.2 mg/kg/d of specific anti-CD21 and anti-CD24 murine monoclonal antibodies (MoAbs) for 10 days. The treatment was well tolerated. Thirty-six of the 59 episodes of BLPD in the 58 patients presented complete remission (61%). The relapse rate was low (3 of 36, 8%). Multivariate analysis identified the following risk factors for partial or no response to anti-B-cell MoAb therapy: multivisceral disease (P </= .005), central nervous system involvement (P </= .05), and late onset of BLPD (P </= .005). The overall long-term survival was 46% (median follow-up, 61 months); it was lower among BMT patients (35%) than organ transplant patients (55%). None of the patients who had received BMT for hematological malignancy survived for 1 year. Eight of these 11 patients presented monoclonal BLPD. Tumor burden was the only other variable that contributed significantly to poor survival. Thus, as assessed from this long-term study, the use of anti-B-cell MoAbs therefore appears to be a safe and relatively effective therapy for severe posttransplant BLPD.
Benkerrou
M
M
Department of Pediatric Immunology, Biostatistics, Pediatric Cardiology, Unité Inserm U429, Hôpital Necker Enfants Malades, Paris, France.
Jais
J P
JP
Leblond
V
V
Durandy
A
A
Sutton
L
L
Bordigoni
P
P
Garnier
J L
JL
Le Bidois
J
J
Le Deist
F
F
Blanche
S
S
Fischer
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D051927:CD24 Antigen; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D015331:Cohort Studies; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000401:mortality / Q000628:therapy* / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D017464:Receptors, Complement 3d / Q000276:immunology*; D012074:Remission Induction; D012307:Risk Factors; D016019:Survival Analysis; D014180:Transplantation / Q000009:adverse effects*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051927:CD24 Antigen; C497889:CD24 protein, human; C497890:Cd24a protein, mouse; D008562:Membrane Glycoproteins; D017464:Receptors, Complement 3d