Anti–B-Cell Monoclonal Antibodies in the Treatment of Severe B-Cell Lymphoproliferative Syndrome Following Bone Marrow and Organ Transplantation

Fischer, Alain; Blanche, Stéphane; J, Le Bidois; Bordigoni, Pierre; Jl, Garnier; Niaudet, Patrick; Morinet, F.; F, Le Deist; Am, Fischer; Griscelli, C

doi:10.1056/nejm199105233242102

Cited by 323 publications

(123 citation statements)

References 22 publications

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“…Prospectively, CD24 might aid the clinician in the selection of an appropriate therapy for individual patients. In this circumstance, it is of relevance to know that the intravenous administration of CD24-specific antibodies has been sucessfully used therapeutically to treat transplantation-associated B-cell proliferative syndrome (Fischer et al, 1991;Garnier et al, 2002). This new therapeutic option might deserve consideration in NSCLC patients as well.…”

Section: Discussionmentioning

confidence: 99%

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

et al. 2003

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Originally identified as a B-cell marker, expression of the cell surface molecule CD24 has meanwhile been observed in a variety of human malignancies. It appears to function as a ligand of P-Selectin, an adhesion molecule that is present in activated platelets and endothelial cells. We aimed to determine the rate of CD24 expression in our nonsmall cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters including patients' survival. A total of 89 NSCLC were analysed immunohistochemically using a monoclonal CD24 antibody (clone 24C02) and a standard detection system (LSAB, DAKO) on NSCLC tissue microarrays (TMA). The staining was semiquantitatively scored (0, 1+, 2+, 3+) and grouped into high (2+, 3+)-and low (0, 1+)-level expression for statistical analysis. A high level of CD24 expression was observed in 45% of the cases, preferentially adenocarcinomas. Patients whose tumours had a high CD24 expression showed a significantly shorter median survival time of 23 months vs 38 months (P ¼ 0.033, log-rank test). Similarly tumour, grading, nodal status and clinical stage were significant prognostic markers in univariate survival analysis. Importantly, in the Cox regression-based multivariate analysis, CD24 expression (P ¼ 0.025) together with tumour stage (P ¼ 0.006) and grade (P ¼ 0.011) proved to be independent prognostic parameters. We hypothesise that the decreased survival of NSCLC patients with strongly CD24-positive tumours is related to an enhanced propensity of haematogenous metastasis formation, which might be P-Selectin mediated.

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Section: Discussionmentioning

confidence: 99%

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

et al. 2003

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“…Anti-B cell MoAb have been reported to be effective in controlling EBV-LPD when the CNS is not involved. 3 The reason why anti-B cell MoAb were not effective against CNS EB-LPD remains to be elucidated, but the suggestion is that penetration of MoAb into the CNS might be poor.…”

Section: Discussionmentioning

confidence: 99%

Donor lymphocyte transfusion for the treatment of Epstein–Barr virus-associated lymphoproliferative disorder of the brain

Nagafuji

Eto

Hayashi

et al. 1998

Bone Marrow Transplant

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Summary:EBV-associated lymphoproliferative disorder (LPD) is a rare but serious complication in marrow transplant recipients. A 31-year-old Japanese woman in the second chronic phase of CML received an allogeneic BMT from her HLA 2-locus-incompatible 62-year-old father. Around day +200, she developed EBV-LPD of the right parieto-temporal lobe which caused slowly progressive left hemiparesis. Two courses of donor lymphocyte transfusions (DLT) of 10 6 CD3 + T cells/kg of body weight failed to suppress her central nervous system (CNS) EBV-LPD. The patient died of recurrent blastic crisis of CML. This case suggests that DLT may be ineffective for the treatment of CNS EBV-LPD. Keywords: Epstein-Barr virus-associated lymphoproliferative disorder; donor lymphocyte transfusion; central nervous system EBV-associated lymphoproliferative disorder (LPD) is a rare but serious complication in marrow transplant recipients. 1,2 Although there are reports of successful treatment of polyclonal or oligoclonal proliferations with agents such as interferon-␣ and intravenous ␥-globulin, high-dose acyclovir, and anti-B-cell MoAb, 3-5 monoclonal disease has remained refractory to treatment in marrow transplant recipients.Recently, donor lymphocyte transfusions (DLT) have been shown to be an effective treatment for EBV-LPD. 6,7 We report the case of a Japanese woman, who developed EBV-LPD of the right cerebrum following allogeneic BMT and who was then treated with DLT. Case reportA 31 year-old Japanese woman was admitted to our hospital for the treatment of myeloid blastic crisis (BC) of CML Correspondence: Dr K Nagafuji, Department of Hematology, Hara Sanshin General Hospital, 1-8 Taihaku-machi, Hakata-ku, Fukuoka 812, Japan Received 4 August 1997; accepted 22 December 1997 in July 1996. She entered the second chronic phase after treatment with vincristine and prednisolone. The patient had no HLA-identical siblings, nor were there any HLAidentical unrelated donors in the Japan Marrow Donor Program. Because of the poor prognosis in BC, we decided to perform a BMT using her HLA 2-locus-incompatible 62-year-old father as donor. The donor was seropositive for human T cell leukemia virus type 1 (HTLV-1), while the recepient was seronegative. 8 Both the recipient and the donor were seropositive for EBV (VCA IgG ×40 VCA IgM Ͻ×10 EBNA ×10, VBCA IgG ×640 VCA IgM Ͻ×10 EBNA ×10, respectively).The pre-transplant conditioning consisted of BU 4 mg/kg orally in divided doses daily on days −8 to −5, and CY 50 mg/kg i.v. daily on days −4 to −2. Because of ABO major incompatibility, bone marrow mononuclear cells isolated by density-gradient centrifugation (1.8 × 10 8 /kg of body weight) were given. Tacrolimus (FK506; Fujisawa, Osaka, Japan) in combination with MTX was used for GVHD prophylaxis. Grade II GVHD of the skin developed on day +11 but this responded well to high-dose methylprednisolone therapy. Granulocytes exceeded 0.5 × 10 9 /l on day +16, and platelets exceeded 50 × 10 9 /l on day +26. Prolonged administration of immunosuppressive agents wa...

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“…Several patients, including the presented one, were treated with cytokines or IVIG to improve immune response, but outcome was variable (Table I). Acyclovir and ganciclovir were given by other authors in the presumption of an association with EBV, and monoclonal antibodies to pan-B-cell antigens were successfully used in treating several patients with EBV-related LPD in the post-transplant setting [16]. Noteworthy, LPD did not progress in the present patient after surgery.…”

Section: Discussionmentioning

confidence: 75%

B‐Cell lymphoproliferative disorder not associated with Epstein‐Barr Virus in a child with relapsed acute lymphoblastic leukemia

Lehrnbecher

Trusen

Deinlein

et al. 2002

Med. Pediatr. Oncol.

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Lymphoproliferative disorder (LPD) is described in only a few children receiving chemotherapy for cancer. In all of them, an association between LPD and EBV (Epstein‐Barr Virus) was found. We report on a patient who developed LPD not associated with EBV while receiving chemotherapy for relapsed acute lymphoblastic leukemia (ALL). Despite discontinuation of chemotherapy, administration of intravenous immunoglobulins and surgery the patient died. Growing experience with this disorder may allow better treatment options in the future and will show whether LPD not associated with EBV requires different therapeutic strategies. Med Pediatr Oncol 2003;40:13–17, © 2003 Wiley‐Liss, Inc.

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Anti–B-Cell Monoclonal Antibodies in the Treatment of Severe B-Cell Lymphoproliferative Syndrome Following Bone Marrow and Organ Transplantation

Abstract: Intravenous administration of anti-B-cell antibodies may be effective in controlling diffuse, severe, oligoclonal B-cell proliferation not involving the central nervous system.

Cited by 323 publications

References 22 publications

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

Donor lymphocyte transfusion for the treatment of Epstein–Barr virus-associated lymphoproliferative disorder of the brain

B‐Cell lymphoproliferative disorder not associated with Epstein‐Barr Virus in a child with relapsed acute lymphoblastic leukemia

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