Treatment of posttransplant lymphoproliferative disease with rituximab: the remission, the relapse, and the complication

Erik A M Verschuuren, Servi J C Stevens, Gustaaf W van Imhoff, Jaap M Middeldorp, Conny de Boer, Gerard Koëter, T Hauw The, Wim van Der Bij

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Rituximab, a humanized anti-CD20 monoclonal antibody, is a promising new tool for the treatment of posttransplant lymphoproliferative disease (PTLD), especially for patients transplanted with rejection prone transplants of vital organs, such as patients after lung transplantation. Thus far, no major complications have been described. We treated three lung transplant recipients with Rituximab because of PTLD.

METHODS: Patients were treated with four weekly doses of 375 mg/m2 of Rituximab. Epstein-Barr virus (EBV) DNA was monitored with quantitative-competitive polymerase chain reaction and circulating B cells with flow cytometry.

RESULTS: Treatment with Rituximab resulted in a complete remission in all patients without signs of or progression of bronchiolitis obliterans syndrome. Patient 1 relapsed after 2 months with a partly CD20-negative PTLD but is in stable remission after radiotherapy. Patient 2 is in complete remission 16 months after treatment, but patient 3 developed a hypogammaglobulinemia and died of invasive aspergillosis after 6 months. EBV DNA was detectable in the blood samples of patients 2 and 3 before treatment with Rituximab and became negative instantly after Rituximab. In all three patients, B cells are absent in the peripheral blood 7 months (at death), 16 months, and 16 months after treatment with Rituximab. Antiproliferating agents, such as mycophenolate mofetil (MMF), might prolong B-cell depletion.

CONCLUSIONS: Rituximab was effective for the treatment of PTLD without progression of transplant dysfunction in our patients. Complications were a partly CD20-negative relapse of PTLD and a hypogammaglobulinemia. Attention should be paid to immunoglobulin G (IgG) levels, especially in patients treated with antiproliferating agents such as MMF.

Original languageEnglish
Pages (from-to)100-4
Number of pages5
JournalTransplantation
Volume73
Issue number1
Publication statusPublished - 15 Jan 2002

Cite this

Verschuuren, E. A. M., Stevens, S. J. C., van Imhoff, G. W., Middeldorp, J. M., de Boer, C., Koëter, G., ... van Der Bij, W. (2002). Treatment of posttransplant lymphoproliferative disease with rituximab: the remission, the relapse, and the complication. Transplantation, 73(1), 100-4.
Verschuuren, Erik A M ; Stevens, Servi J C ; van Imhoff, Gustaaf W ; Middeldorp, Jaap M ; de Boer, Conny ; Koëter, Gerard ; The, T Hauw ; van Der Bij, Wim. / Treatment of posttransplant lymphoproliferative disease with rituximab : the remission, the relapse, and the complication. In: Transplantation. 2002 ; Vol. 73, No. 1. pp. 100-4.
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Verschuuren, EAM, Stevens, SJC, van Imhoff, GW, Middeldorp, JM, de Boer, C, Koëter, G, The, TH & van Der Bij, W 2002, 'Treatment of posttransplant lymphoproliferative disease with rituximab: the remission, the relapse, and the complication' Transplantation, vol. 73, no. 1, pp. 100-4.

Treatment of posttransplant lymphoproliferative disease with rituximab : the remission, the relapse, and the complication. / Verschuuren, Erik A M; Stevens, Servi J C; van Imhoff, Gustaaf W; Middeldorp, Jaap M; de Boer, Conny; Koëter, Gerard; The, T Hauw; van Der Bij, Wim.

In: Transplantation, Vol. 73, No. 1, 15.01.2002, p. 100-4.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Treatment of posttransplant lymphoproliferative disease with rituximab

T2 - the remission, the relapse, and the complication

AU - Verschuuren, Erik A M

AU - Stevens, Servi J C

AU - van Imhoff, Gustaaf W

AU - Middeldorp, Jaap M

AU - de Boer, Conny

AU - Koëter, Gerard

AU - The, T Hauw

AU - van Der Bij, Wim

PY - 2002/1/15

Y1 - 2002/1/15

N2 - BACKGROUND: Rituximab, a humanized anti-CD20 monoclonal antibody, is a promising new tool for the treatment of posttransplant lymphoproliferative disease (PTLD), especially for patients transplanted with rejection prone transplants of vital organs, such as patients after lung transplantation. Thus far, no major complications have been described. We treated three lung transplant recipients with Rituximab because of PTLD.METHODS: Patients were treated with four weekly doses of 375 mg/m2 of Rituximab. Epstein-Barr virus (EBV) DNA was monitored with quantitative-competitive polymerase chain reaction and circulating B cells with flow cytometry.RESULTS: Treatment with Rituximab resulted in a complete remission in all patients without signs of or progression of bronchiolitis obliterans syndrome. Patient 1 relapsed after 2 months with a partly CD20-negative PTLD but is in stable remission after radiotherapy. Patient 2 is in complete remission 16 months after treatment, but patient 3 developed a hypogammaglobulinemia and died of invasive aspergillosis after 6 months. EBV DNA was detectable in the blood samples of patients 2 and 3 before treatment with Rituximab and became negative instantly after Rituximab. In all three patients, B cells are absent in the peripheral blood 7 months (at death), 16 months, and 16 months after treatment with Rituximab. Antiproliferating agents, such as mycophenolate mofetil (MMF), might prolong B-cell depletion.CONCLUSIONS: Rituximab was effective for the treatment of PTLD without progression of transplant dysfunction in our patients. Complications were a partly CD20-negative relapse of PTLD and a hypogammaglobulinemia. Attention should be paid to immunoglobulin G (IgG) levels, especially in patients treated with antiproliferating agents such as MMF.

AB - BACKGROUND: Rituximab, a humanized anti-CD20 monoclonal antibody, is a promising new tool for the treatment of posttransplant lymphoproliferative disease (PTLD), especially for patients transplanted with rejection prone transplants of vital organs, such as patients after lung transplantation. Thus far, no major complications have been described. We treated three lung transplant recipients with Rituximab because of PTLD.METHODS: Patients were treated with four weekly doses of 375 mg/m2 of Rituximab. Epstein-Barr virus (EBV) DNA was monitored with quantitative-competitive polymerase chain reaction and circulating B cells with flow cytometry.RESULTS: Treatment with Rituximab resulted in a complete remission in all patients without signs of or progression of bronchiolitis obliterans syndrome. Patient 1 relapsed after 2 months with a partly CD20-negative PTLD but is in stable remission after radiotherapy. Patient 2 is in complete remission 16 months after treatment, but patient 3 developed a hypogammaglobulinemia and died of invasive aspergillosis after 6 months. EBV DNA was detectable in the blood samples of patients 2 and 3 before treatment with Rituximab and became negative instantly after Rituximab. In all three patients, B cells are absent in the peripheral blood 7 months (at death), 16 months, and 16 months after treatment with Rituximab. Antiproliferating agents, such as mycophenolate mofetil (MMF), might prolong B-cell depletion.CONCLUSIONS: Rituximab was effective for the treatment of PTLD without progression of transplant dysfunction in our patients. Complications were a partly CD20-negative relapse of PTLD and a hypogammaglobulinemia. Attention should be paid to immunoglobulin G (IgG) levels, especially in patients treated with antiproliferating agents such as MMF.

KW - Antibodies, Monoclonal

KW - Antibodies, Monoclonal, Murine-Derived

KW - Antineoplastic Agents

KW - DNA, Viral

KW - Drug Therapy, Combination

KW - Epstein-Barr Virus Infections

KW - Female

KW - Follow-Up Studies

KW - Herpesvirus 4, Human

KW - Humans

KW - Immunoglobulin G

KW - Immunosuppressive Agents

KW - Lung Transplantation

KW - Lymphoproliferative Disorders

KW - Middle Aged

KW - Polymerase Chain Reaction

KW - Postoperative Complications

KW - Recurrence

KW - Retrospective Studies

KW - Rituximab

KW - Time Factors

KW - Journal Article

M3 - Article

VL - 73

SP - 100

EP - 104

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 1

ER -

Verschuuren EAM, Stevens SJC, van Imhoff GW, Middeldorp JM, de Boer C, Koëter G et al. Treatment of posttransplant lymphoproliferative disease with rituximab: the remission, the relapse, and the complication. Transplantation. 2002 Jan 15;73(1):100-4.