Anti-CD20 monoclonal antibody (rituximab) therapy for acute cardiac humoral rejection: a case report

Aranda, Juan M.; Scornik, Juan C.; Normann, Sigurd J.; Lottenberg, Richard; Schofield, Richard S.; Pauly, Daniel F.; Miles, Matthew; Hill, James A.; Sleasman, John W.; Skoda-Smith, Suzanne

doi:10.1097/00007890-200203270-00013

Cited by 96 publications

(59 citation statements)

References 4 publications

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“…Rejection was successfully reversed with specific monoclonal antibodies against CD20. As reported by Aranda and associates, 22 humor rejection in a cardiac transplant patient partially responded to steroids, muromonab-CD3, cyclophosphamide, and plasmapheresis. However, the patient's condition eventually improved with the addition of monoclonal anti-CD20 antibody (rituximab therapy).…”

supporting

confidence: 67%

Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature

Akl

Sheashaa²,

Rahim³

et al. 2019

Exp Clin Transplant

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Transplant is the optimal therapy for patients with end-stage renal disease. Acute cellular rejection refractory to treatment remains a major risk factor for graft loss and poor outcomes. In this study, we describe a 39-year-old man who received a living-related kidney transplant. Two days after transplant, the patient displayed acute deterioration of graft function. Conventional anti-rejection therapy was initiated, but graft function did not improve. Biopsy revealed acute cellular rejection (grade IIA), and C4d and HLA antibodies were negative. Immuno histochemistry phenotyping revealed clusters of CD20-positive lymphocytes, with 80% being CD3 positive. Rituximab was prescribed, and graft function improved dramatically. After 1 week, a second graft biopsy was done due to lagging of graft function, shown by serum creatinine of 2.1 mg/dL. Biopsy revealed regenerating acute tubular necrosis with disappearance of the CD20-positive lymphocyte cluster infiltrates. Two year, after transplant, the patient's graft function maintained stable. Phenotyping of the cellular infiltrate is important as it may lead to a proper selection of immunosuppression and consequent improvement of graft outcome. Key words: Acute humoral rejection, B-cell-mediated rejection, CD20-mediated rejection, Renal transplantation, Rituximab IntroductionTransplant remains the optimal treatment for patients with end-stage renal disease. 1 Acute graft rejection remains a common complication and affects long-term graft survival. 2,3 Advances in immunosuppressive protocols have led to improvements in acute graft rejection episodes. 3-6 However, acute graft rejection, especially antibody-mediated rejection (AMR), can cause graft loss in some patients and can shorten graft function time in others. The presence of CD20-positive cells in the graft has been associated with poor reversibility of graft function and a trend toward poor graft survival even without AMR. 7-9 Anti-CD20 antibodies (rituximab) have been used as rescue therapy for CD20-mediated refractory acute rejection with successful outcomes. 7,10-15 Herein, we report a case of refractory acute cellular rejection with clusters of CD20-positive lymphocyte graft infiltrates, resistant to steroid pulses, plasmapheresis, and switching of immunosuppressive drug regimen, which was successfully treated with anti-CD20 antibodies. Case ReportA 39-year-old-male with type 2 insulin-dependent diabetes presented with end-stage kidney disease and with both kidneys having small size. The patient had been on regular hemodialysis for 3 years.The patient received a right iliac renal allograft from his 27-year-old brother. The sibling donor had a different compatible blood group, one mismatched HLA DR, negative repeated complement-dependent crossmatch test, and 7% donor nonspecific panel reactive antibody (PRA) class I and 0% PRA class II. There were no complications during the transplant procedure and postoperative period, with total ischemia time of 55 minutes and immediate diuresis. Induction immunosuppr...

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supporting

confidence: 67%

Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature

Akl

Sheashaa²,

Rahim³

et al. 2019

Exp Clin Transplant

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“…5) It has been approved for the treatment of lymphoma. Recently, there have been several case reports in which rituximab was found to be effective for the treatment of AMR, though still off-label.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, there have been several case reports in which rituximab was found to be effective for the treatment of AMR, though still off-label. [5][6][7]11) T-cells are unaffected by rituximab, and as a consequence opportunistic infection rarely occurs in association with its administration. 7) A single administration of rituximab was enough to manage %PRA and %B-cell count at low levels in our case, and histological findings for rejection immediately disappeared along with marked improvement in cardiac function.…”

Section: Discussionmentioning

confidence: 99%

“…3,4) Recently, rituximab, a chimeric anti-CD20 monoclonal antibody that binds to the antigen expressed on B-cells, has been effective for AMR in several case reports though it is still offlabel. [5][6][7] AMR usually occurs early after HTx, and reports of it occurring a long time after HTx are rare. We experienced a patient with acute decompensated HF caused by CR and AMR simultaneously 12 years after HTx, which might be attributable to poor adherence to medication.…”

Section: R Ecent Advances In Immunosuppressive Therapy Havementioning

confidence: 99%

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Successful Treatment of Hemodynamic Compromise Caused by Antibody-Mediated and Cellular Rejection in a Recipient 12 years After Heart Transplantation

et al. 2013

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SummaryHeart transplantation (HTx) is an established therapy for stage D heart failure due to recent advances in immunosuppressive regimens. However, antibody-mediated rejection remains an unsolved problem because of its refractoriness to standard immunosuppressive therapy with high mortality and graft loss. We experienced a 16-year old patient with hemodynamic compromise caused by both cellular and antibody-mediated rejection 12 years after HTx. The rejection was refractory to repeated steroid pulse treatment, intravenous immunoglobulin administration, and intensifying immunosuppression including addition of everolimus. Eventually, she was successfully treated with repeated plasma exchange accompanied by a single administration of the anti-CD20 monoclonal antibody rituximab. (Int Heart J 2013; 54: 328-331)

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“…However, even with aggressive treatment, AMR is associated with an increased risk for recurrence (3). Treatment with rituximab, total lymphoid irradiation (TLI) and photopheresis has been reported in patients with recurrent or refractory rejection (47)(48)(49)(50)(51). Rituximab, a high-affinity CD20 specific antibody, has been used with success as initial therapy in a case series of 8 patients in hemodynamically significant AMR resulting in improved LVEF in all patients with corresponding resolution of immunofluorescent staining in a follow-up ranging from 2 to 39 months (49).…”

Section: Treatmentmentioning

confidence: 99%

Acute Antibody-Mediated Rejection Following Heart Transplantation

Uber¹,

Self²,

Bakel

et al. 2007

American Journal of Transplantation

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Acute antibody-mediated rejection (AMR) in heart transplantation is often associated with hemodynamic compromise, and is associated with increased mortality and development of accelerated transplant coronary artery disease (TCAD). The diagnosis of AMR has historically been controversial and outcomes with aggressive immunosuppressive therapy including plasmapheresis and cyclophosphamide are poor. Advances in diagnostic techniques like the demonstration of immunopathologic evidence for antibodymediated rejection by deposition of the complement split product C4d in tissue and detection of anti-HLA antibodies by flow cytometry will assist in further characterizing AMR. Immunosuppression targeting B-lymphocytes and use of m-TOR inhibitors to alter the predilection to develop TCAD and improve survival in AMR remains to be proven.

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Anti-CD20 monoclonal antibody (rituximab) therapy for acute cardiac humoral rejection: a case report

Cited by 96 publications

References 4 publications

Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature

Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature

Successful Treatment of Hemodynamic Compromise Caused by Antibody-Mediated and Cellular Rejection in a Recipient 12 years After Heart Transplantation

Acute Antibody-Mediated Rejection Following Heart Transplantation

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