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Acute Humoral Rejection in a Lung Recipient: Reversion With Bortezomib

2009; Wolters Kluwer; Volume: 89; Issue: 1 Linguagem: Inglês

10.1097/tp.0b013e3181c280f9

1534-6080

Jorge Neumann, H. Tarrasconi, Andréa Silveira Bortolotto, Tiago Machuca, R Canabarro, H. Sporleder, Sandra Fernandes, Sadi Marcelo Schio, C. Costa, Spencer Marcantônio Camargo, Leticia Sánchez-Valdeón, José Jesus Camargo, Fabíola Adélia Perin, José Carlos Felicetti, Tatiana Michelon,

Pneumocystis jirovecii pneumonia detection and treatment

Anti–donor human leukocyte antigen antibodies have been recognized as a major cause of graft loss in the last few years (1, 2). A new agent, bortezomib, is showing a great potential in the treatment of renal allograft recipients under acute humoral rejection (3, 4). We report the first case of use of this agent in a lung allograft recipient. A 54-year-old female patient with two previous pregnancies, with pulmonary emphysema class IV, and with repeated hospitalizations in intensive care units due to need of mechanical ventilation was included on the waiting list for a lung transplant. She received the graft on March 19, 2009. The donor was a 44-year-old woman who was a victim of cerebrovascular hemorrhage. The transplant was performed after a T-cell-negative flow crossmatch in the serum of the day and in a previous sample (45 days old) and was marginally negative against B cells on the sample of the day and was positive in that previous sera. All the cytotoxicity crossmatches were negative. In the immediate posttransplant period, the patient had important instability attributed to infection. She received antibiotics without improvement. A biopsy was performed on the seventh postoperative day (PO), and the result was compatible with severe acute rejection, positive for C4d deposition. She was pulsed with corticosteroids with only discrete functional improvement, remaining in mechanical ventilation. On the 15th PO, the clinical status was deteriorating. The crossmatch by flow was repeated and revealed that she remained negative against donor T cells, but the reaction against donor B cells was highly positive, in a level about 10 times superior to the day of the transplant (channel shift of 74 increased to 750). The biopsy performed on this day showed persistence of serious acute rejection. Analysis of her serum by single antigen beads for human leukocyte antigen class I and II (OneLambda, Canoga Park, CA) revealed the presence of anti-DR13, present in the donor, with a fluorescence of 9.931, increased from 2.385 on the day of the transplant. We started bortezomib on the same protocol being used for kidney recipients (4 doses of 1.3 mg/m2 at 4-day intervals). The initial clinical response was highly favorable. Biopsies on the 40th, 47th, and 60th PO resulted in complete reversion of the rejection. During this period, she presented with bacterial bronchopneumonia, reactivation of cytomegalovirus disease, and infectious tracheobronchitis, all successfully treated. Analysis of the serum on the 97th PO with single antigens disclosed that the fluorescence intensity of the anti-donor DR13 had fallen to 2.439, similar to the pretransplant levels. Now, the patient is (150 days of follow-up) at home with complete radiological recovery of the graft and normal O2 saturation with ambient air at rest. This is the first report on the use of bortezomib (Valcade) in a lung recipient. Initial studies in kidney have shown the great potential of this agent in the reversion of humoral rejections. We believe that it might be beneficial to recipients of other organs as well. Jorge Neumann Heloisa Tarrasconi Andrea Bortolotto Tiago Machuca Raquel Canabarro Heloisa Sporleder Sandra Fernandes Laboratory of Transplantation Immunology Santa Casa Hospital Porto Alegre, Brazil Sadi Schio Clarisse Costa Spencer Camargo Leticia Sanchez Jose Camargo Fabiola Perin Jose Felicetti Lung Transplant Service Santa Casa Hospital Porto Alegre, Brazil Tatiana Michelon Post Graduate Division, Pathology Federal University of Health Sciences Porto Alegre, Brazil