Blaes AH, Peterson BA, Bartlett N, Dunn DL, Morrison VA.. Rituximab therapy is effective for posttransplant lymphoproliferative disorders after solid organ transplantation: results of a phase II trial. Cancer 104: 1661-1667

Department of Medicine, The University of Minnesota, Minneapolis, Minnesota 55455, USA.
Cancer (Impact Factor: 4.89). 10/2005; 104(8):1661-7. DOI: 10.1002/cncr.21391
Source: PubMed


Posttransplant lymphoproliferative disorders (PTLD) remain an uncommon complication of solid organ transplantation with a high mortality rate reported after conventional therapies. Alternative treatments such as rituximab have been explored.
Eleven patients with PTLD, who were CD20 positive, received an intravenous dose of rituximab, 375 mg/m2, weekly x 4 weeks, repeated every 6 months for 2 years in responding patients. The median age of the patients was 56 years (range, 43-68 yrs), and 9 patients were male. The type of solid organ transplantation that these patients received included lung (five patients), kidney (four patients), heart (one patient), and kidney/pancreas (one patient). The median time from transplantation to a PTLD diagnosis was 9 months (range, 1-122 mos). Diagnostic B-cell histology was diffuse large cell lymphoma or polymorphous process. No patient had bone marrow or central nervous system involvement. Primary extranodal disease was noted in 82% of patients. Immunosuppressive therapy was decreased at the time of diagnosis.
Rituximab was well tolerated, with mild infusional blood pressure alterations noted in two patients. The median follow-up period was 10 months (range, 1-32 mos). The overall response rate was 64%, with 6 complete responses (CR), 1 partial response, 2 cases of progressive disease, and 2 deaths. The median duration of CR was 8 months (range, 2-19+ mos). The median time to treatment failure was 10 months (range, 5-25+ mos). The median survival was 14 months (range, < 1-32+ mos). Four patients were alive at the time of last follow-up.
Single-agent rituximab may offer a response and survival advantage in patients with PTLD. Further evaluation of rituximab in these disorders, potentially in combination with other therapies, is warranted.

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    • "Patients who do not respond to reduction in IS and rituximab can be given combined chemotherapy. However, combined chemotherapy with rituximab should be considered as first-line therapy for patients who are not suitable for reduction in IS or who have EBV-negative, late-onset aggressive disease, or for patients who have high tumor burden requiring an upfront rapid intervention [24,25,26,27,28]. In conclusion, EBV-negative PTLDs can be considered as a distinct group of PTLD resembling lymphomas of immunocompetent subjects due to late occurrence, higher proportion of monomorphic cases, and clinically more aggressive behavior. "
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    ABSTRACT: Three cases of Epstein-Barr virus (EBV)-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.
    Turkish Journal of Haematology 03/2014; 31(1):79-83. DOI:10.4274/Tjh.2012.0010 · 0.36 Impact Factor
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    • "Oertel and colleagues achieved 52% remission in recipients of solid organ transplant including lung, who had developed PTLD, and noted a survival of 37 months after PTLD [63]. Similar results have been reported from other centers, with clinical remission rates of ~60% [64–66]. Nevertheless, long-term survival may still be impacted, studies are difficult to interpret due to uncontrolled treatment protocols, and timing and dosing period of therapy have yet to be determined. "
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    ABSTRACT: Posttransplant lymphoproliferative disease (PTLD) after lung transplantation occurs due to immunosuppressant therapy which limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and transformation of B cells. Mechanistically, EBV survives due to latency, escape from cytotoxic T cell responses, and downregulation of host immunity to EBV. Clinical presentation of EBV may occur within the lung allograft early posttransplantation or later onset which is more likely to be disseminated. Improvements in monitoring through EBV viral load have provided a means of earlier detection; yet, sensitivity and specificity of EBV load monitoring after lung transplantation may require further optimization. Once PTLD develops, staging and tissue diagnosis are essential to appropriate histopathological classification, prognosis, and guidance for therapy. The overall paradigm to treat PTLD has evolved over the past several years and depends upon assessment of risk such as EBV-naïve status, clinical presentation, and stage and sites of disease. In general, clinical practice involves reduction in immunosuppression, anti-CD20 biologic therapy, and/or use of plasma cell inhibition, followed by chemotherapy for refractory PTLD. This paper focuses upon the immunobiology of EBV and PTLD, as well as the clinical presentation, diagnosis, prognosis, and emerging treatments for PTLD after lung transplantation.
    Clinical and Developmental Immunology 03/2013; 2013(6):430209. DOI:10.1155/2013/430209 · 2.93 Impact Factor
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    • "Our patient had an elevated lactate dehydrogenase ratio and multi-organ PTLD. Recently, anti-CD20 monoclonal antibody (rituximab) monotherapy or a combination therapy with combination chemotherapy with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (CHOP) was reported to be effective for PTLD [9,10]. These alternative therapies would have been considered if the reduction of immunosuppressants was not effective in this case. "
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    ABSTRACT: Because the normal ovary is assumed to be devoid of lymphoid tissue, it is unusual for it to be an initial manifestation of malignant lymphoma. This case is the first report, to our knowledge, of post-transplant lymphoproliferative disorder involving the ovary as an initial manifestation. Twenty-nine weeks after a living renal transplantation, a 38-year-old Japanese female, whose ethnic origin was Asian, presented with abdominal pain and a chronic high fever. Computed tomography revealed a right ovarian tumor and liver metastases. The patient underwent oophrectomy based on the clinical diagnosis of liver metastasis from the primary ovarian tumor. The pathological diagnosis was Epstein-Barr Virus-associated post-transplant lymphoproliferative disorder. While ovarian malignant lymphoma has a poor prognosis, complete remission of liver involvement in this case was achieved only with a reduction of immunosuppressants. Clinicians should remember that malignant lymphoma could initially involve the ovary, especially if the patient is immunosuppressed after transplantation therapy.
    Journal of Medical Case Reports 06/2010; 4:184. DOI:10.1186/1752-1947-4-184
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