T-cell Posttransplant Lymphoproliferative Disorders Research Articles

T-Cell Posttransplant Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: Case Series and Systemic Review.

Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.

Posttransplant Cutaneous Anaplastic Large Cell Lymphoma

Post-transplant lymphoproliferative disorders (PTLD) are frequent in organ recipients; they are most often of B lymphocyte origin; on the other hand, CD30+ t-cell PTLD remain rare; we report the observation of a case of CD30+ anaplastic large cell lymphoma in a renal transplant recipient.

Prior antithymocyte globulin therapy and survival in post-transplant lymphoproliferative disorders

Background: Treatment with antithymocyte globulin (ATG) is a well-recognized risk factor for the development of post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation, but it is unknown how its use affects overall survival after PTLD. Methods: A total of 114 patients with PTLD and available data on immunosuppressive regimen were included from a nation-wide case series of solid organ transplant recipients in Sweden. Prior use of ATG was correlated to clinical features, PTLD subtype, and survival. Results: A total of 47 (41%) patients had received ATG prior to the diagnosis of PTLD. The ATG-treated patients were more likely to be recipients of hearts or lungs, and less likely of kidneys (p < 0.01). They had experienced more acute rejections (p = 0.02). The PTLDs arose earlier, median 2.0 vs. 6.6 years post-transplant (p = 0.002) and were more often situated in the allograft (32% vs. 7%, p < 0.001) in patients with prior ATG vs. no ATG treatment. The PTLDs in the ATG group were more often Epstein–Barr virus-positive (80% vs. 40%, p < 0.001). There were more polymorphic PTLDs (17% vs. 1.5%, p = 0.004) and less T-cell PTLDs (4% vs. 19%, p = 0.02) in the ATG group than in the no ATG group. Diffuse large B-cell lymphoma was equally common in patients with and without prior ATG therapy, but the non-germinal center subtype was more frequent in the ATG group (p = 0.001). In an adjusted Cox proportional hazards regression model, prior ATG treatment and better performance status were associated with superior overall survival, whereas older age, T-cell subtype of PTLD, presence of B symptoms, and elevated lactate dehydrogenase were associated with inferior overall survival. Patients receiving ATG solely as rejection therapy had superior overall survival compared with those receiving ATG as induction therapy or both (p = 0.03). Conclusions: ATG therapy, especially rejection therapy, prior to PTLD development is an independent prognostic factor for superior overall survival after PTLD diagnosis.

An Unusual Posttransplant T-cell Lymphoma After Liver Transplantation: A Case Report

Posttransplantation lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities ranging from benign lymphocytic proliferations to high-grade malignant lymphomas. The majority of PTLDs are associated with reactivation of Epstein-Barr virus (EBV), which induces B-cell proliferation and occurs in the setting of severe immune suppression after solid organ or bone marrow transplantation. T-cell/natural killer cell PTLDs are relatively rare, constituting ∼15% of all cases. T-cell PTLDs are usually aggressive, and outcomes are poor. This article describes an unusual case of T-cell PTLD with a favorable outcome. The patient is a 57-year-old man who underwent a liver transplantation due to hepatitis C cirrhosis. He developed graft-versus-host disease with skin and gastrointestinal involvement and generalized lymphadenopathy 4 months after transplantation. Histologic sections of an excised axillary lymph node showed atypical medium and larger T-lymphocytes that were positive for CD3, CD5, CD43, and CD8 but were negative for B-cell antigens, CD56, and in situ hybridization for EBV-encoded RNA. Polymerase chain reaction analysis revealed monoclonal T-cell receptor gamma chain gene rearrangement. A diagnosis of high-grade T-cell PTLD was made. The patient was treated with 4 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone and is currently in remission, 4 years after therapy. The rapid presentation of an EBV-negative T-cell PTLD with a nonaggressive course and complete response to treatment is an unusual presentation of posttransplantation T-cell lymphoma, which is usually associated with a high mortality rate.

II. Challenges in the management of post-transplant lymphoproliferative disorder.

II. Challenges in the management of post-transplant lymphoproliferative disorder.

Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.

Signet Ring Cell Primary Cutaneous CD30+ Lymphoproliferative Disorder Presenting as a Monomorphic T-Cell Posttransplant Lymphoproliferative Disease

T-cell posttransplant lymphoproliferative disorders are rare, with peripheral T-cell lymphoma not otherwise specified being the most common type. Although cases of the signet ring cell variant of primary cutaneous CD30+ lymphoproliferative disorder have been reported, such cases have not been described in the posttransplant setting. We describe a case with emphasis on the special contextual differential diagnostic considerations.

Concomitant Epstein-Barr Virus (EBV)-Positive B-Cell and EBV-Negative T-Cell Posttransplant Lymphoproliferative Disorders After Renal Allografting: Pathogenetic Implications

Concomitant Epstein-Barr Virus (EBV)-Positive B-Cell and EBV-Negative T-Cell Posttransplant Lymphoproliferative Disorders After Renal Allografting: Pathogenetic Implications

Presence of monoclonal T-cell populations in B-cell post-transplant lymphoproliferative disorders

As has been previously shown, the lack of immune surveillance plays a major role in the unchecked proliferation of Epstein–Barr virus (EBV)-infected B cells in the pathogenesis of B-cell post-transplant lymphoproliferative disorders. We hypothesised that the lack of immune surveillance should possibly also affect T cells, and this should lead to subsequent emergence of T-cell clones. The presence of both B- and T-cell clones in post-transplant lymphoproliferative disorders samples has rarely been demonstrated in the past. We systematically evaluated 26 B-cell post-transplant lymphoproliferative disorder, 23 human immune deficiency virus-associated B-cell lymphoma and 10 immune-competent diffuse large B-cell lymphoma samples for B- and T-cell clonality (polymerase chain reaction and heteroduplex analysis using BIOMED-2 protocol), T-cell subsets (immunohistochemistry) and EBV association (in situ hybridisation using EBER). One-half of B-cell post-transplant lymphoproliferative disorders showed evidence of monoclonal T-cell expansion, and among the T cells present in the tissue samples, CD8-positive cells predominated. Although 9/13 (69%) B-cell post-transplant lymphoproliferative disorders with the presence of monoclonal T-cell population had a CD4:CD8 ratio of ≤0.4, 0/13 of the cases without monoclonal T-cell expansion had a ratio ≤0.4 (P=0.002). Only 2/26 (8%) demonstrated significant cytological atypia in the CD3/CD8-positive cells. There was no association between EBV and presence of T-cell clones. T-cell clones were not identified in lymphomas other than B-cell post-transplant lymphoproliferative disorders. Among 53.8% cases of EBV-positive B-cell post-transplant lymphoproliferative disorders with associated clonal expansion of T-cells tested, none had EBV-positive T cells. We conclude that half of B-cell post-transplant lymphoproliferative disorders are associated with clonal expansion of CD8-positive T cells, most of which do not amount to the coexistence of a T-cell post-transplant lymphoproliferative disorders.

Metachronous EBV-associated B-cell and T-cell Posttransplant Lymphoproliferative Disorders in a Heart Transplant Recipient

Posttransplant lymphoproliferative disorders (PTLDs) may occur as a complication of immunosuppression in patients who have received solid organ or bone marrow allografts. Most PTLDs are of B-cell lineage, whereas T-cell proliferations are rare. The majority of B-cell lesions are associated with Epstein-Barr virus infection. The occurrence of both B-cell and T-cell PTLDs in the same patient is extremely rare and only 6 cases have been previously published. We report a case of a 63-year-old man who developed 2 metachronous Epstein-Barr virus-related PTLDs beginning 10 years after heart transplantation. A polymorphic B-cell PTLD developed first that completely regressed after immunosuppressive therapy was partially withdrawn. Then, a monomorphic T-cell PTLD developed 31 months later. The patient died 17 months later owing to disease progression. We highlight the diagnostic challenge of this case that required numerous ancillary studies for lineage assessment and classification. Such studies are often needed in patients with a history of immunosuppression.

An overview of the pathogenesis and natural history of post-transplant T-cell lymphoma (corrected and republished article originally printed in Leukemia & Lymphoma, June 2007; 48(6): 1237 – 1241)

Post-transplantation lymphoproliferative disorders (PTLDs) are well recognized complications of solid organ transplantation. The vast majority of early PTLDs are B-cell non-Hodgkin lymphomas. PTLDs of T-cell origin occur much less frequently and account for only a minority of cases. T-cell PTLDs have been reported to occur primarily at extranodal sites, commonly affecting bone marrow or splenic tissues. The small bowel is an uncommon site of origin of these tumors with only seven cases of primary intestinal post-transplant T-cell lymphomas reported in the literature. We hereby report a new case of primary intestinal post-transplant T-cell lymphoma, arising 18 years following renal transplantation, along with a literature review of all published cases.

Simian virus 40 in posttransplant lymphoproliferative disorders

Simian virus 40 (SV40) is an oncogenic DNA virus, which is an emergent pathogen implicated in some human malignancies, including B-cell lymphomas. As with other malignancies that occur during immunosuppression, it is hypothesized that SV40 infections may be associated with some posttransplant lymphoproliferative disorders (PTLDs). Specimens were tested initially for Epstein-Barr virus (EBV) by in situ hybridization for EBV-encoded small RNA and/or by immunohistochemical staining for EBV-latent membrane protein 1. Coded DNA specimens extracted from formalin-fixed, paraffin-embedded tissues from 22 PTLD cases were examined by polymerase chain reaction using primers for the SV40 large tumor antigen (T-ag) gene and confirmed by sequence analysis. In addition, samples were assessed for the expression of SV40 T-ag by immunohistochemical staining. Epstein-Barr virus was detected in 18 (82%) of 22 PTLD cases. Simian virus 40 T-ag sequences were detected in 2 (13%) of the 16 cases with amplifiable DNA: one with EBV-negative T-cell PTLD and the other with EBV-positive B-cell monomorphic PTLD. Immunohistochemical staining showed expression of SV40 T-ag in 1 of 2 cases containing viral DNA sequences and in none of the SV40 T-ag DNA-negative samples. Expression of SV40 T-ag was restricted to malignant cells and not to reactive lymphocytes. These results suggest that SV40 may be associated with a small subset of PTLD cases. Additional studies are needed to determine the role of SV40 in EBV-negative PTLD.

Characteristic Pattern of Chromosomal Imbalances in Posttransplantation Lymphoproliferative Disorders: Correlation with Histopathological Subcategories and EBV Status

Posttransplantation lymphoproliferative disorders (PTLDs) are a spectrum of lymphoid proliferations, occurring in immunosuppressed organ transplant recipients. They comprise early lesions, polymorphic (P-PTLD), monomorphic (M-PTLD), and Hodgkin/Hodgkin-like lymphoma PTLD (HL-PTLD) lesions. Most of them are associated with Epstein-Barr virus (EBV). Little is known about their genetic changes. We have studied 35 PTLDs[7 P-PTLDs (3/7 polyclonal IgH), 26 M-PTLDs (22 B-cell PTLD, 4 T-cell PTLD), 2 HL-PTLDs], using comparative genomic hybridization (CGH), a DNA-based technique allowing a screening of chromosomal imbalances without needing cultured cells. RESULTS.: Overall incidence of chromosomal imbalances: 51.5 %. The most frequent gains involved 8q24, 3q27 [4 cases each]; 2p24p25, 5p, 9q22q34, 11, 12q22q24, 14q32, 17q, 18q21 [2 cases each]. Nonrandom losses were 17p13 [4 cases]; 1p36, 4q [3 cases each]; 17q23q25, Xp [2 cases each]. Three high-level amplifications were detected: 4p16, 9p22p24, 18q21q23. In this latter imbalance, involvement of Bcl2 has been confirmed by FISH. The nonrandom CGH imbalances occurring in M-PTLD are usually described in lymphomas of immunocompetent patients and contain genes known to be involved in lymphomagenesis, while genomic abnormalities detected in half cases of EBV positive P-PTLD are mostly unknown. This study reported nonrandom chromosomal imbalances in PTLD and also identified early genomic alterations in EBV positive P-PTLD. These results raise two questions: the role of such lesions in the development and progression of those EBV induced-lymphoproliferations and their clinical significance especially in P-PTLD.

Primary ???Cutaneous??? T-Cell Anaplastic Large Cell Lymphoma, CD30+, Neutrophil-Rich Variant with Subcutaneous Panniculitic Lesions, in a Post-Renal Transplant Patient

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.

EBV-Associated B- and T-Cell Posttransplant Lymphoproliferative Disorders Following Primary EBV Infection in a Kidney Transplant Recipient

Posttransplant lymphoproliferative disorders (PTLDs) usually are of B-cell lineage and associated with Epstein-Barr virus (EBV). PTLDs of T-cell lineage are much less common and infrequently associated with EBV. We report a rare case of a girl in whom B-cell and T-cell PTLDs developed following 2 EBV-negative kidney transplants. Within 2 years of the second transplantation, the originally EBV-negative patient developed both an EBV-associated clonal B-cell PTLD involving lymph nodes and an EBV-positive T-cell PTLD involving bone marrow and liver. These proliferations occurred concurrently with evidence of primary EBV infection and high plasma viral load. The patient eventually died of multiorgan failure 5 years after the initial transplant (3 years after the second transplant). To our knowledge, only 4 cases of both B-cell and T-cell PTLDs have been reported. Only 2 cases have been proven to be monoclonal and EBV-associated, as in this case, the first following kidney transplantation.

EBV-Associated B-and T-Cell Posttransplant Lymphoproliferative Disorders Following Primary EBV Infection in a Kidney Transplant Recipient

Posttransplant lymphoproliferative disorders (PTLDs) usually are of B-cell lineage and associated with Epstein-Barr virus (EBV). PTLDs of T-cell lineage are much less common and infrequently associated with EBV. We report a rare case of a girl in whom B-cell and T-cell PTLDs developed following 2 EBV-negative kidney transplants. Within 2 years of the second transplantation, the originally EBV-negative patient developed both an EBV-associated clonal B-cell PTLD involving lymph nodes and an EBV-positive T-cell PTLD involving bone marrow and liver. These proliferations occurred concurrently with evidence of primary EBV infection and high plasma viral load. The patient eventually died of multiorgan failure 5 years after the initial transplant (3 years after the second transplant). To our knowledge, only 4 cases of both B-cell and T-cell PTLDs have been reported. Only 2 cases have been proven to be monoclonal and EBV-associated, as in this case, the first following kidney transplantation.

T‐cell post‐transplantation lymphoproliferative disorders after cardiac transplantation: a single institutional experience

Post-transplantation lymphoproliferative disorders (PTLDs) are a well-recognized and potentially life-threatening complication of solid organ transplantation. While the vast majority of PTLDs are B-cell lymphoproliferations, T-cell PTLDs are rarely seen. Among 898 patients receiving cardiac transplants between 1990 and 2003, 34 patients (3.8%) developed PTLDs with two (0.2%) T-cell PTLDs, 31 (3.5%) B-cell PTLDs and one (0.1%) natural killer cell PTLD. An additional three cases of T-cell PTLD were identified among all cardiac transplant patients followed at our institution. These T-cell PTLDs comprised a heterogeneous group of Epstein-Barr virus negative lymphoproliferations that developed late after transplantation and followed an aggressive course.

EBV Positive Primary Cutaneous CD30+ Large T-Cell Lymphoma in a Heart Transplanted Patient: Case Report

Most post-transplant lymphoproliferative disorders (PTLDs) are of B-cell origin, whereas T-cell lymphomas rarely occur. We detail the clinicopathological features of the first case of Epstein-Barr virus (EBV)-associated primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL) in the setting of heart transplant. A 71-year-old patient, 111 months after transplant, presented with multiple cutaneous lesions on the left thigh; histological and immunohistochemical examinations led to diagnosis of T-cell CD30+ ALCL. In situ hybridization demonstrated the presence of EBV-positive tumour cells. The patient received radiotherapy, but he relapsed at the same cutaneous site with loco-regional nodal spread. Chemotherapy was administered resulting in complete remission; four years later the patient is alive and well. Our findings indicate that primary cutaneous EBV+ CD30+ ALCLs should be included within the T-cell PTLDs spectrum; further studies are required to confirm whether they may be also considered, in transplantation settings, a distinct lymphoma subset with relatively favourable outcome.

Post Transplant T-Cell Lymphoma: A Case Series of Four Patients from a Single Unit and Review of the Literature

Post-transplant lymphoproliferative disorders (PTLDs) occur in approximately 1% of renal graft recipients. Of these, up to 15 percent are of the T-cell type. In this study, we present four cases of T-cell lymphoma from our renal transplant population, each of whom presented with non-specific symptoms, pancytopenia and/or liver dysfunction, with no obvious lymphadenopathy. They were all diagnosed with rare subsets of T-cell PTLD that included hepato-splenic T-cell lymphoma and anaplastic large cell lymphoma (ALCL). At the time of presentation, the patients were too ill for treatment to be initiated and succumbed to their illness. Increased awareness of this condition may allow for earlier diagnosis and improve its prognosis.

Current induction immunosuppression and post-heart transplant lymphoproliferative disorders

Background The use of high-dose OKT3 has been reported to be associated with a high incidence of posttransplant lymphoproliferative disorders (PTLD) in heart transplantation (HTx) recipients. The incidence and characteristics of PTLD with current induction protocols remain largely unknown. The aim of our study was to analyze the incidence and characteristics of PTLD in a large series of HTx recipients treated with low-dose OKT3 induction. Methods From 1984 to 2002, a retrospective review of diagnosis, treatment, and evolution of PTLD cases was performed on the 560 patients who underwent HTx in our center. Results The incidence of PTLD was 1% (6/560). The disease occurred early after HTx in two cases and between 13 and 121 months in the other four. Molecular studies showed evidence of Epstein-Barr virus (EBV) infection in four patients. B-cell proliferation was observed in five cases, and T-cell proliferation in the other one. Various therapies were employed for each patient. Ganciclovir and reduction in immunosuppression were the most common measures. Interestingly, OKT3 was used as a specific anti-T-cell proliferation agent with some success in the one case of T-cell PTLD. Complete remission was achieved in just two patients, whereas the other four (67%) died, mostly due to other conditions. Conclusions The use of low-dose OKT3 as induction therapy did not increase the incidence of PTLD in our series. Late appearance of disease prevailed among our patients. Despite a multidisciplinary approach to therapy, including the use of OKT3 against T-cell proliferation, the mortality rate was high (67%).