Post-transplant lymphoproliferative disorders after lung transplantation: first-line treatment with rituximab may induce complete remission

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are potentially lethal complications of solid organ transplantation. We, here, report on our experience with rituximab, an anti-CD20 monoclonal antibody, as first-line treatment for PTLD in six lung transplant recipients. PATIENTS AND METHODS: Two of the patients developed PTLD during the first year after transplantation, while four developed late-onset PTLD. One patient presented with PTLD localized to the graft, one had unilateral cervical lymph nodes, and the others presented with multi-organ involvement. All patients had diffuse large B-cell lymphoma. Immunosuppressive therapy was reduced and rituximab was administered at a dose of 375 mg/m(2)/wk for 4 wk. RESULTS: One patient did not respond to the first two courses of rituximab, received conventional chemotherapy, and achieved complete remission; four patients achieved complete remission after four courses with a median relapse-free survival of 34 months (range: 14-55); and one patient did not respond and died. The diagnosis of complete remission was established by conventional imaging techniques combined to whole-body positron emission tomography scan. CONCLUSIONS: We conclude that reduction in immunosuppression combined to first-line treatment with rituximab may induce long-term complete remission in lung transplant recipients presenting PTLD.     

Posttransplant lymphoproliferative disorder in pediatric renal transplantation

Of 84 renal transplants performed in our center since 1986, six recipients (7.1%) developed posttransplant lymphoproliferative disorder (PTLD). All received quadruple immunosuppression with Minnesota anti-lymphoblastic globulin or anti-thymocyte globulin, methylprednisolone, cyclosporine, and azathioprine or mycophenolate mofetil. Five were seronegative for Epstein-Barr virus (EBV) when they received their renal transplant. All patients received prophylactic acyclovir treatment postrenal transplant and none developed a cytomegalovirus (CMV) infection. All patients were positive for EBV by serology and polymerase chain reaction at the time of diagnosis of PTLD. Clinical features at presentation included fever (6/6), adenopathy (4/6), hypertrophied adenoids (4/6), liver involvement (2/6), and allograft involvement (2/6), 2–78 months (4/6<6 months) postrenal transplant. Histopathology of PTLD tissue revealed T cell rich/ Hodgkin disease-like B cell PTLD in one patient, polymorphic PTLD in four, and monomorphic (large B cell lymphoma) PTLD in one. Immunophenotyping of the PTLD biopsy specimen revealed predominant T cells in three, mixed B and T cells in two patients, and B cell in one. No aneuploid populations were identified by flow cytometric DNA ploidy assay. DNA from the PTLD tissue revealed weak to moderate IgH gene rearrangement in four of six patients but no T cell receptor β-chain or c-myc gene rearrangement on Southern blot analysis. The child with monomorphic (large B cell lymphoma) PTLD was clonal with λ light chain restriction on immunophenotyping. Treatment consisted of reduced immunosuppression and ganciclovir/ acyclovir in all patients. CMV hyperimmune globulin was used as an adjunctive therapy in two patients. Chemotherapy was needed in only one patient. A single rejection episode occurred in two children following reduction in immunosuppression, which reversed following intravenous methylprednisolone therapy. PTLD resolved in all patients and at present all patients are alive with functional grafts 2–54 months post diagnosis. Our experience suggests that reduced immunosuppression and anti-viral treatment is adequate in most cases of PTLD, but chemotherapy and hyperimmune globulin therapy may be beneficial in cases resistant to first-line therapy. Since all but one of our patients were EBV seronegative at the time of transplant, vigilance is especially important for early detection of PTLD in this group of the pediatric renal transplant population. Received: 17 November 1998 / Revised: 4 February 1999 / Accepted: 4 February 1999     

Salvage chemotherapy for refractory and relapsed posttransplant lymphoproliferative disorders (PTLD) after treatment with single-agent rituximab

BACKGROUND: Single-agent rituximab has demonstrated encouraging efficacy and tolerability in posttransplant lymphoproliferative disorders (PTLDs) failing to respond to immunosuppression reduction (IR). This retrospective analysis was undertaken to determine the efficacy and safety of salvage therapy in recipients of solid organ transplants with progression of PTLD after rituximab first-line therapy. METHODS: Eleven patients who had received IR and single-agent rituximab were analyzed. Of these, 10 had received CHOP salvage chemotherapy. One patient with limited disease received tumor irradiation and further IR. Most patients (73%) had late PTLD (median onset of disease 145 months posttransplant), and most (83%) had monomorphic histology; 36% had EBV-association. RESULTS: IR and irradiation therapy re-induced complete remission (CR) and allowed long-term disease control in a patient with polymorphic PTLD relapse. CHOP therapy achieved CR in five (50%) and partial remission (PR) in two (20%) patients. Four of five (80%) patients achieving CR remained in CR at a median follow-up of 44.2 months. Of the patients achieving PR, one is currently alive, and the second died from transplant rejection after converting to CR after consolidative chemotherapy. Patients with stable disease (two) and progressive disease (one) have died from PTLD. There was one possible CHOP-associated death (acute cardiac event) and two patients had to be switched to less-toxic monotherapies. Median overall survival was 46.5 months (95% confidence interval: 23.6-49.1 months). CONCLUSIONS: CHOP salvage therapy achieved a favorable overall response rate of 70% in this setting, indicating that PTLD generally remains chemotherapy-sensitive after progression following first-line rituximab.     

Humanized anti-CD20 monoclonal antibody (Rituximab) treatment for post-transplant lymphoproliferative disorder

INTRODUCTION: Post-transplant lymphoproliferative disorders (PTLD) is a consequence of Epstein-Barr virus (EBV) infection and is a B-cell hyperplasia with CD-20 positive lymphocytes. The treatment of PTLD includes reduction/withdrawal of immunosuppression and chemotherapy. This study reports our center experience with humanized monoclonal antibody against CD-20 (Rituximab) for the treatment of PTLD. MATERIAL AND METHODS: Eight cases of PTLD after solid organ transplantation [six kidney, one kidney/pancreas (KP) and one liver] occurred between September 1998 and October 2001. The mean time between transplant and the diagnosis of PTLD was 57.3 months (range 3 months to 10 yr). Five patients underwent cadaveric transplant, five males and six were Caucasians with mean age of 48 yr (range 20-67 yr). RESULTS: The clinical presentation was as follows: lymphadenopathy--5, gastrointestinal bleeding--2 and tonsillar enlargement--1. The diagnosis was made by a lymph node biopsy in five, a gastric ulcer biopsy in two and a tonsillar biopsy in one case. Six of them had polymorphous, two had monoclonal B-cell lymphoma, and all were positive for CD-20. Six were related to EBV, documented by latent membrane protein (LMP) or Epstein-Barr encoded RNA (EBER) staining. Immunosuppression at the time of PTLD diagnosis consisted of tacrolimus in six cases and cyclosporine A (CsA) in two with mycophenolate mofetil (MMF) and azathioprine--3 each and sirolimus--1. Rituximab was administered at a dose of 375 mg/m2 once a week for 4 wk. There were no side effects seen with this therapy. Immunosuppression was reduced in all patients. Complete remission was observed in seven cases (one required two courses). One patient who did not respond received chemotherapy. Patients were followed for a mean period of 22.5 months (range 10-45 months post-PTLD diagnosis. At the last follow-up all eight patients were alive, seven with a functioning graft and one on maintenance dialysis. Three of these patients had been in remission for more than 2.5 yr. CONCLUSION: Rituximab is an effective agent in the treatment of PTLD without the morbidity characteristic of chemotherapy. Chemotherapy should be reserved only for those refractory to Rituximab therapy.     

Posttransplant Lymphoproliferative Disorder After Clinical Islet Transplantation: Report of the First Two Cases

We report the first two cases of posttransplant lymphoproliferative disorder (PTLD) in recipients of islet transplants worldwide. First, a 44‐year‐old recipient of three islet infusions developed PTLD 80 months after his initial transplantation, presenting with abdominal pain and diffuse terminal ileum thickening on imaging. He was treated with surgical excision, reduction of immunosuppression, and rituximab. Seven months later, he developed central nervous system PTLD, presenting with vertigo and diplopia; immunosuppression was discontinued, resulting in graft loss, and he was given high‐dose methotrexate and underwent consolidative autologous stem cell transplantation. He remains in remission 37 months after the initial diagnosis. Second, a 58‐year‐old female recipient of two islet infusions developed PTLD 24 months after initial islet infusion, presenting with pancytopenia secondary to extensive bone marrow involvement. Immunosuppression was discontinued, resulting in graft loss, and she received rituximab and chemotherapy, achieving complete remission. Both patients were monomorphic B cell PTLD subtype by histology and negative for Epstein–Barr virus in tissue or blood. These cases document the first occurrences of this rare complication in islet transplantation, likely secondary to prolonged, intensive immunosuppression, and highlight the varying clinical manifestations of PTLD. Further studies are needed to determine incidence rate and risk factors in islet transplantation.     

Posttransplant lymphoproliferative disease: treatment and outcome in renal transplant recipients

Posttransplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoid diseases that occur after solid organ and bone marrow transplantation. We performed a retrospective study to assess the incidence, response to treatment, and patient and graft survival after PTLD. PATIENTS: Between January 1980 and December 2002, 1.96% (n=10) of 509 renal transplant recipients developed PTLD. Seventy percent were men. Mean age was 40 years (range 21-65). They were classified into four groups based upon the type of PTLD: group I, early lesion (n=1); group II, polymorphic PTLD (n=1); group III, monomorphic PTLD (n=7) including five non-Hodgkin lymphoma [NHL] and two Burkitt (BL); and group IV, Hodgkin lymphoma (HL) (n=1). The mean time from transplantation to diagnosis was 77 months (range 4-138). Although only 20% of cases were early presentation, Epstein-Barr virus (EBV) was found in the tumor cells of seven cases. Treatment was individualized according to PTLD type: for group I, immunosuppression reduction (IR); group II, IR plus acyclovir; group III, withdrawal or IR plus chemotherapy and/or surgery in all but one patient who was also treated with anti-CD20 monoclonal antibody and radiotherapy. Interferon was also used in one patient. For group IV, treatment was IR plus radiotherapy. RESULTS: A complete response was achieved in nine cases (90%) with one recurrence. Three patients returned to dialysis. One patient with BL died. CONCLUSIONS: The incidence of PTLD in our center was 1.96%. Patient survival after PTLD was 90%, with 60% maintaining allograft function. Individualized treatment according to extension, histology, and location is mandatory to obtain a high survival rate.     

Post-transplant lymphoproliferative diseases in Asian solid organ transplant recipients: late onset and favorable response to treatment

Chan TSY, Hwang Y‐Y, Gill H, Au W‐Y, Leung AYH, Tse E, Chim C‐S, Loong F, Kwong Y‐L. Post‐transplant lymphoproliferative diseases in Asian solid organ transplant recipients: late onset and favorable response to treatment. Abstract: Nineteen consecutive patients with post‐transplant lymphoproliferative disorders (PTLD) in an Asian population were reviewed. The histopathologic diagnoses were monomorphic (CD20‐positive diffuse large B‐cell lymphoma, n = 14); plasmacytic (n = 1); Burkitt‐like (n = 1); natural killer cell lymphoma (n = 1); lymphomatoid papulosis (n = 1); and classical Hodgkin lymphoma (n = 1). Early‐onset (相似文献   

Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder: duration of posttransplant lymphoproliferative disorder-induced operational graft tolerance,interleukin-18 course,and results of retransplantation

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD, and in whom we were able to perform IL-18 analyses. RESULTS: Patients were followed for up to 7 years after PTLD diagnosis. Treatment consisted of immunosuppression cessation with radiation therapy in cases with overt monomorphic lymphomas. All patients' PTLDs were resolved, and all patients but one (whose graft was removed) demonstrated a period of operational graft tolerance of up to 5 years. Five patients underwent retransplantation without sign of recurrence of the PTLD up to 3 years after transplantation. In the eight patients analyzed, IL-18 increased significantly during PTLD regression and follow-up in those with long-term operational tolerance. CONCLUSION: We report on a series of patients with resolved PTLDs demonstrating long-term recurrence-free survival, of whom most experienced a long period of operational graft tolerance. IL-18 seems to play a role in the resolution of the PTLDs. Five patients underwent retransplantation with standard immunosuppression without recurrence. A previous diagnosis of PTLD should not be regarded as a contraindication for later retransplantation.     

Successful treatment of posttransplant lymphoproliferative disease with prolonged rituximab treatment in intestinal transplant recipients

BACKGROUND: Posttransplant Epstein-Barr virus-associated B-cell lymphoproliferative disease (PTLD) has a higher incidence after intestinal transplantation than after transplantation of other solid organs and is associated with a high mortality. A new anti-CD20 monoclonal antibody, rituximab, has shown efficiency in the treatment of B-cell lymphoma, including PTLD, but its use has not yet been reported in intestinal transplant recipients. METHODS: We retrospectively reviewed five patients who were diagnosed with PTLD from March 1999 to August 2001, after intestinal transplantation. These patients were primarily managed with rituximab, associated with reduction or interruption of immunosuppression and antiviral therapy with ganciclovir and cytomegalovirus immune globulin. Rituximab was administered at weekly doses of 375 mg/m until full remission was ascertained, and the interval between doses was then increased. No patient received chemotherapy. RESULTS: One patient had nonmalignant lymphoproliferation, and four had malignant PTLD, as assessed by histopathology and monoclonality of the tumor. Two pediatric patients had severe generalized disease. All patients had received OKT3 as treatment of rejection before developing PTLD. All tumors showed proliferation of CD20 cells and were positive for Epstein-Barr virus by in situ hybridization. All patients responded to rituximab therapy and have achieved full remission with a follow-up of 3 to 30 (median, 8) months. CONCLUSION: Prolonged rituximab treatment, in association with reduction of immunosuppression and antiviral therapy, is highly efficient as part of the first-line treatment of CD20 B-cell PTLD after intestinal transplantation.     

Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is an Epstein-Barr virus-associated malignancy that occurs in the setting of pharmacologic immunosuppression after organ transplantation. With the increased use of organ transplantation and intensive immunosuppression, this disease is becoming more common. We explore reduction in immunosuppression as an initial therapy for PTLD. METHODS: We analyzed our organ transplant patient database to identify patients with biopsy-proven PTLD who were initially treated with reduction of their immunosuppressive medications with or without surgical resection of all known disease. RESULTS: Forty-two adult patients were included in this study. Thirty patients were treated with reduction in immunosuppression alone. Twelve patients were treated with both reduction in immunosuppression and surgical resection of all known disease. Thirty-one of 42 patients (73.8%) achieved a complete remission. Of those patients who were treated with reduction in immunosuppression alone, 19 of 30 (63%) responded with a median time to documentation of response of 3.6 weeks. Multivariable analysis showed that elevated lactate dehydrogenase (LDH) ratio, organ dysfunction, and multi-organ involvement by PTLD were independent prognostic factors for lack of response to reduction in immunosuppression. In patients with none of these poor prognostic factors, 16 of 18 (89%) responded to reduction in immunosuppression in contrast to three of five (60%) with one risk factor and zero of seven (0%) with two to three factors present. The analysis also showed that increased age, elevated LDH ratio, severe organ dysfunction, presence of B symptoms (fever, night sweats, and weight loss), and multi-organ involvement by PTLD at the time of diagnosis are independent prognostic indicators for poor survival. With median follow-up of 147 weeks, 55% of patients are alive with 50% in complete remission. CONCLUSIONS: Reduction in immunosuppression is an effective initial therapy for PTLD. Clinical prognostic factors may allow clinicians to identify which patients are likely to respond to reduction in immunosuppression.     

Incidence and clinical characteristics of posttransplant lymphoproliferative disorders: report from a single center

Abstract In the period 1973‐1998, among 2139 allograft recipients treated with standard immunosuppression, posttransplant lymphoproliferative disorders (PTLD) developed in 19 patients (0.9%): one plasmacytic hyperplasia, two polymorphic PTLD, one myeloma, and 15 lymphomas. PTLD developed 1 year after transplantation (tx) in 14 patients. Five patients were diagnosed at autopsy, 2 were lost to follow up, 3 died before therapy could be instituted, and 1 patient has just started chemotherapy. Of the 8 evaluable patients, 2 received acyclovir and are alive in complete remission (CR) and 6 received chemotherapy ± surgery. Of these 6, 4 died of lymphoma and/or infection, 1 died of unrelated causes in CR, and 1 is alive in CR. PTLD is a severe complication of tx, usually running an aggressive course which may preclude prompt diagnosis and treatment. Nevertheless, therapy is feasible and must be tailored on the histologic subtype. Seventy‐four percent of patients were diagnosed with late‐onset PTLD stressing the need for long‐term follow up.     

Successful outcome with a "quintuple approach" of posttransplant lymphoproliferative disorder

BACKGROUND: The treatment of posttransplant lymphoproliferative disorder (PTLD) remains empirical. We review our treatment of seven cases of PTLD consisting of five interventions: 1) reduction of immunosuppression; 2) antiviral drugs; 3) interferon-alpha; 4) gamma-globulins; and 5) anti-CD19 monoclonal antibodies. METHODS AND RESULTS; Seven consecutive patients who had undergone a simultaneous pancreas-kidney, liver, heart, or kidney transplantation were treated. One patient acquired a primary EBV infection with an oligoclonal immunoblastic lymphoma early after pancreas-kidney transplantation; all others developed a monoclonal polymorphic or immunoblastic lymphoma 2 to 123 months after transplantation. In all patients extranodal sites were involved, in three the graft was also involved. Five patients received the full quintuple approach and all rapidly obtained a complete remission (CR) with a median follow-up of 31 months (7-74 months). Of the two patients who did not receive interferon-alpha for fear of graft rejection one responded slowly with a CR after 7 months, and the other obtained a rapid CR followed by a relapse at 4 months. All three patients with a liver or heart transplant could keep their graft. All patients are still alive with a median follow-up of 31 months (7-74 months). CONCLUSION: This combined approach resulted in a favorable outcome in patients with high risk monoclonal PTLD after solid organ transplantation.     

Plasmacytoma-like post-kidney-transplant lymphoproliferative disorder confined to renal allograft and urinary tract: A case report

Post-transplantation lymphoproliferative disorder (PTLD) is a well-know complication after organ transplantation. We report a case of a patient who developed an extramedullary plasmacytoma-like PTLD around his transplanted kidney treated with standard multiple myeloma chemotherapy. Three years after benefiting of a deceased donor kidney transplant for an end stage kidney disease secondary to nephroangiosclerosis, our patient developed an extra-medullary plasmacytoma confined to the transplant compartment. The transplant function was unaltered, and due to the absence of reduction of the lesion after immunosuppression reduction, a chemotherapy by bortezomib-cyclophosphamide-dexamethasone (VCD) known to be efficient in multiple myeloma was initiated. After 6 cycles, positron emission tomography (PET) scan showed complete metabolic remission confirming the biological exams. This case report suggests that a chemotherapy such as VCD can efficiently treat plasmacytoma-like PTLD allowing graft survival. Therefore, transplant removal may not be mandatory as the best second line treatment after unsuccessfulness reduction of immunosuppression.     

Outcomes of kidney retransplantation in recipients with prior post‐transplant lymphoproliferative disorder

Post‐transplant lymphoproliferative disease (PTLD) is an uncommon but serious complication of solid organ transplantation. Reduction in immunosuppression is the mainstay of PTLD treatment, but it may precipitate graft loss. Retransplantation remains controversial, as immunosuppression resumption may trigger PTLD relapse. Herein, we describe the experience of eight patients who underwent kidney retransplantation after successful PTLD treatment. Epstein–Barr virus (EBV) serology was not known before the first transplantation. PTLD was diagnosed 62.5 months (range 5–323 months) after transplantation and was confined to the renal allograft (n = 1), lymph nodes (n = 2), gastrointestinal tract (n = 4), or central nervous system (n = 1). Immunosuppression tapering (8/8), chemotherapy (6/8), oral cavity lymphoma excision (1/8), and allograft nephrectomy (1/8) led to hematological remission in all patients. Retransplantation was performed at a median of 55.5 months (range 29–95   months) after PTLD diagnosis. After a median follow‐up of 62.5 months (range 2–125 months) allograft survival was 87.5% (seven functioning grafts, one failed graft from chronic rejection), with no recurrence of PTLD. In all, five patients remain alive; the other three died from causes other than PTLD. In conclusion, kidney retransplantation appears to be safe in patients with prior PTLD and without major risk of hematological recurrence provided that PTLD has remitted.     

Treatment of EBV-Related Post-Renal Transplant Lymphoproliferative Disease with a Tailored Regimen Including EBV-Specific T Cells

The treatment of EBV-associated post-transplant lymphoproliferative disease (PTLD) poses a considerable challenge. Efforts have been made to define regimens based on combination of the available therapeutic agents, chosen and tailored on a patient-by-patient basis, with the aim of augmenting event-free patient and graft survival. Recently, autologous EBV-specific cytotoxic T-lymphocytes (CTL) have proved effective in enhancing EBV-specific immune responses and reducing viral load in organ transplant recipients with active infection. We investigated the use of a tailored combined approach including autologous EBV-specific CTL for the treatment of EBV-related PTLD developing after pediatric kidney transplantation. Five patients with disseminated monoclonal (n = 3) or localized polyclonal (n = 2) PTLD unresponsive to reduction of immunosuppression were enrolled. The patients with disseminated PTLD received 4-5 courses of reduced-dosage polychemotherapy, accompanied by rituximab on the first day of each course, while localized disease was removed surgically. At treatment completion, autologous EBV-specific CTL were infused. All patients showed a complete response to treatment, without therapy-related toxicity or rejection, and persist in remission with good renal function at a median follow-up of 31 months. These preliminary results suggest that a combined chemoimmunotherapy regimen including virus-specific T-cells is well tolerated and potentially effective as first-line treatment of EBV-related PTLD.     

Anti-CD20 monoclonal antibody treatment of Epstein-Barr virus-induced intrahepatic lymphoproliferative disorder following liver transplantation

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLDs) are a common cause of death in transplant patients. Their incidence following liver transplantation is reported to be between 0.5% and 4%. Despite various therapeutic approaches, there is still no consensus on a treatment strategy. The treatment of transplant recipients with monoclonal antibodies directed against B-cell antigens is a new, therapeutic approach with which, however, little clinical experience has so far been gained. Two patients developed intrahepatic PTLD 7 and 15 months, respectively, after transplantation. In one case, this was diagnosed as polymorphic PTLD, in the other as monomorphic, monoclonal PTLD. After having their immunosuppression terminated, 4 weeks after establishment of the diagnosis, both patients were treated with anti-CD20 antibodies (rituximab) at a dose of 375 mg/m(2) on days 1, 8, 15 and 22. Treatment with rituximab was tolerated well by both patients. One of the patients in whom cholestasis parameters remained high underwent re-transplantation. In one of the cases, the histological work-up confirmed necrosis of 90% of the tumour cells, and complete remission in the other. Both patients died of secondary complications 10 weeks and 10 months, respectively, after the diagnosis of PTLD. We can conclude that treatment of PTLD with Rituximab led to remission in both of our patients. Nevertheless, progression of cholestasis persisted, and both patients ultimately died of complications unrelated to PTLD.     

Posttransplant lymphoproliferative disorders after liver transplantation: analysis of early and late cases in a 255 patient series

We reviewed the incidence and the impact of posttransplant lymphoproliferative disorders (PTLDs) on patient survival among a consecutive series of 255 patients. Five cases of PTLD were observed in adults: two cases were early (less than 1 year) and three cases, late lymphomas. The EBV positivity and the degree of immunosuppression were the main risk factors. We labeled cases as early or late according to whether the time elapsed from the transplant to the first clinical evidence of PTLD was less than 12 months. The median time from transplant to diagnosis of PTLD was 8 (early) and 108 (late) months. All cases were treated by reduction in immunosuppressive therapy with conventional chemotherapy and rituximab. The early cases with lymphoma located at the hepatic hilum died due to local complications (biliary sepsis and hemobilia), after an initial partial response to chemotherapy. The three patients with late cases are in remission after a mean follow-up of 23 months.     

Successful Renal Retransplantation after Post-Transplant Lymphoproliferative Disease

Post-transplant lymphoproliferative disease (PTLD) is a rare but severe complication of renal transplantation. Reduction of immunosuppression is essential for controlling PTLD but may induce graft loss. Retransplantation after PTLD is considered dangerous, because immunosuppressive treatment resumption may trigger hematological relapse. We retrospectively report six patients (five adults, one child) who underwent a second renal transplantation after successfully treated PTLD. Epstein-Barr virus (EBV) serology was positive before the first transplantation in all patients except the child. Post-transplant lymphoproliferative disease was detected 6.6 months (range 4.5-9.4) after transplantation. Lymphoproliferation was always monomorphic, B-cell, and EBV-related. Post-transplant lymphoproliferative disease was confined to the renal allograft (n = 4), multilocular (n = 1) or cerebral (n = 1). Immunosuppression tapering (6/6) and transplantectomy (5/6) led to hematological remission in all patients. Retransplantation was performed 77 months (range 50-128) after PTLD diagnosis. Immunosuppression included steroids (n = 6), ATG (n = 2), anti-CD25 (n = 2), cyclosporine (n = 4), tacrolimus (n = 2), mycophenolate mofetil (n = 4) and azathioprine (n = 1). After a median follow up of 30 months (range 24-47) patient survival was 100%, with no recurrence of PTLD. In conclusion, renal retransplantation can be considered in patients with monomorphic PTLD history, without major risk of hematological recurrence.     

Lymphomas occurring late after solid-organ transplantation: influence of treatment on the clinical outcome

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) that occur late after solid-organ transplantation are usually a monoclonal proliferation frequently characterized by the lack of the Epstein-Barr virus genome in tumor cells. The clinical outcome and the best management for patients who present with late PTLDs still remain unclear. PATIENTS AND METHODS: Thirty patients who developed PTLDs more than 12 months (range 13-156) after heart, kidney, or liver transplantation were retrospectively evaluated. Median age was 36.7 years (range 1-70). Fifty-five percent of patients presented with advanced-stage (III-IV) lymphoma, 43% of patients presented with B symptoms, and 40% of patients showed extranodal involvement. Twenty-four cases (75%) were categorized as monoclonal monomorphic PTLD. RESULTS: Three patients died of progressive multiorgan failure before any treatment was initiated. Overall, 17 (63%) patients obtained a clinical response (14 patients had complete remission [CR] and 3 patients had partial remission [PR]). Eight (47%) patients are still alive and in CR, two (12%) patients died in CR, and seven (41%) patients relapsed. With a median follow-up of 6 months (range 0.5-42.8), the median overall survival was 6.2 months. Both clinical response and survival were significantly influenced by the treatment. Indeed, all patients treated for limited disease with surgery or radiotherapy in combination with modulation of immunosuppression obtained CR and are still alive and in CR. On the contrary, 33% of patients who received chemotherapy obtained a clinical response, whereas 15% of patients who received chemotherapy showed progressive disease and 50% of patients who received chemotherapy died of toxicity (infectious or multiorgan failure). CONCLUSIONS: We suggest that patients with late PTLDs and limited disease may benefit from local treatment. For patients who require chemotherapy, we suggest that it should be administered to minimize the risk of infection complications.