B-Cell lymphoproliferative syndrome and peripheral blood CD20+ cells expansion after hematopoietic stem cell transplantation: association with fludarabine and anti-thymocyte globulin containing conditioning regimen

Lange, Andrzej; Klimczak, Aleksandra; Dłubek, Dorota; Dybko, Jarosław

doi:10.1016/j.transproceed.2003.10.043

Cited by 14 publications

(13 citation statements)

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“…For example, anti-thymocyte globulin depletes T cells and thus protects from graft rejection, but its use clearly contributes to subsequent PTLD (104,105,172). Fludarabine, azathioprine, and other agents causing profound T cell suppression or mutagenicity are also implicated in PTLD pathogenesis (99,119,172).…”

Section: Risk Factors For Ptldmentioning

confidence: 99%

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

2010

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SUMMARYEpstein-Barr virus (EBV) DNA measurement is being incorporated into routine medical practice to help diagnose, monitor, and predict posttransplant lymphoproliferative disorder (PTLD) in immunocompromised graft recipients. PTLD is an aggressive neoplasm that almost always harbors EBV DNA within the neoplastic lymphocytes, and it is often fatal if not recognized and treated promptly. Validated protocols, commercial reagents, and automated instruments facilitate implementation of EBV load assays by real-time PCR. When applied to either whole blood or plasma, EBV DNA levels reflect clinical status with respect to EBV-related neoplasia. While many healthy transplant recipients have low viral loads, high EBV loads are strongly associated with current or impending PTLD. Complementary laboratory assays as well as histopathologic examination of lesional tissue help in interpreting modest elevations in viral load. Circulating EBV levels in serial samples reflect changes in tumor burden and represent an effective, noninvasive tool for monitoring the efficacy of therapy. In high-risk patients, serial testing permits early clinical intervention to prevent progression toward frank PTLD. Restoring T cell immunity against EBV is a major strategy for overcoming PTLD, and novel EBV-directed therapies are being explored to thwart virus-driven neoplasia.

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Section: Risk Factors For Ptldmentioning

confidence: 99%

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

2010

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“…In particular, it is noteworthy that almost all reported cases of PTLD occurring following RIC have been with regimens that combine both fludarabine and serotherapy with either Campath or ATG, both of which persist at the time of graft infusion and thus T-deplete the graft in vivo (Tables IV and V). This combination is profoundly immunosuppressive [54], although it is unlikely that fludarabine by itself has a major impact on the infused graft. In contrast, the Seattle regimen utilises a lower dose of fludarabine and no serotherapy.…”

Section: Other Published Datamentioning

confidence: 99%

EBV-related disease following haematopoietic stem cell transplantation with reduced intensity conditioning

Cohen

Cooper

Chakrabarti

et al. 2007

Leukemia & Lymphoma

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The use of reduced intensity regimens has decreased early mortality following stem cell transplantation. However, the increased immunosuppression following these protocols results in profound and often prolonged lymphopenia, resulting in an increased incidence of viral reactivation. We and others have observed a high incidence of EBV viraemia and post-transplant lymphoproliferative disease (PTLD) following reduced-intensity conditioning regimens, reflecting the delayed recovery of EBV-specific immunity after such transplants. The clinical and histological features at presentation are similar to that seen after conventional intensity conditioning. Given the increasing use of reduced intensity conditioning (RIC) transplants, we review the risk factors for EBV related disease following transplantation with RIC, the potential for pre-emptive therapy of PTLD based on monitoring EBV viraemia and management options in such patients.

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“…[14][15][16] Until recently, most data analyzing the incidence of PTLD, its management, and prognosis after allo-SCT came from case reports or small single-center series. [17][18][19][20][21][22] In 2014, Fox et al 23 published a detailed series of 69 EBV-associated PTLD after alemtuzumab-based allo-SCT, highlighting the increased risk of this complication after in vivo serotherapy, not just with ATG but also with the pan-lymphocyte depletion obtained with alemtuzumab. Nevertheless, there is scarce information concerning changes in the frequency of diagnosed cases of PTLD and its prognosis over time in all allo-SCT recipients in a multicenter national level.Therefore, we conducted a multicenter retrospective study to estimate the frequency, clinical presentation, and management of PTLD after allo-SCT in Spain over a 15-year period as well as analyzing potential prognostic factors for long-term outcomes after PTLD in a real-world clinical scenario.…”

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confidence: 99%

Frequency, characteristics, and outcome of PTLD after allo‐SCT: A multicenter study from the Spanish group of blood and marrow transplantation (GETH)

García‐Cadenas

Yáñez

Jarque

et al. 2019

European J of Haematology

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on behalf of the Spanish group of blood and marrow transplantation (GETH) 15García-Cadenas and Yáñez equally contributed to this work. Abstract Post-transplant lymphoproliferative disorder (PTLD) is an infrequent complication of allogeneic stem cell transplant (allo-SCT). Aims: To estimate the frequency and management of PTLD in Spain and to identify prognostic factors influencing outcomes. Methods: Multicenter, retrospective analysis of allo-SCT performed in 14 transplant units over a 15-year period.Results: 102 PTLD were diagnosed among 12 641 allo-SCT, leading to an estimated frequency of 0.8%. PTLD was diagnosed at a median of 106 days after SCT. Eightyseven cases (85%) were diagnosed between 2007 and 2013. At diagnosis, 22% and 17% of the patients had gastrointestinal tract and CNS involvement. Eighty-seven (85%) received rituximab treatment, alone or in combination with immunosuppression reduction, with an ORR of 50.6%. With a median follow-up for survivors of 58 months, the 2-year overall survival (OS) was 33% and the PTLD-related mortality 45%. Age ≥ 40 years, malignant underlying disease, non-response to rituximab, and severe thrombocytopenia or lymphocytopenia at PTLD diagnosis were associated with worse overall survival. Conclusions:Only a small proportion of allografted patients were diagnosed a PTLD.Its clinical course was highly aggressive, and prognosis poor, especially in those failing rituximab. The prognostic impact found of the platelet, and lymphocyte count at diagnosis requires further confirmation. K E Y W O R D S allo-SCT, EBV, infection, PTLD, rituximab 466 | GARCÍA-CADENAS Et Al. 1 | INTRODUC TI ON Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) are an uncommon but potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Major risk factors for developing PTLD are T-cell depletion (TCD) of the graft, mismatched or unrelated donor (URD), umbilical cord blood transplantation and elderly patient age. 1-4The use of pre-emptive therapy with rituximab, triggered by positive results of routine monitoring of EBV DNAemia, has emerged as the preferred strategy for PTLD prevention in high-risk patients. [5][6][7][8] Additional therapeutic options (besides rituximab) for established PTLD include reduction of immunosuppression whenever feasible, chemotherapy or EBV-specific T cells, which have shown promising results but are often not available. [9][10][11][12][13] The early use of rituximab has surely reduced the rate of established PTLD and improved the short-term outcome in patients with PTLD, but there are concerns regarding its real impact on long-term survival. Death from PTLD in non-responders, relapse in responders, and infection-related mortality due to delayed B-and T-cell immune reconstitution all contribute to the low long-term survival. 14-16Until recently, most data analyzing the incidence of PTLD, its management, and prognosis after allo-SCT came from case reports or small single-center series. [17][18][1...

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B-Cell lymphoproliferative syndrome and peripheral blood CD20+ cells expansion after hematopoietic stem cell transplantation: association with fludarabine and anti-thymocyte globulin containing conditioning regimen

Cited by 14 publications

References 3 publications

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

EBV-related disease following haematopoietic stem cell transplantation with reduced intensity conditioning

Frequency, characteristics, and outcome of PTLD after allo‐SCT: A multicenter study from the Spanish group of blood and marrow transplantation (GETH)

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