Increased incidence of EBV-associated lymphoproliferative disorders after allogeneic stem cell transplantation from matched unrelated donors due to a change of T cell depletion technique

Meijer, Ellen; Slaper‐Cortenbach, Ineke; Thijsen, Steven; Dekker, A. W.; Verdonck, Leo F.

doi:10.1038/sj.bmt.1703362

Cited by 38 publications

(26 citation statements)

References 17 publications

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“…The discrepancies in PTLD occurrence between our study and previous reports 1,7,9,12 are likely a result of differences in patient populations studied, use of different T lymphocyte depletion methods and differences in diagnosing/defining PTLD. The highest occurrence of PTLD was found in the study of Meijer et al 12 (5/7, that is, 71%), in which both ex vivo-selective T lymphocyte depletion of the graft and ATG administration with conditioning were used. Chiang et al 7 used both ex vivo-selective T lymphocyte depletion of the graft and in vivo ATG given post transplant (not with conditioning), and reported the occurrence of PTLD of 6%.…”

Section: Discussioncontrasting

confidence: 96%

“…1,[6][7][8][9][10][11][12] In the largest study to date, which included 26 901 allogeneic HCT recipients, the cumulative incidence of PTLD was 0.2% with no T-cell depletion, 2.8% with selective (B lymphocyte sparing) T lymphocyte depletion of grafts ex vivo and 1.7% in patients receiving ATG as in vivo T lymphocyte depletion for GvHD prophylaxis or treatment. 1 In the published studies, diagnostic criteria for PTLD and strategies for its prevention varied or were not described.…”

Section: Introductionmentioning

confidence: 99%

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High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Hoegh-Petersen

Goodyear

Geddes

et al. 2010

Bone Marrow Transplant

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The largest study on post-allogeneic hematopoietic cell transplant lymphoproliferative disorder (PTLD) epidemiology showed a cumulative incidence of 1.7% in patients receiving antithymocyte globulin (ATG). We had noted an apparently higher incidence in our transplant recipients whose conditioning included ATG. Therefore, we formally determined the incidence of PTLD through chart review. We also evaluated whether counts of EBV-specific T lymphocytes measured by cytokine flow cytometry could identify patients at risk of developing PTLD. Among 307 allogeneic transplant recipients, 25 (8.1%) developed PTLD. This was biopsy proven in 11 patients, and was fatal in seven patients. Patient age, EBV serostatus, donor type/match or GVHD did not influence PTLD risk significantly. Median onset of PTLD was 55 (range, 28-770) days post transplant. Day 28 EBV-specific T lymphocyte counts were not significantly different in 11 patients who developed PTLD and 31 non-PTLD patients matched for published risk factors for PTLD. In summary, when using conditioning with thymoglobulin 4.5 mg/kg, the incidence of PTLD is relatively high and cannot be predicted by day 28 cytokine flow cytometry-determined EBV-specific T lymphocyte counts. Thus, in this scenario PTLD prevention may be warranted, for example, using EBV DNAemia monitoring with preemptive therapy.

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Section: Discussioncontrasting

confidence: 96%

Section: Introductionmentioning

confidence: 99%

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Hoegh-Petersen

Goodyear

Geddes

et al. 2010

Bone Marrow Transplant

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“…The T-cell/B-cell ratio has been reported to be associated with Epstein-Barr virus-associated lymphoproliferative disorders after bone marrow transplantation from matched unrelated donors. 15 The EBMT prospective study comparing outcomes between patients treated with rATG or hATG showed increased infectious deaths with rATG; 16 in addition, a recent Japanese study on rATG in children also showed an increased infection rate. 17 Moreover, imbalanced lymphocyte subsets of activated CD4 + (CD38 + ), double-negative T cells (CD3 + CD4 -CD8 -), and regulatory T cells in rATGtreated patients may also affect immune system functions.…”

Section: Discussionmentioning

confidence: 99%

In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia

et al. 2014

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“…Meijer et al 38 report that, by maintaining a T/B cell ratio in the graft of X0.25, the risk of EBV-LPD can be significantly reduced in matched unrelated donor BMT. The role of this in autologous stem cell transplantation must be investigated.…”

Section: Discussionmentioning

confidence: 99%

An unexpectedly high incidence of Epstein–Barr virus lymphoproliferative disease after CD34+ selected autologous peripheral blood stem cell transplant in neuroblastoma

Powell

Bunin

Callahan

et al. 2004

Bone Marrow Transplant

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Summary:The risk of Epstein-Barr virus lymphoproliferative disease (EBV-LPD) increases with the use of highly immunosuppressive therapies. Allogeneic BMT, especially supported by T-cell-depleted stem cell products, is a risk factor for EBV-LPD. Although the risk of EBV-LPD after autologous transplantation is low, case reports of this complication in the autologous setting exist. We report a higher incidence than previously described of EBV-LPD in children undergoing sequential high-dose chemotherapy supported with CD34 selected peripheral blood stem cells (CD34 þ PBSC). The median time to LPD after tandem transplant was 3 months (range 1-5 months). Five patients out of 156 (3.5%) developed EBV-LPD while enrolled on two trials of tandem autologous SCT in high-risk pediatric malignancies. Both studies employed five cycles of induction therapy, followed by tandem autologous PBSC transplants. In all, 108 out of 156 patients received CD34 þ PBSC; 48 received unselected PBSC. All patients contracting LPD were from the CD34 selected group. Treatment of EBV-LPD included rituximab in four out of five patients, IVIg in two out of five patients, and gancyclovir in two out of five patients. EBV-LPD resolved in four out of five patients. We conclude that the combination of tandem SCT and CD34 selection may have increased immunosuppression in these patients to a point where there is an elevated risk of EBV-LPD.

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Increased incidence of EBV-associated lymphoproliferative disorders after allogeneic stem cell transplantation from matched unrelated donors due to a change of T cell depletion technique

Abstract: Summary:Here, the influence of T vs T and B cell depletion on the incidence of EBV-associated lymphoproliferative disorder (EBV-LPD) after bone marrow transplantation (

Cited by 38 publications

References 17 publications

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia

An unexpectedly high incidence of Epstein–Barr virus lymphoproliferative disease after CD34+ selected autologous peripheral blood stem cell transplant in neuroblastoma

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