Reconstitution of the Epstein-Barr virus–specific cytotoxic T-lymphocyte response following T-cell–depleted myeloablative and nonmyeloablative allogeneic stem cell transplantation

Chakrabarti, Suparno; Milligan, Donald; Pillay, Deenan; Mackinnon, Stephen; Holder, Kathleen; Kaur, Narinder; McDonald, Dorothy; Fegan, Christopher; Waldmann, Herman; Hale, Geoff; Rickinson, Alan B.; Steven, Neil

doi:10.1182/blood.v102.3.839

Cited by 60 publications

(45 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preemptive treatment with rituximab was started when the EBV-DNA level exceeded 1000 copies per 10 5 cells on more than one occasion as recently described by Blaes et al 15 With this strategy, EBV reactivation, defined as a viral load of 1000 copies per 10 5 cells, was detected in five patients for a cumulative incidence of 9 and 17% at 6 months and 2 years, respectively, after RIC UCBT, which is comparable to the incidence reported after RIC BM and PBSC HSCT. 24,25 This is also comparable with the cumulative incidence of EBV reactivation that we reported for 175 consecutive patients who received RIC allo-HSCT in our institution (15% at 6 months). However, with the strategy of preemptive treatment of EBV reactivation, none of these patients developed EBV-LPD.…”

Section: Discussionsupporting

confidence: 76%

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

Perić

Cahu

Chevallier

et al. 2011

Bone Marrow Transplant

View full text Add to dashboard Cite

This single centre study assessed the incidence, kinetics and predictive factors of EBV reactivation and EBVrelated lymphoproliferative diseases (LPD) in 33 consecutive patients who received a reduced intensity conditioning (RIC) before umbilical cord blood transplantation (UCBT). During the first 6 months after UCBT, weekly all patients were DNA-PCR screened in the peripheral blood for EBV reactivation and were clinically monitored for clinical features attributable to EBV. The cumulative incidences of EBV reactivation (defined as an EBV load 41000 EBV copies per 10 5 cells measured at least once during follow-up) at 6 months and 2 years after UCBT were 9 (95% confidence interval (CI), 2-22%) and 17% (95% CI, 6-33%), respectively. In 28 patients (85%), the EBV load remained negative at all times, and none of these patients experienced any sign of LPD. Five patients (15%) experienced at least one EBV reactivation episode. EBV reactivation was observed at a median of 132 days (range, 85-438) after UCBT. Two patients developed EBV-related LPD (cumulative incidence, 6% at 3 years). With a median follow-up of 468 days (range, 92-1277) post UCBT, the OS was 62% at 3 years. Five patients died of disease progression and seven patients died of transplant-related complications, including one case of EBV-related LPD. Univariate analysis did not identify any significant risk factor associated with EBV reactivation. We conclude that patients undergoing RIC UCBT are at risk for EBV reactivation, with the need for close EBV monitoring and the use of preemptive rituximab treatment as some cases may progress to lifethreatening LPD.

show abstract

Section: Discussionsupporting

confidence: 76%

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

Perić

Cahu

Chevallier

et al. 2011

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…At first, a total dose of 100 mg of alemtuzumab spread over 5 days was widely used [3,25]. Alemtuzumab at this dose was highly effective for preventing acute and chronic GVHD, but it delayed immune recovery and increased the incidence of viral infection [26,27]. In addition, patients who underwent reduced-intensity HSCT with alemtuzumab and CSA as GVHD prophylaxis required donor lymphocyte infusion for disease control more frequently than those who received GVHD prophylaxis with CSA and methotrexate [28].…”

Section: Discussionmentioning

confidence: 99%

In vivo T‐cell depletion with alemtuzumab in allogeneic hematopoietic stem cell transplantation: Combined results of two studies on aplastic anemia and HLA‐mismatched haploidentical transplantation

et al. 2013

View full text Add to dashboard Cite

We evaluated the efficacy of in vivo T-cell depletion with alemtuzumab in two prospective studies according to the International Conference on Harmonisation (ICH)-Good Clinical Practice (ICH-GCP) guidelines; one was for patients with aplastic anemia (AA study) and the other was for patients who were undergoing hematopoietic stem cell transplantation (HSCT) from a 2-or 3-antigen-mismatched haploidentical donor (MM study). The final dose of alemtuzumab in these studies was 0.16 mg/kg/day for 6 days. At this dose, all of the 12 and 11 patients in the AA and MM studies, respectively, achieved initial engraftment and the incidences of Grade II-IV acute graft-versus-host disease (GVHD) were 0% and 18%. While cytomegalovirus (CMV) frequently reactivated, none of the patients developed fatal CMV disease. Transplantation-related mortality within 1 year after HSCT was observed in only two and one patients, respectively. The numbers of CD41 and CD81 T-cells and T-cell receptor rearrangement excision circles remained low within 1 year after HSCT. These findings suggest that the use of alemtuzumab at this dose in a conditioning regimen enables safe allogeneic HSCT even from a 2-or 3-antigen-mismatched donor. However, the use of a lower dose of alemtuzumab should be explored in future studies to accelerate immune recovery after HSCT. Am. J. Hematol. 88:294-300, 2013. V C 2013 Wiley Periodicals, Inc. IntroductionGraft-versus-host disease (GVHD) is an important complication after allogeneic hematopoietic stem cell transplantation (HSCT), especially in the presence of an HLA-mismatch between the donor and recipient. Alemtuzumab is a humanized monoclonal antibody against CD52, and the use of alemtuzumab in the conditioning regimen before HSCT has been shown to decrease the incidences of acute and chronic GVHD through the in vivo depletion of donor T cells [1]. A growing body of evidence supports the efficacy of alemtuzumab at preventing acute GVHD in a variety of HSCT settings [2][3][4][5][6][7][8][9]. In addition, we and others have reported that alemtuzumab enables HLA-mismatched haploidentical HSCT without the ex vivo depletion of donor T cells [10,11]. We administered alemtuzumab at 0.2 mg/kg/day for 6 days before allogeneic HSCT from a 2-or 3-anitigen-mismatched related donor in 12 patients [10]. All patients achieved neutrophil engraftment and the cumulative incidence of Grade III to IV acute GVHD was only 9%. Rizzieri et al. used alemtuzumab at a total dose of 100 mg spread over 5 days in reduced-intensity haploidentical HSCT without ex vivo T-cell depletion [11]. The incidences of Grade III-IV acute GVHD and transplant-related mortality were 8% and 10.2%, respectively. Therefore, in vivo T-cell depletion using alemtuzumab enables haploidentical HSCT without excessive GVHD.With regard to allogeneic HSCT for aplastic anemia (AA), alemtuzumab has been incorporated into the conditioning regimen to achieve sustained engraftment with minimal toxicity and GVHD [12]. The incidence of graft failure was 9.5% for HSCT from an HLA-ma...

show abstract

“…on May 9, 2018. by guest www.bloodjournal.org From less rigorous T-cell depletion used in nonmyeloablative unrelated donor SCT. 38 Our study was not designed with sufficient power to demonstrate clinical efficacy. While infections and viral reactivations were frequent, the overall incidence of directly infectious deaths was low (2 of 16).…”

Section: Discussionmentioning

confidence: 99%

Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation

Amrolia

Muccioli-Casadei

Huls

et al. 2006

Blood

226

165

View full text Add to dashboard Cite

and Epstein-Barr virus (EBV)-specific responses in 4 of 6 evaluable patients at dose level 2 as early as 2 to 4 months after transplantation, whereas such responses were not observed until 6 to 12 months in dose-level 1 patients. The incidence of significant acute (2 of 16) and chronic graft-versus-host disease (GVHD; 2 of 15) was low. These data demonstrate that allodepleted donor T cells can be safely used to improve T-cell recovery after haploidentical SCT and may broaden the applicability of this approach.

show abstract

Reconstitution of the Epstein-Barr virus–specific cytotoxic T-lymphocyte response following T-cell–depleted myeloablative and nonmyeloablative allogeneic stem cell transplantation

Cited by 60 publications

References 25 publications

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

In vivo T‐cell depletion with alemtuzumab in allogeneic hematopoietic stem cell transplantation: Combined results of two studies on aplastic anemia and HLA‐mismatched haploidentical transplantation

Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation

Contact Info

Product

Resources

About