Does peritransplantation use of rituximab reduce the risk of EBV reactivation and PTLPD?

Savani, Bipin N.; Pohlmann, Paula R.; Jagasia, Madan; Chinratanalab, Wichai; Kassim, Adetola A.; Engelhardt, Brian G.; Greer, John P.; Schuening, Friedrich; Goodman, Stacey

doi:10.1182/blood-2009-04-213892

Cited by 18 publications

(22 citation statements)

References 12 publications

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“…Elimination of host and donor memory B cells by low-dose rituximab in the conditioning regimen could reduce the incidence of EBV reactivation and post-transplantation lymphoproliferative disorders post-SCT. None of our patients developed EBV reactivation in this series similar to our earlier observation [20]. Excellent tolerance, decreased GVHD, minimal rehospitalization, and reduced risk of EBV reactivation might significantly reduce the expense, morbidity, and mortality associated with FCR NST allo-SCT.…”

Section: Discussionsupporting

confidence: 88%

Immunomodulatory nonablative conditioning regimen for B-cell lymphoid malignancies

Chinratanalab

Reddy

Greer

et al. 2012

Experimental Hematology

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Twenty-six patients with recurrent CD20+ B-cell lymphoid malignancies received fludarabine, cyclophosphamide, and rituximab–based nonablative conditioning followed by either matched related (n = 18) or unrelated (n = 8) donor allogeneic stem cell transplantation (allo-SCT) between March 2008 and May 2011. Median age of patients at transplantation was 59 years (range, 41–64 years). At diagnosis, 20 (77%) had stage IV disease; 23 (88%) received ≥3 regimens, 14 (54%) received ≥4 regimens, and 4 (15%) had earlier autologous-SCT. All patients had either chemosensitive or stable disease and nine (35%) were in complete remission before transplantation. At the time of analysis, 17 patients were alive with an estimated 2-year overall survival and progression-free survival rate of 63% and nonrelapse mortality of 25%. Grade II to IV acute graft-vs-host-disease occurred in 8 (31%) and chronic graft-vs-host-disease in 6 (23%) patients (extensive, n = 3). Causes of death include progressive disease in four, acute graft-vs-host-disease in two (both after receiving donor lymphocyte infusion for mixed chimerism with residual disease), infection in one, and other (e.g., substance abuse, leukoencephalopathy) in two. Six patients required rehospitalization within 100 days of SCT (mean = 10 days; range, 3–18 days). Our data support fludarabine, cyclophosphamide, and rituximab–based nonablative conditioning allo-SCT in CD20+ B-cell lymphoid malignancies and it is time to compare this regimen with an alternative reduced-intensity conditioning regimen in B-cell malignancies.

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Section: Discussionsupporting

confidence: 88%

Immunomodulatory nonablative conditioning regimen for B-cell lymphoid malignancies

Chinratanalab

Reddy

Greer

et al. 2012

Experimental Hematology

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“…Other studies found a correlation between EBVreactivation and several factors, such as the degree of HLA mismatch between donor and recipient, manipulation of the graft to deplete T cells, degree and duration of immunosuppression used to prevent and treat GVHD, and the use of ATG and Campath. 22,23 A recent analysis by Savani et al 45 suggested that EBV reactivation and the possible development of PTLD is reduced in patients with lymphoid malignancies treated with rituximab during the course of their disease before allo-SCT. Though this did not reach statistical significance, in our study there was a fewer number of patients with lymphoid malignancies in the group of patients who experienced an episode of EBV reactivation (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Features of Epstein-Barr Virus (EBV) reactivation after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation

et al. 2011

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This single centre study assessed the incidence, kinetics and predictive factors of Epstein-Barr Virus (EBV) reactivation and EBV-related lymphoproliferative diseases (LPDs) in 175 consecutive patients who received a reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cumulative incidence of EBV reactivation at 6 months after allo-HSCT defined as an EBV PCR load above 1000 copies of EBV DNA/10 5 cells was 15%, and none of these patients experienced any sign or symptom of LPD. A total of 17 patients, who had EBV DNA levels exceeding 1000 copies/10 5 cells on two or more occasions, were pre-emptively treated with rituximab. With a median follow-up of 655 (range, 92-1542) days post allo-HSCT, there was no statistically significant difference in term of outcome between those patients who experienced an EBV reactivation and those who did not. In multivariate analysis, the use of antithymocyte globulin as part of the RIC regimen was the only independent risk factor associated with EBV reactivation (relative risk ¼ 4.9; 95% confidence interval, 1.1-21.0; P ¼ 0.03). We conclude that patients undergoing RIC allo-HSCT using anti-thymocyte globulin as part of the preparative regimen are at higher risk for EBV reactivation. However, this did not impact on outcome, as quantitative monitoring of EBV viral load by PCR and preemptive rituximab therapy allowed for significantly reducing the risk of EBV-related LPD.

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“…However, if rituximab is used during the conditioning regimen, it should theoretically have less of an impact on donor derived B cell reconstitution compared to posttransplantation administration for EBV reactivation or PTLD where effects are long lasting. When patients received rituximab before (within 6 months of) allo-SCT for B cell lymphoid malignancies (n = 38), we observed no EBV reactivation reported even in patients with 3 risk factors for PTLD (including CBT recipients) and no increased infection [66]. In a another study, the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia (SAA) added rituximab on day 5 of their fludarabine, cyclophosphamide, low-dose total body irradiation (TBI), and ATG conditioning regimen for unrelated donor transplants in acquired SAA [67].…”

Section: Epstein-barr Virus (Ebv)-related B Cell Lymphoproliferative mentioning

confidence: 99%

Strategies to Prevent EBV Reactivation and Posttransplant Lymphoproliferative Disorders (PTLD) after Allogeneic Stem Cell Transplantation in High-Risk Patients

Reddy

Rezvani

Barrett

et al. 2011

Biology of Blood and Marrow Transplantation

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Epstein-Barr virus (EBV)-associated postallogeneic stem cell transplantation (SCT) lymphoproliferative disorder (PTLD) is often life threatening. The risk of EBV reactivation is highest in older patients, T cell-depleted SCT (in vivo or vitro), and in unrelated or mismatched SCT. Cumulative numbers of patients with EBV reactivation and PTLD are rising as more patients at high risk for EBV reactivation and PTLD are receiving allo-SCT. Novel but easily applicable strategies are needed to prevent EBV reactivation and PTLD to serve the needs of the increasingly enlarging population of high-risk SCT recipients across the globe.

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Does peritransplantation use of rituximab reduce the risk of EBV reactivation and PTLPD?

Cited by 18 publications

References 12 publications

Immunomodulatory nonablative conditioning regimen for B-cell lymphoid malignancies

Immunomodulatory nonablative conditioning regimen for B-cell lymphoid malignancies

Features of Epstein-Barr Virus (EBV) reactivation after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation

Strategies to Prevent EBV Reactivation and Posttransplant Lymphoproliferative Disorders (PTLD) after Allogeneic Stem Cell Transplantation in High-Risk Patients

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