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

Powell, Jonathan; Bunin, Nancy; Callahan, Colleen; Aplenc, Richard; Griffin, Gregory; Grupp, Stephan A.

doi:10.1038/sj.bmt.1704402

Cited by 43 publications

(26 citation statements)

References 40 publications

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“…However, by taking into account the clinical status at transplant, this effect was confirmed only for patients rescued while in complete remission. Thus, the present results do not support the need for a generalized use of purging procedures, also in view of the increased risk of EBV-related lymphoproliferative disorders in CD34 + -transplanted patients (24). TH and GD2-s quantitative RT-PCR assays have already been used to detect neuroblastoma cell contamination (19, 20, 25 -28); however, this is the first study in which the two assays were done simultaneously on PBSC samples.…”

Section: Discussionmentioning

confidence: 43%

Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients

Corrias¹,

Haupt²,

Carlini³

et al. 2006

Clinical Cancer Research

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Purpose: Contribution of peripheral blood stem cell (PBSC) contaminating tumor cells to subsequent relapse and overall survival of neuroblastoma patients remains controversial. Experimental Design: Neuroblastoma cell contamination of 27 PBSC harvests from stage IV neuroblastoma patients was assessed by quantitative RT-PCR for both tyrosine hydroxylase (TH) and GD2 synthase (GD2-s). The effect of PBSC contamination on survival was then analyzed. Results: Seven PBSC tested negative for both markers; 19 were positive for GD2-s, 6 for TH, with 5 positive for both. Survival of the 20 patients with positive PBSC did not differ from that of the patients with negative PBSC (log-rank test, P = 0.134 and 0.218 for event-free survival and overall survival, respectively). By considering the TH and GD2-s results independently, a borderline (P = 0.053) negative effect on event-free survival was observed in patients reinfused with GD2-s-positive PBSC. When the status at transplant was taken into account, only the event-free survival of the patients rescued when in complete remission with GD2-s-negative PBSC was better, although not significantly, than that of patients infused with GD2-s-positive PBSC. Conclusions: Our results obtained in a small cohort of homogeneously treated stage IV patients suggest that patient survival is not affected by PBSC contamination with the exception of a borderline negative effect on event-free survival in patients rescued when in complete remission.

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Section: Discussionmentioning

confidence: 43%

Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients

Corrias¹,

Haupt²,

Carlini³

et al. 2006

Clinical Cancer Research

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“…This suggests that the combination of CD34 selection and tandem transplant is more immunosuppressive than autologous SCT using unpurged PBSC. 20,31 A second study found similar results using three sequential HDC procedures. 7 : EFS at 3 years was 57%.…”

Section: Dosing Of Pbscsupporting

confidence: 64%

Stem cell transplantation for neuroblastoma

Fish

Grupp

2007

Bone Marrow Transplant

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“…The most widely used antibody is rituximab, a chimeric murine/human monoclonal anti-CD20 antibody. Rituximab has been used as prophylaxis and treatment for PTLD after HSCT, with initial response rates between 55% and 100%, [44][45][46][47] a range that probably reflects differences in the treated patient populations. Rituximab also has activity in PTLD after SOT, in which response rates of 44% to 100% have been reported in several small studies.…”

Section: Targeting B Cellsmentioning

confidence: 99%

How I treat EBV lymphoproliferation

Heslop

2009

Blood

276

253

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Epstein-Barr virus (EBV)- IntroductionEpstein-Barr virus (EBV) lymphoproliferative disease (LPD) is the result of the outgrowth of EBV-infected B cells that would normally be controlled by an effective EBV-specific cytotoxic T-cell response. LPD may occur during both primary and secondary immune deficiencies and even in some persons without documented immunodeficiency. In this article, I focus on EBV type III latency B-cell lymphoproliferation, which occurs during the immunosuppression that follows hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT). To understand the etiology of these lymphoproliferations and how manipulation of the immune system may be a treatment option, it is important to first understand the biology of EBV. Biology of EBVEBV is a latent ␥-herpesvirus that infects more than 90% of the world's population. Primary lytic infection occurs in the oropharynx and may be asymptomatic or present as infectious mononucleosis. 1 EBV is highly immunogenic; and during primary infection, normal persons mount a vigorous humoral and cellular immune response with the cellular component consisting of CD4 ϩ and CD8 ϩ T cells, which control both primary infection and the periodic reactivations that occur in all EBV-seropositive persons. 2 Indeed, analyses using multimers to enumerate EBV-specific T cells have shown that up to 1% to 5% of circulating T cells in a normal EBV-seropositive person may be specific for EBV. 3,4 After clearance of primary infection, EBV persists as an episome in infected B cells, establishing latent infection characterized by the expression of only a limited array of subdominant EBV antigens. There are 4 types of latency, distinguished by the pattern of EBV antigen expression in infected memory B cells (Figure 1).Most infected circulating memory B cells express no viral antigens (type 0 latency), allowing them to remain invisible to the host immune system. 5 EBNA1, which acts on a latent origin of replication, is responsible for coordinating replication of the latent episome in concert with replication of the host cells and is therefore expressed in all types of latency associated with cell division. 6 Type 1 latency is associated with expression of only EBNA-1 and is seen in circulating B cells when they proliferate and in Burkitt lymphoma. In type 2 latency, LMP1 and LMP2 are also expressed in addition to EBNA1, and this pattern of expression is seen in germinal center B cells in healthy tonsils. The most immunogenic form of latency is type 3, in which all nuclear proteins (EBNAs -1, -2, -3A, -3B, -3C, and -LP) and 2 membrane proteins (LMP1 and LMP2) are expressed together with 2 small RNAs (EBERs). Type 3 latency occurs in B cells immortalized in vitro by EBV into permanently growing lymphoblastoid cell lines. Type 3 latency B cells are rarely detected in healthy seropositive persons, but their occurrence can be inferred from the high frequency of T cells specific for the EBNA3 proteins that persist long-term, and it is probable that periodic reactivat...

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

Cited by 43 publications

References 40 publications

Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients

Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients

Stem cell transplantation for neuroblastoma

How I treat EBV lymphoproliferation

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