Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation and Antithymocyte Globulin Preparative Regimen

Schaenman, Joanna; Shashidhar, Sumana; Rhee, Chanu; Wong, Jonathan; Navato, Shelly; Wong, Ruby M.; Ho, Dora Y.; Arai, Sally; Johnston, Laura; Brown, Janice

doi:10.1016/j.bbmt.2010.08.010

Cited by 17 publications

(15 citation statements)

References 25 publications

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“…This is in line with a prior publication showing early CMV viremia due to impaired viral control in patients given grafts after TLI-ATG conditioning (23). Whether this is due to TLI/ATG conditioning or to the use of ATG itself remains to be determined.…”

Section: Discussionsupporting

confidence: 75%

“…In an effort at preventing GVHD, the Stanford group has developed another nonmyeloablative conditioning that combines total lymphoid irradiation (TLI, 8 Gy total dose) with anti-thymocyte globulin (ATG; 7.5 mg/kg thymoglobulin total dose; refs. [18][19][20][21][22][23]. This approach allowed sustained engraftment with a low incidence of GVHD.…”

Section: Introductionmentioning

confidence: 99%

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Immune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Following Flu-TBI versus TLI-ATG Conditioning

Hannon

Béguin

Ehx

et al. 2015

Clinical Cancer Research

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Purpose: A conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin (ATG) has been developed to induce graft-versus-tumor effects without graft-versus-host disease (GVHD).Experimental Design: We compared immune recovery in 53 patients included in a phase II randomized study comparing nonmyeloablative HCT following either fludarabine plus 2 Gy total body irradiation (TBI arm, n ¼ 28) or 8 Gy TLI plus ATG (TLI arm, n ¼ 25).Results: In comparison with TBI patients, TLI patients had a similarly low 6-month incidence of grade II-IV acute GVHD, a lower incidence of moderate/severe chronic GVHD (P ¼ 0.02), a higher incidence of CMV reactivation (P < 0.001), and a higher incidence of relapse (P ¼ 0.01). While recovery of total CD8þ T cells was similar in the two groups, with median CD8 þ Tcell counts reaching the normal values 40 to 60 days after allo-HCT, TLI patients had lower percentages of na€ ve CD8 T cells. Median CD4 þ T-cell counts did not reach the lower limit of normal values the first year after allo-HCT in the two groups. Furthermore, CD4 þ T-cell counts were significantly lower in TLI than in TBI patients the first 6 months after transplantation. Interestingly, while median absolute regulatory T-cell (Treg) counts were comparable in TBI and TLI patients, Treg/na€ ve CD4 þ T-cell ratios were significantly higher in TLI than in TBI patients the 2 first years after transplantation. Conclusions: Immune recovery differs substantially between these two conditioning regimens, possibly explaining the different clinical outcomes observed (NCT00603954).

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Immune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Following Flu-TBI versus TLI-ATG Conditioning

Hannon

Béguin

Ehx

et al. 2015

Clinical Cancer Research

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“…TLI regimens may have the appeal of offering improved protection from GVHD when compared with RIC regimens, while also limiting the volumes of normal tissue exposed when compared with any TBI regimen. Certainly, further study is warranted; increased odds of early CMV viremia have been demonstrated following TLI, 70 and other potential toxicities have yet to be explored. Having said this, TLI represents an appealing alternative to TBI in certain populations.…”

Section: Tli For Immunosuppression During Bmtmentioning

confidence: 99%

TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions

Hill‐Kayser

Plastaras

Tochner

et al. 2010

Bone Marrow Transplant

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TBI has been used widely in the setting of BMT over the past 3 decades. Early research demonstrated feasibility and efficacy in the myeloablative setting, in preparation first for allogenic BMT and later for autologous stem cell rescue. As experience with TBI increased, its dual roles of myeloablation and immunosuppression came to be recognized. Toxicity associated with myeloablative TBI remains significant, and this treatment is generally reserved for younger patients with excellent performance status. Reduced intensity conditioning regimens may be useful to provide immunosuppression for patients who are not candidates for myeloablative treatment. Efforts to reduce toxicity through protection of normal tissue using methods of normal tissue blocking and use of TLI, rather than TBI, continue. In the future, modalities such as helical tomotherapy, proton radiotherapy and radioimmunotherapy, may have roles in delivery of radiation to the BM and lymphoid structures with reduced normal tissue toxicity. With further investigation, these efforts may expand the therapeutic ratio associated with TBI, allowing safer delivery to a broader range of patients.

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“…CMVseropositive patients were associated with early CMV reactivation in TLI-ATG. 33 CMV reactivation has been reported to be associated with a reduced risk of relapse, but only in patients with acute myeloid leukemia and not in those with lymphoma. 34,35 Unless the mechanism of CMV in enhancing GVL manifests differently in TLI-ATG, the enhanced GVL is likely to be related to the sex-mismatch.…”

mentioning

confidence: 99%

Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy

et al. 2015

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Sex-mismatched hematopoietic cell transplantation is linked to increased graft-versus-host disease and mortality in myeloablative conditioning. Here we evaluated outcomes of 1,041 adult transplant recipients at two centers between 2006 and 2013 and investigated how the effect of sex-mismatching differed in myeloablative, reducedintensity, and non-myeloablative total lymphoid irradiation with anti-thymocyte globulin conditioning. Among patients who underwent myeloablative conditioning, male recipients with female donors had increased chronic graft-versus-host disease (hazard ratio 1.83, P<0.01), increased non-relapse mortality (hazard ratio 1.84, P=0.022) and inferior overall survival (hazard ratio 1.59, P=0.018). In contrast, among patients who received reduced-intensity conditioning, male recipients with female donors had increased acute graft-versus-host disease (hazard ratio 1.96, P<0.01) but no difference in non-relapse mortality or overall survival. Among the patients who underwent total lymphoid irradiation with anti-thymocyte globulin, male recipients with female donors showed no increase in graft-versus-host disease or non-relapse mortality. Notably, only in the cohort receiving total lymphoid irradiation with antithymocyte globulin were male recipients with female donors significantly associated with reduced relapse (hazard ratio 0.64, P<0.01), and allo-antibody responses against H-Y antigens were predictive of reduced relapse. In the cohort given total lymphoid irradiation with anti-thymocyte globulin, the graft-versus-leukemia effect resulted in superior overall survival in recipients of sex-mismatched grafts (HR 0.69, P=0.037). In addition, only in the cohort treated with total lymphoid irradiation with anti-thymocyte globulin were female recipients with male donors associated with reduced relapse (hazard ratio 0.59, P<0.01) and superior survival (hazard ratio 0.61, P=0.014) compared with sex-matched pairs. We conclude that the risks and benefits of sex-mismatched transplants appear to differ according to conditioning strategy and this could affect donor selection. Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nH. Nakasone et al. 1478haematologica | 2015; 100 (11) factors and disease status are among the major drivers determining the conditioning intensity for HLA-matched or single-allele mismatched transplantation. In general, after selection of conditioning, if multiple potential donors are available, other factors such as blood type and sex of the donor versus recipient are evaluated. To determine a potential effect of sex-mismatching within each conditioning type, we evaluated the outcomes of 1,041 adult recipients at two centers between 2006 and 2013. We found that the impact of sex-mismatched transplants differs according to conditioning strategy. Myeloablative conditioned, sex-mismatched Female→Male patients showed increased non-relapse mortality and reduced overall survi...

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Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation and Antithymocyte Globulin Preparative Regimen

Cited by 17 publications

References 25 publications

Immune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Following Flu-TBI versus TLI-ATG Conditioning

Immune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Following Flu-TBI versus TLI-ATG Conditioning

TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions

Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy

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