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Impact of haploidentical hematopoietic cell transplantation conditioning intensity on the incidence and severity of post-transplantation viral infections

Bone Marrow Transplantation volume 51, pages 1602–1604 (2016)Cite this article

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In hematological malignancy patients without an available HLA-identical sibling or matched unrelated donor, the use of T-cell replete related donor haploidentical hematopoietic cell transplantation (haplo-HCT), using post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis, is rapidly increasing.1, 2 PT-Cy mitigates the risk of GvHD by targeting alloreactive donor T cells rapidly proliferating early after an HCT, whilst sparing regulatory T cells, and nondividing hematopoietic stem and progenitor cells.3 Viral reactivations and infections are an important cause of morbidity and mortality after allogeneic HCT. They appear to be more common after T-cell depleted compared with T-cell replete haplo-HCT.4 The relative resistance of non-alloreactive donor memory T cells (responsible for cellular immunity against viral pathogens) to PT-Cy5 could mitigate the risk of viral infections following T-cell replete haplo-HCT. However, there is a paucity of published data about the incidence, and severity of viral reactivations and infections following PT-Cy-based haplo-HCT.6 Moreover, the impact of conditioning regimen intensity on the risk of viral infectious complications after PT-Cy-based haplo-HCT is not known. In the current single-center study, we analyze the incidence of viral infectious complications following T-cell replete haplo-HCT, relative to the intensity of conditioning regimens.

We retrospectively evaluated the incidence of viral reactivations and infections in the first 180 days after transplantation. All adult patients (age ⩾18 years) receiving a haplo-HCT (n=43) at our transplant center between 2012 and 2015 were eligible for this study. Patient characteristics are described in Table 1. GvHD prophylaxis in all patients consisted of PT-Cy, tacrolimus and mycophenolate mofetil. All patients received antiviral prophylaxis with acyclovir 800 mg twice daily. Quantitative nucleic acid amplified tests (NAAT) were performed on peripheral blood specimens to monitor for CMV (weekly), EBV (every other week) and adenoviral reactivation (every other week). Human herpes virus-6 (HHV-6) NAAT was performed as clinically indicated. BK polyoma (BK) virus NAAT in urine was performed on patients with signs or symptoms suspicious for cystitis. Upper respiratory tract viral swabs or viral testing on lower respiratory tract specimens (obtained via broncho alveolar lavage) were carried out for patients presenting with signs or symptoms of respiratory tract infections. All invasive viral infections requiring treatment, and/or hospitalization and CMV reactivations that required preemptive antiviral therapy were considered in our analysis. Viral infections were defined according to the European Society for Blood and Marrow Transplantation Infectious Disease Working Party definitions.7 BK virus-associated hemorrhagic cystitis was graded according to Common Terminology Criteria for Adverse Events version 4.0. The study was approved by the Institutional Review Board of Medical College of Wisconsin.

Table 1 Baseline patient characteristics
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Authors and Affiliations

  1. Department of Medicine, Division of Hematology/Oncology, Blood and Marrow Transplantation Program, Medical College of Wisconsin, Milwaukee, WI, USA

    R V Raj, P Hari, M Pasquini, N Epperla, A D'Souza, T Fenske, B E Shaw, J D Rizzo, W Drobyski & M Hamadani

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  1. R V Raj
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  2. P Hari
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  3. M Pasquini
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Correspondence to M Hamadani.

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Raj, R., Hari, P., Pasquini, M. et al. Impact of haploidentical hematopoietic cell transplantation conditioning intensity on the incidence and severity of post-transplantation viral infections. Bone Marrow Transplant 51, 1602–1604 (2016). https://doi.org/10.1038/bmt.2016.216

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