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Impact of extended infusional mesna prophylaxis on the incidence of BK viruria and hemorrhagic cystitis following post-transplantation cyclophosphamide and CTLA4Ig-based haploidentical transplantation

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Abstract

Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)–based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2–65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 104 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 104 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 104 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.

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Abbreviations

CMV:

Cytomegalovirus

COSBL:

Costimulation blockade

CTLA4:

Cytotoxic T lymphocyte–associated protein 4

DLI:

Donor lymphocyte infusions

BKV:

BK virus

GVHD:

Acute graft-versus-host disease

HC:

Hemorrhagic cystitis

HFD:

Haploidentical family donor

HLA:

Human leukocyte antigen

HCT:

Hematopoietic cell transplantation

IST:

Immune-suppressive therapy

KIR:

Killer immunoglobulin-like receptor

LPD:

Lymphoproliferative disorders

MAC:

Myeloablative conditioning

NK:

Natural killer cell

NRM:

Non-relapse mortality

OS:

Overall survival

PCR:

Polymerase chain reaction

PTHPS:

Post-transplantation hemophagocytic syndrome

PTCy:

Post-transplantation cyclophosphamide

RIC:

Reduced intensity conditioning

TCD:

T cell depletion

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Author information

Authors and Affiliations

  1. Cellular Therapy and Immunology, Manashi Chakrabarti Foundation, Kolkata, India

    Sarita Rani Jaiswal, Aditi Chakrabarti & Suparno Chakrabarti

  2. Department of Blood and Marrow Transplantation, Dharamshila Narayana Superspeciality Hospital, New Delhi, India

    Sarita Rani Jaiswal & Suparno Chakrabarti

  3. Department of Blood and Marrow Transplantation & Hematology, Dharamshila Hospital and Research Centre, Vasundhara Enclave, New Delhi, 110096, India

    Sarita Rani Jaiswal

  4. Department of Urology, Dharamshila Narayana Superspeciality Hospital, New Delhi, India

    Paras Singhal

  5. Molecular Diagnostics and R&D, Dr LalPathLabs Ltd, New Delhi, India

    Atul Thatai

  6. Department of Pathology and Microbiology, Dharamshila Narayana Superspeciality Hospital, New Delhi, India

    Gitali Bhagwati & Hema Malini Aiyer

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  1. Sarita Rani Jaiswal
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Contributions

SRJ and SC designed and performed the study; SRJ and AT performed the experiments; GB, HA, and PS collected the data; SRJ and SC analyzed the data; and SRJ, AC, and SC wrote the manuscript. All the co-authors reviewed and approved the manuscript.

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Correspondence to Sarita Rani Jaiswal.

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Jaiswal, S.R., Singhal, P., Thatai, A. et al. Impact of extended infusional mesna prophylaxis on the incidence of BK viruria and hemorrhagic cystitis following post-transplantation cyclophosphamide and CTLA4Ig-based haploidentical transplantation. Ann Hematol 99, 839–845 (2020). https://doi.org/10.1007/s00277-020-03930-w

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