Hemorrhagic cystitis after hematopoietic stem cell trans-plantation: much progress and many remaining issues
Year: 2007
Type: article
Abstract: The manuscript by Xu et al1 addresses an important question in the field of allogeneic hematopoietic progenitor cell transplantation (HPCT): how to identify those patients at risk for hemmoraghic cystitis. The authors performed a retrospective analysis of 250 patients undergoing allogeneic HPCT following myeloablative conditioning with busulfan and cyclophosphamide using a standard post-transplant immunoprophylaxis with cyclosporine, short-course methotrexate and mycophenylate. Post-transplant hematuria was relatively common, occurring in 29% of allogeneic transplant recipients in this single institution series. Most of the documented hematuria was macroscopic (68% of cases), but 30% of patients had grade 3 or grade 4 hematuria, with the presence of blood clots in the urine. The investigators' initial hypothesis was that hemorrhagic cystitis would be related to the development of cytomegalovirus (CMV) viremia or CMV infection in the bladder. CMV viremia, monitored by PCR of blood samples, occurred in 40% of patients tested, and was treated pre-emptively with ganciclovir or foscarnate. CMV viremia was associated with hemorrhagic cystitis in univariate analysis, but it was not an independent factor in the multivariable model. Multivariate logistic regression indicated that the development of grades 2-4 acute graft-versus-host disease (GVHD) and transplants using grafts from volunteer unrelated donors or HLA mis-matched related donors were independently associated with the development of hemorrhagic cystitis. However, in 15 patients with documented CMV-viruria, 9 developed hemorrhagic cystitis, illustrating a biological association of CMV with hemorrhagic cystitis. Hemorrhagic cystitis developed after or coincident with the occurrence of acute GVHD in 44 of 72 patients, suggesting an etiologic relationship of hemorrhagic cystitis with acute GVHD. Why then, does hemorrhagic cystitis follow the development of acute GVHD? The data by Xu et al suggest two alternatives that should be examined in follow-up studies. First, there is an association of GVHD with an increased risk of infectious complications, particularly CMV, in the setting of allogeneic transplantation, and GVHD may increase the risk of opportunistic viral infections in the bladder that contribute to hemorrhagic cystitis. One weakness of the current manuscript is the lack of measurements of BK virus in the urine, another viral agent that has been proposed as the etiologic agent for hemorrhagic cystitis.2,3 A second explanation for the results of Xu et al is that acute GVHD may directly involve the epithelium of the bladder itself. If so, topical application of immunosuppressive drugs to the bladder epithelium, as have recently been shown to be helpful in the management of acute GVHD involving the gut, may prove to be therapeutic for patients with severe hemorrhagic cystitis following alllogeneic HPCT. Xu et al are to be commended for a careful study that adds to our knowledge of hemorrhagic cystitis, and suggests important areas for future clinical research.
Source: Chinese Medical Journal
Author: Edmund K. Waller
Institutions: Emory University, Winship Cancer Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
OpenAlex ID: W2256604744