Hemorrhagic cystitis after allogeneic bone marrow transplantation in children: clinical characteristics and outcome

Abstract

Hemorrhagic cystitis (HC) is a well-documented adverse event experienced by patients undergoing hematopoietic stem cell transplantation. When severe, HC causes significant morbidity, leads to renal complications, prolongs hospitalization, increases health-care costs, and occasionally contributes to death. We retrospectively studied the medical records of 245 children undergoing an initial allogeneic bone marrow transplantation for malignant disease at St. Jude Children's Research Hospital between 1992 and 1999 to describe the clinical course of HC in all patients and to identify the risk factors for HC in this cohort. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation. Grafts from unrelated or mismatched related donors were depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All patients received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of grafts from matched siblings also received pentoxifylline or short-course methotrexate. Severe HC developed in 27 patients (11.0%). The median duration of HC was 73 days (range, 5-619 days); 12 patients had ongoing HC at the time of death. In univariate analyses, patients were at increased risk of severe HC if they were male (P =.021) or had received T cell-depleted grafts (P =.017), grafts from unrelated donors (P =.021), a lower total nucleated cell dose (P =.032), or antithymocyte globulin (P =.0446). Multiple regression analysis revealed male sex (beta =.97; P =.027) and unrelated donor graft recipients (beta =.83; P =.039) to be significant factors.

BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts

“…Male gender tended to be associated with the development of HC, which has been occasionally reported previously by others and by us. 12,20,29 When analysing HSCT events separately in patients receiving URD or RD grafts, we disclosed some important differences. Having BK viruria and being transplanted after MC posed an increased risk of HC only in the URD setting and not when undergoing HSCT with an RD graft.…”

“…In addition, we and others have reported that allogeneic HSCT patients with unrelated donor (URD) grafts had a higher risk of HC compared to patients with related donor (RD) grafts. 13,20,21 A major histocompatibility antigen (HLA-A*, -B* and -DRB1*) mismatch is unfavourable from a transplantation point of view, while a mismatch of a minor histocompatibility antigen (HLA-C*, DQA*, DQB* and DPA* and DPB*) may result in fewer problems. However, no stringent studies have been performed on the effect of recipient-donor HLA matching and the development of HC.…”

A prospective study of BK-virus-associated haemorrhagic cystitis in paediatric patients undergoing allogeneic haematopoietic stem cell transplantation

“…16 The determination of BK load by quantitative PCR has been shown to increase the specificity and positive predictive value of BK detection in HSCT patients with HC; in particular, a BK load in urine of 410 6 copies/ml and a BK load in plasma of 410 3-4 copies/ml have been shown to be significantly associated with the development of HC. 3,13,[15][16][17][18] Importantly, the paediatric data published so far have mainly addressed the epidemiological aspects and analysed the risk factors, 1,19,20 while data on the association between BK viral infection and HC post-HSCT are more limited. 11,17,21 We report the results of a prospective study on the incidence of late-onset HC, together with risk factors, and also report the sensitivity, specificity, and positive and negative predictive values of BK viruria and viraemia for developing HC, in paediatric onco-haematological patients undergoing allogeneic HSCT.…”

Treatment of post-hematopoietic stem cell transplantation hemorrhagic cystitis with intravesicular sodium hyaluronate

“…HC may result in prolonged hospitalization after HSCT, and can be associated with severe morbidity and mortality. 3,9 Several factors have been associated with an increased incidence of HC, such as male sex, inclusion of cyclophosphamide and/or busulfan in the conditioning regimen, previous bladder irradiation, allogeneic (vs autologous) SCT, matched unrelated donor transplantation and development of grade II-IV acute GVHD. 2,10,11 Depending on the time of presentation, HC can be divided into earlyonset (which occurs mainly during the first week after transplantation) and late-onset.…”

“…Moreover, the formation of blood clots can lead to hydronephrosis and renal failure. 3 Early presentation of HC is mainly caused by direct toxicity of the conditioning regimen to the uroepithelium, while viral reactivation contributes to the pathogenesis of late onset HC. 4,5 Many therapeutic modalities have been tested in the treatment of established HC refractory to supportive measures, but none of them has been proved to be effective to date.…”