Refractory Hemorrhagic Cystitis after Hematopoeitic Stem Cell Transplantation: Clinical Benefit of Factor XIII.

Abstract

Hemorrhagic cystitis (HC) is a life threatening complication after haematopoietic stem cell transplantation (SCT). The aim of this study was to value clinical benefit of FXIII in severaly affected patients remaining symptomatic after conventional conservative treatments. Patients and methods Data from patients treated with factor XIII for severe HC after allogeneic SCT were reviewed. Severity of hematuria was evaluated according to National Cancer Institute common toxicity criteria. Clinical improvement was defined as complete or partial resolution of macroscopic hematuria, changes in the irritative urinary symptoms, and decrease of platelet transfusions. Results Nine patients (4 women, 5 men) were treated with one or two infusions of 50 UI/kg body weight of factor XIII between 1998 to 2007. Patients characteristics are summarized in the table.Patients characteristicsAgeDiagnosisConditioning regimenSource of SCStatus at time of HCGrade HCUrethral catherizationTime of resolution*17Lymphoma 4BU/CYBMaGVHD IIIIVYes10 days45B-ALLBU/CYBMaGVHD IIIIVYesNo resolution38AML 2BU/MelPBaGVHD IIIIIYes10 days29T-ALLBU/CYBMno GVHIIIYes10 days32AML 1TBI/CYBMaGVHD IIIIVYesNo resolution47CMLBU/CYBMno GVHIINo4 days58MMBU/MelPBaGVHD IIIINo4 days42AML 1Fluda/MelBMaGVHD IIINo2 days39ALLTBI/Fluda/CYUCBaGVHD IIINo2 daysALL: acute lymphoblastic leukemia, AML: acute myeloblastic leukemia, CML: chronic myeloid leukemia, MM: myeloid metaplasia, BU: busulfan, CY: cyclophosphamide, Mel: melphalan, Fluda: fludarabine, TBI : total body irradiation, BM: bone marrow, PB: peripheral blood, UCB: unit cord blood, aGVHD: acute graft versus host diseaseFXIII concentrate were administred between 8 and 15 days after the beginning of urinary symptoms except for two patients [Day 30 ; Day 46]. Only one patient showed a low FXIII level before injection. In four cases, several infusions were necessary. All patients were in thombocytopenia (platelets <50 G/L) and required platelet transfusions (a pool by day in average). In seven patients, clots quickly disappeared (48h) and haematuria resolved gradually. Need for platelet transfusions was less frequent for 5 patients. Two patients presenting severe HC (IV), uncontrolled GVHD (III) and serious clinical state failed all treatment modalities; they just received one infusion of FXIII. Treatment for GVHD has been associated with viruses complications. No patient died as a direct result of HC. There was no adverse event. Discussion FXIII can be beneficial in refractory HC, particularly if it is used before bleeding complications became uncontrolled. FXIII plays an important role in the recovery process of mucosal injury, as in Crohn's disease and in ulcerative colitis. Recently, a report mentioned the potential beneficial effect of palifermin in HC, limited by serious adverse events. Ours observations suggest that patients may benefit more from this treatment with several infusions. Immunosuppression of acute GVHD seems to be an important factor. Reduction of immunosuppressive therapy to promote elimination of virus may result in clinical improvement, as has been described for renal transplant recipients. Such a strategy is limited by the risk of GVHD. Conclusion The use of FXIII can improve the major symptoms of severe HC independently of FXIII plasma level. Clinical benefit of FXIII may be optimised by a early management of hematuria, and by several infusions administered weekly.