Refractory Hemorrhagic Cystitis after Hematopoeitic Stem Cell Transplantation: Clinical Benefit of Factor XIII.
Authors: Chaumard N. , Legrand F. , Larosa F. , Deconinck Eric 
Published: October 2019

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 characteristics Age Diagnosis Conditioning regimen Source of SC Status at time of HC Grade HC Urethral catherization Time of resolution* ALL: 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 disease 17 Lymphoma 4 BU/CY BM aGVHD III IV Yes 10 days 45 B-ALL BU/CY BM aGVHD III IV Yes No resolution 38 AML 2 BU/Mel PB aGVHD II III Yes 10 days 29 T-ALL BU/CY BM no GVH III Yes 10 days 32 AML 1 TBI/CY BM aGVHD III IV Yes No resolution 47 CML BU/CY BM no GVH II No 4 days 58 MM BU/Mel PB aGVHD II II No 4 days 42 AML 1 Fluda/Mel BM aGVHD I II No 2 days 39 ALL TBI/Fluda/CY UCB aGVHD I II No 2 days

FXIII 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.