Urological complications associated with adult allogeneic stem cell transplantation
Authors: Laila Schneidewind, Thomas Neumann, Kathrin Zimmermann, Christian Andreas Schmidt, William Krüger
Journal: American Journal of Hematology (2017)

Every year 50 000 patients receive stem cell transplantation worldwide, but data are lacking about urological complications associated with this therapy. Most studies were performed in paediatric stem cell transplantation or are retrospective analyses with a small number of cases. The complications mentioned were mostly urological infections and haematuria.1 Another complication that arises under this therapy is the BK polyomavirus associated hemorrhagic cystitis (BKHC), which can occur in 5%-60% of the cases.2 Other viruses which can lead to cystitis or even hemorrhagic cystitis following allogeneic stem cell transplantation are polyomavirus JC and uropathogenic adenoviruses.3 Since urological complications can cause severe problems with increased morbidity and rarely mortality, further investigations are needed.4 We conducted a prospective, single-center, noninterventional trial on urological complications assopciated with first adult allogeneic stem cell transplantation with a follow up time of one year after inpatient treatment. To our knowledge this is the first prospective study about urological complications under this therapy worldwide. The inclusion criteria were patient over 18 years receiving their first allogeneic stem cell transplantation due to hematological disease. The use of low dose alemtuzumab (10 mg at day −2; respectively 20 mg in case of mismatch) for Graft versus host disease (GvHD) prophylaxis was mandatory. No exclusion criteria were defined. From November 2013 until December 2015 we were able to include 40 patients in our study. Statistical calculations were made by using SPSS 23.0 (SPSS Inc., Chicago, Ill., USA). All reported P-values were based on a two-sided hypothesis, P < .05 was considered to be significant. Between November 2013 and December 2015, we were able to include 40 adult patients with a mean age of 52.8 years. Twenty seven (67.5%) of these patients were male and 13 (32.5%) were female. Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 15; 37.5%). The majority of patients received intermediate intense conditioning protocols (n = 31; 77.5%). On the whole, urological complications during inpatient treatment were quite common in this study population (n = 26; 65.5%). Acute renal failure (n = 14; 35.0%) and bacterial UTI (n = 7; 17.5%) were the most frequent complications. BKHC occurred only one time (n = 1; 2.5%). But viruria with absence of urogenital symptom and after infusion of the stem cell product occurred more often, e.g., BK viruria 11 (27.5%). Table 1 gives an overview of all urological complications and viruria during inpatient treatment. We did not observe adenoviruria after infusion of the stem cell product in this study population. Additionally, we tested if BK viruria or JC viruria were associated with renal failure or acute GvHD, as previously reported. Interestingly, BK viruria was significantly associated with acute renal failure (P = .007; Fisher exact test). In this population, there was no significant association of BK and JC viruria with acute GvHD. The main result of our study is that urological complications under this therapy are very common, (e.g., 65.5%) during inpatient treatment. On the whole, bacterial UTI and acute renal failure are the most frequent complications. BKHC only occurred one time in our study population which is clearly less than described in the literature.2 One major risk factors for BKHC mentioned in other studies was myeloablative conditioning5; in our study population, a majority of patients were conditioned with an intermediate intense protocol. BK and JC viruria without urogenital symptoms are more frequent. We found no case of adenoviruria after stem cell transplantation, so we must conclude that this virus is not that important in the adult population like it is in paediatric stem cell transplantation.5 Interestingly, BK viruria was significantly associated with acute renal failure. Acute renal failure was described in retrospective analysis before, so we must conclude that BK virus can also lead to nephropathy in allogeneic stem cell transplantation like it is well known in kidney transplantation.4 We found no association with polyomavirus BK and JC with GvHD contrary to what was described in other studies.6 Regarding GvHD prophylaxis, our study was quite homogenous, since all patients received alemtuzumab. Other studies had more heterogenous populations or all participants received antithymogloboline for GvHD prophylaxis.6 We conclude that urological complications, especially polyomavirus associated urogenital infections, are important and considerable during adult allogeneic stem cell transplantation. The authors would like to thank all participating patients and all nurses or study nurses of the University Medicine Greifswald Department of Hematology/Oncology who made this study a success. Thank you for your great help and advice!