ISSN: 1300-7777 E-ISSN: 1308-5263
BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment [Turk J Hematol]
Turk J Hematol. 2016; 33(3): 223-230 | DOI: 10.4274/Tjh.2015.0131  

BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment

Young Hoon Park, Joo Han Lim, Hyeon Gyu Yi, Moon Hee Lee, Chul Soo Kim
Inha University Faculty of Medicine and Hospital, Department of Hematology-Oncology, Incheon, Republic of Korea

Objective: BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide
therapy for BKV-HC.
Materials and Methods: From January 2005 to June 2014, among the 69 patients that underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively.
Results: HC was observed in 30 patients (43.5%), and among them, 18 of the cases (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (minimum-maximum: 13-63). Patients received Allo-SCT for acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1). The donor types were human leukocyte antigen (HLA)-matched sibling donor for six patients, HLA-matched unrelated donor for nine, and haploidentical familial donor for two. The median onset and duration of BKV-HC was on day 21 after transplantation (minimum-maximum: 7-97) and 22 days (minimum-maximum: 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response, one had partial response, and five had no response. Among the five nonresponders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, achieving complete response (n=2) and partial response (n=2). The median duration from the start of leflunomide therapy to response was 13 days (minimum-maximum: 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating.
Conclusion: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who do not respond to supportive care, leflunomide may be a feasible option without significant toxicity.

Keywords: BK virus, Hemorrhagic cystitis, Allogeneic stem cell transplantation, Leflunomide


Allojenik Kök Hücre Transplantasyonu Sonrası BK Virüs Hemorajik Sistiti: Klinik Özellikleri ve Leflunomid Tedavisinin Etkisi

Young Hoon Park, Joo Han Lim, Hyeon Gyu Yi, Moon Hee Lee, Chul Soo Kim
Inha University Faculty of Medicine and Hospital, Department of Hematology-Oncology, Incheon, Republic of Korea

Amaç: BK-virüs hemorajik sistiti (BKV-HS) allojenik kök hücre nakli (Allo-KHN) uygulanan hastalarda morbidite ve mortalitenin önemli bir nedenidir. Bu çalışmada Allo-KHN sonrası BKV-HS olan olguların klinik özellikleri ve leflunomid tedavisinin BKV-HS’deki etkinliği araştırılmıştır.
Gereç ve Yöntem: Kliniğimizde Ocak 2005-Haziran 2014 arası Allo- KHN uygulanmış 69 hastada, BKV-HS geçirmiş olanlar retrospektif olarak değerlendirildi.
Bulgular: Otuz hastada (%43,5) HS gözlendi. Bu olguların 18’inde (%26,1) BKV-HS’si saptandı. Hastaların (12’si erkek, altısı kadın) medyan yaşı 45 (13-63) idi. Hastalara akut miyeloid lösemi (n=11), aplastik anemi (n=4), miyelodisplastik sendrom (n=2) ve non-Hodgkin lenfoma (n=1) nedeni ile Allo-KHN uygulanmıştı. Altısında insan lökosit antijeni (İLA)-uygun kardeş, dokuzunda İLA-uygun akraba dışı donör ve ikisinde haplo-identik donör kullanılmıştı. Transplant sonrası BKV-HS medyan başlangıç zamanı 21 gün (7-97 gün), medyan süresi 22 gün (6-107 gün) idi. On bir olguda (%62,1) derece I-II, yedi olguda (%38,9) derece III-IV (yüksek derecede) HS saptandı. Yüksek derece HS’li yedi hastanın, birinde tam yanıt, birinde kısmi yanıt elde edilirken, beş hastada yanıt alınamadı. Yanıt alınmayan beş hastanın birisi BKV-HS ilişkili komplikasyonlardan kaybedildi. Geri kalan dört hasta leflunomid ile tedavi edildi. Bu hastaların ikisinde tam yanıt, ikisinde kısmi yanıt elde edildi. Leflunomidin başlangıcından itibaren medyan yanıt süresi 13 gündü (8-17 gün). Tüm hastalar leflunomidi iyi tolere ederken, üç hastada anoreksi ve abdominal gaz şikayetleri dahil hafif şiddetli gastrointestinal yan etkiler gözlendi.
Sonuç: Allo-KHN sonrası izlemde BKV-HS yaygın olarak gözlenmiştir. Destek tedavisine yanıt vermeyen yüksek derece BKV-HS’li olgularda leflunomid, anlamlı toksisitesi olmaksızın bir seçenek olabilir.

Anahtar Kelimeler: BK virüs, Hemorajik sistit, Allojenik kök hücre transplantasyonu, Leflunomid


Young Hoon Park, Joo Han Lim, Hyeon Gyu Yi, Moon Hee Lee, Chul Soo Kim. BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. Turk J Hematol. 2016; 33(3): 223-230

Corresponding Author: Chul Soo Kim, Japan


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