BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment
Yıl: 2016 Cilt: 33 Sayı: 3 Sayfa Aralığı: 223 - 230 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022
BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment
Öz: 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 Yöntemler: Kliniğimizde Ocak 2005-Haziran 2014 arası AlloKHN 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 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 Kelime: Konular:
Allojenik Kök Hücre Transplantasyonu Sonrası BK Virüs Hemorajik Sistiti: Klinik Özellikleri ve Leflunomid Tedavisinin Etkisi
Öz: 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 . 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 and 22 days . Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (highgrade) 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
Anahtar Kelime: Konular:
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- Gargiulo G, Orlando L, Alberani F, Crabu G, Di Maio A, Duranti L, Errico A, Liptrott S, Pitrone R, Santarone S, Soliman C, Trunfio A, Selleri C, Bruno B, Mammoliti S, Pane F. Haemorrhagic cystitis in haematopoietic stem cell transplantation (HSCT): a prospective observational study of incidence and management in HSCT centres within the GITMO network (Gruppo Italiano Trapianto Midollo Osseo). Ecancermedicalscience 2014;8:420.
- Siguier M, Sellier P, Bergmann JF. BK-virus infections: a literature review. Med Mal Infect 2012;42:181-187.
- Yang CC, Hurd DD, Case LD, Assimos DG. Hemorrhagic cystitis in bone marrow transplantation. Urology 1994;44:322-328.
- Yaghobi R, Ramzi M, Dehghani S. The role of different risk factors in clinical presentation of hemorrhagic cystitis in hematopoietic stem cell transplant recipients. Transplant Proc 2009;41:2900-2902.
- Sencer SF, Haake RJ, Weisdorf DJ. Hemorrhagic cystitis after bone marrow transplantation. Risk factors and complications. Transplantation 1993;56:875-879.
- Dropulic LK, Jones RJ. Polyomavirus BK infection in blood and marrow transplant recipients. Bone Marrow Transplant 2008;41:11-18.
- Bedi A, Miller CB, Hanson JL, Goodman S, Ambinder RF, Charache P, Arthur RR, Jones RJ. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. J Clin Oncol 1995;13:1103-1109.
- dela Cruz J, Pursell K. BK virus and its role in hematopoietic stem cell transplantation: evolution of a pathogen. Curr Infect Dis Rep 2014;16:417.
- Raval M, Gulbis A, Bollard C, Leen A, Chemaly R, Shpall E, Lahoti A, Kebriaei P. Evaluation and management of BK virus-associated nephropathy following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2011;17:1589-1593.
- Pahari A, Rees L. BK virus-associated renal problems--clinical implications. Pediatr Nephrol 2003;18:743-748.
- Arthur RR, Shah KV, Baust SJ, Santos GW, Saral R. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med 1986;315:230-234.
- Razonable RR, Eid AJ. Viral infections in transplant recipients. Minerva Med 2009;100:479-501.
- Leung AY, Mak R, Lie AK, Yuen KY, Cheng VC, Liang R, Kwong YL. Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation. Bone Marrow Transplant 2002;29:509-513.
- Mori Y, Miyamoto T, Kato K, Kamezaki K, Kuriyama T, Oku S, Takenaka K, Iwasaki H, Harada N, Shiratsuchi M, Abe Y, Nagafuji K, Teshima T, Akashi K. Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2012;18:458-465.
- Rorije NM, Shea MM, Satyanarayana G, Hammond SP, Ho VT, Baden LR, Antin JH, Soiffer RJ, Marty FM. BK virus disease after allogeneic stem cell transplantation: a cohort analysis. Biol Blood Marrow Transplant 2014;20:564-570.
- Zaman RA, Ettenger RB, Cheam H, Malekzadeh MH, Tsai EW. A novel treatment regimen for BK viremia. Transplantation 2014;97:1166-1171.
- Farasati NA, Shapiro R, Vats A, Randhawa P. Effect of leflunomide and cidofovir on replication of BK virus in an in vitro culture system. Transplantation 2005;79:116-118.
- Leca N. Leflunomide use in renal transplantation. Curr Opin Organ Transplant 2009;14:370-374.
- Josephson MA, Gillen D, Javaid B, Kadambi P, Meehan S, Foster P, Harland R, Thistlethwaite RJ, Garfinkel M, Atwood W, Jordan J, Sadhu M, Millis MJ, Williams J. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation 2006;81:704-710.
- Wu KH, Weng T, Wu HP, Peng CT, Sheu JN, Chao YH. Effective treatment of severe BK virus-associated hemorrhagic cystitis with leflunomide in children after hematopoietic stem cell transplantation: a pilot study. Pediatr Infect Dis J 2014;33:1193-1195.
- Chen XC, Liu T, Li JJ, He C, Meng WT, Huang R. Efficacy and safety of leflunomide for the treatment of BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients. Acta Haematol 2013;130:52-56.
- Przepiorka D, Anderlini P, Saliba R, Cleary K, Mehra R, Khouri I, Huh YO, Giralt S, Braunschweig I, van Besien K, Champlin R. Chronic graft-versus- host disease after allogeneic blood stem cell transplantation. Blood 2001;98:1695-1700.
- Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995;15:825-828.
- Kim SY, Lee JW, Lee KM, Cho BS, Eom KS, Kim YJ, Lee S, Min CK, Kim HJ, Cho SG, Kim DW, Min WS, Kim CC. Viruria in adult hemorrhagic cystitis patients following allogeneic hematopoietic stem cell transplantation and implication of antiviral treatment. Korean J Hematol 2007;42:114-121.
- Gorczynska E, Turkiewicz D, Rybka K, Toporski J, Kalwak K, Dyla A, Szczyra Z, Chybicka A. Incidence, clinical outcome, and management of virus- induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2005;11:797-804.
- Gilis L, Morisset S, Billaud G, Ducastelle-Lepretre S, Labussiere-Wallet H, Nicolini FE, Barraco F, Detrait M, Thomas X, Tedone N, Sobh M, Chidiac C, Ferry T, Salles G, Michallet M, Ader F; Lyon BK Virus Study Group. High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2014;49:664-670.
- Vats A, Shapiro R, Singh Randhawa P, Scantlebury V, Tuzuner A, Saxena M, Moritz ML, Beattie TJ, Gonwa T, Green MD, Ellis D. Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults. Transplantation 2003;75:105-112.
- Kadambi PV, Josephson MA, Williams J, Corey L, Jerome KR, Meehan SM, Limaye AP. Treatment of refractory BK virus-associated nephropathy with cidofovir. Am J Transplant 2003;3:186-191.
- Thamboo TP, Jeffery KJ, Friend PJ, Turner GD, Roberts IS. Urine cytology screening for polyoma virus infection following renal transplantation: the Oxford experience. J Clin Pathol 2007;60:927-930.
- Gonzalez-Fraile MI, Canizo C, Caballero D, Hernandez R, Vazquez L, Lopez C, Izarra A, Arroyo JL, de la Loma A, Otero MJ, San Miquel JF. Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis. Transpl Infect Dis 200;3:44-46.
- Held TK, Biel SS, Nitsache A, Kurth A, Chen S, Gelderblom HR, Sieqert W. Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir. Bone Marrow Transplant 2000;26:347-350.
- Hatakeyama N, Suzuki N, Kudoh T, Hori T, Mizue N, Tsutsumi H. Successful cidofovir treatment of adenovirus-associated hemorrhagic cystitis and renal dysfunction after allogenic bone marrow transplant. Pediatr Infect Dis J 2003;22:928-929.
- Leung AY, Suen CK, Lie AK, Liang RH, Yuen KY, Kwong YL. Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. Blood 2001;98:1971-1978.
| APA | PARK Y, LIM J, Yİ H, LEE M, KİM C (2016). BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. , 223 - 230. |
| Chicago | PARK Young Hoon,LIM Joo Han,Yİ Hyeon Gyu,LEE Moon Hee,KİM Chul Soo BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. (2016): 223 - 230. |
| MLA | PARK Young Hoon,LIM Joo Han,Yİ Hyeon Gyu,LEE Moon Hee,KİM Chul Soo BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. , 2016, ss.223 - 230. |
| AMA | PARK Y,LIM J,Yİ H,LEE M,KİM C BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. . 2016; 223 - 230. |
| Vancouver | PARK Y,LIM J,Yİ H,LEE M,KİM C BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. . 2016; 223 - 230. |
| IEEE | PARK Y,LIM J,Yİ H,LEE M,KİM C "BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment." , ss.223 - 230, 2016. |
| ISNAD | PARK, Young Hoon vd. "BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment". (2016), 223-230. |
| APA | PARK Y, LIM J, Yİ H, LEE M, KİM C (2016). BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. Turkish Journal of Hematology, 33(3), 223 - 230. |
| Chicago | PARK Young Hoon,LIM Joo Han,Yİ Hyeon Gyu,LEE Moon Hee,KİM Chul Soo BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. Turkish Journal of Hematology 33, no.3 (2016): 223 - 230. |
| MLA | PARK Young Hoon,LIM Joo Han,Yİ Hyeon Gyu,LEE Moon Hee,KİM Chul Soo BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. Turkish Journal of Hematology, vol.33, no.3, 2016, ss.223 - 230. |
| AMA | PARK Y,LIM J,Yİ H,LEE M,KİM C BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. Turkish Journal of Hematology. 2016; 33(3): 223 - 230. |
| Vancouver | PARK Y,LIM J,Yİ H,LEE M,KİM C BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment. Turkish Journal of Hematology. 2016; 33(3): 223 - 230. |
| IEEE | PARK Y,LIM J,Yİ H,LEE M,KİM C "BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment." Turkish Journal of Hematology, 33, ss.223 - 230, 2016. |
| ISNAD | PARK, Young Hoon vd. "BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment". Turkish Journal of Hematology 33/3 (2016), 223-230. |
