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 Table of Contents  
EDITORIAL
Year : 2018  |  Volume : 9  |  Issue : 3  |  Page : 79-80

Treatment of refractory hemorrhagic cystitis after hematopoietic stem cell transplantation in a case of acute myeloid leukemia with mesenchymal stem cell infusion


Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences; Department of Internal Medicine, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Amir-Al Momenin Hospital, Tehran, Iran

Date of Web Publication31-Oct-2018

Correspondence Address:
Dr. Nasim Valizadeh
Assistant Professor of Hematology/Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Amir-Al Momenin Hospital, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joah.joah_16_18

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How to cite this article:
Valizadeh N. Treatment of refractory hemorrhagic cystitis after hematopoietic stem cell transplantation in a case of acute myeloid leukemia with mesenchymal stem cell infusion. J Appl Hematol 2018;9:79-80

How to cite this URL:
Valizadeh N. Treatment of refractory hemorrhagic cystitis after hematopoietic stem cell transplantation in a case of acute myeloid leukemia with mesenchymal stem cell infusion. J Appl Hematol [serial online] 2018 [cited 2018 Nov 14];9:79-80. Available from: http://www.jahjournal.org/text.asp?2018/9/3/79/244534

Dear Editor,

Mesenchymal stem cells (MSCs) have anti-inflammatory and tissue-repairing effects and have been used safely to heal therapy-induced tissue toxicity.[1],[2]

Here, we report safety and efficacy of MSC infusion in the treatment of Post hematopoietic stem cell transplantation (HSCT) hemorrhagic cystitis in a case of acute myeloid leukemia (AML).

An 18-year-old male with AML admitted for haploidentical allogeneic HSCT. After conditioning with busulfan, cyclophosphamide, and antithymocyte globulin, he was underwent HSCT. On days 3 and 4 after HSCT, he received cyclophosphamide again. On day 18 after HSCT, he developed hematuria and hemorrhagic cystitis. Urinary catheterization was done, and continuous bladder irrigation and hydration were initiated. He developed neutropenic fever and cytomegalovirus infection, and thus, broad-spectrum antibiotics and ganciclovir were administered. Hemorrhagic cystitis was prolonged, and he underwent intravesical administration of hyaluronic acid weekly for 2 times. After the last course, he developed bilateral hydronephrosis with rising in serum creatinine level and underwent suprapubic cystostomy. Bladder irrigation was continued, but hematuria did not resolve. We decided to infuse MSCs from bone marrow source due to their anti-inflammatory and tissue-repairing properties. The Hematology-Oncology and Stem Cell Transplantation Research Center which this work was done has ethical approval for the use of MSCs in patients. MSCs (65 × 106 cell dose) were infused without any toxicity. After 48 h, we saw a dramatic improvement in hematuria. After 2 weeks, he received another MSC (62 × 106 cell dose) infusion and gross hematuria disappeared during a week. He was discharged about 6 months after HSCT. In the follow-up visits in the clinic, he did not have any macroscopic hematuria.

In this case of AML with prolonged hemorrhagic cystitis after allogeneic HSCT for AML, we found rapid recovery of hemorrhagic cystitis after MSC infusion without any toxicity.

MSCs are multipotent cells derived from stromal tissue. They have capacity to differentiate into different types of cells depending on the tissue matrix and actively contribute to their milieu by secreting soluble products.[1]

MSCs have low immunogenicity and immunomodulatory effects. Some possible clinical indications for MSCs include acute and chronic graft-versus-host disease (GVHD) and some degenerative tissue repair.[2]

MSCs have been used for the treatment of hemorrhagic cystitis following stem cell transplantation due to their repairing properties.[3],[4],[5]

Ringdén et al. used MSCs to heal therapy-induced tissue toxicity following allogeneic HSCT in 10 patients of which seven had hemorrhagic cystitis, two had pneumomediastinum, and one had perforated colon and peritonitis. The median cell dose was 1.0 (range 0.7–2) × 106/kg. In five patients, the severe hemorrhagic cystitis resolved after MSC infusion. Pneumo mediastinum was resolved after MSC infusions in two patients and healing was occurred by MSC infusion in the patient with steroid-resistant GVHD of gut that experienced perforated diverticulitis and peritonitis in this study.[4]

Wang et al. analyzed the efficacy and safety of MSC infusions in 7 of 33 patients with severe and late-onset hemorrhagic cystitis after allogeneic HSCT. Median dose of MSC was 1.0 (0.8–1.6) × 106/kg. Five of seven patients responded to treatment.[5]

Literature review showed efficacy of MSC infusion for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation (ASCT).

Here, we report MSC infusion in a case of AML with prolonged, refractory hemorrhagic cystitis after haploidentical HSCT. In haploidentical HSCT, cyclophosphamide is included not only in conditioning regimen but also for GVHD prophylaxis, and then, probability of severe forms of hemorrhagic cystitis is high. This case with gross hematuria received initially supportive care including urinary catheterization, continuous bladder irrigation, and hydration and did not respond, and hence, we administered intravesical hyaluronic acid weekly for 2 times but hematuria did not resolve and complicated with bilateral hydronephrosis and then suprapubic cystostomy was performed. Because of persistent hematuria, we decided to infuse MSCs resulting in dramatic improvement in hematuria after 48 h. After 2 weeks, he received the second course of MSC infusion and gross hematuria has disappeared completely during a week and he was discharged home after 6 months of hospitalization.

Prior studies showed safety and efficacy of MSC infusion in 0.8–2 × 106/kg cell dose[4],[5] for the treatment of hemorrhagic cystitis after HSCT. In this case, we saw safety and efficacy of repeated infusions of MSCs (62–65 × 106 cell dose in 2-week interval) for the treatment of hemorrhagic cystitis after haploidentical HSCT.

We recommend earlier administration of MSC infusion in severe forms of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation for decrease in morbidity, duration of hospitalization, and need to blood product transfusion.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

We would like to thank Soheila Khalilvand, the head nurse and the all stuff of bone marrow transplantation (BMT 4) ward, Dr. Kamran Alimoghaddam, the chair of Hematology-Oncology and Stem Cell Transplantation Research Center, Dr. Ardeshir Ghavamzadeh, the director of Hematology-Oncology and Stem Cell Transplantation Institute who recommended the use of MSCs infusion for this case with hemorrhagic cystitis, and Dr. Mohsen Nikbakht, PhD of Medical biotechnology, a faculty member in the Hematology, Oncology and Stem Cell Transplantation Research Center who cultured and prepared MSCs.

 
  References Top

1.
Dimarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Front Immunol 2013;4:201.  Back to cited text no. 1
    
2.
Ringden O. Immunomodulatory effects of mesenchymal stem cells and use in allogeneic hematopoietic stem cell transplantation. Cell J (Yakhteh) 2013;15 Suppl 1:15.  Back to cited text no. 2
    
3.
Jia R, Yang XF, Lu Y. Treatment of hemorrhagic cystitis following stem cell transplantation with umbilical cord-mesenchymal stem cells in 8 children. Zhongguo Dang Dai Er Ke Za Zhi 2012;14:554-7.  Back to cited text no. 3
    
4.
Ringdén O, Uzunel M, Sundberg B, Lönnies L, Nava S, Gustafsson J, et al. Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum and perforated colon. Leukemia 2007;21:2271-6.  Back to cited text no. 4
    
5.
Wang Y, Chen F, Gu B, Chen G, Chang H, Wu D, et al. Mesenchymal stromal cells as an adjuvant treatment for severe late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Acta Haematol 2015;133:72-7.  Back to cited text no. 5
    




 

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