scholarly journals Risk Factors and Different Therapeutic Patterns of Late-Onset Hemorrhagic Cystitis after Haploidentical Allogeneic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3261-3261
Author(s):  
Qiaozhu Zeng ◽  
Yun He ◽  
Xiaolu Zhu ◽  
Xiao Liu ◽  
Haixia Fu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Late Onset ◽  
Hemorrhagic Cystitis ◽  
Hematopoietic Stem ◽  
Before And After

Introduction Late-onset hemorrhagic cystitis (LOHC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with an incidence ranging from 6.5% to 70% and leads to prolonged hospitalization and even death (Silva Lde P et al, Haematologica, 2010; LAM et al, Transpl Infect Dis, 2017). The pathogenesis of LOHC remains obscure, but in our previous study, viral infections and acute graft-versus-host disease (aGVHD) have frequently been shown to be associated with its development (Han et al., Am. J. Hematol, 2014). Therapeutic strategies for LOHC are still not standardized due to the complicated clinical background and given the paradoxical phenomenon that immunosuppressive agents, such as steroids, are necessary for aGVHD but cause an immunosuppressive state. We aimed to investigate the incidence, risk factors and outcomes of LOHC after allogeneic stem cell transplantation. Additionally, for the first time, we propose four therapeutic patterns and their impact on prognosis of LOHC to aid in clinical decision making. Methods This retrospective, nested, case-control study reviewed data from 2158 patients who received allo-HSCT from January 2014 to December 2018. In total, 364 (16.87%) patients were diagnosed with LOHC. Individual matching was performed by randomly selecting 3 controls from the same cohort for each identified LOHC patient according to the time of allo-HSCT. Standard basic measures included hyperhydration, forced diuresis, insertion of a vesical catheter for intermittent or continuous bladder irrigation and evacuation of clots. Patients with grade III-IV LOHC were divided into four groups according to immunosuppressant use (steroid, MMF and Basiliximab) 1 week before and after the onset of LOHC: an intensified-intensified (I-I) group, intensified-not intensified (I-N) group, not intensified-intensified (N-I) group and not intensified-not intensified (N-N) group. "Intensified" was defined as an increase in any immunosuppressant, and "not intensified" was defined as maintenance or tapering of all immunosuppressants. Data concerning the baseline characteristics, incidence, treatment patterns and outcomes were recorded. Results In total, 364 patients developed LOHC at a median of 29 days (range, 23-37.75 days), with a cumulative incidence of 16.87%. AML (HR =0.493 95% CI, 0.244-0.997; p=0.049), AA (HR =0.444, 95% CI,0.18-1.096; p=0.078), HLA match(HR =0.149, 95% CI, 0.036-0.616; p=0.009), days to platelet engraftment(HR =1.023, 95% CI, 0.998-1.049;p=0.069)and CMV viremia (HR =2.365, 95% CI, 1.179,4.733;p=0.015)were associated with LOHC. Only HLA match (HR =0.111, 95% CI, 0.014-0.878; p=0.037)remained significant in the multivariate analysis. 6.5%, 12.9%, 48.39% and 32.26% patients with III-IV LOHC were divided into I-I, I-N, N-I and N-N groups, respectively. There were no significant differences in overall survival (p=0.05) and the incidence of CMV viremia (p=0.187) among the four groups. The incidence of relapse (p=0.007) and the incidence of aGVHD (p=0.01) was highest in the I-I group, followed by the N-I, I-N and N-N groups. 50% of the patients in N-I group showed the improvement of LOHC, which is significantly highest among the four groups(p=0.000). However, no statistical significance was found regarding the CMV viremia turning shade or the improvement of aGVHD. Non-relapse mortality (NRM) was observed in 25% of patients without resolution of LOHC. NRM was 0% among patients without intensified immunosuppression but was 25%, 0% and 50% among those with intensified immunosuppression before LOHC, after LOHC and before and after LOHC, respectively. Conclusion The independent risk factors for LOHC after allo-HSCT were HLA mismatch. Avoiding intensified immunosuppression that damages endothelium or reactivates the related virus may improve transplant outcome. The N-N pattern could reduce the incidence of CMV viremia or aGVHD in the LOHC patients, and the N-I pattern might be more promising as a therapeutic strategy for LOHC. Disclosures No relevant conflicts of interest to declare. Disclosures No relevant conflicts of interest to declare.

scholarly journals BK virus-associated hemorrhagıc cystitis in patients wıth allogeneıc hematopoıetıc cell transplantation: report of three cases

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Duygu Mert ◽  
Hikmetullah Batgi ◽  
Alparslan Merdin ◽  
Sabahat Çeken ◽  
Mehmet Sinan Dal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hemorrhagic Cystitis ◽  
Immunosuppressive Treatment ◽  
Active Agent ◽  
Bk Virus ◽  
Cell Transplant ◽  
Hematopoietic Stem

BK virus is a human polyoma virus. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine. The reduction of immunosuppression is effective in the treatment of BK virus infection. There are also several agents with anti-BK virus activity. Cidofovir is an active agent against a variety of DNA viruses including poliomyoma viruses and it is a cytosine nucleotide analogue. Intravenous immunoglobulin IgG (IVIG) also includes antibodies against BK and JC (John Cunningham) viruses. Hereby, we report three cases of hemorrhagic cystitis. Hemorrhagic cystitis developed in all these three cases of allogeneic stem cell transplantation due to acute myeloid leukemia (AML). BK virus were detected as the cause of hemorrhagic cystitis in these patients. Irrigation of the bladder was performed. Then levofloxacin 1×750 mg intravenous and IVIG 0.5 gr/kg were started. But the hematuria did not decreased. In the first case, treatment with leflunomide was started, but patient died due to refractory AML and severe graft-versus-host disease after 4th day of leflunamide and levofloxacin treatments. Cidofovir treatment and the reduction of immunosuppressive treatment decreased the BK virus load and resulted symptomatic improvement in the second case. Initiation of cidofovir was planned in the third case. Administration of cidofovir together with the reduction of immunosuppression in the treatment of hemorrhagic cystitis associated with BK virus in allogeneic stem cell transplant recipients could be a good option.

Mesenchymal Stromal Cells as an Adjuvant Treatment for Severe Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

2014 ◽  
Vol 133 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Ying Wang ◽  
Feng Chen ◽  
Bing Gu ◽  
Guanghua Chen ◽  
Huirong Chang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Stromal Cells ◽  
Late Onset ◽  
Hemorrhagic Cystitis ◽  
Gross Hematuria ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

The management of severe late-onset hemorrhagic cystitis (LO-HC) after allogeneic hematopoietic stem cell transplantation (HSCT) is still challenging. Because mesenchymal stromal cells (MSCs) possess anti-inflammatory and tissue repair-promoting properties, we retrospectively analyzed the efficacy and safety of MSC infusions in 7 of 33 patients with severe LO-HC after allogeneic HSCT. During treatment, each patient received at least one MSC infusion of Wharton's jelly derived from the umbilical cord of a third-party donor. In 6 patients, MSC treatment was initiated within 3 days of gross hematuria onset, while the 7th patient received an infusion 40 days later. The median dose was 1.0 (0.8-1.6) × 106/kg. Five of 7 patients responded to treatment. Notably, gross hematuria promptly disappeared in 3 patients after 1 infusion, with a time to remission not seen in patients without MSC infusion. Two patients showed no response even after several infusions. No acute or late complications were recorded. Our findings indicate that MSC transfusion might be a feasible and safe supplemental therapy for patients with severe LO-HC after allogeneic HSCT.

The Therapeutic Effect of Lenalidomide Is Enhanced After Allogeneic Stem Cell Transplantation: Results of a Case-Control Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1996-1996
Author(s):  
Vittorio Montefusco ◽  
Francesco Spina ◽  
Elena Zamagni ◽  
Giorgia Saporiti ◽  
Francesca Patriarca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Matching Criteria

Abstract Abstract 1996 Introduction. Lenalidomide (Len) is a highly effective drug against multiple myeloma (MM). It acts through several mechanisms, such as a direct cytotoxic effect, anti-angiogenesis, microenvironment modifications, and immunomodulation. The latter property is particularly interesting in the allogeneic hematopoietic stem cell transplantation (Allo-HSCT) setting, since Len may interact favourably with the graft-versus-myeloma (GVM) effect. Preliminary results from retrospective studies on heterogeneous patient populations have suggested that Len is more effective when given after Allo-HSCT. In order to verify this observation, we have conducted a case-matched analysis comparing Len after autologous stem cell transplantation (Auto-HSCT) vs. Len after Allo-HSCT. The hypothesis is that Len may be more potent when administered after Allo-HSCT. Methods and results. In this retrospective study the matching criteria was represented by the number of treatment lines received before Len. In an attempt to uniform the treatment regimens, an intra-centre matching was recommended. To April 2011 we collected data from 39 patients in each group. Baseline characteristics between Auto and Allo patients were similar, except for age at diagnosis (53 years, range 39–70, in Auto patients; 47 years, range 29 – 61, in Allo patients). The median number of previous lines of treatment was 3 (range 1–6 ) for both groups. Twenty-one out 39 (54%) Allo patients received Allo-HSCT as second or subsequent line of therapy. Thirty-two (82%) Auto and 35 (90%) Allo patients received bortezomib in previous lines. Similarly, 34 (87%) Auto and 12 (54%) Allo patients were previously treated with thalidomide. Len was always combined with dexamethasone. Median time between Auto-HSCT and Len start was 38 months (range 7–159), and for Allo-HSCT 29 months (range 4–215). Best responses were for Auto and Allo patients as follows: 5 vs. 4 CR, 6 vs. 8 VGPR, 11 vs. 12 PR, 6 vs. 8 SD, 11 vs. 7 PD. Time from Len start to the best response was 4 months for both groups. With a median follow-up of 11.5 months (range 1–39), 1 year and 2 year progression-free survival were 41% and 6% for Auto patients, and 52% and 44% for Allo patients (p=0.03), respectively. Two years overall survival was 48% for Auto and 75% for Allo patients (p=0.03). Similar results were observed regardless of previous thalidomide treatment. No unexpected toxicities were reported. Two (10%) patients had worsening of a pre-existent extensive chronic GVHD. Discussion and Conclusion. The comparison between Auto and Allo patients has shown a benefit in terms of PFS and OS in favor of Len administered after AlloHSCT. This observation supports the hypothesis that Len is synergistic with the GVM effect. Since Len has a potent immunomodulatory effect, this can raise concerns about its use after AlloHSCT. A Dutch prospective study showed that the early administration of Len 10 mg daily after non-myeloablative Allo-HSCT induces late onset acute GVHD in a substantial proportion of patients, causing the premature discontinuation of the study. On the contrary, our retrospective study has shown that a later administration is feasible and safe, without an excess of GVHD, suggesting that a more mature immune system can better tolerate Len. Moreover, since in all cases dexamethasone was given in combination with Len, its immunosuppressive effect may have harnessed the Len-induced immune activation. In conclusion our study suggests that Len is particularly active after AlloHSCT, still retaining a favorable toxicity profile. Disclosures: No relevant conflicts of interest to declare.

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