scholarly journals Risk Factors of BK Virus Cystitis in Haematopoietic Stem Cell Transplantation-a Retrospective Monocentric Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3361-3361
Author(s):  
Eléonore Kaphan ◽  
Raphaele Germi ◽  
Martin Carre ◽  
Claude-Eric Bulabois ◽  
Sebastien Bailly ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cells ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Clinical Symptoms ◽  
Bk Virus ◽  
Post Transplantation ◽  
Peripheral Stem Cells

Abstract Background: BK virus (BKV) is a human polyomavirus. Reactivation occurs during deep immunosuppression as in hematopoietic stem cell transplantation (HSCT) and renal transplantation, leading to hemorrhagic cystitis (HC) and nephropathy respectively. In HSCT, systematic PCR for BKV in urine is positive for 50 to 100% of patients (pts), but only 5 to 40% develop a BKV HC. Thus, BKV PCR is usefull to confirm a diagnostic of BKV HC but not to predict its occurrence. Several risk factors to develop BKV HC have been studied, especially mismatched HLA and haploidentical HSCT. Objectives: The aim of this retrospective study was to ascertain the risk factors to develop BKV HC. Methods: A retrospective study was performed by considering data from Grenoble University Hospital in the national retrospective register ProMISe, from the SFGM-TC. The period of the study covered from January 2014 to January 2018. PCR BKV in urine was performed when pts presented hematuria grade 2 or higher with clinical symptoms of cystitis. Viral nucleic acid was extracted from the urine samples with the EasyMag platform (Biomérieux) and the qPCR with BK Virus R-GENE®kit (ARGENE) on a LightCycler 480 (ROCHE). BKV HC is defined by the association of clinical symptoms of cystitis, haematuria grade 2 or higher and a BKV viruria >7 log10 copies/mL. Univariable and multivariable logistic regression model were used to identify risk factors for BK cystitis. Results: 188 HSCT were performed during the study period. After exclusion of 13 pts for early mortality (<30 days) and 4 for engraftment failure, 171 pts were finally considered for analysis, from whom 43 (25.1%) developed a BKV HC. The median age of patients presenting with BKV HC was 44 years (23-62) and males represented 67.4 %. Acute leukemia was the most common indication of HSCT (74.4%), followed by myelodysplastic syndromes (9.3%), lymphoma (6.9%), myeloproliferative neoplasms (4.7%) and aplastic anemia (4.7%). In most cases, pts were not in complete response at transplant (51.2%). First autologous or allogenic HSCT had previously been performed for 30.2% of pts. The majority of pts had a transplant with peripheral stem cells as graft source (76.6%), and had a transplant with mismatched HLA (9/10, n=9, 20.9%) or haploidentical donors (n=13, 30.2%). Twenty-nine pts (67.4%) received reduced-intensity conditioning and twenty-two pts (51.2%) received cyclophosphamide post allograft to prevent Graft Versus Host Disease (GVHD). BKV HC prophylaxis relied on hyperhydratation and mesna during the conditioning regimen. The median time to develop HC was 42 days post-transplantation (30-55) mainly with a grade 3 HC (53.5%). The median viruria was 9 log (9-10). Cidofovir was administered as curative treatment to 20 pts (46.5%) and 25 pts (58%) needed bladder irrigation and forced diuresis. The median level of platelets at diagnosis was 58 G/L (29-123). At diagnosis of BKV HC, 32.6% of pts presented a bacterial cystitis and 62.8% an acute renal failure. Allogenic HSCT was complicated by an acute GVHD in 88.4% of pts and 69.8% were treated by corticosteroids. CMV reactivation was observed in 39.5% of pts, and HHV6 in 18.6%. In univariate analysis, post-transplant cyclophosphamide (p<0.001), age below 40 years (p<0.001), history of previous auto or allograft (p=0.007), allograft with mismatched HLA (9/10 and haploidentical) (p<0.001), use of peripheral stem cells (p=0.047), engraftment of platelets >100 days (p=0.016), acute GVHD (p=0.007), corticotherapy (p<0.001), co-infection by HHV6 (p=0.006), association to bacterial cystitis (p=0.002), acute renal failure (p=0.009) and platelets below 50G/L (p<0.001) were significantly associated with increased risk of BKV HC. After logistic regression, the risk factors associated with BKV HC were reduced to: exposition post-transplantation to cyclophosphamide (OR 4.1, 1.5-10.7, p=0.004), age below 40 years (OR 4.1, 1.6-10.9, p=0.004), corticosteroids therapy (OR 3.9, 1.6-9.5, p=0.033), acute renal failure (OR 3.8, 1.5-9.6, p=0.0056), bacterial cystitis (OR 3.3, 1.2-8.7, p=0.0175), and platelets below 50G/L (OR 3.8, 1.382-10.486, p=0.097). Conclusion: BKV HC was observed in 25.1% of patients. Exposition to cyclophosphamide, young age, corticosteroids therapy and bacterial cystitis are potential risk factors of BKV HC. Surprisingly, young age was not expected as risk factor. Disclosures No relevant conflicts of interest to declare.

Hyperlipidemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3457-3457
Author(s):  
Bradley W Blaser ◽  
Haesook Kim ◽  
Jorge Plutzky ◽  
Edwin Alyea ◽  
Vincent Ho ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Cardiovascular Risk ◽  
Total Cholesterol ◽  
Acute Gvhd ◽  
Univariable Analysis ◽  
Post Transplantation ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis

Abstract Abstract 3457 An increased incidence of cardiovascular complications has been documented in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several cross-sectional retrospective studies have described the incidence of cardiovascular risk factors such as lipid elevation late after allo-HSCT, but none have yet considered changes in cholesterol and triglyceride levels within the first two years. We performed a retrospective analysis of all patients who underwent allo-HSCT at the Dana-Farber Cancer Institute from 1998 to 2008 and who survived more than 100 days. Of these, 761 had at least one measurement of total cholesterol or triglyceride level from day 30 to 2 years following transplantation. The decision to check lipid levels was made at the discretion of the outpatient physician. Among the patients with measured cholesterol or triglyceride levels, median age at transplantation was 49 (range 17–73), 58% received grafts from unrelated donors, and 55% received myeloablative conditioning. Greater than 95% of patients received tacrolimus based GVHD prophylaxis. Sirolimus was part of GVHD prophylaxis for 50%. The cumulative incidence of grades 2–4 acute GVHD was 27%. Seventy-three percent of patients were hypercholesterolemic (total cholesterol >=200 mg/dL) and 87% were hypertriglyceridemic (triglycerides >=150 mg/dL) within the study time period post-transplantation. In contrast, only 32% of patients were hypercholesterolemic and 59% were hypertriglyceridemic in the ninety days prior to transplantation. Median time to detection of first elevated total cholesterol and triglycerides was 116 and 108 days after transplantation, respectively. Among all patients, median change between peak pre- and post-transplantation levels was 62 mg/dL for total cholesterol and 109 mg/dL for triglycerides. Median peak total cholesterol and triglyceride levels after transplantation were 241 mg/dL and 275 mg/dL, respectively. In univariable analysis (see Table), myeloablative conditioning, age, or diagnosis did not affect development of hypercholesterolemia or hypertriglyceridemia. However, sirolimus prophylaxis did correlate with hypertriglyceridemia (OR 1.91, 95% CI 1.23–2.95, P = 0.004), but not hypercholesterolemia (OR 1.21 95% CI 0.87–1.67). The development of grade 2–4 acute GVHD was associated with both hypercholesterolemia (OR 1.7 95% CI 1.2–2.6, P = 0.007) and hypertriglyceridemia (OR 2.2 95% CI 1.2–3.9, P = 0.007). A search of the outpatient prescription records of all 761 patients with lipid measurements revealed that HMG-CoA reductase inhibitors (statins) were prescribed for 35% of patients after transplantation. These data are the first to document the incidence of hyperlipidemia in the first two years after allo-transplantation when most patients remain under the care of the transplantation physician and lipid-lowering therapy may be under-utilized. Hyperlipidemia is common in these patients, particularly in those with acute GVHD. Whether the hyperlipidemia observed early after transplantation is associated with adverse cardiovascular events is currently under investigation. Given the cardiovascular risk associated with hyperlipidemia, the tolerability of statins, and the suggestion that statins may have favorable immunomodulatory effects as seen in solid organ transplantation, further prospective evaluation of lipid abnormalities and their treatment seems well warranted. Table 1. Univariable Analysis of Risk Factors for Post-Transplantation Hyperlipidemia Cholesterol >=200 mg/dL Triglyceride >= 150 mg/dL OR 95% CI P OR 95% CI P Age >= 50 1.29 0.93 – 1.79 0.12 0.85 0.55 – 1.30 0.45 Myeloid neoplasm 0.97 0.70 – 1.35 0.84 1.10 0.71 – 1.70 0.66 Sirolimus prophylaxis 1.21 0.87 – 1.67 0.25 1.91 1.23 – 2.95 0.004 Myeloablative conditioning 0.94 0.68 – 1.29 0.68 1.05 0.68 – 1.62 0.81 Grade 2–4 acute GVHD 1.7 1.2 – 2.6 0.007 2.2 1.2 – 3.9 0.007 Disclosures: No relevant conflicts of interest to declare.

BKV Disease during the First 100 Days after Allogeneic Hematopoietic Stem Cell Transplantation - Results of a Screening Program and Retrospective Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3403-3403 ◽  
Author(s):  
Philip Posdzich ◽  
Marco Herling ◽  
Silke Leitzke ◽  
Laura Hamacher ◽  
Veronica Di Christanziano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Acute Gvhd ◽  
Screening Program ◽  
Hemorrhagic Cystitis ◽  
Bk Virus ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract BK virus (BKV) is a human polyomavirus often acquired in childhood which can reactivate after allogeneic hematopoietic stem cell transplantation (HSCT). BKV reactivation may present indifferent ways from asymptomatic viruria to hemorrhagic cystitis or nephritis. Methods We evaluated 377 patients (159 male, 218 female, median age 52 years) who were transplanted at the University of Cologne between 2008 and 2013 to assess incidence and risk factors for BKV disease after allogeneic HSCT. All 377 patients were screened routinely for BKV in urine and serum. We defined BKV disease as hemorrhagic cystitis (HC) with BK virus >100.000/ml in urine, hematuria (2+ until 4+ in dipstick test) and negative urine microbiology. To find risk factors for BKV disease, the impact of conditioning, CMV status, graft-versus-host disease (GvHD), underlying disease, donor mismatch and stem cell source was analyzed. Results According to our definition, BKV cystitis occurred in 37 of 377 patients (9,8%) in the first 100 days after HSCT. In 14 of these 37 patients (37,8%) BKV was also detected in serum. BKV was detected in the urine of 194 patients (51,4%) at any time during the screening program, but only 19,1% developed hemorrhagic cystitis. Sixty-two percent of patients suffering from BKV disease were female, 37,8% male. BKV disease was diagnosed in 13,3% of patients not in complete remission as opposed to 5,4 % of patients in complete remission prior to conditioning (p = 0,010). BKV disease was less common in matched related or unrelated (7,7%) as compared to mismatched or haplo-identical donors (16,7%; p=0,012). Acute GvHD grade II to IV was described in 122 of 377 patients (32,36%). Of them, 13,9% suffered from BKV cystitis in comparison to 7,84% with no or grade I acute GvHD, which did not reach statistical significance. We could not detect any correlation between BKV disease and administration of cyclophosphamide, total body irradiation or anti-thymocyte globuline. There was no association with the graft source. BKV disease was no predictor for non-relapse mortality, overall and relapse-free survival. Conclusion BKV disease is a common complication after allogeneic HSCT. The virus can be found in the urine of about half of our transplanted patients, but only a small proportion developed an HC. State of remission before conditioning and donor mismatch are associated with the development of BKV disease, which had no impact on survival in our cohort. Disclosures Scheid: Novartis: Other: funding outside this work; Celgene: Other: funding outside this work; Janssen: Other: funding outside this work.

scholarly journals Post Transplantation Fludarabine and Cyclophosphamide Selected and Promoted Low Dose of Unrelated UCB Implanation in Combined Transplantation of Haploid and UCB Stem Cells in Childhood Leukemia: 40 Cases Report in Double Center

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2875-2875
Author(s):  
Yuhua Xiao ◽  
Sixi Liu ◽  
Chunfu Li ◽  
Wing Hang Leung ◽  
Xiaoqin Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Low Dose ◽  
Acute Gvhd ◽  
Implantation Rate ◽  
Virus Reactivation ◽  
Post Transplantation ◽  
Platelet Recovery ◽  
Cd34 Cells ◽  
Risk Of Relapse

Abstract Background: For patients without HLA matched donor, Haploid stem cell transplantation with PTCY method has relatively higher risk of relapse and graft-versus-host disease (GVHD). Umbilical cord blood (UCB) is readily available and has helped expand the donor pool to almost all patients requiring a transplant. Meanwhile UCB transplant improves EFS in leukaemia with lower risk of relapse and GVHD. However, the clinical application of UCB is limited due to lower implantation rate because of its low dose of stem cells than other sources of hematopoietic stem cells (HSC). Aims: This study is to explore the feasibility and efficacy of post-transplantation fludarabine and cyclophosphamide to select and promote the unrelated UCB to engraft in combined transplantation of haploid and UCB stem cells for the treatment of childhood and adolescent leukemia. Methods: Total 40 children and adolescent patients with leukemia in Nanfang Hospital and Shenzhen Children's Hospital enrolled this study from Sept.2019 to Jun.2021. These patients were diagnosed as AML (20 HR, 5 IR, 2 relapsed AML), ALL (5 HR, 2 IR, 2 relapsed ALL), AL (1), JMML (2), MDS (1) and BPDCN (1) with a median age of 80 months (range 7 months -17 years). The biggest body weight reached to 77kg. The haploid stem cell was 5/10-9/10 mismatched and UCB was selected as 6/10-10/10 HLA matched or mismatched. The condition regimen was busulfan+fludarabine+CY+Ara-C. Haploid PBSC was infused in day0. All received PTCy 50 mg/kg and post-transplantation fludarabine 40mg/m 2 on days 3 and 4 along with tacrolimus or cyclosporine and mycophenolate mofetil for prophylaxis of acute GVHD. UCB was infused in day6. A median of haploid stem cells of 20.00×10 8/kg (13.00-32.10) of mononuclear cells was infused while a median of UCB cells of 4.32×10 7/kg (1.48-22.78) of total nucleated cells was infused. A median of CD34+ cells of haploid stem cells 13.00×10 6/kg (1.51-32.00) was infused while a median of CD34+ cells of UCB cells 1.74×10 5/kg (0.26-4.80) was infused. The survival rate, umbilical cord blood implantation rate, hematopoietic recovery and the rate of transplant-related complications were analyzed. Results: At a median follow-up of 8 months (range 1-21 months), there were 2/40（5%）cases of transplant-related death. All surviving patients were leukemia free, with one-year overall survival rate 92.8±5.0%. Among these patients, 37/40(92.5%, 95%CI: 84.0%~100.0%) of patients achieved complete chimerism of unrelated UCB cells and 3/40(7.5%, 95%CI: -1.0%~16.0%) of patients achieved mixed chimerism of unrelated UCB cells and haploid cells. In these transpltantation, the CD34+ cell dose of UCB less than 1.0×10 5/kg accounted for 10/40 (25.0%), and less than 2.0×10 5/kg accounted for 23/40 (57.5%).Two patients had primary poor graft function. Neutrophil reconstitution was achieved in 39/40 patients with a median time of 29 days (range 17 - 44 days) without G-CSF after transplantation. Platelet recovery was achieved in 37/40 patients with a median time of 37 days (range 8-92 days). There was a significant linear relationship between platelet recovery time and the dose of total nucleated cells and CD34+ cells in UCB（r=-0.368, P=0.025; r=-0.355, P=0.031）.The incidence of gradeⅠand gradeⅡGVHD was 32.5%（95%CI:17.3%-47.7%）and 42.5%（95%CI:26.5%-58.5%）, respectively. There was no grade Ⅲ-Ⅳ aGVHD and only 1/40(2.5%) case of extensive chronic GVHD. The incidence of chronic limited GVHD was 22.5% (95%CI: 9.0%-36.0%). Twenty-four of 40(60.0%, 95%CI:44.1%-75.9%) patients experienced clinically significant CMV reactivations or infections. One of 40（2.5%, 95%CI: -2.6%-7.6%）patients experienced EB virus reactivation. Two of 40（5.0%, 95%CI: -2.1%-12.1%）patients experienced human herpesvirus 6 infection. Thirteen of 40（32.5%, 95%CI: 17.3%-47.7%）patients presented with hemorrhagic cystitis. Conclusion: In our primary clinical study, post-transplantation fludarabine and cyclophosphamide could effectively select and promote the unrelated UCB to implant rather than haploid cells in combined transplantation of haploid and UCB stem cells even if the CD34+ cells of UCB less than 1.0×10 5/kg. Although acute GVHD was common but just milder degree and with lower incidence of EB virus reactivation. This new strategy has the potential to promote the wilder clinical use of unrelated UCB in the treatment of leukemia. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Relapse risk factors during allogeneic stem cell transplantation in children, adolescents and young adults with acute lymphoblastic leukemia

2021 ◽  
Vol 18 (3) ◽  
pp. 375-384
Author(s):  
D. V. Prudnikau ◽  
N. P. Kirsanava ◽  
Yu. E. Mareika ◽  
N. V. Minakovskaya ◽  
O. V. Aleinikova
Keyword(s):  
Risk Factors ◽  
Stem Cells ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Disease Relapse ◽  
Post Transplantation ◽  
Graft Versus Host ◽  
Hsc Transplantation

More than 20–25 % of patients with acute leukemia underwent transplantation of HSC from HLA-identical sibling or unrelated donor had relapse.Therefore, the purpose of this study was to evaluate the influence of different factors on the risk of post-transplantation relapse in children and teenagers with acute lymphoblastic leukemia (ALL).The gender, the age of a donor at the time of transplantation; the gender, the age of a recipient at the time of transplantation; the type, the number of relapses of previous HSCTs; the type of conditioning; the type of transplantation; the source of stem cells; transplant parameters; the acute (aGVHD) and chronic (cGVHD) graft-versus-host disease or its absence; the KIRalloreactivity of donor NK cells were estimated as risk factors for the disease relapse in our study.We established that the recipient’s age of less than 4 years at the time of transplantation (p = 0.0042); the time of relapse (very early and early) (p = 0.0047); the absence of aGVHD (p = 0.0183) or cGVHD (p = 0.0384) have been the important factors for the disease relapse of patients with ALL after allogeneic HSC transplantation.

Maximal initiative dose of simvastatin causing acute renal failure through rhabdomyolysis: Risk factors, pathomechanism and therapy related to a case

2009 ◽  
Vol 3 (1) ◽  
pp. 139-146
Author(s):  
Daniel Deme ◽  
Aref Al-Hadad ◽  
Tünde Varga ◽  
Erika Szántó ◽  
Katalin Sándor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Failure ◽  
Acute Renal Failure

scholarly journals Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation

2021 ◽  
Vol 9 (2) ◽  
pp. e001818 ◽  
Author(s):  
Chantal Saberian ◽  
Noha Abdel-Wahab ◽  
Ala Abudayyeh ◽  
Hind Rafei ◽  
Jacinth Joseph ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Checkpoint Inhibitors ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Acute Myeloid

BackgroundImmune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.MethodsA retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.ResultsFour patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2–4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).ConclusionsICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

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