scholarly journals Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation

2002 ◽  
Vol 29 (11) ◽  
pp. 903-906 ◽  
Author(s):  
L Hambach ◽  
M Stadler ◽  
E Dammann ◽  
A Ganser ◽  
B Hertenstein
Keyword(s):  
Stem Cell ◽  
Mycophenolate Mofetil ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cmv Infection ◽  
Increased Risk

Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 epression in monocyte-derived dendritic cells

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 534-536 ◽  
Author(s):  
Markus Mezger ◽  
Michael Steffens ◽  
Melanie Beyer ◽  
Carolin Manger ◽  
Johannes Eberle ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Invasive Aspergillosis ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Serum Levels ◽  
Risk Haplotype ◽  
Nucleotide Polymorphisms ◽  
Increased Risk

Patients after allogeneic stem-cell transplantation (alloSCT) have an increased risk for invasive aspergillosis (IA). Here, recipients of an allograft with IA (n = 81) or without IA (n = 58) were screened for 84 single nucleotide polymorphisms in 18 immune relevant genes. We found 3 markers in chemokine (C-X-C motif) ligand 10 (CXCL10, 4q21, 11 101 C > T, P = .007; 1642 C < G, P = .003; −1101 A < G, P = .001) significantly associated with an increased risk of developing IA. Furthermore, immature dendritic cells (iDCs) exposed to Aspergillus fumigatus germlings showed markedly higher CXCL10 expression, if carrying the wild type genotype, compared with the “CGAG” high risk haplotype. In addition, serum from patients with proven/probable IA showed increased serum levels of CXCL10, compared with immunocompromised patients without IA. Thus, polymorphisms in CXCL10 determine chemokine secretion by iDCs upon exposure to A fumigatus and most likely thereby genetically determine the risk of IA after alloSCT.

scholarly journals Single step multiple genotyping by MALDI-TOF mass spectrometry, for evaluation of minor histocompatibility antigens in patients submitted to allogeneic stem cell transplantation from HLA-matched related and unrelated donor

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Federica Cattina ◽  
Simona Bernardi ◽  
Vilma Mantovani ◽  
Eleonora Toffoletti ◽  
Alessandra Santoro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Sibling Pairs ◽  
Graft Versus Host ◽  
Maldi Tof ◽  
Increased Risk

The outcome of patients underwent to allogeneic stem cell transplantation (allo- SCT) is closely related to graft versus host disease (GvHD) and graft versus leukemia (GvL) effects which can be mediated by mHAgs. 23 mHAgs have been identified and reported to be differently correlated with GVHD or GVL and the aim of this work was develop a method to genotype the mHAgs described so far. For this study we used MALDI-TOF iPLEX Gold Mass Array technology. We tested 46 donor/recipient matched pairs that underwent allo-SCT because of Philadelphia positive (Ph+) chronic myeloid leukemia (n=29) or Ph+ acute lymphoblastic leukemia (n=17). Our data show that sibling pairs had a lesser number of mHAgs mismatches compared to MUD pairs. Notably, donor/recipient genomic mismatch on DPH1 was correlated with an increased risk of acute GvHD and LB-ADIR-1R mismatch on graft versus host direction was correlated with a better RFS with no increase of GvHD risk. Our work provides a simple, accurate and highly automatable method for mHAgs genotyping and suggest the role of mHAgs in addressing the immune reaction between donor and host.

Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3286-3289
Author(s):  
Tobias Eckle ◽  
Lothar Prix ◽  
Gerhard Jahn ◽  
Thomas Klingebiel ◽  
Rupert Handgretinger ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Human Cytomegalovirus ◽  
Allogeneic Stem Cell Transplantation ◽  
Hcmv Infection ◽  
Antiviral Drug ◽  
Increased Risk

Three seropositive pediatric recipients of allogeneic stem cell transplantation out of a group of 42 patients receiving T-cell–depleted, unrelated transplants and 37 patients receiving T-cell–depleted, haploidentical transplants were monitored longitudinally for human cytomegalovirus (HCMV) infection and the emergence of antiviral drug resistance. Early in the posttransplant course, all 3 patients developed HCMV mutations conferring drug resistance to ganciclovir. One child additionally developed multidrug resistance to foscarnet and cidofovir, with mutations in the viral phosphotransferase gene (UL97) and the DNA-polymerase gene (UL54) being found. These data show that resistant HCMV infection does not necessarily correlate with a severe clinical outcome. The early detection of genotypic resistance up to 129 days before the emergence of phenotypic resistance and the dissociation of resistance patterns among different body sites emphasize the importance of genotypic analyses of different DNA specimens for an efficient antiviral therapy. T-cell–depleted children having transplantation might be at an increased risk for the development of drug resistance.

scholarly journals Evaluation of Murex CMV DNA Hybrid Capture Assay for Detection and Quantitation of Cytomegalovirus Infection in Patients following Allogeneic Stem Cell Transplantation

1998 ◽  
Vol 36 (5) ◽  
pp. 1333-1337 ◽  
Author(s):  
Holger Hebart ◽  
Daphne Gamer ◽  
Juergen Loeffler ◽  
Claudia Mueller ◽  
Christian Sinzger ◽  
...  
Keyword(s):  
Stem Cell ◽  
Blood Culture ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cmv Infection ◽  
Hybrid Capture ◽  
Capture Assay ◽  
Cmv Disease

Murex hybrid capture DNA assay (HCS) is a solution hybridization antibody capture assay for detection and quantitation of cytomegalovirus (CMV) DNA in leukocytes. To determine whether CMV HCS is sensitive enough to initiate and monitor antiviral therapy after allogeneic stem cell transplantation (SCT), 51 consecutive SCT recipients were prospectively screened for the appearance of CMV infection by HCS, PCR, and culture assays from blood samples. Preemptive antiviral therapy was initiated after the second positive PCR result in all patients, as previously reported, and HCS was not considered for clinical decision making. A total of 417 samples were analyzed. Of these, 21 samples were found to be positive by PCR and HCS, 88 samples were PCR positive but HCS negative, and 308 were negative by both assays. Concordance of results between PCR and HCS and between HCS and blood culture was observed in 78.9 and 95.9% of the samples assayed, respectively. PCR was found to be more sensitive than HCS, and HCS was more sensitive than the blood culture assay (P < 0.0001). Four patients with symptomatic CMV infection were PCR positive prior to the onset of CMV-related symptoms, whereas HCS detected CMV DNA in three patients prior to and one at onset of CMV disease. The numbers of genomes per milliliter of blood were higher in patients with symptomatic CMV infection than in those with asymptomatic CMV infection (P = 0.06). None of the HCS-negative patients developed CMV disease. Thus, all patients with CMV disease were correctly identified by HCS; however, the lower sensitivity limit of the HCS assay may still be insufficient to allow diagnosis of CMV infection early enough to prevent CMV disease in patients following allogeneic SCT.

Fatal Infectious Complications Developing Late after Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3239-3239
Author(s):  
Andreas Bjorklund ◽  
Johan Aschan ◽  
Olle Ringden ◽  
Jacek H. Winiarski ◽  
Per T. Ljungman
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Control Group ◽  
Cmv Infection ◽  
Respiratory Dysfunction

Abstract Background and aim: The procedure of allogeneic stem cell transplantation (SCT) has evolved during the past decades. Infectious complications are still a major problem contributing to the transplantation related mortality (TRM). The epidemiology and outcome of early infections after SCT are well described. However, less is known has about late infections after SCT. Thus, the aim of this study was to determine risk factors for fatal infections occurring later than 6 months after allogeneic SCT. Material and methods: Our study is based on 938 consecutive SCT patients transplanted 1976–2003 of whom 688 (73%) had survived for at least 6 months after SCT. A retrospective chart review was performed identifying 44 (6.4%) patients surviving for at least 6 months, having died from infection. Patients who had relapsed in their malignant disease were excluded. A control group of 176 patients (4 per case) was identified using relapse-free survival for at least 6 months and year of SCT as the matching criteria. Five controls were excluded leaving 171 patients in the control population. Risk factors for death from late infections were identified by logistic regression. Results: 29 patients (66%) developed their fatal infection within 18 months and 37 (84%) within 5 years after SCT. 37 patients (84%) had ongoing chronic graft versus host disease (GVHD) and 36/44 (82%) had ongoing immunosupression at the time of death. 57 controls had died after 6 months from SCT; 32 of 57 from relapse. Comparing patients and controls in univariate analyses, the mean age was 30.6 years in the cases and 26.5 years in the controls (p=.13). 22/44 (50%) cases had been transplanted from an unrelated or mismatched donor, compared to 57/171 (33%) controls, p=.053; and 35/44 (80%) cases had received a conditioning regimen including myeloablative dose of TBI compared to 113/171 (66%) in the control group, p&lt;.05). Regarding post-transplant complications 40/44 (91%) cases had experienced cGVHD compared with 101/171 (59%) controls, p&lt;.001. 21/44 (48%) cases had developed obstructive respiratory dysfunction compared with 46/171 (27%) controls, p=.01; and more cases (33/44; 75%) than controls (85/171; 50%;) had experienced CMV infection. In multivariate analysis chronic GVHD (OR 9.2; p&lt;.001), use of a mismatched or unrelated donor (OR 4.8; p&lt;.001), and having had a CMV reactivation (OR 8.3; p=.004) increased the risk. Age, acute GVHD, TBI or obstructive respiratory dysfunction had no significant impact on the risk for late fatal infection. Conclusion: Infections later than 6 months after SCT are important contributors to late TRM. Risk factors for late fatal infections include chronic GVHD, use of alternative donors and CMV infection.

Pre-Transplant Weight Loss and Total Serum Protein Predict Relapse Of Acute Myeloid Leukaemia After Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3314-3314
Author(s):  
Thomas Luft ◽  
Sascha Dietrich ◽  
Aleksandar Radujkovic ◽  
Friedrich Stölzel ◽  
Christine Falk ◽  
...  
Keyword(s):  
Weight Loss ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Total Serum ◽  
Metabolic Risk ◽  
Increased Risk ◽  
The Impact ◽  
Acute Myeloid

Abstract Background Although allogeneic stem cell transplantation (alloSCT) represents a curative chance for higher risk acute myeloid leukaemia (AML), relapse occurs in a significant proportion of patients. The impact of nutritional status on the outcome of allogeneic stem cell transplantation (alloSCT) is controversial. This study investigates the influence of pre-transplant body mass index (BMI), weight loss, and serological indicators of nutritional homeostasis on relapse and death of acute myeloid leukemia (AML) after alloSCT. Methods Pre-transplant weight loss and BMI along with serum levels of total serum protein (TSP), albumin, C-reactive protein, and leptin were collected retrospectively in a training cohort of 149 patients allografted for AML and correlated with clinical outcome. A metabolic risk score was established and tested in an independent validation cohort (n=167). Results Pre-transplant weight loss exceeding 2%, TSP lower than 70 g/L, and decreased leptin levels were associated with a significantly increased risk of relapse and death. In contrast, we did not observe a consistent pattern for the impact of nutritional indicators on non-relapse mortality (NRM). Multivariate analyses adjusting for age, cytogenetic risk, treatment line, blast count at alloSCT, donor, and conditioning confirmed weight loss and low TSP as independent risk factors of relapse and overall survival, but not of NRM. Weight loss >2% and low TSP were used to build a metabolic score for prediction of relapse risk and mortality. In multivariate analyses with clinical confounders, patients with both metabolic risk factors had a strongly increased risk of relapse (p=0.0003, HR 15.62, 95%CI 3.51-69.71) and death (p=0.002, HR 3.64, 95%CI 1.62-8.18) compared to patients without metabolic risk factor. The risk prediction of the metabolic score could be confirmed in the validation cohort (Figure 1). Conclusions Altered nutritional homeostasis prior to alloSCT predicts the risk of recurrence of AML after transplantation. Studies addressing pretransplant nutritional interventions in order to reduce AML relapse rates are warranted. Disclosures: No relevant conflicts of interest to declare.

Donor Genotypes For Interleukin-17A Gene Single Nucleotide Polymorphisms (SNPs) Allow Anticipation Of Complications After HLA-Identical Allogeneic Stem Cell Transplantation (allo-SCT)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4619-4619
Author(s):  
Elena Buces ◽  
Carolina Martínez-Laperche ◽  
Milagros González-Rivera ◽  
A Bosch-Vizcaya ◽  
Beatriz Martin-Antonio ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Nucleotide Polymorphisms ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hematopoietic Stem ◽  
Increased Risk

Introduction Graft versus host disease (GvHD) is the main cause of morbimortality after allogeneic stem cell transplantation (allo-SCT). Several single-nucleotide polymorphisms (SNPs) in in the promoter region of cytokine genes have shown to alter their expression and are therefore associated with donor-recipient alloreactivity and, ultimately, with SCT outcome. Interleukin 17 (IL-17) is secreted by CD4+ T-cells and has been implicated in the pathogenesis of various autoimmune diseases but its importance in SCT is not well-known. Objective To analyse the influence of IL-17A SNP genotypes on the risk and severity of GvHD and other complications after HLA-identical allo-SCT. Patients and Methods Genomic DNA obtained from peripheral blood samples belonging to 546 patients and their HLA-identical sibling donors (Table 1) included in the DNA Bank of the Spanish Group for Hematopoietic Stem Cell Transplantation (GETH). Genotyping of the polymorphisms of interest, rs8193036 (-737C>T), rs2275913 (-197G>A), rs3819024 (-444A>G), rs4711998 (-877A>G), were performed by multiplex primer extension followed by mass spectrometry (MALDI-TOF; Sequenom MassArray). Results Genotype frequencies are shown in Table 2 and the association between IL-17A genotypes and complications after allo-SCT are shown in Table 3. Patients transplanted from donors harboring genotype CC for the SNP rs8193036 show increased risk of grade III-IV acute GvHD (7/26 vs 47/397, p=0.035) and of grade II-IV acute GvHD (13/26 vs 133/409, p=0.048). Patients transplanted from donors harboring allele A in the SNP rs4711998 show increased risk of extensive chronic GvHD (53/161 vs 43/177, p=0.045). Relapse rate was not related with IL-17A SNP genotypes. Finally a higher risk of toxicity-related mortality (TRM) was observed in patients transplanted from donors harboring allele A for SNP rs2275913 (78/293 vs 46/227, p=0.048), donors harboring allele G for SNP rs3819024 (78/279 vs 46/242, p=0.011) and donors harboring allele A for SNP rs4711998 (68/250 vs 55/229, p=0.044). Conclusions IL-17A SNP genotyping might be useful to anticipate complications after sibling HLA-identical allo-SCT and, therefore, to improve the clinical management of transplanted patients. This results further support the idea of a genetic predisposition to certain complications after allo-SCT. Paper presented on behalf of the GvHD/Immunotherapy committee of the Spanish Group for Hematopoietic Transplantation (GETH). Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document