scholarly journals Assessing the impact on intestinal microbiome and clinical outcomes of antibiotherapy optimisation strategies in haematopoietic stem cell transplant recipients: study protocol for the prospective multicentre OptimBioma study

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034570
Author(s):  
Silvia Jiménez-Jorge ◽  
Gema Labrador-Herrera ◽  
Clara M Rosso-Fernández ◽  
Nancy Rodríguez-Torres ◽  
María Eugenia Pachón-Ibáñez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcomes ◽  
Intestinal Microbiota ◽  
Acute Gvhd ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Microbiota Composition ◽  
Prospective Longitudinal ◽  
The Impact ◽  
Microbiota Diversity

IntroductionHaematopoietic stem cell transplantation (HSCT) is a life-saving treatment for a number of haematological diseases. Graft versus host disease (GVHD) is its main complication and hampers survival. There is strong evidence that intestinal microbiota diversity of the recipient may increase the risk of GVHD worsening survival. Antibiotic regimens used during the early phase of the transplant may influence clinical outcomes by reducing intestinal microbiota diversity. Present guidelines of European Conference on Infections in Leukaemia exhort to optimising antibiotic use in haematological patients including HSCT recipients. The present study aims to investigate if, in HSCT recipients, the optimisation of antibacterial use may preserve intestinal microbiota composition reducing the incidence and severity of acute GVHD and improving relevant clinical outcomes.Methods and analysisThis is a prospective longitudinal observational study of two cohorts of HSCT recipients: (1) the intervention cohort includes patients treated in centres in which a predefined strategy of antibiotherapy optimisation is implemented, with the objective of optimising and reducing antibiotic administration according to clinical criteria and (2) the control cohort includes patients treated in centres in which a classic permissive strategy of antibiotic prophylaxis and treatment is used. Adult patient receiving a first HSCT as a treatment for any haematological condition are included. Clinical variables are prospectively recorded and up to five faecal samples are collected for microbiota characterisation at prestablished peritransplant time points. Patients are followed since the preconditioning phase throughout 1-year post-transplant and four follow-up visits are scheduled. Faecal microbiota composition and diversity will be compared between both cohorts along with acute GVHD incidence and severity, severe infections rate, mortality and overall and disease-free survival.Ethics and disseminationThe study was approved between 2017 and 2018 by the Ethical Committees of participant centres. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.Trial registration numberNCT03727113

scholarly journals Impact of donor age and kinship on clinical outcomes after T-cell–replete haploidentical transplantation with PT-Cy

2020 ◽  
Vol 4 (16) ◽  
pp. 3900-3912 ◽  
Author(s):  
Jacopo Mariotti ◽  
Anna Maria Raiola ◽  
Andrea Evangelista ◽  
Angelo Michele Carella ◽  
Massimo Martino ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Clinical Outcomes ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Cell Transplant ◽  
Donor Age ◽  
Hematopoietic Cell Transplant ◽  
The Impact ◽  
Risk Of Relapse

Abstract Donor selection contributes to improve clinical outcomes of T-cell–replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P < .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index >3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.

Allogeneic haematopoietic stem cell transplantation—clinical outcomes: impact of leg muscle strength

2021 ◽  
pp. bmjspcare-2021-003256
Author(s):  
Shin Kondo ◽  
Kumiko Kagawa ◽  
Takashi Saito ◽  
Masahiro Oura ◽  
Kimiko Sogabe ◽  
...  
Keyword(s):  
Stem Cell ◽  
Muscle Strength ◽  
Stem Cell Transplantation ◽  
Clinical Outcomes ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Haematopoietic Stem Cell Transplantation ◽  
Haematopoietic Stem Cell ◽  
Lower Extremity Muscle ◽  
The Impact

ObjectivesMuscle strength decline is reported to predict mortality in many cancers. However, there is little knowledge of the relation between muscle strength decline and clinical outcomes of allogeneic haematopoietic stem cell transplantation (allo-HSCT). This study aimed to determine the impact of pre-transplant lower extremity muscle strength (LEMS) on post-transplant overall survival (OS) and non-relapse mortality (NRM).MethodsIn this retrospective cohort study, 97 adult patients underwent allo-HSCT during 2012–2020. LEMS was defined as knee extension force divided by patient’s body weight. The patients were divided into low and high LEMS groups based on pre-transplant LEMS. OS was measured using the Kaplan-Meier method and the Cox proportional hazards model. The cumulative incidence of NRM was evaluated using the Fine and Gray method, with relapse considered as a competing risk event.ResultsProbability of OS was significantly lower in the low LEMS groups (HR 2.48, 95% CI 1.20 to 5.12, p=0.014) than in the high LEMS group on multivariate analysis. Five-year OS was 25.8% and 66.4% in the low and high LEMS groups, respectively. Risk of NRM was significantly higher in the low LEMS group (HR 4.49, 95% CI 1.28 to 15.68, p=0.019) than in the high LEMS group. The cumulative incidence of NRM was 41.4% and 11.1% in the low and high LEMS groups, respectively.ConclusionsPre-transplant LEMS was a significant factor in predicting OS and NRM.

scholarly journals NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Neema P. Mayor ◽  
Bronwen E. Shaw ◽  
J. Alejandro Madrigal ◽  
Steven G. E. Marsh
Keyword(s):  
Stem Cell ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Responses ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Gene Markers ◽  
The Impact ◽  
Transplant Complications ◽  
Candidate Gene Markers

Haematopoietic stem cell transplantation (HSCT) is a valuable tool in the treatment of many haematological disorders. Advances in understanding HLA matching have improved prognoses. However, many recipients of well-matched HSCT develop posttransplant complications, and survival is far from absolute. The pursuit of novel genetic factors that may impact on HSCT outcome has resulted in the publication of many articles on a multitude of genes. Three NOD2 polymorphisms, identified as disease-associated variants in Crohn’s disease, have recently been suggested as important candidate gene markers in the outcome of HSCT. It was originally postulated that as the clinical manifestation of inflammatory responses characteristic of several post-transplant complications was of notable similarity to those seen in Crohn’s disease, it was possible that they shared a common cause. Since the publication of this first paper, numerous studies have attempted to replicate the results in different transplant settings. The data has varied considerably between studies, and as yet no consensus on the impact of NOD2 SNPs on HSCT outcome has been achieved. Here, we will review the existing literature, summarise current theories as to why the data differs, and suggest possible mechanisms by which the SNPs affect HSCT outcome.

Donor KIR Genotype Does Not Affect VZV Reactivation after Allogeneic Haematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3236-3236
Author(s):  
Sujaatha Narayanan ◽  
Sandeep Nagra ◽  
Premini Mahendra ◽  
Fiona J. Clark ◽  
Charles F. Craddock ◽  
...  
Keyword(s):  
At Risk ◽  
Stem Cell ◽  
Protective Effect ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Allogeneic Hsct ◽  
Donor Type ◽  
The Individual ◽  
The Impact ◽  
Cmv Reactivation

Abstract Background. Varicella zoster virus (VZV) reactivation is a common occurrence after allogeneic haematopoietic stem cell transplant (HSCT) and a cause of significant morbidity. We have recently demonstrated the protective effect of donor KIR genotpye against cytomegalovirus (CMV) reactivation- specifically the protective effect of the broad ’B’ haplotype containing multiple activating KIR genes1. This retrospective study was designed to investigate whether donor KIR genotype confers an equivalent protective effect against VZV reactivation. Method. 152 patients who underwent allogeneic HSCT at a single centre were identified. Those with pre-transplant serology consistent with previous exposure to VZV were defined as at risk of VZV reactivation. All patients received aciclovir 800mg daily as routine prophylaxis. The diagnosis of VZV reactivation was made clinically. Cases of VZV reactivation were identified by examination of the case records. KIR genotyping was performed on donor DNA using PCR-SSP. The individual KIR genes KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5 and 3DS1, as well as the broad KIR haplotypes ’A’ and ’B’, were assessed by univariate and multivariate analysis for an effect on VZV reactivation. Also assessed was the impact of recipient HLA-C type, recipient HLA-Bw4/Bw6, donor type (sex-matched sibling, sex-mismatched sibling, volunteer unrelated), reduced intensity conditioning (RIC) regimen, the use of alemtuzemab as in vivo T cell depletion, CMV reactivation, and grade 2 or greater GVHD requiring steroid therapy. Results. 128 (84.2%) patients had evidence of past infection and thus were deemed at risk of VZV reactivation. Of these, 47 (36.7%) had clinical evidence of reactivation. 60% of transplants were from a donor possessing the broad ’B’ haplotype. The rate of reactivation in the presence of donor ’B’ haplotype was 40% compared to 32% when no donor ’B’ haplotype was present (p=0.237). None of the individual donor KIRs were shown to significantly reduce the rate of VZV reactivation. Neither the use of a RIC regimen nor the presence of alemtuzemab in the conditioning regimen were shown to have an impact. None of the other factors analysed were associated with an increased rate of zoster reactivation. Conclusion. Donor KIR genotype does not influence VZV reactivation after allogeneic HSCT. This contrasts with the findings for CMV reactivation. No influence of donor type, conditioning or GVHD could be demonstrated. This suggests 1) that there are differing mechanisms that control the reactivation of different Herpes viruses after transplantation and 2) that KIRs may have specificity for CMV.

Comparison of Clinical Outcomes and Day 30 Lymphocyte Recovery Between Two aGVHD Prophylaxis Regimens In Matched Unrelated Hematopoietic Stem Cell Transplant (MUD) Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2340-2340
Author(s):  
Zartash Gul ◽  
Mustafa Abdul-Hussein ◽  
Ivo Ditah ◽  
Joseph P. Uberti ◽  
Muneer H. Abidi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcomes ◽  
Hematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
All Cause Mortality ◽  
The Impact ◽  
Cmv Status

Abstract Abstract 2340 Background: Compared to HLA related hematopoietic stem cell transplants (HSCT), matched unrelated donor transplant (MUD) is associated with higher rates of transplant related mortality (TRM), primarily due to a higher incidence of acute graft versus host disease (aGVHD) and infections. Several investigators have shown that early lymphocyte recovery predicts less TRM, overall morality, aGVHD, and relapse post transplant, in HLA matched related HSCT. Only Lablanc et al demonstrated that Lymphocyte recovery at day 30(L30) is associated with improved outcomes in MUD patients, with the use of antibody mediated in-vivo lymphocyte depletion. We sought to compare clinical outcomes, L30, and the ability of L 30 to predict clinical outcomes in two contemporaneous cohorts of MUD patients treated with two different regimens for aGVHD prophylaxis. Methods: We retrospectively evaluated all consecutive MUD patients at our institution, who received aGVHD prophylaxis regimen Mycophenolate Mofetil and Tacrolimus (MT) between January 2008 and June of 2010, {Group 1(Grp 1), N =70 }. The second group (Grp2, N=40) received Tacrolimus, Sirolimus and Thymoglobulin on phase II protocol (TST), between July 2008 and June 2010. Thymoglobulin was administered at a total dose of 4.5mg/kg on days -3,-2, & -1. Clinical outcomes and L30 were compared between the groups using chi square test. We evaluated the impact of L30 above or below 400/microliter (mic) on 6 month all cause mortality, TRM, relapse, aGVHD and infections in each group separately using log rank test. Results: Groups 1 and 2 were not significantly different with respect to age, CMV status and gender for both donor and recipient. Groups were unbalanced for hematological diagnosis. There was more advanced disease in Grp1 and more HLA mismatches in Grp2. Conditioning regimens included Busulphan/Fludarabine with or without Total Body Irradiation (TBI), Fludarabine/Melplan/TBI, Etoposide/TBI, Cytoxan/TBI, and Rituxan, Carmustine, Cytarabine, Etoposide and Melphan (R BEAM). The incidence of aGVHD (Grades I-IV) was significantly higher in Grp1 vs Grp2 (74% vs 26%, P=0.001). CMV reactivation, 6 months mortality and TRM were not significantly different between the 2 groups (P=0.58), (P=0.2), (P=0.26) respectively. A marginally significant increase in relapse was noted in Grp2 (P=0.046). Compared to Grp1, Grp2 had a significantly lower proportion of patients with L30 greater than 400/mic (Grp1 50% vs Grp2 74%, P=0.01). However this difference disappeared on day 60 (Grp1 67% vs Grp2 76% P=0.32), day 90 (Grp1 71% vs Grp2 75% P=0.66) and day 180 (Grp1 87% vs Grp 2 92% P=0.55) post transplant. More EBV reactivations occurred in Grp2 (20% vs 4%, P= 0.008). In a multivariate model, gender, CMV status, age (for both donor & recipient), and donors CD34+ counts, diagnosis at transplant, disease status at MUD and the degree of mismatch were not independent predictors of L30. In Grp 1, L30 above 400/mic was significantly associated with a lower all cause mortality (HR 0.2, CI= 0.06–0.82), lower TRM (HR=0.16, CI=0.042-0.61) at 6 months, and a non-significant decrease in the incidence of aGVHD (HR 0.6 CI 0.26–1.46). However, in Grp2 L30 above 400/mic was not associated with the same clinical outcomes. L30 (above or below 400/mic) was also not associated with CMV or EBV reactivation in either group. Conclusion: Compared to aGVHD prophylactic regimen MT, the use of triple immune suppression TST was associated with less aGVHD, and lower lymphocyte recovery at day 30 post transplant. L30 above 400/mic predicted less overall mortality and TRM at 6 months in Grp1. Further studies exploring recovery and kinetics of lymphocyte subsets may explain the difference in the ability of L30 to predict clinical outcomes between the two groups. Disclosures: Off Label Use: Bortezomib is currently not approved for maintenance therapy after Autologous stem cells transplant. Abidi: Millennium: Speakers Bureau. Lum: Transtarget Inc: Equity Ownership. Al-Kadhimi: Genzyme Pharmaceutical: Research Funding.

scholarly journals Chromosome Y–encoded antigens associate with acute graft-versus-host disease in sex-mismatched stem cell transplant

2018 ◽  
Vol 2 (19) ◽  
pp. 2419-2429 ◽  
Author(s):  
Wei Wang ◽  
Hu Huang ◽  
Michael Halagan ◽  
Cynthia Vierra-Green ◽  
Michael Heuer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcomes ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Solid Organ ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
A Genome

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curative option for blood cancers, but the coupled effects of graft-versus-tumor and graft-versus-host disease (GVHD) limit its broader application. Outcomes improve with matching at HLAs, but other factors are required to explain residual risk of GVHD. In an effort to identify genetic associations outside the major histocompatibility complex, we conducted a genome-wide clinical outcomes study on 205 acute myeloid leukemia patients and their fully HLA-A–, HLA-B–, HLA-C–, HLA-DRB1–, and HLA-DQB1–matched (10/10) unrelated donors. HLA-DPB1 T-cell epitope permissibility mismatches were observed in less than half (45%) of acute GVHD cases, motivating a broader search for genetic factors affecting clinical outcomes. A novel bioinformatics workflow adapted from neoantigen discovery found no associations between acute GVHD and known, HLA-restricted minor histocompatibility antigens (MiHAs). These results were confirmed with microarray data from an additional 988 samples. On the other hand, Y-chromosome–encoded single-nucleotide polymorphisms in 4 genes (PCDH11Y, USP9Y, UTY, and NLGN4Y) did associate with acute GVHD in male patients with female donors. Males in this category with acute GVHD had more Y-encoded variant peptides per patient with higher predicted HLA-binding affinity than males without GVHD who matched X-paralogous alleles in their female donors. Methods and results described here have an immediate impact for allo-HCT, warranting further development and larger genomic studies where MiHAs are clinically relevant, including cancer immunotherapy, solid organ transplant, and pregnancy.

scholarly journals Late Effects After Haematopoietic Stem Cell Transplantation in ALL, Long-Term Follow-Up and Transition: A Step Into Adult Life

2021 ◽  
Vol 9 ◽  
Author(s):  
Tamara Diesch-Furlanetto ◽  
Melissa Gabriel ◽  
Olga Zajac-Spychala ◽  
Alessandro Cattoni ◽  
Bianca A. W. Hoeben ◽  
...  
Keyword(s):  
Stem Cell ◽  
Late Effects ◽  
Adult Life ◽  
Haematopoietic Stem Cell ◽  
Childhood And Adolescence ◽  
Cell Transplant ◽  
Adult Services ◽  
Timely Access ◽  
The Impact

Haematopoietic stem cell transplant (HSCT) can be a curative treatment for children and adolescents with very-high-risk acute lymphoblastic leukaemia (ALL). Improvements in supportive care and transplant techniques have led to increasing numbers of long-term survivors worldwide. However, conditioning regimens as well as transplant-related complications are associated with severe sequelae, impacting patients' quality of life. It is widely recognised that paediatric HSCT survivors must have timely access to life-long care and surveillance in order to prevent, ameliorate and manage all possible adverse late effects of HSCT. This is fundamentally important because it can both prevent ill health and optimise the quality and experience of survival following HSCT. Furthermore, it reduces the impact of preventable chronic illness on already under-resourced health services. In addition to late effects, survivors of paediatric ALL also have to deal with unique challenges associated with transition to adult services. In this review, we: (1) provide an overview of the potential late effects following HSCT for ALL in childhood and adolescence; (2) focus on the unique challenges of transition from paediatric care to adult services; and (3) provide a framework for long-term surveillance and medical care for survivors of paediatric ALL who have undergone HSCT.

Expression of Activation Marker, CMRF-44, on Blood CD11c+ Dendritic Cells Is Closely Associated with the Severity of Acute GVHD after Allogeneic Haematopoietic Stem Cell Transplant.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 600-600
Author(s):  
Jenny Lau ◽  
Mary Sartor ◽  
Slavica Vuckovic ◽  
David Munster ◽  
Derek N. Hart ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Predictive Marker ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Predictive Tool ◽  
Host Disease ◽  
Graft Versus Host

Abstract AIM: Dendritic cells (DC) are considered central to the development of graft versus host disease (GVHD) following allogeneic haematopoietic stem cell transplantation (alloHSCT). Both donor and host DC are thought to initiate allogeneic immune responses by presenting host antigens to donor T lymphocytes. We studied the potential of CMRF-44, a novel monoclonal antibody identifying activated circulating blood DC, as a predictive marker of acute GVHD. METHODS: In a prospective study, peripheral blood was taken from 40 patients twice weekly up to 100 days post-alloHSCT. Circulating myeloid (CD11chi) and plasmacytoid (CD123hi) DCs were enumerated and the expression of CMRF-44 was assessed on CD11chi DC by four colour flow cytometry. Multivariate analyses were performed using a non-parametric Mann-Whitney U-test and Receiver Operating Characteristic (ROC) curves. RESULTS: Following alloHSCT, the severity of acute GVHD correlated with the number of total DC in the blood (p=0.035). Furthermore, low myeloid and plasmacytoid DC numbers were significantly associated with grade 2-4 acute GVHD (p=0.046 and 0.017 respectively). In 40 alloHSCT patients, 27 developed acute GVHD. CMRF-44 was expressed on CD11c+ DC in all cases prior to the onset of acute GVHD. Of the 13 patients without GVHD, 8 had no circulating CMRF-44+ CD11c+ DC. CMRF-44 expression was independent of the reconstitution of myeloid DC (p=0.73). Patients who had CMRF-44+ CD11c+ DC in more than 20% of their post-transplant monitoring samples were more likely to develop acute GVHD (p=0.001, OR=37.1). In addition, patients with more severe grade 2–4 GVHD had significantly higher percentages of CMRF-44+ CD11c+ DCs (p=0.001). CMRF-44 expression at greater than or equal to 12% of CD11chi DCs had a sensitivity of 87.5 for prediction of grade 2–4 acute GVHD, and a specificity of 91.7. CONCLUSION: CMRF-44 expression on blood CD11c+ DC is highly associated with the onset of acute GVHD. These results suggest that CMFR-44 may be used as a predictive tool to identify patients at risk of severe GVHD and to direct therapy. Furthermore, it reinforces the potential application of suitably engineered CMRF-44 antibodies for the prevention or treatment of graft versus host disease.

scholarly journals VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients

BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e026093 ◽  
Author(s):  
Anne Conrad ◽  
Mathilde Boccard ◽  
Florent Valour ◽  
Vincent Alcazer ◽  
Aydee-Tamara Tovar Sanchez ◽  
...  
Keyword(s):  
Cohort Study ◽  
Stem Cell ◽  
Immune Function ◽  
Immune Status ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Serological Response ◽  
Vaccine Response ◽  
Functional Assays ◽  
Prospective Longitudinal

IntroductionImmune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT.Methods and analysisA prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus,Haemophilus Influenzaetype b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide orStaphylococcus aureusenterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function.Ethics and disseminationEthical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals.Trial registration numberNCT03659773; Pre-results.

Impact of HLA Allele Mismatch on the Outcome of Patients with Reduced-Intensity Allogeneic Haematopoietic Stem Cell Transplantation from Unrelated Donors: Analysis of 103 Patients of the French Registry.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3149-3149 ◽  
Author(s):  
Andrea Toma ◽  
Marie-Lorraine Balere-Appert ◽  
Zina Chir ◽  
Jean-Michel Boiron ◽  
Pierre Bordigoni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Haematopoietic Stem Cell ◽  
Unrelated Donors ◽  
Grade Ii ◽  
The Impact ◽  
Hla Mismatches ◽  
Reduced Intensity

Abstract Reduced-intensity conditioning regimens (RIC) had become a classical strategy of allogeneic hematopoietic stem cell transplantation (HSCT) and many patients are now transplanted with unrelated donor. The aim of this restrospective study was to evaluate the impact of HLA mismatches between donor (D) and recipient (R) at the allelic level on survival after RIC. We analyzed 103 patients registered in France from Jan 1999 to Dec 2003 with a median age of 46 years (18–67). All patients had hematologic malignancies: AL (n=35), MM (n=18), CLL (n=5), NHL (n=11), HD (n=9), CML (n=12), MDS (n=9), and MPS (n=4). 39% of the patients were in an advanced phase of the disease at time of HSCT. Anti-thymocytes globulins (ATG) were part of the conditioning regimen for 77% of patients. The main source of stem cells was PBSC (n=65). Seventy-one D/R pairs (69%) were 10/10 HLA match at the allelic level. Mismatches concerned 5, 6, 15, 2 and 7 D/R pairs for HLA-A, -B, -C, -DRB1 and -DQB1, respectively. The results showed that 96% of patients engrafted. Acute GVHD grade II to IV and grade III/IV occurred in 46% and 19% of patients, respectively. The risk of developing cGvHD was 45% at 2 years. Overall survival (OS) was 42% at five years. Among the 47 patients alive, the median disease free survival (DFS) was 28 months. Among non-HLA parameters studied, the only factor associated with a good OS was the diagnosis of lymphoid disease (HD or NHL or CLL) (p=0.003). Recipient age <46y was only associated with less acute GvHD grade II to IV (p=0.008). Among HLA mismatches, we found that HLA-A and/or -B allelic mismatches had a negative impact on OS (p=0.006), DFS (p=0.006), acute GvHD grade II to IV (p=0.05). On the other hand, HLA-C or -DQB1 mismatches did not impact on OS, DFS, acute or chronic GvHD. We could not analyze DRB1 mismatch since there was only 2 patients reported. In conclusion, HSCT following RIC, with match or mismatch unrelated donors, is a feasible approach with best results observed for patients with lymphoid malignancies (NHL, CLL or HD). Among allelic HLA mismatches, HLA-A and/or -B seemed to be deleterious as compared to HLA-C or DQB1. These results help to identify most suitable donors and patients who are likely to benefit from RIC with unrelated donors when there is not a fully HLA match donor available.

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