Search

Chronic graft versus host disease (cGVHD) is a debilitating and costly complication following haemopoietic stem cell transplantation (HSCT). This study describes the economic burden associated with cGVHD. Direct costs associated with specialised healthcare utilisation (inpatient admissions and outpatient visits), as well as indirect costs associated with sickness absence-associated productivity loss were estimated in patients who underwent allogeneic HSCT in Sweden between 2006 and 2015, linking population-based health and economic registers. To capture the period of chronic GVHD, patients were included who survived > 182 days post-HSCT (start of follow-up), and cGVHD was classified based on patient treatment records to correct for any diagnosis underreporting. Patients were classified as 'non-cGVHD' if they received no immunosuppressive treatment, 'mild cGVHD' if they received only systemic corticosteroid treatment or immunosuppressive treatment, or 'moderate-severe cGVHD' if they received extracorporeal photopheresis (ECP) only, corticosteroid treatment and immunosuppressive treatment, or systemic corticosteroid treatment and ECP treatments. Patients with moderate-severe cGVHD spent more time in healthcare, had higher healthcare resource costs and higher sickness absence-related productivity loss compared to patients with non- or mild cGVHD. The cumulative total costs during the first 3 years of follow-up were EUR 14,887,599, EUR 20,544,056, and EUR 47,811,835 for non-, mild, and moderate-severe groups, respectively. The longterm costs incurred with cGVHD following HSCT continue to be very high and significantly impacted by cGVHD severity. This study adds real-world health resource and economic insight relevant for policy-makers and healthcare providers when considering the clinical challenge of balancing immunosuppression to reduce cGVHD. [ABSTRACT FROM AUTHOR]

Background: There remains a significant mortality in recipients with MF who undergo allogeneic stem cell transplant (allo‐HSCT). The combination of antithymocyte globulin (ATG) and post‐transplant cyclophosphamide (PTCy) provides good control of graft‐versus‐host disease (GVHD) when peripheral blood stem cell grafts are used. Methods: We report the outcome of 37 recipients with myelofibrosis who underwent reduced‐intensity conditioning (RIC) allo‐HSCT with ATG and PTCy. Median follow‐up was 16.4 months. Results: Nine (24.3%) recipients received 10/10 MRD grafts, 17 (45.9%) 10/10 MUD grafts, 4 (10.8%) 9/10 MUD grafts, and 7 (18.9%) haploidentical donor grafts. Six (16.3%) patients had graft failure. The cumulative incidence of grade II‐IV and grade III‐IV aGVHD at day +100 and moderate/severe chronic GVHD at 1 year was as follows: 13.5%, 5.4%, and 17%. There were no deaths secondary to GVHD. One‐year overall survival (OS), relapse‐free survival (RFS), non‐relapse mortality (NRM), and GVHD‐free/RFS (GRFS) were respectively 74.4%, 71.3%, 23%, and 43.3%. Those recipients who had worse KPS ≤ 80% had worse OS and RFS. Conclusion: RIC allo‐HSCT with ATG and PTCy results in high OS and RFS in patients with myelofibrosis and absence of mortality secondary to GVHD. Further investigations are required to reduce NRM and graft failure rates. [ABSTRACT FROM AUTHOR]

Abstract: Graft failure is a significant complication following allogeneic hematopoietic cell transplantation (alloHCT). It may result from rejection caused by recipient T cells, natural killer (NK) cells, or antibodies. It is increased in HLA-mismatched grafts, unrelated grafts, T cell-replete transplants, sensitized patients, and in patients treated with reduced-intensity conditioning (RIC). In recipients of unrelated grafts, graft failure is increased in patients receiving major AB0 blood group mismatched transplants (P = .008). Recent data also suggest that donor-specific antibodies to CD34+/VEGFR-2+ cells may be involved in graft failure after alloHCT. Graft failure may be overcome by more intensified conditioning, increased cell dose, or more effective immunosuppression. With more frequent use of RIC, cord blood grafts and other HLA-mismatched transplants, graft failure is an increasing problem after alloHCT. [Copyright &y& Elsevier]

Severe hemorrhagic cystitis (HC) may be a life-threatening complication in allogeneic stem cell transplantation (SCT). In order to improve the strategies for prophylaxis and treatment, we retrospectively analyzed data on patients who underwent SCT at our center from 1990 through 2005. Patients with HC were identified through our database and their medical charts were reviewed. Grades 2–5 and 3–5 HC developed in 109/834 patients (13.1%) and 27/834 patients (3.2%), respectively. The frequency of HC decreased over the time from 18.0% in 1990–1992 to 9.5% in 2002–2005 (p = 0.005). HC started on a median of 35 (0–166) days post-transplant and persisted for a median of 23 (2–270) days. Transplant-related mortality was 21% in patients without HC, 15% in those with HC of grade 2, 55% in those with grade 3, and 71% in patients with HC of grades 4–5 (p < 0.001). In multivariate analysis, the risk factors for HC were myeloablative conditioning, busulphan, cytomegalovirus infection, hematological malignancy, and acute graft-versus-host disease (aGVHD). With four risk factors, the risk of HC development was 31%. Risk factors for severe HC of grades 3–5 were aGVHD and bacteremia. [ABSTRACT FROM AUTHOR]

Jaksch M, Uzunel M, Remberger M, Sundberg B, Mattsson J. Molecular monitoring of T-cell chimerism early after allogeneic stem cell transplantation may predict the occurrence of acute GVHD grades II–IV.Clin Transplant 2005: 19: 346–349.© Blackwell Munksgaard, 2005Mixed chimerism (MC) within CD4+ and CD8+ T cell days 7 and 10 after allogeneic stem cell transplantation (SCT) was compared with the occurrence of acute graft-vs.-host disease (GVHD) in 34 patients after SCT. Acute GVHD was diagnosed in 22 patients within the first 3 months after SCT, 15 of these developed acute GVHD grades II–IV. The difference in the clearance rate of host T cell between the two days were compared. We found a significantly higher risk (p = 0.005) for developing acute GVHD grades II–IV in patients with complete donor CD4+ T-cell chimerism day 7 after SCT together with patients who increased 50% or more in donor CD4+ T cells between days 7 and 10 after SCT. Our data suggest that molecular monitoring of MC early after transplantation may be useful as a diagnostic tool in predicting the occurrence of moderate to severe acute GVHD after SCT. [ABSTRACT FROM AUTHOR]

Summary. Certain cytokine gene polymorphisms may be associated with severe acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. The present study analysed 196 patients and their donors for TNF-308 , TNFd, IL-10-1064 and IL-10-1082 gene polymorphisms. Serum analysis of tumour necrosis factor-α (TNF-α) and interleukin 10 (IL-10) levels during conditioning therapy was also performed. Among patients with sibling donors, the TNFd allele 4 was significantly correlated with acute GVHD grades II–IV (P < 0·01). Acute GVHD grades II–IV were more common among patients homozygous for the IL-10-1064 allele 13 (P = 0·02). Patients homozygous for the TNF-308 allele (AA) correlated with higher TNF-α serum levels during conditioning (P = 0·02). [ABSTRACT FROM AUTHOR]

Background. Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). We designed a functional assay for assessment of individual risk for acute GVHD. Study Design and Methods. Blood samples were collected from patients and donors before HSCT. Two groups of seven patients each were selected, one in which individuals developed acute GVHD grades II-IV and one in which none showed any clinical signs of GVHD. Peripheral blood mononuclear cells (PBMCs) isolated from donors were incubated in mixed lymphocyte cultures (MLCs) with recipient PBMCs. The cells were characterized by flow cytometry before and after MLC. Results. Samples from donors in the GVHD group contained significantly lower frequencies of naïve γδ T-cells and T-cells expressing NK-cell markers CD56 and CD94. Donor samples in this group also exhibited lower frequencies of naïve CD95+ T-cells compared to controls. After MLC, there were dissimilarities in the CD4/CD8 T-cell ratio and frequency of CD69+ T-cells between the two patient groups, with the non-GVHD group showing higher frequencies of CD8+ and CD69+ T-cells. Conclusion. We conclude that a thorough flow cytometric analysis of donor cells for phenotype and allogeneic reactivity may be of value when assessing pretransplant risk for severe acute GVHD. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated chimerism and the use of mesenchymal stem cells in umbilical cord blood transplantation. The researchers conducted a retrospective single-center analysis of 50 umbilical cord blood transplantations (UCBTs). It was concluded that mixed chimerism was common in the studied patient group and it could be a concern in patients with malignant diseases.

Abstract: Acute graft-versus-host disease (GVHD) is still a major complication after allogeneic stem cell transplantation. It is initiated by infiltrating donor T cells specific against the host antigens. Because T-cell migration is largely controlled by the expression of chemokines and chemokine receptors, we investigated the relation of acute GVHD and chemokine receptor expression in peripheral blood in 50 patients after allogeneic stem cell transplantation. The gene expression of the chemokine receptors CCR1, CCR2, CCR5, and CXCR3 was monitored by using quantitative real-time polymerase chain reaction. Among the 36 patients diagnosed with acute GVHD, 10 developed a second episode of acute GVHD. Therefore, gene-expression levels could be analyzed in 46 occasions of acute GVHD. When all 4 markers were evaluated at the same time, increased gene-expression levels of at least 1 of the 4 markers were seen in 44 of 46 episodes of acute GVHD. The median increase of the 4 markers ranged from 3× to 12× in connection with acute GVHD. It is interesting to note that we saw increasing gene-expression levels a few days before acute GVHD was diagnosed clinically at 17, 15, 22, and 19 occasions for CCR5, CXCR3, CCR1, and CCR2, respectively. The median number of days before diagnosis ranged from 3 to 5. Although they are not specific for acute GVHD, quantitative monitoring of the gene expression of chemokine receptors may be a valuable molecular method to monitor and diagnose acute GVHD. [Copyright &y& Elsevier]

• The Centre for International Blood and Marrow Transplant Registry (CIBMTR) score classifies most patients with chronic graft-versus-host disease (GVHD) into low-risk groups. • A novel prognostic risk score further refines the CIBMTR low-risk groups. • The novel risk score improves on the CIBMTR in identifying high-risk chronic GVHD. • The novel risk score classifies patients with respect to failure-free survival. • The novel risk score groups patients according to other relevant clinical outcomes. The Centre for International Blood and Marrow Transplant Registry (CIBMTR) score has been shown to be prognostic for overall survival (OS) and nonrelapse mortality (NRM) but has been shown in several single-center studies to classify a large proportion of patients with chronic graft-versus-host disease (cGVHD) in the lower risk groups (RG1 to RG2), thereby limiting its prognostic utility for those patients. We evaluate the CIBMTR score, the Global Severity Score (GSS), and a novel risk score developed to improve on the limitations of the CIBMTR with respect to clinically relevant outcomes, including failure-free survival (FFS), in patients receiving frontline systemic treatment for cGVHD. We identified 277 patients between 2002 and 2012 at the Princess Margaret Cancer Centre in Toronto, Canada, who developed cGVHD and were treated with at least 1 line of systemic therapy. cGVHD was graded by GSS, and patients were stratified by CIBMTR. We evaluated OS, NRM, relapse, and FFS within GSS grade groups, as well as CIBMTR RGs, and used a novel prognostic risk score. The median FFS duration was 164 days in the severe GSS group versus 238 days in the moderate-grade group and 304 days in mild-grade group (P =.001). The median FFS duration was 501 days in CIBMTR RG1 versus 291 days in RG2 and 166 days in RG3 to RG6 (P =.003). A novel risk score combining the GSS and CIBMTR scores was prognostic of OS, NRM, and FFS and was able to subdivide patients with cGVHD in CIBMTR RG1 to RG2 into distinct prognostic risk categories. The CIBMTR risk score and the GSS are well correlated with FFS, OS, and NRM following frontline systemic treatment for cGVHD. A new risk score model combining the CIBMTR risk score and the GSS could enhance risk stratification in the lower CIBMTR risk groups. [ABSTRACT FROM AUTHOR]

Frailty and poor Functional Status can adversely affect the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT). Our alloHCT team felt the need to assess Fragility and Functional Status (F&FS) of all alloHCT recipients as standard evaluation. This study summarizes the implementation of the program. In May 2018 the multidisciplinary transplant team members reviewed options for F&FS assessment in our clinics with the aim of adopting Geriatric Assessment tools which were prognostic, easy to administer within the existing clinic appointment and space. After reviewing literature, it was decided to adopt 8 different tests (details in Table1). A one page scoring tool was built by the clinical nurse coordinators to capture the results of each test (Fig 2). If any part of assessment was missed, it could be completed at the next visit or admission. It took the study team 45 days to implement the program. The tests are easy to perform and can be done by any clinical team member during the patient's transplant trajectory. There is no incremental increase in waiting time. Over a 6 month period, 283 patients were assessed using the F&FS. There was incomplete information in 57 of these patients, mainly during early implementation. The correlation of these test results with transplant outcomes was selected for presentation at the 2019 ASH meeting (Abstract #380). F&FS assessment can be used as a standard of care testing for all patients being considered for alloHCT with proper planning and teamwork. [ABSTRACT FROM AUTHOR]