Presence of Parvovirus B19 but Not Herpesvirus Genome in Acute Skin Rash after Allogeneic Stem Cell Transplantation Correlates with Outcome
Acta haematologica. 2020;:1-10
INTRODUCTION Skin rash is a first symptom of acute graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (ASCT) but can also be caused by viruses. The relevance of virus DNA analyses in skin rash for diagnosis and clinical outcome is unknown. OBJECTIVES To record the frequencies of detection of herpes and parvovirus B19 (ParvoB19) DNA in skin rash within 100 days after ASCT and to analyze their relevance for diagnosis, clinical course, and non-relapse mortality (NRM). METHODS We retrospectively identified 55 patients with virus DNA analysis for CMV, EBV, HHV6, HHV8, HSV, VZV, or ParvoB19. We assessed the rate of virus DNA detection and studied associations with histological diagnosis, virus DNA from concomitantly analyzed blood, clinical presentation, exanthema treatment, and NRM. RESULTS CMV, EBV, HHV6, HHV8, HSV, VZV and ParvoB19 DNA were detected in 12.5, 11.8, 10, 0, 0, 2.9, and 26.7% of exanthemas. Histopathological diagnosis was not associated with virus polymerase chain reaction (PCR) results. Detection of CMV, EBV, or HHV6 DNA but not ParvoB19 in skin and blood was associated with PCR results (p = 0.016; p < 0.001; p = 0.067; p = n.a.). Detection of CMV, EBV, HHV6, or ParvoB19 DNA in the skin was not significantly associated with patient, ASCT, or GvHD characteristics. Detection of ParvoB19 but not herpes virus DNA was associated with less immunosuppressive treatment (p = 0.015) and lower NRM (p = 0.041). In multivariate analyses, detection of ParvoB19 was associated with a lower NRM. CONCLUSIONS Detection of ParvoB19 DNA in exanthema after ASCT might be associated with lower NRM.
Vancomycin use and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation
Blood advances. 2020;4(12):2640-2643
Prevalence and significance of sarcopenia in multiple myeloma patients undergoing autologous hematopoietic cell transplantation
Bone marrow transplantation. 2020
Sarcopenia, defined as loss of muscle mass, can occur with aging. We conducted a single-center retrospective analysis to evaluate the impact of muscle quality in multiple myeloma (MM), a hematologic cancer of older adults, undergoing autologous hematopoietic cell transplantation (autoHCT). Healthy muscle was quantified by measuring the percent of high-density muscle within the L3 psoas muscle using a novel computed tomography method in 142 eligible patients. Early post-transplant complications were assessed in the first 100 days after transplant. Sarcopenia, defined as =80% high-density muscle, was found in 72 (51%) patients. Sarcopenic obesity, defined as sarcopenia and a BMI?=?30, was found in 32 (23%) patients. One or more early complications occurred in 22 (16%) patients. Cardiovascular events accounted for 36% of all complications. Patients with sarcopenia had more cardiac complications (12.5%) than patients without (2.9%, p?=?0.03). Multivariate analysis revealed increased BMI at transplant, but not sarcopenia, was associated with worse OS (hazard ratio: 1.11, 95% confidence interval: 1.02-1.22, p?=?0.02). Our analysis suggests that sarcopenia is prevalent in MM and associated with increased early post-transplant cardiovascular complications in MM. Obesity, regardless of sarcopenia, is associated with worse survival in MM. Our study generates hypothesis-generating data to risk-stratify patients being considered for autoHCT.
Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Frontiers in immunology. 2020;11:1505
Chronic graft-vs.-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that autoantibodies play an important role in the development of cGVHD. Anti-nuclear autoantibodies (ANA) is the most frequently detected autoantibodies in patients with cGVHD, but the role of anti-Ro52 autoantibodies (anti-Ro52) in cGVHD remains largely unknown. In this study, we analyzed autoantibodies from 84 patients after allo-HSCT, including 42 with active cGVHD and 42 without cGVHD. Autoantibodies were found in 36 (42.9%) patients. Among these autoantibody-positive patients, 28 (77.8%) patients had active cGVHD. The most frequent autoantibodies in patients with active cGVHD were ANA (50.0%), anti-Ro52 (28.6%) and anti-mitochondrial autoantibodies type 2 (4.8%). We further explored the association between anti-Ro52 and cGVHD. Patients with active cGVHD had higher anti-Ro52 levels than patients without cGVHD (P < 0.05). The increases of anti-Ro52 levels were more significant in patients with moderate/severe cGVHD compared to those of patients without cGVHD (P < 0.05). Stratified and multivariable logistic regression analysis demonstrated that moderate/severe cGVHD was an independent risk factor for the levels of anti-Ro52 (P < 0.01). ROC analysis confirmed anti-Ro52 as a risk factor for progression of skin cGVHD. Moreover, the anti-Ro52 levels were highly correlated with the levels of B cell-activating factor (BAFF) and IgG1 antibodies. Our study demonstrates that anti-Ro52 is associated with cGVHD. The increased levels of anti-Ro52 were associated with higher levels of BAFF and IgG1 antibodies, suggesting a mechanistic link between elevated anti-Ro52 levels and aberrant B cell homeostasis.
Post-transplant multimorbidity index and quality of life in patients with chronic graft-versus-host disease-results from a joint evaluation of a prospective German multicenter validation trial and a cohort from the National Institutes of Health
Bone marrow transplantation. 2020
Comorbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT) impairs quality of life (QoL), physical functioning, and survival. We developed a new standardized measure to capture comorbidity after transplantation, the Post-transplant Multimorbidity Index (PTMI) in a cohort of 50 long term survivors. We subsequently evaluated the content validity and impact on survival and QoL within a multicenter trial, including 208 patients (pts) after alloHSCT, who were prospectively evaluated applying the FACT-BMT, the Human Activity Profile (HAP), the SF-36 v.2, PTMI and the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). The most prevalent comorbidities were compensated arterial hypertension (28.4%), ambulatory infections (25.5%), iron overload (23%), mild renal function impairment (20%), and osteoporosis (13%). Applying the PTMI 13% of patients had no comorbidity, while 37.1% had 1-3 comorbidities, 27.4% had 4-6 comorbidities, and 13.5% had > 6 comorbidities. Chronic graft-versus-host disease (cGvHD) was significantly associated with the PTMI, while age and prior acute GvHD were not. In contrast, the HCT-CI was not associated with the presence of cGvHD. cGvHD was significantly associated with depression (r?=?0.16), neurological disease (r?=?0.21), osteoporosis (r?=?0.18) and nonmelanoma skin cancer (r?=?0.26). The PTMI demonstrated strong measurement properties and compared to the HCT-CI captured a wider range of comorbidities associated with cGvHD.
Risk factors for mixed chimerism in children with hemophagocytic lymphohistiocytosis after reduced toxicity conditioning
Pediatric blood & cancer. 2020;:e28523
BACKGROUND Reduced toxicity conditioning for hematopoietic stem cell transplantation of patients with hemophagocyticlymphohistiocytosis (HLH) results in favorable survival, however at the expense of relevant rates of mixed chimerism. Factors predisposing to mixed chimerism remain to be determined. PROCEDURE Patients with primary HLH transplanted 2009-2016 after treosulfan- or melphalan-based conditioning regimens were analyzed in a retrospective multicenter study for survival, engraftment, chimerism, and adverse events. Mixed chimerism was considered substantial if < 25% donor chimerism occurred and/or if secondary cell therapy was administered. Donor type, graft source, type of alkylating agent, type of serotherapy, and remission status were analyzed as potential risk factors in a multivariable logistic regression model. RESULTS Among 60 patients, engraftment was achieved in 95%, and the five-year estimated overall survival rate was 75%. Prevalence of any recipient chimerism was 48%. Substantial recipient chimerism was recorded in 32% of patients. Secondary post-HSCT cell therapy was administered in 30% of patients. A human leukocyte antigen (HLA)-mismatched donor (< 10/10) was the only significant risk factor for the occurrence of substantial recipient chimerism (P = 0.01; odds ratio, 5.8; CI 95%, 1.5-26.3). CONCLUSION The use of an HLA-matched donor is the most important factor to avoid substantial recipient chimerism following treosulfan -or melphalan-based conditioning in primary HLH.
The role of candidate genetic polymorphisms in the interaction between voriconazole and cyclosporine in patients undergoing allogeneic hematopoietic cell transplantation: An explorative study
Current research in translational medicine. 2020
PURPOSE To evaluate polymorphisms in genes of drug metabolizing enzymes and transporters involved in cyclosporine and/or voriconazole disposition among patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). METHODS DNA from forty patients was genotyped using the DMETPlus array. The average ratio of cyclosporine concentration/dose (C/D in (ng/mL)/(mg/kg)) per participant's weight was computed using available trough levels and daily doses. RESULTS The C/D cyclosporine ratio was significantly higher when it was administered with voriconazole as compared to when it was administered alone: median: 116.75 vs. 25.40 (ng/mL)/(mg/kg) with and without voriconazole respectively, (P < 0.001). There was also a significant association between the C/D cyclosporine ratio combined with voriconazole and the ABCB1 2677 G > T > A (rs2032582) genetic polymorphism (P = 0.05). In parallel, ABCB1 variant allele carriers had higher creatinine in combination therapy with a median creatinine (mg/dL) of 0.74 vs. 0.56 for variant allele carriers vs. reference; P = 0.003. Interestingly, CYP2C9, CYP2C19, and CYP3A5 extensive metabolizers tended to be associated with lower cyclosporine C/D ratio when combined with voriconazole, but the results were not statistically significant. CONCLUSION To the best of our knowledge, this is the first pharmacogenetic study on the interaction between voriconazole and cyclosporine in patients undergoing allo-HCT. Results suggest that the ABCB1 2677 G > T > A genetic polymorphism plays a role in this interaction with cyclosporine related nephrotoxicity. Pre-emptive genotyping for this genetic variant may be warranted for cyclosporine dose optimization. Larger studies are needed to potentially show significant associations with more candidate genes such as CYP3A4/5, CYP2C9, and CYP2C19, among others.
Impact of donor and recipient characteristics on graft-versus-host disease and survival in HLA-matched sibling hematopoietic stem cell transplantation
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2020;:102743
OBJECTIVE To analyze the impact of donor- and recipient-related factors on Graft-versus-host disease (GVHD) and overall survival of transplantation from matched sibling donors. METHOD we retrospectively analyzed the clinical features of 68 consecutive hematological patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched sibling from 2011 and 2017. RESULTS The incidence of - acute GVHD (aGVHD) and chronic GVHD (cGVHD) after transplantation was 13.6 % and 19.7 %, respectively. We also noted the donor and recipient characteristics had no impact on - aGVHD incidence.We found sex mismatch (F-M) did not increase the risk of cGVHD in the model if a female donor was younger than 30 years (P = 1.000), but cGVHD increased if the female donor was ≥30 years (P = 0.002). Recipients≥40 years undergoing HCT from donors ≥30 years were at higher risk for cGVHD (P = 0.021). Development of - aGVHD and cGVHD had no effect on overall survival (P = 0.159, 0.081). Non-remission status at allo-HCT was linked to lower overall survival (P = 0.001). CONCLUSION The incidence of cGVHD was higher when male recipients received hematopoietic progenitor cells from female ≥30 years donors, and when older than 40 years recipients received hematopoietic progenitor cells from ≥30 years donors. Patients in non-remission status at allo-HCT was inclined to have lower overall survival.
Long-term stability of microbiome diversity and composition in fecal samples stored in eNAT medium
Fecal samples collected for microbiome analyses are typically frozen to avoid postcollection changes in microbial composition. eNAT is a guanidine thiocyanate-based medium that stabilizes microbial DNA and allows safe specimen handling and shipping by inactivating microorganisms. We collected fecal samples (n = 50) from children undergoing hematopoietic stem cell transplantation. We divided samples into three aliquots: (a) stored in RNAlater and immediately transferred to -80 degrees C; (b) stored in eNAT medium and immediately transferred to -80 degrees C; and (c) stored in eNAT medium at ambient temperature (~20 degrees C) for 30 days prior to transfer to -80 degrees C. Mean (standard deviation) Shannon diversity and Chao1 indices in sample aliquots were 2.05 (0.62) and 23.8 (16.6), respectively. Comparing samples frozen immediately in RNAlater to samples frozen immediately in eNAT, there were no differences in Shannon diversity (p = .51), Chao1 richness (p = .66), and overall microbiome composition (p = .99). Comparing eNAT samples frozen immediately to samples stored at ambient temperature, we identified no differences in Shannon diversity (p = .65), Chao1 richness (p = .87), and overall microbiome composition (p = .99). Storage of fecal samples in eNAT at ambient temperature for 30 days did not alter microbiome richness, diversity, or composition. eNAT may be a useful medium for fecal microbiome studies, particularly when cold chain storage is unavailable.
Impact of Clostridioides difficile infection on the outcome of patients receiving a hematopoietic stem cell transplantation
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2020
OBJECTIVES Clostridioides difficile infections (CDI) are common in autologous (auto-HSCT) or allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. However, the impact of CDI on patient outcome is controversially discussed. We conducted this study to examine the impact of CDI on patient outcome. METHODS We performed a retrospective single center study including 191 lymphoma patients receiving an auto-HSCT and 276 acute myeloid leukemia (AML) patients receiving an allo-HSCT. The primary endpoint was overall survival (OS). Secondary endpoints were causes of death and, for the allo-HSCT cohort, GvHD- and relapse-free survival (GRFS). RESULTS The prevalence of CDI was 17.6% in the AML allo-HSCT and 7.3% in the lymphoma auto-HSCT cohort. A higher prevalence of blood stream infections, but no differences concerning OS or cause of death were found for patients with CDI in the auto-HSCT cohort. In the allo-HSCT cohort, OS and GRFS were similar between both groups. However, the main cause of death was relapse among non-CDI patients, but infectious disease in the CDI group with less deaths due to relapse. CONCLUSIONS CDI was not associated with a worse survival in patients receiving a hematopoietic stem cell transplantation and even came along with less relapse-related deaths in the AML allo-HSCT cohort.