scholarly journals 1762. Genotype Prevalence and Molecular Characteristics of Human Adenovirus in Pediatric Hematopoietic Stem Cell Transplant Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S648-S649
Author(s):  
Jesse Blumenstock ◽  
Despoina M Galetaki ◽  
Craig L K Boge ◽  
Sydney G Shuster ◽  
Alix Seif ◽  
...  
Keyword(s):  
Molecular Typing ◽  
Human Adenovirus ◽  
Common Species ◽  
Molecular Characteristics ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Convenience Sample ◽  
Hematopoietic Stem ◽  
Clinical Specimens ◽  
The Impact

Abstract Background Human adenovirus (HAdV) is a documented source of morbidity and mortality after hematopoietic cell transplant (HCT); however, there are limited data documenting HAdV species and type in this population. Understanding the molecular characteristics of HAdV could inform the development and assessment of interventions. The species and type of HAdV-positive specimens are detailed using an archived convenience sample of specimens obtained in pediatric HCT recipients. Methods The cohort included autologous and allogeneic HCT recipients between January 2000 and December 2013. An archived clinical repository of frozen specimens was interrogated to identify residual HAdV-positive specimens, which were sent to Lovelace Respiratory Research Institute (LRRI) to determine species and type. Medical chart review was performed to determine whether an isolate was related to HAdV disease or HAdV-attributable death. Results There were 547 HAdV PCR-positive clinical specimens from 87 HCT recipients. Of the 547 specimens, 289 were identified from an archived repository and sent to LRRI to determine species and type, and HAdV was successfully isolated and typed from 61 (Figure 1). Species C was the most common species (59.0%) with C2 being the most frequent type (34.4%). Of the 15 recipients with type C2, plasma was the most common specimen source (57.1%). Three recipients with C2 had this species and type detected from multiple sources (Tables 1 and 2). Among those with a typing result, type C2 also was responsible for 33.3% of all HAdV-attributed disease and 38.1% of all HAdV-attributed death. Conclusion Species C was the most common species to be isolated in a convenience sample of HAdV-positive clinical specimens from a single-center cohort of pediatric HCT recipients. Type C2 was most commonly associated with HAdV disease and attributable death. These results suggest HAdV species and type influence the impact of HAdV in this patient population. The findings need to be confirmed in prospective cohorts but suggest real-time molecular typing may be relevant and provide possible targets for the development of future interventions. These results must be interpreted with caution; not all clinical specimens were available for molecular typing, and it is possible C2 is easier to isolate from archived specimens. Disclosures All authors: No reported disclosures.

scholarly journals Impact of Obesity on Voriconazole Pharmacokinetics among Pediatric Hematopoietic Cell Transplant Recipients

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Takuto Takahashi ◽  
Angela R. Smith ◽  
Pamala A. Jacobson ◽  
James Fisher ◽  
Nathan T. Rubin ◽  
...  
Keyword(s):  
Linear Regression Analysis ◽  
Area Under The Curve ◽  
Therapeutic Index ◽  
Multiple Linear Regression Analysis ◽  
Future Research ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Hematopoietic Stem ◽  
Minimum Concentration ◽  
The Impact

ABSTRACT Voriconazole (VCZ) is an antifungal agent with wide inter- and intrapatient pharmacokinetic (PK) variability and narrow therapeutic index. Although obesity was associated with higher VCZ trough concentrations in adults, the impact of obesity had yet to be studied in children. We characterized the PK of VCZ in obese patients by accounting for age and CYP2C19 phenotype. We conducted intensive PK studies of VCZ and VCZ N-oxide metabolite in 44 hematopoietic stem cell transplantation (HSCT) recipients aged 2 to 21 years who received prophylactic intravenous VCZ every 12 hours (q12h). Blood samples were collected at 5 and 30 minutes; at 1, 3, 6, and 9 hours after infusion completion; and immediately before the next infusion start. We estimated PK parameters with noncompartmental analysis and evaluated for an association with obesity by multiple linear regression analysis. The 44 participants included 9 (20%) with obesity. CYP2C19 metabolism phenotypes were identified as normal in 22 (50%), poor/intermediate in 13 (30%), and rapid/ultrarapid in 9 patients (21%). Obesity status significantly affects the VCZ minimum concentration of drug in serum (Cmin) (higher by 1.4 mg/liter; 95% confidence interval [CI], 0.0 to 2.8; P = 0.047) and VCZ metabolism ratio (VCZRATIO) (higher by 0.4; 95% CI, 0.0 to 0.7; P = 0.03), while no association was observed with VCZ area under the curve (AUC) (P = 0.09) after adjusting for clinical factors. A younger age and a CYP2C19 phenotype were associated with lower VCZ AUC. Obesity was associated with decreased metabolism of VCZ to its inactive N-oxide metabolite and, concurrently, increased VCZ Cmin, which is deemed clinically meaningful. Future research should aim to further characterize its effects and determine a proper dosing regimen for the obese.

Donor T Cells from B Cell Deficient Mice Inhibit B Cell Development in Normal Recipients after Hematopoietic Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3265-3265
Author(s):  
Antonia M.S. Mueller ◽  
Jessica A. Allen ◽  
David Miklos ◽  
Judith A. Shizuru
Keyword(s):  
T Cells ◽  
B Cell ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Hematopoietic Stem ◽  
Donor Chimerism ◽  
Donor T Cells ◽  
The Impact

Abstract Allogeneic hematopoietic cell transplant (HCT) recipients often exhibit B cell (BC) lymphopenia due, in part, to graft-versus-host-disease (GVHD). Here, we studied the impact of donor T cells (TC) on BC deficiency post minor antigen-mismatched HCT. Following lethal irradiation, BALB.B mice were given FACS purified hematopoietic stem cells (HSC: cKIT+Thy1.1loLin-Sca-1+) alone, with whole splenocytes (SP), CD4 or CD8 TC from minor antigen-mismatched C57BL/6 (B6) mice. Chimerism analyses were performed on day (d) 30, 60, and 90. When pure HSC were transplanted, BCs reconstituted promptly (median 33% of lymphocytes [d30]; 61% [d60]; 74% [d90]), whereas TC engraftment was retarded and did not achieve full donor chimerism. Addition of SP or CD4 TCs, or to a lesser degree CD8 TCs, delayed BC reconstitution, with extremely low percentages of BCs beyond d60. This BC suppression correlated with the degree of acute GVHD, and BC numbers increased with recovery from GVHD. Additionally, this BC suppression was in stark contrast to TC development, with TC transfer resulting in early conversion to full donor chimerism. To test if previous events in the donor sensitize TCs against BC features (e.g. minor antigens), thereby promoting anti-BC cytotoxicity post-HCT, TCs from B6 muMT mice were co-transplanted with HSC. muMT mice are devoid of mature BCs because they lack the mu chain; consequently, their TCs were not exposed to BCs prior to transfer. Remarkably, BC engraftment was completely prevented through d90. TCs regenerated faster, but the vast majority originated from spleen and not HSC. To differentiate this lack of BC engraftment from GVHD-associated, alloreactive BC lymphopenia, syngenic B6 recipients were used. Again, initially complete blockade of BC engraftment was observed, although this suppression was overcome earlier post-HCT as compared to the minor-mismatched pair (median % BC d60: ’HSC only’ recipients 52%; +CD4 17%; +CD8 48%). To clarify if this phenomenon was a purely cytotoxic reaction of muMT TC against BCs, we used WT B6 HSC +/− SP as donors and lethally or sublethally irradiated muMT mice as recipients. All groups, including sublethally irradiated animals, where host muMT TC were still present, engrafted BCs making a direct anti-BC cytotoxicity unlikely as the sole cause of the BC inhibition. FACS analysis of bone marrow was used to assess the developmental stages of BCs (Hardy fractions (Fr.) A-F) and revealed GVHD recipients with peripheral B lymphopenia have a shift of B220+ cells from more mature Fr. D-F to immature Fr. A-C stages and a lower proportion of IgM expressing BC. Recipients of the muMT TCs showed, in addition to a shift to more immature stages, a clear block in BC development with an absent switch to the expression of IgM (stage D to E)(Fig. 1). In conclusion, muMT TCs are capable of blocking BC maturation when transferred into WT mice, suggesting defective TC activity in muMT animals necessary for the co-development of both BCs and TCs. Furthermore, this study provides evidence that mature TCs are capable of interfering with BC regeneration post-HCT. Hence, our HCT combinations using WT and muMT B6 mice provide a powerful tool to study the role of TC function in the process of donor BC development post-HCT.

scholarly journals Race as a Factor in Donor Selection and Survival of Children with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplant in Florida

2021 ◽  
Author(s):  
Biljana Horn ◽  
Deepak Chellapandian ◽  
Nikhil Lamba ◽  
Gauri Sunkersett ◽  
Jorge GalvezSilva ◽  
...  
Keyword(s):  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hla Matching ◽  
Hematopoietic Cell Transplant ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Related Donor ◽  
The Impact ◽  
To Receive

Background Previous studies have explored post-hematopoietic cell transplant (HCT) outcomes by race in adults; however, pediatric data addressing this topic are scarce. Procedure This retrospective registry study included 238 White (W) and 57 Black (B) children with hematologic malignancies (HM) receiving first allogeneic HCT between 2010 and 2019 in one of five Florida pediatric HCT centers. Results We found no differences between W and B children by transplant characteristics, other than donor type. There was a significant difference in use of HLA-mismatched donors (HLA-MMD) (53% W, 71% B, p=0.01). When comparing HLA-MMD use to fully HLA-matched donors, B had RR of 1.47 [95% CI 0.7-3] of receiving a mismatched unrelated donor (MMUD), RR of 2.34 [95% CI 1.2-4.4] of receiving a mismatched related donor (MMRD), and a RR of 1.9 [95% CI 0.99-3.6] of receiving a mismatched cord blood donor (MMCBD) HCT, respectively. There was no significant difference in the incidence of aGVHD (48% W, 35% B), p=0.1 or cGVHD (19% W 28% B, p=0.1), or primary cause of death. Overall 24-month survival was 61% [95% CI 54-68%] for W, and 60% [95% CI 38-68] for B children, log-rank p=0.72. While HLA matching improved survival in W children, the number of B children receiving HLA-matched HCT was too small to identify the impact of HLA matching on survival. Conclusions In this contemporary cohort of children with HM we found that B children were more likely to receive HLA-MMD transplants, but this did not adversely affect survival or GVHD rates.

scholarly journals Effect of Early Post-Transplantation Tacrolimus Concentration on the Risk of Acute Graft-Versus-Host Disease in Allogenic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 613
Author(s):  
Nidhi Sharma ◽  
Qiuhong Zhao ◽  
Bin Ni ◽  
Patrick Elder ◽  
Marcin Puto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Tacrolimus Concentration ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
The Impact ◽  
Risk Of Relapse ◽  
Acute Graft

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.

scholarly journals A review on recipients of hematopoietic stem cell transplantation patients with COVID-19 infection

2021 ◽  
Vol 8 ◽  
pp. 204993612110132
Author(s):  
Kamal Kant Sahu ◽  
Ahmad Daniyal Siddiqui
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Real World Data ◽  
Hematopoietic Stem ◽  
Geographical Regions

For the last few months, various geographical regions and health sectors have been facing challenges posed by the current COVID-19 pandemic. COVID-19 has led to significant disruption in the normal functioning of potentially life-saving therapies of hematopoietic cell transplant and chimeric antigen receptor therapy. As transplant physicians are gaining more information and experience regarding the undertaking of these complex procedures during the ongoing COVID-19 pandemic, we believe it is important to discuss the challenges faced, prognostic risk factors, and outcomes of COVID-19 in post-hematopoietic stem cell transplantation patients based on the available real-world data.

scholarly journals The Hematopoietic Cell Transplant Pharmacist: A Call to Action

Pharmacy ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 3 ◽  
Author(s):  
Amber Clemmons
Keyword(s):  
Cellular Therapy ◽  
Pharmacy Practice ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Call To Action ◽  
American Society ◽  
State Of The Science ◽  
Available Information ◽  
The Impact

Recently, the required training and credentials for as well as the various roles of the hematopoietic cell transplant (HCT) pharmacist have been endorsed by the leading organizations in cellular therapy, the American Society of Transplant and Cellular Therapy and the European Society of Blood and Bone Marrow Transplantation. While these documents establish the roles a HCT pharmacist can fulfill within the multi-disciplinary team, few reports have evaluated the impact of the HCT pharmacist on clinical, financial, or quality outcomes. Further, a paucity of information has been reported on types of practice models, such as the use of collaborative practice agreements, or described effective methods to overcome the barriers to the increased utilization of HCT pharmacists. Herein, a brief summary of available information is provided to aid readers in understanding the state of the science for pharmacists practicing in this specialty with the goal to stimulate further research to justify the roles of HCT pharmacists and the correlation of such research to various outcome measures. Practitioners are encouraged to build upon this existing knowledge to create the novel integration and elevation of pharmacy practice to improve outcomes for patients, providers, and payors.

scholarly journals Immunosuppressive Compounds Affect the Fungal Growth and Viability of Defined Aspergillus Species

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 273 ◽  
Author(s):  
Stanislaw Schmidt ◽  
Michael Hogardt ◽  
Asuman Demir ◽  
Frauke Röger ◽  
Thomas Lehrnbecher
Keyword(s):  
Fungal Growth ◽  
Invasive Fungal Disease ◽  
Inhibitory Effect ◽  
Immunosuppressive Drugs ◽  
Aspergillus Species ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Species Specific ◽  
The Impact

Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.

scholarly journals The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

2019 ◽  
Vol 3 (4) ◽  
pp. 670-680 ◽  
Author(s):  
Moshe Yeshurun ◽  
Daniel Weisdorf ◽  
Jacob M. Rowe ◽  
Martin S. Tallman ◽  
Mei-Jie Zhang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Low Grade ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Graft Versus Leukemia ◽  
The Impact ◽  
Risk Of Relapse

Abstract Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

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