scholarly journals Cytomegalovirus (CMV) Cell-Mediated Immunity and CMV Infection After Allogeneic Hematopoietic Cell Transplantation: The REACT Study

2020 ◽  
Author(s):  
Roy F Chemaly ◽  
Lynn El Haddad ◽  
Drew J Winston ◽  
Scott D Rowley ◽  
Kathleen M Mulane ◽  
...  
Keyword(s):  
At Risk ◽  
Hematopoietic Cell Transplantation ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Cell Mediated Immunity ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Patients At Risk

Abstract Background Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. CMV cell-mediated immunity (CMV-CMI) as determined by a peptide-based enzyme-linked immunospot (ELISPOT) CMV assay may identify patients at risk for clinically significant CMV infection (CS-CMVi). Methods The CS-CMVi was defined as CMV viremia and/or disease necessitating antiviral therapy. CMV-CMI was characterized as high when the intermediate-early 1 (IE-1) antigen spot counts (SPCs) were >100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both >100 SPCs per 250 000 cells (cutoff 2), and a low CMV-CMI when SPCs were below these thresholds. In this prospective multicenter study, we evaluated CMV-CMI every 2 weeks from the pretransplant period until 6 months posttransplantation in 241 allo-HCT recipients with positive CMV serostatus. The primary endpoint was CS-CMVi occurring within 2 weeks of the last measurement of CMV-CMI. Results CS-CMVi occurred in 70 allo-HCT recipients (29%). CMV-CMI was low in patients who experienced CS-CMVi (94%), whereas those who had a high CMV-CMI were less likely to have CS-CMVi (P < .0001). Patients with CS-CMVi had higher all-cause mortality (P = .007), especially those with low CMV-CMI (P = .035). On multivariable analysis, CMV-CMI, sex, race, antithymocyte globulin, and steroid use were independent predictors of CS-CMVi, and the time from transplant to engraftment was the only predictor of mortality. Conclusions Measurement of CMV-CMI using a novel ELISPOT assay would be useful clinically to monitor allo-HCT recipients and distinguish between those at risk of developing CS-CMVi and requiring antiviral prophylaxis or therapy and those who are protected.

scholarly journals Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant

2018 ◽  
Vol 24 (3) ◽  
pp. S385-S386
Author(s):  
Annette Artau ◽  
Samuel L. Aitken ◽  
Firas El Chaer ◽  
Amrita Prayag ◽  
Lynn El Haddad ◽  
...  
Keyword(s):  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant

scholarly journals 1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S486-S486
Author(s):  
Annette Artau ◽  
Samuel L Aitken ◽  
Marjorie Batista ◽  
Firas El Chaer ◽  
Amrita Prayag ◽  
...  
Keyword(s):  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant

scholarly journals Steroid-dependent acute GVHD after allogeneic hematopoietic cell transplantation: risk factors and clinical outcomes

2021 ◽  
Vol 5 (5) ◽  
pp. 1352-1359
Author(s):  
Najla El Jurdi ◽  
Ahmad Rayes ◽  
Margaret L. MacMillan ◽  
Shernan G. Holtan ◽  
Todd E. DeFor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Steroid Dependent ◽  
Steroid Sensitive

Abstract Acute graft-versus-host disease (aGVHD) has various risk factors and outcomes. We defined distinct aGVHD treatment response groups based on response to first-line corticosteroids: steroid sensitive (SS), steroid resistant (SR), and the rarely studied steroid dependent (SD) aGVHD. In 1143 consecutive adult and pediatric allogeneic hematopoietic cell transplant recipients, 385 (34%) developed aGVHD, with 10% having SS aGVHD, 9% SD aGVHD, and 14% SR aGVHD. The only factor significantly associated with SD in comparison with SS was older age (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4-11.3, when comparing 18- to 60-year-olds with <18-year-olds). Factors significantly associated with SR in comparison with SS were unrelated donor (OR, 3.0; 95% CI, 1.2-7.4) and Minnesota high-risk aGVHD (OR, 2.4; 95% CI, 1.3-4.6). SR aGVHD was independently associated with higher risk for 2-year overall mortality (hazards ratio [HR], 1.8; 95% CI, 1.2-2.8) and nonrelapse mortality (NRM; HR, 2.1; 95% CI, 1.2-3.9). SS and SD GVHD groups had similar overall survival and NRM. The cumulative incidence of chronic GVHD was highest in the SD group, followed by the SR and SS groups (46%, 41%, and 29%, respectively). SD and SS GVHD had similar prognoses, both markedly better than those of the SR groups.

scholarly journals Contribution of Sleep Disruption and Sedentary Behavior to Fatigue in Survivors of Allogeneic Hematopoietic Cell Transplant

2021 ◽  
Author(s):  
Ashley M Nelson ◽  
Kelly A Hyland ◽  
Brent Small ◽  
Brittany Kennedy ◽  
Asmita Mishra ◽  
...  
Keyword(s):  
Sedentary Behavior ◽  
Hematopoietic Cell Transplantation ◽  
Sleep Efficiency ◽  
Hematopoietic Cell ◽  
Poor Sleep ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Disturbed Sleep ◽  
Objectively Measured

Abstract Background Fatigue is a prominent quality of life concern among recipients of hematopoietic cell transplantation (HCT). Purpose The present study investigated whether objectively measured sleep efficiency and sedentary behavior are related to greater reports of fatigue. Methods Eighty-two allogeneic HCT recipients who were 1–5 years post-transplant and returning for a follow-up visit participated (age M = 56, 52% female, 56% leukemia). They wore an actigraph assessing sleep efficiency and sedentary behavior for one week and completed an electronic log assessing fatigue each evening during the same period. Results Twenty-six percent of patients reported clinically meaningful fatigue. On average, fatigue was mild (M = 2.5 on 0–10 scale, SD = 2.0), sleep was disturbed (sleep efficiency M = 78.9%, SD = 8.9), and patients spent the majority of time in sedentary (M = 55.4%, SD = 10.2) or light (M = 35.9%, SD = 8.6) activity. Multilevel model analysis of between-person differences indicated that patients who experienced less efficient sleep the previous evening provided greater evening reports of average fatigue, b = –0.06, 95% CI (–0.11, –0.01). Similarly, within-person analyses indicated that when patients experienced less efficient sleep the previous evening or were more sedentary as compared to their average, they provided greater evening reports of average fatigue, b = –0.02, 95% CI (–0.05, –0.004); b = 4.46, 95% CI (1.95, 6.97), respectively. Conclusions Findings demonstrate that poor sleep and daily sedentary behavior are related to evening reports of fatigue and should be considered modifiable targets for intervention.

scholarly journals Cytomegalovirus Infection in Solid Organ and Hematopoietic Cell Transplantation: State of the Evidence

2020 ◽  
Vol 221 (Supplement_1) ◽  
pp. S23-S31 ◽  
Author(s):  
Ghady Haidar ◽  
Michael Boeckh ◽  
Nina Singh
Keyword(s):  
T Cell ◽  
Hematopoietic Cell Transplantation ◽  
Solid Organ Transplantation ◽  
Immune Monitoring ◽  
Hematopoietic Cell ◽  
Preemptive Therapy ◽  
Solid Organ ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Cell Transplant

Abstract This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT) but is associated with high rates of neutropenia and delayed-onset postprophylaxis disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients but is infrequently utilized after SOT due to logistical considerations, though these may be overcome by novel methods to monitor CMV viremia using self-testing platforms. We review recent developments in CMV immune monitoring, vaccination, and monoclonal antibodies, all of which have the potential to become part of integrated strategies that rely on viral load monitoring and immune responses. We discuss novel therapeutic options for drug-resistant or refractory CMV infection, including maribavir, letermovir, and adoptive T-cell transfer. We also explore the role of donor factors in transmitting CMV after SOT. Finally, we propose a framework with which to approach CMV prevention in the foreseeable future.

scholarly journals Increasing access to allogeneic hematopoietic cell transplant: an international perspective

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 264-274
Author(s):  
Vanderson Rocha ◽  
Giancarlo Fatobene ◽  
Dietger Niederwieser ◽  
Keyword(s):  
Health Care ◽  
Information Exchange ◽  
Hematopoietic Cell Transplantation ◽  
International Perspective ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Resource Constrained ◽  
Hematopoietic Cell Transplant ◽  
Economic Changes ◽  
Allogeneic Hematopoietic Cell Transplant

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly complex, costly procedure for patients with oncologic, hematologic, genetic, and immunologic diseases. Demographics and socioeconomic status as well as donor availability and type of health care system are important factors that influence access to and outcomes following allo-HCT. The last decade has seen an increase in the numbers of allo-HCTs and teams all over the world, with no signs of saturation. More than 80 000 procedures are being performed annually, with 1 million allo-HCTs estimated to take place by the end of 2024. Many factors have contributed to this, including increased numbers of eligible patients (older adults with or without comorbidities) and available donors (unrelated and haploidentical), improved supportive care, and decreased early and late post-HCT mortalities. This increase is also directly linked to macro- and microeconomic indicators that affect health care both regionally and globally. Despite this global increase in the number of allo-HCTs and transplant centers, there is an enormous need for increased access to and improved outcomes following allo-HCT in resource-constrained countries. The reduction of poverty, global economic changes, greater access to information, exchange of technologies, and use of artificial intelligence, mobile health, and telehealth are certainly creating unprecedented opportunities to establish collaborations and share experiences and thus increase patient access to allo-HCT. A specific research agenda to address issues of allo-HCT in resource-constrained settings is urgently warranted.

Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant

Blood ◽  
2004 ◽  
Vol 104 (10) ◽  
pp. 3386-3392 ◽  
Author(s):  
Karen L. Syrjala ◽  
Sureyya Dikmen ◽  
Shelby L. Langer ◽  
Sari Roth-Roemer ◽  
Janet R. Abrams
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Population Based ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Neurocognitive Performance ◽  
Long Term Effects ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Neuropsychologic Testing

Abstract Research indicates that myeloablative hematopoietic cell transplantation (HCT) impairs neurocognitive function. However, prospective studies on long-term effects are lacking. This longitudinal study examined neurocognitive changes over the first year in 142 adult recipients of allogeneic HC transplants who received neuropsychologic testing before transplantation and again after 80 days and 1 year. Age-, sex-, and education-adjusted population-based standardized scores were used for normative comparisons. Performance on all tests declined from before transplantation to 80 days (P < .05) and improved by 1 year (P < .05), returning to pretransplantation levels on all tests except for grip strength and motor dexterity. Although verbal fluency and memory recovered by 1 year, both were below norms at all 3 testing times (P < .01). Logistic regressions indicated that patients without chemotherapy, other than hydroxyurea, previous to HCT and patients not receiving chronic graft-versus-host disease (GVHD) medication at 1 year had lower risk of impaired function (P < .05). In conclusion, HCT was associated with significant generalized decline in neurocognitive performance at 80 days, with subsequent recovery to pretransplantation levels by 1 year for most survivors, except on motor tasks. Results indicate that long-term cognitive decrements, as distinct from motor disabilities, infrequently derive directly from HCT. (Blood. 2004;104:3386-3392)

scholarly journals Targeting the CD27-CD70 Pathway to Improve Outcomes in Both Checkpoint Immunotherapy and Allogeneic Hematopoietic Cell Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Forat Lutfi ◽  
Long Wu ◽  
Sarah Sunshine ◽  
Xuefang Cao
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitor ◽  
Hematopoietic Cell ◽  
Mixed Chimerism ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Novel Approach ◽  
Immune Therapies

Immune checkpoint inhibitor therapies and allogeneic hematopoietic cell transplant (alloHCT) represent two distinct modalities that offer a chance for long-term cure in a diverse array of malignancies and have experienced many breakthroughs in recent years. Herein, we review the CD27-CD70 co-stimulatory pathway and its therapeutic potential in 1) combination with checkpoint inhibitor and other immune therapies and 2) its potential ability to serve as a novel approach in graft-versus-host disease (GVHD) prevention. We further review recent advances in the understanding of GVHD as a complex immune phenomenon between donor and host immune systems, particularly in the early stages with mixed chimerism, and potential novel therapeutic approaches to prevent the development of GVHD.

scholarly journals Detection and treatment of cerebral toxoplasmosis in an aplastic pediatric post-allogeneic hematopoietic cell transplant patient: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Danielle Brewer ◽  
Margaret L. MacMillan ◽  
Mark R. Schleiss ◽  
Satja Issaranggoon Na Ayuthaya ◽  
Jo-Anne Young ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Cerebral Toxoplasmosis ◽  
Hematopoietic Cell Transplant ◽  
Cell Free Dna ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Free Dna ◽  
Invasive Method

Abstract Background Cerebral toxoplasmosis infection presents with non-specific neurologic symptoms in immunocompromised patients. With lack of measurable adaptive immune responses and reluctance to sample affected brain tissue, expedient diagnosis to guide directed treatment is often delayed. Case presentation We describe the use of cerebrospinal fluid polymerase chain reaction and plasma cell-free DNA technologies to supplement neuroimaging in the diagnosis of cerebral toxoplasmosis in an immunocompromised pediatric patient following allogeneic hematopoietic cell transplantation for idiopathic severe aplastic anemia. Successful cerebral toxoplasmosis treatment included antibiotic therapy for 1 year following restoration of cellular immunity with an allogeneic stem cell boost. Conclusions Plasma cell-free DNA technology provides a non-invasive method of rapid diagnosis, improving the likelihood of survival from often lethal opportunistic infection in a high risk, immunocompromised patient population.

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