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.

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 (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.

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.

scholarly journals The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease

Blood ◽  
2017 ◽  
Vol 129 (8) ◽  
pp. 927-933 ◽  
Author(s):  
Anna Staffas ◽  
Marina Burgos da Silva ◽  
Marcel R. M. van den Brink
Keyword(s):  
Intestinal Microbiota ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Experimental Studies ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Host Disease ◽  
Graft Versus Host ◽  
Allogeneic Hematopoietic Cell Transplant

AbstractHematopoietic cell transplantation (HCT) is a critical treatment of patients with high-risk hematopoietic malignancies, hematological deficiencies, and other immune diseases. In allogeneic HCT (allo-HCT), donor-derived T cells recognize host tissues as foreign, causing graft-versus-host disease (GVHD) which is a main contributor to morbidity and mortality. The intestine is one of the organs most severely affected by GVHD and research has recently highlighted the importance of bacteria, particularly the gut microbiota, in HCT outcome and in GVHD development. Loss of intestinal bacterial diversity is common during the course of HCT and is associated with GVHD development and treatment with broad-spectrum antibiotics. Loss of intestinal diversity and outgrowth of opportunistic pathogens belonging to the phylum Proteobacteria and Enterococcus genus have also been linked to increased treatment-related mortality including GVHD, infections, and organ failure after allo-HCT. Experimental studies in allo-HCT animal models have shown some promising results for prebiotic and probiotic strategies as prophylaxis or treatment of GVHD. Continuous research will be important to define the relation of cause and effect for these associations between microbiota features and HCT outcomes. Importantly, studies focused on geographic and cultural differences in intestinal microbiota are necessary to define applicability of new strategies targeting the intestinal microbiota.

scholarly journals Case Report: Immune Dysregulation Due to Toxoplasma gondii Reactivation After Allogeneic Hematopoietic Cell Transplant

2021 ◽  
Vol 9 ◽  
Author(s):  
Robert B. Lindell ◽  
Michael S. Wolf ◽  
Alicia M. Alcamo ◽  
Michael A. Silverman ◽  
Daniel E. Dulek ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Hematopoietic Cell Transplantation ◽  
Altered Mental Status ◽  
Immune Dysregulation ◽  
Multiple Organ ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
High Index Of Suspicion

Disseminated toxoplasmosis is an uncommon but highly lethal cause of hyperferritinemic sepsis after hematopoietic cell transplantation (HCT). We report two cases of disseminated toxoplasmosis from two centers in critically ill adolescents after HCT: a 19-year-old who developed fever and altered mental status on day +19 after HCT and a 20-year-old who developed fever and diarrhea on day +52 after HCT. Both patients developed hyperferritinemia with multiple organ dysfunction syndrome and profound immune dysregulation, which progressed to death despite maximal medical therapies. Because disseminated toxoplasmosis is both treatable and challenging to diagnose, it is imperative that intensivists maintain a high index of suspicion for Toxoplasma gondii infection when managing immunocompromised children, particularly in those with known positive T. gondii serologies.

Unintended Consequences of Pretransplant Vancomycin-Resistant Enterococcus Screening on Antimicrobial Stewardship Among Allogeneic Hematopoietic Cell Transplant Recipients

2018 ◽  
Vol 39 (6) ◽  
pp. 730-733 ◽  
Author(s):  
Erica J. Stohs ◽  
Trenton MacAllister ◽  
Steven A. Pergam ◽  
Elizabeth M. Krantz ◽  
Rupali Jain ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Unintended Consequences ◽  
Hematopoietic Cell ◽  
Antimicrobial Use ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

We examined vancomycin-resistant enterococci (VRE)-directed antimicrobial use and VRE bacteremia in a cohort of allogeneic hematopoietic cell transplantation patients from a center where VRE screening is standard prior to transplant. In this cohort, VRE bacteremia (VREB) was infrequent. In patients without VREB, colonized patients received VRE therapy more often than noncolonized patients.Infect Control Hosp Epidemiol2018;39:730–733

Optimizing the use of trimethoprim-sulfamethoxazole for prevention of PCP and opportunistic infections in allogeneic hematopoietic cell transplant recipients.

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 138-138 ◽  
Author(s):  
Emily Baneman ◽  
Nina Kim ◽  
Meenakshi Rana ◽  
Anne Sigrid Renteria ◽  
Amir S. Steinberg ◽  
...  
Keyword(s):  
Real Time ◽  
Hematopoietic Cell Transplantation ◽  
Opportunistic Infections ◽  
Liver Function Tests ◽  
Pneumocystis Pneumonia ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Provider Education ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant

138 Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is preferred for prevention of Pneumocystis pneumonia (PCP), toxoplasmosis and other opportunistic infections after allogeneic hematopoietic cell transplantation (HCT), but it is often withheld due to potential adverse events (AE). From July 2016-June 2017 we observed that 31% of allogeneic HCT recipients at our hospital were prescribed TMP-SMX throughout the high risk period (day +30-180). Therefore, we developed an intervention to explore reasons for such a low prescription rate and to optimize TMP-SMX use. Methods: Our institution’s HCT practice guidelines were revised to include indications for TMP-SMX and alternative agents for PCP and Toxoplasma prophylaxis and specific clinical and laboratory criteria for withholding TMP-SMX. Education on the guidelines was provided to transplant clinicians. Outpatient encounters were prospectively audited from January to April 2018. Providers received real-time feedback with recommendations in accordance with our guidelines prior to patients’ visits. Results: We reviewed 321 outpatient encounters among 112 patients. Seventy-six (68%) patients were on TMP-SMX prophylaxis at the first reviewed encounter. Cytopenias were the most common reason for withholding TMP-SMX, occurring in 50 (57%) encounters, followed by elevated liver function tests (LFTs) (13.6%), hyperkalemia (3.4%), elevated creatinine (3.4%), rash or hypersensitivity (3.4%), and unknown/other (22%) . In 73 encounters in which patients received alternative or no PCP prophylaxis, we recommended changing to TMP-SMX. This intervention was accepted in 15 patients, 11(73%) of whom tolerated TMP-SMX well. In the remaining four patients, TMP-SMX was subsequently discontinued due to unrelated AE (N = 3) and possible TMP-SMX-associated elevated LFTs (N = 1). Conclusions: Provider education and real-time feedback led to increased utilization of TMP-SMX for prevention of PCP and other opportunistic infections in HCT recipients without an increase in TMP-SMX-related adverse effects. Further study is needed to understand the low clinician acceptance rate of the intervention.

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