scholarly journals Isavuconazonium Sulfate Use in Multi-Modal Management of Invasive Mucormycosis in Four Pediatric Allogeneic Hematopoietic Cell Transplant Patients

2021 ◽  
Vol 26 (8) ◽  
pp. 863-867
Author(s):  
Asmaa Ferdjallah ◽  
Kristina M. Nelson ◽  
Kailey Meyer ◽  
Cathryn A. Jennissen ◽  
Christen L. Ebens
Keyword(s):  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Safety Data ◽  
Drug Level ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Loading Dose ◽  
Duration Of Treatment ◽  
Hematopoietic Cell Transplant

Prolonged neutropenia increases the risk for lethal invasive fungal infections (IFIs) such as those caused by Rhizopus species. Isavuconazonium sulfate is a new triazole that lacks pediatric dosing recommendations. Clinical courses of 4 pediatric patients with IFIs in the peri-allogeneic hematopoietic cell transplantation (alloHCT) period between 2015 and 2017 were reviewed. The reviews included previously unreported pharmacokinetic and safety data, and the IFIs included Rhizopus. Isavuconazonium sulfate was initiated with a loading dose followed by daily dosing, adjusted to a goal trough concentration of >3 mg/L based on adult literature. This target was achieved at a median of 7 days, demonstrating varying rates of metabolism. Renal insufficiency, electrolyte disturbances, and transaminitis were noted, although attribution was confounded by other alloHCT complications. One patient survived infection-free to hospital discharge and 1 of 3 deceased patients had evidence of an unresolved IFI (case 2). Case 2 was subtherapeutic for 39% of the duration of treatment, compared with others at an average of 29%, suggesting this target trough to be clinically relevant because case 2 demonstrated positive sinus and nasal cultures for Rhizopus on autopsy. We recommend initiation of isavuconazonium 10 mg/kg with a maximum dose of 372 mg. A loading dose of 10 mg/kg is used every 8 hours for 6 doses followed by 10 mg/kg dosing every 24 hours. Monitoring must continue beyond steady state. If early monitoring is not possible, we recommend a first drug level at week 3. If dose increases are required, a partial reload has been more successful instead of increasing daily doses. Further larger studies are needed to demonstrate optimum dosing in pediatric patients.

scholarly journals Isavuconazonium Sulfate Use in Multi-Modal Management of Invasive Zygomycosis in Four Pediatric Allogeneic Hematopoietic Cell Transplant Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-27
Author(s):  
Asmaa Ferdjallah ◽  
Kristina M Nelson ◽  
Kailey Meyer ◽  
Cathryn A Jennissen ◽  
Christen L. Ebens
Keyword(s):  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Safety Data ◽  
Drug Level ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Loading Dose ◽  
Duration Of Treatment ◽  
Hematopoietic Cell Transplant

Prolonged neutropenia increases risk for lethal invasive fungal infection (IFI) such as Rhizopus. Isavuconazonium sulfate is a new triazole that lacks pediatric dosing recommendations. Clinical courses of 4 pediatric patients with IFI in the peri-allogeneic hematopoietic cell transplantation (alloHCT) period between 2015 and 2017 were reviewed, including previously unreported pharmacokinetic and safety data. IFI included Rhizopus and presumed fungal meningitis. Isavuconazonium sulfate was initiated with a loading dose followed by daily dosing, adjusted to a goal trough >3 ug/mL based on adult literature. This target was achieved at a median of 7 days, demonstrating varying rates of metabolism. Renal insufficiency, electrolyte disturbances, and transaminitis were noted, though attribution was confounded by other alloHCT complications. 1 patient survived infection-free to hospital discharge and 1 of 3 deceased patients had evidence of unresolved IFI (Case 2). Case 2 was subtherapeutic for 39% of the duration of treatment, compared to others at an average of 29%, suggesting this target trough to be clinically relevant. We recommend initiation of isavuconazonium sulfate at 10 mg/kg with a max dose of 372 mg. A loading dose of 10 mg/kg is utilized every 8 hours for 6 doses followed by 10 mg/kg dosing every 24 hours. Monitoring must continue beyond steady state. If early monitoring is not possible, we recommend a first drug level at week 3. If dose increases are required, a partial reload has been more successful instead of increasing daily doses. Further larger studies are needed to demonstrate optimum dosing in pediatric patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

Outcomes of Human Adenovirus Infection and Disease in a Retrospective Cohort of Pediatric Hematopoietic Cell Transplant Recipients

2018 ◽  
Vol 8 (4) ◽  
pp. 317-324 ◽  
Author(s):  
Brian T Fisher ◽  
Craig L K Boge ◽  
Hans Petersen ◽  
Alix E Seif ◽  
Matthew Bryan ◽  
...  
Keyword(s):  
Retrospective Cohort ◽  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Case Fatality ◽  
Human Adenovirus ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Allogeneic Transplant ◽  
Hematopoietic Cell Transplant

Human adenoviruses were commonly detected in this cohort of pediatric patients undergoing hematopoietic cell transplantation, and the case-fatality rate in allogeneic transplant recipients was high (25.9%). Preemptive cidofovir therapy was not associated with a reduction in the progression to human adenovirus disease.

scholarly journals Late infectious complications in hematopoietic cell transplantation survivors: a population-based study

2020 ◽  
Vol 4 (7) ◽  
pp. 1232-1241
Author(s):  
Aimee M. Foord ◽  
Kara L. Cushing-Haugen ◽  
Michael J. Boeckh ◽  
Paul A. Carpenter ◽  
Mary E. D. Flowers ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Antimicrobial Prophylaxis ◽  
Population Based ◽  
Infectious Complications ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
History Of

Abstract Few studies have compared the incidence of infections occurring ≥2 years after hematopoietic cell transplant (HCT) with other cancer patients and the general population. In this study, ≥2-year HCT survivors who were Washington residents treated from 1992 through 2009 (n = 1792; median age, 46 years; 52% allogeneic; 90% hematologic malignancies) were matched to individuals from the state cancer registry (n = 5455, non-HCT) and driver’s license files (n = 16 340; Department of Licensing [DOL]). Based on hospital and death registry codes, incidence rate ratios (IRRs; 95% confidence interval [CI]) of infections by organism type and organ system were estimated using Poisson regression. With 7-year median follow-up, the incidence rate (per 1000 person-years) of all infections was 65.4 for HCT survivors vs 39.6 for the non-HCT group (IRR, 1.6; 95% CI, 1.3-1.9) and 7.2 for DOL (IRR, 10.0; 95% CI, 8.3-12.1). Bacterial and fungal infections were each 70% more common in HCT vs non-HCT cancer survivors (IRR, 1.7; P < .01), whereas the risk for viral infection was lower (IRR, 1.4; P = .07). Among potentially vaccine-preventable organisms, the IRR was 3.0 (95% CI, 2.1-4.3) vs the non-HCT group. Although the incidences of all infections decreased with time, the relative risk in almost all categories remained significantly increased in ≥5-year HCT survivors vs other groups. Risk factors for late infection included history of relapse and for some infections, history of chronic graft-versus-host disease. Providers caring for HCT survivors should maintain vigilance for infections and ensure adherence to antimicrobial prophylaxis and vaccination guidelines.

Approaches to the Management of Invasive Fungal Infections in Hematologic Malignancy and Hematopoietic Cell Transplantation

2009 ◽  
Vol 27 (20) ◽  
pp. 3398-3409 ◽  
Author(s):  
Mauricette Michallet ◽  
James I. Ito
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Hematologic Malignancy ◽  
Treatment Strategies ◽  
Underlying Disease ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Increased Risk

Patients with hematologic malignancy and hematopoietic cell transplant (HCT) recipients are at increased risk for invasive fungal infection (IFI) as a result of immunosuppression or organ damage stemming from their underlying disease, its treatment, or both. Such IFIs can cause significant morbidity and mortality, and the diagnosis and treatment of infected patients frequently are clinically challenging. This article discusses the epidemiology and risk factors for IFI in patients with hematologic malignancy and HCT recipients. The pros and cons of available antifungal agents are discussed, and evolving treatment strategies and recent prophylaxis guidelines from various professional organizations are reviewed. Finally, recommendations are offered for antifungal prophylaxis according to risk group.

scholarly journals Management of Herpesvirus Infections in Hematopoietic Cell Transplant Recipients

2021 ◽  
Vol 2 (1) ◽  
pp. 8-21
Author(s):  
Jan Styczynski
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cellular Therapy ◽  
Hematopoietic Cell ◽  
Host Cells ◽  
Preventive Strategy ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Screening Assay ◽  
Specific Level

Following primary infection, herpesviruses establish latency in infected individuals in the host cells and may reactivate upon external stimuli and during periods of immunosuppression. The objective of this paper was to the present current strategies on preventive and therapeutic management of infections with herpesviruses in recipients of hematopoietic cell transplantation. Strategies of antiviral management include prophylaxis, pre-emptive treatment and targeted treatment. Empirical therapy is not used in antiviral strategies. Prophylaxis can be done at universal (preventive strategy) and specific level. Universal prophylaxis includes non-pharmacologic methods of prevention of infection or reactivation. Risk-adapted specific prophylaxis includes use of specific antivirals or cellular therapy or other specific methods in order to prevent specific infection, in high-risk groups. Pre-emptive therapy means use of therapeutic approaches in asymptomatic infection, detected by a screening assay. Targeted therapy is used in established specific viral end-organ infections. The following sections of the paper refer to prophylaxis and treatment strategies, respectively, against CMV, EBV, HSV, VZV, HHV-6, HHV-7, and HHV-8 after allogeneic hematopoietic cell transplantation.

scholarly journals The Hematopoietic Cell Transplant Comorbidity Index predicts survival after allogeneic transplant for nonmalignant diseases

Blood ◽  
2019 ◽  
Vol 133 (7) ◽  
pp. 754-762 ◽  
Author(s):  
Monica S. Thakar ◽  
Larisa Broglie ◽  
Brent Logan ◽  
Andrew Artz ◽  
Nancy Bunin ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Cox Regression ◽  
Bone Marrow Failure ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Research Database ◽  
Hematopoietic Cell Transplant ◽  
Risk Of Death ◽  
Increased Risk ◽  
Comorbidity Index

Abstract Despite improvements, mortality after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases remains a significant problem. We evaluated whether pre-HCT conditions defined by the HCT Comorbidity Index (HCT-CI) predict probability of posttransplant survival. Using the Center for International Blood and Marrow Transplant Research database, we identified 4083 patients with nonmalignant diseases transplanted between 2007 and 2014. Primary outcome was overall survival (OS) using the Kaplan-Meier method. Hazard ratios (HRs) were estimated by multivariable Cox regression models. Increasing HCT-CI scores translated to decreased 2-year OS of 82.7%, 80.3%, 74%, and 55.8% for patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5, respectively, regardless of conditioning intensity. HCT-CI scores of 1 to 2 did not differ relative to scores of 0 (HR, 1.12 [95% CI, 0.93-1.34]), but HCT-CI of 3 to 4 and ≥5 posed significantly greater risks of mortality (HR, 1.33 [95% CI, 1.09-1.63]; and HR, 2.31 [95% CI, 1.79-2.96], respectively). The effect of HCT-CI differed by disease indication. Patients with acquired aplastic anemia, primary immune deficiencies, and congenital bone marrow failure syndromes with scores ≥3 had increased risk of death after HCT. However, higher HCT-CI scores among hemoglobinopathy patients did not increase mortality risk. In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases.

Brentuximab vedotin as consolidation after hematopoietic cell transplant for relapsed Hodgkin lymphoma in pediatric patients

2019 ◽  
Vol 66 (12) ◽  
Author(s):  
Jamie E. Flerlage ◽  
Xinyu Buttlar ◽  
Matthew Krasin ◽  
Brandon Triplett ◽  
Sue C. Kaste ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Pediatric Patients ◽  
Brentuximab Vedotin ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

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.

Spiritual/religious struggle in hematopoietic cell transplant survivors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9573-9573
Author(s):  
Stephen Duane Watkins King ◽  
George Fitchett ◽  
Kenneth I. Pargament ◽  
Do Peterson ◽  
David A. Harrison ◽  
...  
Keyword(s):  
Religious Coping ◽  
Hematopoietic Cell Transplantation ◽  
Religious Affiliation ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Variable Model ◽  
Adult Age ◽  
Disease Information ◽  
Negative Religious Coping

9573 Background: Spiritual/religious (SR) struggle (e.g., feeling abandoned or punished by God) has been associated with poorer coping and quality of life (QOL), greater depression and pain, and health declines in general cancer populations. Few studies have been conducted among survivors of hematopoietic cell transplantation (HCT). This study examined the prevalence and predictors of SR struggle in HCT survivors. Methods: Data were collected as part of an annual questionnaire of adult (age >18 years) survivors of HCT at Fred Hutchinson Cancer Research Center in Seattle, WA. The 2011 survey included a SR module that incorporated the following items: Negative Religious Coping subscale of Brief RCOPE, subscales from the McGill QOL Questionnaire and the SF-36, Patient Health Questionnaire-8, disease information and socio-demographics. SR struggle was defined as any non-zero response on the Negative Religious Coping subscale of the Brief RCOPE. A multi-variable logistic regression model was used to determine factors associated with SR struggle. Results: Of 2113 returned surveys (52% response rate), 83% returned the SR module (n=1745) and of those 1586 were included in this analysis. Subjects were 49% female; 67% Christian and 20% Agnostic/Atheist/No preference; and 91% white. Mean age was 55 years; survivors ranged from 6 months to 40 years post-transplant. Primary indications for transplant were leukemia (49%), lymphoma (20%), and multiple myeloma (15%). Twenty-eight percent indicated SR struggle. In a multi-variable model, SR struggle showed statistically significant associations with age >=65 years (odds ratio [OR] .57, p=.02); patient report of being religious only (OR 3.5, p<.001) or spiritual only (OR 1.8, p<.001) compared to being both religious and spiritual; depression (OR 1.1, p<.001); and better social support (OR 0.77, p<.001). Time since HCT, religious affiliation and race/ethnicity did not show statistically significant associations with SR struggle. Conclusions: SR struggle is common among HCT survivors, even years after HCT.Further study is needed to determine causal relations, longitudinal trajectory, impact of struggle intensity, and effects of SR struggle on health, mood and social roles for HCT survivors.

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