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Incidence and Risk Factors of Early Onset VOD/SOS Differ in Younger vs Older Adults After Stem Cell Transplantation
Marcoux, C., Saliba, R. M., Wallis, W., Khazal, S. J., Ragoonanan, D., Rondon, G., Tewari, P., Popat, U. R., Oran, B., Olson, A. L., et al
Blood advances. 2024
Abstract
Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-SCT). While increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with post-transplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single center analysis of adult patients 18 years or older undergoing allo-SCT (N=1561) using predominately PTCy as GVHD prophylaxis (72%). We found a higher rate of VOD at 16.8% (20/119) in those aged ≤ 25 years compared to 3.8% (55/1442) in those >25 years, with unique predictors of VOD within each cohort. Multivariate classification and regression tree (CART) analysis confirmed age as the primary independent determinant of the rate of VOD. Within patients aged 18-25 years, disease risk index (DRI) (31% with high/very high DRI vs 12% low/intermediate DRI; p=0.03) and prior lines of chemotherapy (24% with >1 vs 6% with ≤1, p=0.03) were the strongest predictors of VOD. Incidence of VOD in patients > 25 years of age consistently ranged between 3-5% across most risk factors evaluated, with only hepatic factors (baseline elevation of bilirubin, aspartate transferase (AST), alanine aminotransferase (ALT)) or gemtuzumab exposure associated with increased rates of VOD. There was no significant difference in rates of VOD in those receiving PTCy compared to those receiving alternate GVHD prophylaxis. Our data highlight the differences in incidence and predictors in VOD between younger (≤25) and older (>25) adults undergoing allo-SCT.
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Home-Based Spirometry Telemonitoring After Allogeneic Hematopoietic Cell Transplantation: Mixed Methods Evaluation of Acceptability and Usability
Sheshadri, A., Makhnoon, S., Alousi, A. M., Bashoura, L., Andrade, R., Miller, C. J., Stolar, K. R., Arain, M. H., Noor, L., Balagani, A., et al
JMIR formative research. 2022;6(2):e29393
Abstract
BACKGROUND Home-based spirometry (HS) allows for the early detection of lung complications in recipients of an allogeneic hematopoietic cell transplant (AHCT). Although the usability and acceptability of HS are critical for adherence, patient-reported outcomes of HS use remain poorly understood in this setting. OBJECTIVE The aim of this study is to design a longitudinal, mixed methods study to understand the usability and acceptability of HS among recipients of AHCT. METHODS Study participants performed HS using a Bluetooth-capable spirometer that transmitted spirometry data to the study team in real time. In addition, participants completed usability questionnaires and in-depth interviews and reported their experiences with HS. Analysis of interview data was guided by the constructs of performance expectancy, effort expectancy, and social influence from the Unified Theory of Acceptance and Use of Technology model. RESULTS Recipients of AHCT found HS to be highly acceptable despite modest technological barriers. On average, participants believed that the HS was helpful in managing symptoms related to AHCT (scores ranging from 2.22 to 2.68 on a scale of 0-4) and for early detection of health-related problems (score range: 2.88-3.12). Participants viewed HS favorably and were generally supportive of continued use. No significant barriers to implementation were identified from the patient's perspective. Age and gender were not associated with the patient perception of HS. CONCLUSIONS Study participants found HS acceptable and easy to use. Some modifiable technical barriers to performing HS were identified; however, wider implementation of pulmonary screening is feasible from the patient's perspective.
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Risk factors for bronchiolitis obliterans syndrome after initial detection of pulmonary impairment
Alkhunaizi, M., Patel, B., Bueno, L., Bhan, N., Ahmed, T., Arain, M. H., Saliba, R., Rondon, G., Dickey, B. F., Bashoura, L., et al
Transplantation and cellular therapy. 2022
Abstract
INTRODUCTION Pulmonary chronic graft-vs-host-disease (cGVHD), or bronchiolitis obliterans syndrome (BOS), is a highly morbid complication of hematopoietic cell transplant. The clinical significance of a single instance of pulmonary decline not meeting BOS criteria is unclear. METHODS We conducted a retrospective analysis on a cohort of patients who had an initial post-HCT decline in the absolute value of FEV(1) of ≥ 10% or mid-expiratory flow rates of ≥ 25% but not meeting criteria for BOS (preBOS). We examined the impact of clinical variables in patients with preBOS on the risk for subsequent BOS. RESULTS 1325/3170 (42%) patients developed preBOS, of whom 72 (5%) later developed BOS. Eighty-four patients developed BOS without detection of preBOS by routine screening. Among patients with preBOS, and after adjusting for other significant variables, airflow obstruction (HR 2.0, 95% confidence interval [CI] 1.1-3.7, p=0.02), percent-predicted FEV(1) upon decline (HR 0.98, 95% CI 0.97-1.0 p=0.02), active cGVHD (HR 7.7, 95% CI 3.1-19.3, p<0.001), peripheral blood stem cell source (HR 3.8, 95% CI 1.7-8.6, p=0.001), and myeloablative conditioning (HR 2.0, 95% CI 1.1-3.5, p=0.02) were associated with subsequent BOS. The absence of airflow obstruction and cGVHD had a negative predictive value of 100% at six months for subsequent BOS, but the positive predictive value of both factors was low (cGVHD: 3%, any obstruction: 4%, combined: 6%). CONCLUSIONS Several clinical factors at the time of preBOS, particularly active cGVHD and airflow obstruction, increase the risk for subsequent BOS. These factors merit consideration to be included in screening practices to improve the detection of BOS, with the caveat that the predictive utility of these factors is limited by the overall low incidence of BOS among patients with preBOS.
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4.
Cardiac Toxicity after Matched Allogeneic Hematopoietic Cell Transplantation in the Post-Transplant Cyclophosphamide Era
Yeh, J. C., Whited, L. K., Saliba, R. M., Rondon, G., Banchs, J., Shpall, E. J., Champlin, R. E., Popat, U. R.
Blood advances. 2021
Abstract
Graft-versus-host-disease (GVHD) is one of the leading causes of non-relapse mortality (NRM) following allogeneic hematopoietic cell transplantation (alloHCT). Post-transplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicities and few studies have evaluated the cardiac toxicities that arise following PTCy. Here, we completed a retrospective analysis of matched alloHCT patients at our institution who received PTCy or non-PTCy-based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after alloHCT. We included 585 patients in our analysis and found that 38 patients (6.5%) experienced cardiac toxicities after alloHCT. The toxicities observed included arrhythmias (n=21), heart failure (n=14), pericardial effusions (n=10), and myocardial infarction or ischemia (n=7). Patients who received PTCy had a 7.4% incidence of cardiac toxicities, while non-PTCy patients had an incidence of 5.8% (p=0.4). We found that age > 55 years (p=0.02), history of hypertension (p=0.01), arrhythmia (p=0.003), diabetes (p=0.04), and cardiac comorbidities (p<0.001) were significant predictors of cardiac toxicity, while none of the preparative and GVHD prophylaxis regimens used were predictive of cardiac toxicity. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity following alloHCT and found that a higher score correlated with cardiac toxicity incidence. Furthermore, the development of cardiac toxicity was associated with worse 1-yr overall survival (OS) and NRM while the use of PTCy was associated with improvements in 1-year OS and NRM rates.
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5.
Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation
Olson, A., Lin, R., Marin, D., Rafei, H., Bdaiwi, M. H., Thall, P. F., Basar, R., Abudayyeh, A., Banerjee, P., Aung, F. M., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021;:Jco2002608
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Editor's Choice
Abstract
PURPOSE BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.
PICO Summary
Population
Patients who developed BK-virus associated haemorrhagic cystitis (BKV-HC) following allogeneic transplantation (n=59)
Intervention
HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs)
Comparison
Matched-pair analysis of historical controls
Outcome
Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement.
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Idiopathic refractory ascites after allogeneic stem cell transplantation: a previously unrecognized entity
Varma, A., Abraham, S. C., Mehta, R. S., Saini, N. Y., Honhar, M., Rashid, M., Chen, J., Srour, S. A., Bashir, Q., Rondon, G., et al
Blood advances. 2020;4(7):1296-1306
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Abstract
At our center, we observed a series of patients who developed transudative refractory ascites secondary to noncirrhotic, non-veno-occlusive disease (VOD)-related portal hypertension after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients were considered to have idiopathic portal hypertension-related refractory ascites (IRA) if they developed ascites secondary to intrahepatic portal hypertension (serum ascites albumin gradient ≥1.1 g/dL or hepatic venous pressure gradient [HVPG] >5 mm Hg), but did not meet the clinical criteria for classical VOD/sinusoidal obstructive syndrome (SOS) and did not have any alternate etiology of portal hypertension. From our institutional database, we identified 40 patients who developed IRA after allo-HSCT between 2004 and 2018. The patients' median age at the time of allo-HSCT was 54 years (range, 21-73 years). The median time to development of IRA after allo-HSCT was 80 days (range, 16-576 days). The median number of paracentesis was 3 (range, 1-11), and 15 (38%) patients had an intraperitoneal catheter placed for continued drainage of the rapidly accumulating ascites. Portal pressures were measured in 19 patients; 6 (15%) had moderate portal hypertension (HVPG 6-9 mm Hg), and 13 (33%) had severe portal hypertension (HVPG ≥ 10 mm Hg). Liver biopsy was performed in 24 patients. None of the patients met the criteria for classical VOD/SOS (clinical/histological) or cirrhosis (histological). The cumulative incidence of nonrelapse mortality was 63%, and the median survival duration after the development of the IRA was 7 months (range, 0.8-125.6 months). IRA is a poorly understood and often fatal complication of allo-HSCT.
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Azithromycin may increase hematologic relapse rates in matched unrelated donor hematopoietic cell transplant recipients who receive anti-thymocyte globulin, but not in most other recipients
Sheshadri, A., Saliba, R., Patel, B., Ahmed, T., Bueno, L. C., Arain, M. H., Mehta, R. S., Popat, U. R., Hosing, C. M., Rondon, G., et al
Bone marrow transplantation. 2020
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Retrospective analysis of weekly intravenous immunoglobulin prophylaxis versus intravenous immunoglobulin by IgG level monitoring in hematopoietic stem cell transplant recipients
Howell, J. E., Gulbis, A. M., Champlin, R. E., Qazilbash, M. H.
American Journal of Hematology. 2012;87(2):172-4
Abstract
Patients undergoing allogeneic hematopoietic stem cell transplant (allo HCT) have a higher incidence of infections partly due to secondary hypogammaglobulinemia. We evaluated the role of IVIG in allo HCT patients who received prophylactic IVIG 200 mg/kg once weekly regardless of IgG level (Group 1, n = 115) compared with patients who received IVIG based on IgG level <400 mg/dL (Group 2, n = 114). Primary endpoints were the utilization of IVIG, incidence of veno-occlusive disease (VOD), graft-versus-host disease (GVHD), and documented infections within the first 100 days after allo HCT. Patients in both groups were similar except for a higher number of matched unrelated donor (MUD) transplants in Group 2 (62 vs. 41, P = 0.01). There were no significant differences in the incidence all grades of GVHD (55 vs. 50), VOD (2 vs. 0) or infections in the two groups except for a higher incidence of para-influenza infections in group 1 (9 vs. 0, P = 0.003) coinciding with the flu season. We recommend monthly monitoring of IgG level and replacement only if IgG level is <400 mg/dL. Copyright © 2011 Wiley Periodicals, Inc.