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1.
Risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in a letermovir-exposed CMV-free population receiving PTCy
Galli, E., Metafuni, E., Gandi, C., Limongiello, M. A., Giammarco, S., Mattozzi, A., Santangelo, R., Bacigalupo, A., Sorà, F., Chiusolo, P., et al
European journal of haematology. 2024
Abstract
Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%-37% of patients. The impact of transplant- and patient-specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir-exposed, CMV-free patients, treated with the same cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC-score including male gender, TBF conditioning, and HLA-mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient-related factors, chemotherapy-related toxicities-especially due to alkylating agents-and immunological elements.
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2.
Utilization of Photobiomodulation for the Prevention and Treatment of Oral Mucositis
Pritchard, M., Ogg, S. W., Bosi, J., Mandrell, B. N.
Journal of pediatric hematology/oncology nursing. 2024;:27527530231214525
Abstract
Background: Oral mucositis is a significant and common toxicity experienced by patients who receive high-dose chemotherapy as a preparatory regimen for a hematopoietic cell transplant (HCT). Photobiomodulation (PBM) has been found to be feasible with significant efficacy in preventing the progression of oral mucositis in adult patients undergoing HCT. The purpose of this study was to determine the feasibility and efficacy of PBM in pediatric oncology patients undergoing HCT. Method: Forty children and adolescents admitted to the transplant unit for an allogeneic HCT for acute lymphoblastic leukemia or acute myeloid leukemia were treated daily at six sites until day + 20 or engraftment. Results: There were 1,035 patient encounters, with successful treatment of four or more sites during 979 patient encounters for a feasibility 93.3% CI [0.926, 0.039]. We had estimated a meaningful effect size of 20% for PBM and estimated 51% of patients treated with PBM would have at least one day or more of Grade 3 mucositis. The rate of patients who received PBM and developed Grade 3 mucositis was 20% CI [0.091, 0.356]. Patients treated with PBM had fewer days of hospitalization (p = .009) and less severe mucositis in comparison to the matched control group (p = .03). Conclusion: PBM is feasible and effective in preventing and treating oral mucositis and is now supported by the Children's Oncology Group for prevention and treatment of oral mucositis in patients undergoing an allogeneic HCT or receiving head/neck radiation.
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3.
Temporal trends in critical care utilization and outcomes in allogeneic hematopoietic stem cell transplant recipients
Heybati, K., Ochal, D., Hogan, W., Al-Khateeb, H., Sklar, D., Herasevich, S., Litzow, M., Shah, M., Torghabeh, M. H., Durani, U., et al
Annals of hematology. 2024
Abstract
Historically, the prognosis of allogeneic hematopoietic stem cell transplant (allo-HCT) recipients who require intensive care unit (ICU) admission has been poor. We aimed to describe the epidemiological trends of ICU utilization and outcomes in allo-HCT patients. We conducted a retrospective cohort study including adults (≥ 18) undergoing allo-HCT between 01/01/2005 and 31/12/2020 at Mayo Clinic, Rochester. Temporal trends in outcomes were assessed by robust linear regression modelling. Risk factors for hospital mortality were chosen a priori and assessed with multivariable logistic regression modelling. Of 1,249 subjects, there were 486 ICU admissions among 287 individuals. Although older patients underwent allo-HCT (1.64 [95% CI: 1.11 to 2.45] years per year; P = 0.025), there was no change in ICU utilization over time (P = 0.91). The ICU and hospital mortality rates were 19.2% (55/287) and 28.2% (81/287), respectively. There was a decline in ICU mortality (-0.38% [95% CI: -0.70 to -0.06%] per year; P = 0.035). The 1-year post-HCT mortality for those requiring ICU admission was 56.1% (161/287), with no significant difference over time, versus 15.8% (141/891, 71 missing) among those who did not. The frequency and duration of invasive mechanical ventilation (IMV) declined. In multivariable analyses, higher serum lactate, higher sequential organ failure assessment (SOFA) scores, acute respiratory distress (ARDS), and need for IMV were associated with greater odds of hospital mortality. Over time, rates of ICU utilization have remained stable, despite increasing patient age. Several trends suggest improvement in outcomes, notably lower ICU mortality and frequency of IMV. However, long-term survival remains unchanged. Further work is needed to improve long-term outcomes in this population.
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4.
Detection of bronchiolitis obliterans syndrome using nitrogen multiple breath washout in children post-haemopoietic stem cell transplant
Westrupp, N., Berry, C. D., Cole, T., Shanthikumar, S., Welsh, L.
Transplantation and cellular therapy. 2024
Abstract
BACKGROUND Bronchiolitis obliterans syndrome (BOS) is a severe complication following haemopoietic stem cell transplantation (HSCT) and is often undetected until there is significant deterioration in pulmonary function. Lung clearance index (LCI(2.5)) derived from the nitrogen multiple breath washout (N(2)MBW) test may be more feasible and sensitive than spirometry, which is currently used for surveillance and detection of BOS. OBJECTIVE We aimed to examine the feasibility of performing surveillance N(2)MBW in children post-HSCT, and in an exploratory analysis, determine if LCI(2.5) led to earlier detection of BOS when compared to spirometric indices. STUDY DESIGN Participants aged 5 - 17 years were recruited prior to receiving HSCT into a prospective, single-centre, feasibility study at the Royal Children's Hospital, Melbourne. N(2)MBW and spirometry were performed within the month prior to transplant and repeated at 3, 6, 9 and 12 months post-transplant. Data were also collected on the presence of graft-versus-host (GVHD) disease in any organ, including the lungs. RESULTS Twenty-one (12 male) children with a mean age of 13.4 (range 9.2-17.1) years at recruitment participated in this study. Prior to HSCT, all participants had normal LCI(2.5), while 16 (76%) demonstrated normal forced expiratory volume in 1 second (FEV(1)). Ninety-nine percent of N(2)MBW tests were technically acceptable, compared with 66% of spirometry tests. Three participants developed BOS, while two participants died of other respiratory complications. At 6 and 12 months post-transplant, the BOS group had increases in LCI(2.5) ranging from 3 to 5 units and mean reductions in FEV(1) % predicted of 40% to 53% relative to pre HSCT values, respectively. In those who developed BOS, post-HSCT LCI(2.5) values were significantly worse when compared with the no BOS group (p<0.001). Relative changes in LCI(2.5) and FEV(1) were both predictive of BOS at 6 months post HSCT. CONCLUSION This study demonstrates that N(2)MBW is a more feasible test compared with spirometry in children post HSCT. However, in an exploratory analysis, LCI(2.5) did not lead to earlier detection of BOS, when compared to spirometry.
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5.
Analysis of laboratory parameters before the occurrence of hepatic sinusoidal obstruction syndrome in children, adolescents, and young adults after hematopoietic stem cell transplantation
Johann, L., Gruhn, B.
Journal of cancer research and clinical oncology. 2024;150(1):9
Abstract
PURPOSE Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication following hematopoietic stem cell transplantation (HSCT) in which early diagnosis improves patient outcome. The aim of our study was to detect laboratory parameters following HSCT that can predict the occurrence of SOS. METHODS This retrospective study included 182 children, adolescents, and young adults who underwent allogeneic or autologous HSCT for the first time (median age 7.2 years). The diagnosis of SOS was based on the pediatric criteria of European Society for Blood and Marrow Transplantation (EBMT). We investigated 15 laboratory parameters after HSCT before the onset of SOS. RESULTS The overall incidence of SOS was 14.8%. SOS developed in 24 of 126 allogeneic (19.1%) and in 3 of 56 autologous (5.4%) HSCT patients at a median time of 13 days after HSCT. We observed a low SOS mortality rate of 11.1% within 100 days after HSCT. International normalized ratio (INR) ≥ 1.3, activated partial thromboplastin time (aPTT) ≥ 40 s, reptilase time ≥ 18.3 s, factor VIII ≤ 80%, antithrombin III ≤ 75%, protein C ≤ 48%, D-dimer ≥ 315 µg/L, bilirubin ≥ 9 µmol/L, and ferritin ≥ 3100 µg/L showed significant associations with the onset of SOS in the univariate analyses. In the multivariate analysis, INR ≥ 1.3 [odds ratio (OR) = 8.104, p = 0.006], aPTT ≥ 40 s (OR = 10.174, p = 0.001), protein C ≤ 48% (OR = 5.215, p = 0.014), and ferritin ≥ 3100 µg/L (OR = 7.472, p = 0.004) could be confirmed as independent risk factors after HSCT before SOS. If three of the four significant cut-off values were present, the probability of developing SOS was more than 70%. The probability of SOS was 96%, if all four laboratory parameters were changed according to the cut-off values. The values of factor XIII, von Willebrand factor (vWF), von Willebrand factor activity (vWF activity), protein S, fibrinogen, and alanine aminotransferase (ALT) were not relevant for the occurrence of SOS. CONCLUSION In summary, the laboratory parameters INR, aPTT, protein C, and ferritin were very useful to predict the occurrence of SOS. In addition, this is the first report on a significant association between SOS and high values of INR and aPTT after HSCT before SOS.
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6.
Short-Term Impact of Hematopoietic Stem Cell Transplantation on Depressive Behavior, Cognition and Quality of Life in Leukemia Patients
Joshi, R., Garg, A., Khan, Z., Bhurani, D., Nidhi,, Khan, M. A.
Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion. 2024;40(1):83-90
Abstract
Hematopoietic stem cell transplantation (HSCT) or Bone Marrow Transplantation (BMT) has significantly improved the survival rates of patients suffering from hematological malignancies. However, the cure can only be achieved at the price of morbidity and long-term complications. Thus, this study aimed to evaluate the short-term effect of HSCT on depressive behavior, cognition, and quality of life (QoL) in leukemia patients. Sixty patients were included in this prospective observational study. The current study assessed depression using Patient Health Questionnaire (PHQ-9) scale, cognition using Montreal Cognitive Assessment (MOCA) scale and QoL using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) before 7 days of the therapy i.e., preconditioning/baseline (TP1) and after 30 days of the treatment (TP2) in leukemia patients undergoing HSCT. At TP2, there was a significant improvement in PHQ-9 (p = 0.001), MOCA (p < 0.0001), functional scale (p < 0.0001) and global health & QoL scale (p = 0.001) of EORTC QLQ C30 scores whereas there was a significant decrease in symptom scale of EORTC QLQ C30 score (p = 0.005). Furthermore, at TP2 a statistically significant (p < 0.05) negative correlation was observed between MOCA and symptom scale of EORTC QLQ C30 after Pearson correlation analysis. In conclusion, post-30 days of HSCT there was alleviation in depressive behavior, cognition, and QoL in leukemia patients compared to before therapy.
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7.
Incidence, management and outcome of Hepatic Veno-Occlusive disease /Sinusoidal Obstruction Syndrome after hematopoietic stem cell transplant in Thalassemia major patients: A prospective study of Pakistani BMT
Nisar, H., Khan, M., Khattak, T. A., Ghafoor, T., Chaudhry, Q. U. N.
Pakistan journal of medical sciences. 2024;40(3Part-II):259-264
Abstract
OBJECTIVES Hepatic Veno occlusive disease (VOD), also known as sinusoidal obstruction syndrome (VOD/SOS), is a post-transplant life threatening complication. In this study, we aimed to discuss the incidence, management and outcome of VOD in post allogenic transplant patients of beta thalassemia major (BTM). METHODS A prospective study was conducted in Armed Forces Bone Marrow Transplant Center, between 2001-2022. A total of 385 fully Human Leucocyte Antigen (HLA) matched BTM patients, with Ursodeoxycholic acid for prophylaxis, were included in the study. Incidence of VOD was calculated through cumulative incidence estimates. Chi square test and Mann Whitney test were used to compare discrete and continuous variables respectively. VOD was diagnosed and graded according to European Society for Blood and Marrow Transplantation EBMT Pediatric diagnostic criteria. Risk factors for VOD were grouped as recipient, transplant and donor related. Univariate analysis was performed by log-rank test. All patients who developed VOD were managed primarily with fluid restriction and strict input output monitoring. Statistical analyses were performed using SPSS v 25.0. RESULTS Out of 385 transplant patients, forty developed VOD. Median time from date of transplant till onset of VOD was 14 days (range 6-30). Cumulative incidence of all grade VOD was 10.39% (95% CI, 7-14). Eleven out of 40 patients who developed VOD died. Cumulative incidence of Transplant related mortality (TRM) for patients with and VOD was 20.5% (95% CI, 16.6-25.1) vs 27.5% (95% CI, 16.1-42) (p value 0.318) respectively. Among risk factors, age of recipient and fibrosis (p value of 0.04 and 0.000 respectively) were found to be significantly associated with VOD. CONCLUSIONS Careful selection of transplant candidates before transplant can help reduce the incidence of VOD.
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8.
Late transplant-associated thrombotic microangiopathy verified in bone marrow biopsy specimens is associated with chronic GVHD and viral infections
Hill, W., Sotlar, K., Hautmann, A., Kolb, H. J., Ullmann, J., Hausmann, A., Schmidt, M., Tischer, J., Pham, T. T., Rank, A., et al
European journal of haematology. 2024
Abstract
OBJECTIVES To describe late transplant-associated thrombotic microangiopathy (TA-TMA) as chronic endothelial complication in bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS BM specimens along with conventional diagnostic parameters were assessed in 14 single-institutional patients with late TA-TMA (more than 100 days after HCST), including 11 late with history of early TA-TMA, 10 with early TA-TMA (within 100 days), and 12 non TA-TMA patients. Three non-HSCT patients served as control. The time points of BM biopsy were +1086, +798, +396, and +363 days after HSCT, respectively. RESULTS Late TA-TMA patients showed an increase of CD34+ and von Willebrand Factor (VWF)+ microvascular endothelial cells with atypical VWF+ conglomerates forming thickened VWF+ plaque sinus in the BM compared to patients without late TA-TMA and non-HSCT. Severe chronic (p = .002), steroid-refractory GVHD (p = .007) and reactivation of HHV6 (p = .002), EBV (p = .003), and adenovirus (p = .005) were pronounced in late TA-TMA. Overall and relapse-free survival were shorter in late TA-TMA than in patients without late TA-TMA (5-year OS and RFS: 78.6% vs. 90.2%, 71.4% vs. 86.4%, respectively). CONCLUSION Chronic allo-immune microangiopathy in BM associated with chronic, steroid-refractory GVHD and/or viral infections are key findings of late, high-risk TA-TMA, which deserves clinical attention.
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9.
Analysis of early clinical signs and risk factors for severe hemorrhagic cystitis after stem cell transplantation in children
Liu, P., Bai, K., Zhang, Z., Sun, J.
International journal of urology : official journal of the Japanese Urological Association. 2024
Abstract
INTRODUCTION To analyze the characteristics of early clinical symptoms of hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) and the risk factors of severe HC. METHODS We retrospectively analyzed 77 children with post-HSCT HC treated at our hospital between June 2013 and June 2021. Clinical characteristics were collected and catalogued. RESULTS Among the children with urinary tract irritation symptoms (UTIS) as the first symptom, symptoms appeared earlier than hematuria symptoms (28 day vs. 31 day, p = 0.027), and the time progressing to severe HC was significantly longer in these children (12 day vs. 7 day, p = 0.038), but there was no significant difference in the number of participants (57.8% vs. 59.4%, p = 0.889). BK polyomavirus (BKV) infection was an independent risk factor (hazard ratio [HR] = 2.782, p = 0.035) for severe HC, which was also positively associated with multi-viral infection (HR = 2.215, p = 0.020). CONCLUSIONS In HC children, when the first urinary tract symptom was UTIS, it appeared earlier than hematuria, and the time of progression to severe HC was significantly longer, suggesting that we still need more aggressive treatment for these children to prevent the worsening of symptoms. The severity of HC was positively correlated with BKV infection and multiple infections.
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10.
Pre-transplant glomerular hyperfiltration is not a risk factor for increased renal morbidity and mortality in pediatric stem cell transplant patients
Sarkar, N., Myers, K. C., Lane, A., Davies, S. M., Benoit, S. W.
Pediatric blood & cancer. 2024;:e30853
Abstract
Low glomerular filtration rate (GFR) prior to stem cell transplant (SCT) is associated with increased morbidity and mortality. The implications of abnormally high GFRs, or glomerular hyperfiltration, prior to SCT are unknown. Twenty-two of 74 consecutive pediatric SCT patients over 2 years old at a single center were hyperfiltrating prior to SCT, median nuclear medicine GFR 154 mL/min/1.73 m(2) [interquartile range: 146-170]. There was no association between hyperfiltration and any transplant demographics, nor between hyperfiltration and acute kidney injury (p = .8), renal replacement therapy (p = .63), 1-year event-free survival (p = 1), or abnormal creatinine-based estimated GFR at a median follow-up of 4.7 years (p = .73).