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1.
Primary Cancer Matters in Therapy-related Myeloid Neoplasm Patients Receiving Allogeneic Hematopoietic Cell Transplantation: A Study From the Chronic Malignancies Working Party of the EBMT
Robin, M., de Wreede, L. C., Schroeder, T., Stölzel, F., Kröger, N., Koster, L., Platzbecker, U., Finke, J., Ganser, A., Blaise, D., et al
HemaSphere. 2023;7(4):e851
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2.
Allogeneic hematopoietic cell transplantation in patients with therapy-related myeloid neoplasm after breast cancer: a study of the Chronic Malignancies Working Party of the EBMT
Nabergoj, M., Mauff, K., Beelen, D., Ganser, A., Kröger, N., Stölzel, F., Finke, J., Passweg, J., Cornelissen, J., Schub, N., et al
Bone marrow transplantation. 2022
Abstract
We performed a registry study on therapy-related myeloid neoplasm (t-MN), both therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) following treatment for breast cancer who underwent a first allogeneic hematopoietic cell transplant (allo-HCT). Of 252 identified female patients (median age 57 years), 77% were transplanted for t-AML and 23% for t-MDS, with a median time from breast cancer diagnosis to the diagnosis of tMN and subsequent allo-HCT of 3.7 and 4.6 years, respectively. At transplant, 191 patients were in remission for breast cancer, while 4 were not (57 missing). T-MN was in a complete remission at the time of transplant in 67% of patients. 2-year overall survival, relapse free-survival, relapse incidence and non-relapse mortality were 50%, 45%, 33%, and 22%, respectively. Multivariable analysis revealed that if the t-MN was not in CR pre-transplant, this was associated with lower OS, RFS, and a higher relapse incidence. Seventeen cases of breast cancer recurrence were recorded after a median of 2.4 years post-transplant, and relapse of primary breast cancer accounted for 7% of deaths. This study indicates that allo-HCT for t-MN following treatment for breast cancer shows encouraging transplant outcomes. The incidence of breast cancer relapse post-transplant remains a cause for concern.
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3.
20-Year Steady Increase in Survival of Adult Patients with Relapsed Philadelphia-Positive Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Cell Transplantation
Bazarbachi, A., Labopin, M., Aljurf, M., Niittyvuopio, R., Balsat, M., Blaise, D., Yakoub-Agha, I., Grassi, A., Reinhardt, H. C., Lenhoff, S., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2022
Abstract
PURPOSE Relapse after allogeneic hematopoietic cell transplantation (allo-HCT) remains the first cause of transplant failure in patients with Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL). In other hematologic malignancies, therapeutic advances resulted in significant improvement over time in survival of patients relapsing after transplant. PATIENTS AND METHODS We compared outcomes at European Society for Blood and Marrow Transplantation (EBMT) participating centers of 899 adult patients with Ph(+) ALL who relapsed between 2000 and 2019 after allo-HCT performed in first complete remission. Median follow-up for alive patients was 56 months. RESULTS Overall, 116 patients relapsed between 2000 and 2004, 225 between 2005 and 2009, 294 between 2010 and 2014, and 264 between 2015 and 2019. Patient and transplant characteristics were similar over the four time periods except for a progressive increase in unrelated donors, peripheral blood stem cells, reduced intensity conditioning, and in vivo T-cell depletion and a progressive decrease in total body irradiation. The 2-year overall survival (OS) after relapse increased from 27.8% for patients relapsing between 2000 and 2004 to 54.8% for 2015 and 2019 (P = 0.001). A second allo-HCT within 2 years after relapse was performed in 13.9% of patients resulting in a 2-year OS of 35.9%. In multivariate analysis, OS from relapse was positively affected by a longer time from transplant to relapse and the year of relapse. CONCLUSIONS We observed a major progressive improvement in OS from posttransplant relapse for patients with Ph(+) ALL over the years, likely multifactorial including transplant-related factors, posttransplant salvage, and improvement in supportive care. These large-scale real-world data can serve as a benchmark for future studies in this setting.
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4.
Patient preferences for allogeneic haematopoietic stem cell transplantation: how much benefit is worthwhile from the patient's perspective?
Leuthold, N., Cattaneo, M., Halter, J., Hügli, C., Kirsch, M., Petropoulou, A., Erlanger, T. E., Gerull, S., Passweg, J., O'Meara Stern, A.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020
Abstract
Oncological studies have shown that patients consider small benefits sufficient to make adjuvant chemotherapy worthwhile. We sought to determine the minimal survival benefits that patients considered enough to legitimate allogeneic haematopoietic stem cell transplantation (HCT) and the factors associated with patient preferences. One hundred eighty-four patients having previously received allogeneic HCT at our centre were included and completed a questionnaire exploring patient expectations elicited by time trade-off scenarios as well as quality of life (QoL), symptoms of graft-versus host disease (GvHD) and sociodemographic characteristics. The majority of patients considered a minimal survival benefit of at least 5 (38.6%) or 10 years (41.9%) sufficient to justify HCT, with less than 5% considering survival < 1 year sufficient to warrant HCT. In terms of minimal cure rate, a cumulative 14.8% of patients accepted cure rates below 30% and 30.6% rates below 50%. Likelihood-ratio tests were significant for the effect of age at transplant on expected minimal survival (p = 0.007) and cure rates (p = 0.0001); that is, younger patients at HCT were more likely to accept smaller survival and cure rates. Pre-transplant risk score, QoL, GvHD score and sociological factors did not seem to influence patients' expectations. In conclusion, patient expectations of treatment were much higher than what had been reported in oncological studies. Patients who experienced HCT considered a survival superior to 1 year and cure rates above 50% sufficient to make it worthwhile. Younger patients were more likely to accept smaller benefits; no other predictors for preferences could be detected.
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5.
Tear Proteomic Predictive Biomarker Model for Ocular Graft Versus Host Disease Classification
O'Leary, O. E., Schoetzau, A., Amruthalingam, L., Geber-Hollbach, N., Plattner, K., Jenoe, P., Schmidt, A., Ullmer, C., Drawnel, F. M., Fauser, S., et al
Translational vision science & technology. 2020;9(9):3
Abstract
PURPOSE Diagnosis of ocular graft-versus-host disease (oGVHD) is hampered by a lack of clinically-validated biomarkers. This study aims to predict disease severity on the basis of tear protein expression in mild oGVHD. METHODS Forty-nine patients with and without chronic oGVHD after AHCT were recruited to a cross-sectional observational study. Patients were stratified using NIH guidelines for oGVHD severity: NIH 0 (none; n = 14), NIH 1 (mild; n = 9), NIH 2 (moderate; n = 16), and NIH 3 (severe; n = 10). The proteomic profile of tears was analyzed using liquid chromatography-tandem mass spectrometry. Random forest and penalized logistic regression were used to generate classification and prediction models to stratify patients according to disease severity. RESULTS Mass spectrometry detected 785 proteins across all samples. A random forest model used to classify patients by disease grade achieved F1-measure values for correct classification of 0.95 (NIH 0), 0.8 (NIH 1), 0.74 (NIH 2), and 0.83 (NIH 3). A penalized logistic regression model was generated by comparing patients without oGVHD and those with mild oGVHD and applied to identify potential biomarkers present early in disease. A panel of 13 discriminant markers achieved significant diagnostic accuracy in identifying patients with moderate-to-severe disease. CONCLUSIONS Our work demonstrates the utility of tear protein biomarkers in classifying oGVHD severity and adds further evidence indicating ocular surface inflammation as a main driver of oGVHD clinical phenotype. TRANSLATIONAL RELEVANCE Expression levels of a 13-marker tear protein panel in AHCT patients with mild oGVHD may predict development of more severe oGVHD clinical phenotypes.
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6.
Common oral diseases, hyposalivation and survival post-HSCT, a longitudinal study
Uutela, P., Passweg, J., Halter, J., Gerull, S., Weiger, R., Mauramo, E., Waltimo, T., Mauramo, M.
European journal of haematology. 2019
Abstract
OBJECTIVES Haematopoietic stem cell transplantation (HSCT) recipients are at risk of side effects within the oral cavity. The purpose of this study was to examine progression of common oral diseases and hyposalivation and their associations with survival in allogeneic HSCT recipients. METHODS 269 adult HSCT recipients treated with HSCT between 2008 and 2016 were included in this study. The associations of caries, decayed, missing, filled teeth (DMFT) index, radiological attachment loss and stimulated salivary flow rate with six-month survival and the progression of the oral disorders within two years were examined. RESULTS Forty HSCT recipients (14.8%) deceased within six months post-HSCT. Among the deceased recipients, hyposalivation and caries were more common pre-HSCT than in recipients who survived over six months (P<0.05). HSCT recipients with hyposalivation pre-HSCT had higher risk of death (HR:1.90, 95% CI:1.00-3.60; P=0.044) within six months post-HSCT compared to recipients without hyposalivation. Hyposalivation pre-HSCT was associated with a higher DMFT index score (P<0.05) and a smaller number of teeth (P<0.005) 24 months post-HSCT in comparison to those without hyposalivation. CONCLUSIONS Hyposalivation and caries were associated with a lower rate of survival in HSCT recipients. Additionally, hyposalivation predisposed to deterioration of oral health post-HSCT. This article is protected by copyright. All rights reserved.
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7.
Predictors of impaired bone health in long-term survivors after allogeneic stem cell transplantation
Baumgartner, A., Moesch, M., Zumsteg, M., Struja, T., Bernet, S., Medinger, M., Mueller, B., Passweg, J., Bargetzi, M., Schuetz, P.
Bone marrow transplantation. 2019
Abstract
Survival after allogeneic stem cell transplantation (allo-HSCT) has improved, but so have long-term sequelae. We studied risk factors for fractures and impaired bone health in allo-HSCT patients in the Basel HSCT registry from 01/2003 to 12/2014 using cox proportional models adjusted for age, gender and Karnofsky Index. Our primary endpoint was the incidence of fractures. Out of 652 patients, 32 (5.0%) had a new fracture after transplantation (yearly incidence rate of 1.6%, 95% Confidence Interval [95%CI] 1.1-2.3%) and 325 (49.8%) had low bone mineral density (yearly incidence rate of 13.1%, 95%CI 11.6-14.8%), including 36.0% with osteopenia and 13.8% with osteoporosis. We found vitamin D deficiency during follow-up (Hazard Ratio [HR] 1.25, 95%CI 1.11-1.41, p < 0.001), hyperthyroidism before transplantation (HR 4.85, 95%CI 1.05-22.54, p = 0.044), cumulative years of immunosuppressant exposure (HR 1.23, 95%CI 1.07-1.41, p = 0.004 for steroidal and HR 1.09, 95%CI 1.01-1.18, p = 0.025 for non-steroidal drugs) and graft-versus-host disease (acute HR 1.24, 95%CI 1.11-1.40, p < 0.001; chronic HR 2.82, 95%CI 1.12-7.13, p = 0.028) to be significantly associated with fractures. Patients undergoing HSCT are at increased risk of fractures, which is associated with various disease and treatment-specific factors. Early identification of patients at risk may help to improve preventive measures.