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The Glasgow Prognostic Score at Diagnosis Is a Predictor of Clinical Outcome in Patients with Multiple Myeloma Undergoing Autologous Haematopoietic Stem Cell Transplantation.

ABSTRACT: Background: Immunity and inflammatory response affect the tumour microenvironment and the progression of malignancies. Metabolic and inflammatory parameters and ratios of the peripheral blood correlate with outcome in cancer patients. There exist several established and validated inflammation-based scores of prognostic significances including the Glasgow Prognostic Score (GPS). Methods: In this retrospective, multicentre study, we investigated the prognostic capabilities of baseline GPS in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation as a complementary resource for risk stratification. For GPS calculation, a C-reactive-protein (CRP) value of >10 mg/dL counts as one point and an albumin value of <35 g/L connotes another point, resulting in three different subgroups (group I: 0 points; group II: 1 point; and group III: 2 points). Patients with MM admitted to the participating institutions between January 2010 and July 2018 were screened, and established prognostic scores and ratios were assessed. Characteristics significantly associated with overall survival (OS) or progression-free survival (PFS), upon univariate analysis, were included in a Cox proportional hazards model. Results: Following initial assessment, we identified 224 fully evaluable patients who underwent autologous haematopoietic stem cell transplantation for multiple myeloma. A centralised review of pathology and cytogenetic reports was conducted, and a central hematopathology assessment was performed in 175 of 224 cases (78.1%). Proceeding to high-dose chemotherapy and subsequent autologous stem cell transplantation was the main inclusion criterion for all transplant-eligible patients in the study. The median age at diagnosis was 59 years (range: 35-76 years) with a median follow-up of 76 months. Multivariate analysis revealed neutrophil-platelet score (NPS) (HR = 0.528, 95% CI = 0.284-0.984) and B symptoms at primary diagnosis (HR = 1.838, 95% CI = 1.232-2.740) to be independent predictors of PFS while high-risk cytogenetic changes (HR = 2.358, 95% CI = 1.413-3.934, p = 0.001) could be identified as an independent predictor of OS, and GPS to be the only independent predictor of both OS and PFS (OS: HR = 2.127, 95% CI = 1.431-3.162, p < 0.0001 and PFS: HR = 1.405; 95% CI = 1.058-1.867, p = 0.019). Conclusions: Our data show that baseline GPS correlates with rates of relapse and refractory disease in MM patients undergoing autologous transplantation. In a multivariate analysis, these effects were proven to hold prognostic capabilities beyond and independent from established prognosticators. These results require further validation in a prospective setting.

SUBMITTER: Witte HM

PROVIDER: S-EPMC7226410 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The Glasgow Prognostic Score at Diagnosis Is a Predictor of Clinical Outcome in Patients with Multiple Myeloma Undergoing Autologous Haematopoietic Stem Cell Transplantation.

Witte Hanno M HM Bonorden Bastian B Riecke Armin A Biersack Harald H Steinestel Konrad K Merz Hartmut H Feller Alfred C AC Bernard Veronica V Fetscher Sebastian S von Bubnoff Nikolas N Gebauer Niklas N

Cancers 20200409 4

<i>Background:</i> Immunity and inflammatory response affect the tumour microenvironment and the progression of malignancies. Metabolic and inflammatory parameters and ratios of the peripheral blood correlate with outcome in cancer patients. There exist several established and validated inflammation-based scores of prognostic significances including the Glasgow Prognostic Score (GPS). <i>Methods:</i> In this retrospective, multicentre study, we investigated the prognostic capabilities of baselin ...[more]

PMID: 32283706

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Project description:BackgroundThe number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non-malignant diseases and may predict outcomes after autologous HCT.MethodsThis was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non-Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male: <43 cm/m2 [body mass index (BMI) < 25 kg/m2 ] or < 53 cm/m2 [BMI ≥ 25 kg/m2 ] and female: <41 cm/m2 [regardless of BMI]) and obesity [total abdominal adiposity ≥450.0 cm2 (male), ≥396.4 cm2 (female)] were assessed from single-slice abdominal pre-HCT computed tomography images. Length of hospital stay, first unplanned intensive care unit admission, and 30-day unplanned readmission were evaluated based on body composition using multivariable regression analysis, and mortality was evaluated with Kaplan-Meier analysis and Gray's test.ResultsMedian age at HCT was 53.3 years (range, 18.5 to 78.1 years); 26.3% were sarcopenic and an additional 7.8% were sarcopenic obese pre-HCT. Sarcopenic obesity was associated with increased risk of prolonged hospitalization [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.3-9.8], intensive care unit admission (OR = 4.7, 95% CI 1.5-16.1), and unplanned readmission after HCT (OR = 13.6, 95% CI 2.5-62.8). Patients who were sarcopenic obese also had the highest mortality risk at 1 year [hazard ratio (HR): 3.9, 95% CI 1.1-11.0] and 5 years (HR: 2.5, 95% CI 1.1-5.5), compared with patients with normal body composition. Sarcopenia alone, but not obesity alone, was associated with an increased risk of these outcomes, albeit with a lower magnitude of risk than in patients who were sarcopenic obese.ConclusionsSarcopenic obesity was an important predictor of outcomes in patients undergoing autologous HCT. These findings could inform targeted prevention strategies in patients at highest risk of complications after HCT.

Project description:IntroductionAutologous haematopoietic stem cell transplantation improves event-free survival and lung function and reduces skin thickening in patients with progressive diffuse cutaneous systemic sclerosis. Anti-thymocyte globulin is a key lymphoablative constituent of conditioning protocols and is administered in a weight-based dosage. However, whether anti-thymocyte globulin exposure contributes to response to autologous haematopoietic stem cell transplantation and lymphocyte reconstitution in diffuse cutaneous systemic sclerosis patients is unknown. We aimed to explore the relationship between anti-thymocyte globulin exposure, lymphocyte reconstitution and treatment response in diffuse cutaneous systemic sclerosis patients undergoing autologous haematopoietic stem cell transplantation.MethodsA retrospective cohort of 15 diffuse cutaneous systemic sclerosis patients undergoing autologous haematopoietic stem cell transplantation was performed. Clinical characteristics and routine laboratory results were retrieved from electronic medical records. Anti-thymocyte globulin concentrations were measured in cryopreserved plasma samples at four time points (day 1 and week 1, 2 and 4) after stem cell reinfusion. Anti-thymocyte globulin exposure was estimated using a validated population pharmacokinetic model.ResultsDuring a median follow-up of 45 months (interquartile range 19-66), 11 (73%) patients had a treatment response, and 4 (27%) were non-responders. Although all patients received the same weight-based anti-thymocyte globulin dosage, 7.5 mg/kg divided over 3 days, anti-thymocyte globulin exposure varied. Anti-thymocyte globulin exposure was higher in responders than in non-responders (163 AU*day/mL (interquartile range 153-183) and 137 AU*day/mL (interquartile range 101-149), respectively, p = .026). Anti-thymocyte globulin exposure was not correlated with lymphocyte reconstitution or infection rate.ConclusionWeight-based dosing of anti-thymocyte globulin results in variable anti-thymocyte globulin exposure and treatment response across individuals.

Project description:BackgroundMultiple Myeloma (MM) is characterized by the presence of clonal plasma cells. These often result in complications including bone destruction, hypercalcemia, renal insufficiency, and anaemia. Induction with a triplet or quadruplet regimen followed by autologous stem cell transplantation (ASCT) has been the standard of care for transplant eligible patients to achieve durable remission.PurposeThis is a retrospective analytical study to determine the outcome of Multiple Myeloma patients who underwent ASCT in Ampang Hospital.Materials and methodsWe included a 5-year cohort of patients transplanted from 1st July 2014 to 30th June 2019. Data were obtained through electronic medical records. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed using simple and multiple Cox proportional hazard regression analysis. All analyses were done using software R version 3.6.2 with validated statistical packages.Results139 patients were analyzed. The median age at transplant was 56 years old and 56.1% are males (n＝78). The most common subtype is IgG Kappa (n＝67, 48.2%). Only 93 patients in which the International Staging System (ISS) could be determined, and among them, 33.3% of patients (n＝31) have advanced stage Ⅲ disease. The most common induction received before ASCT was a bortezomib based regimen and/or an immunomodulatory (IMiD) based regimen. 63.3% of patients achieved at least a very good partial response (VGPR) before ASCT. Most patients received myeloablative conditioning (MAC) (n＝119, 85.6%). The mean cell dose is 3.68×106/kg. The median time to engraftment was 11 days for both platelet and absolute neutrophil count (ANC). With the median follow-up of 17.3 (range, 6.2-33.4) months, the median OS and PFS were not reached. The 1-year and 2-year PFS were 75% (95% CI 66-82%) and 52% (95% CI 42-62%), respectively. The 1-year and 2-year OS were 82% (95% CI 74-88%) and 70% (95% CI 60-78%), respectively. 6 patients (4.3%) had transplant-related mortality (TRM). IgA subtype was found to adversely affect PFS. Maintenance therapy and the absence of renal impairment was associated with better PFS and OS.Discussion and conclusionsOur study found that ASCT following induction treatment is safe and beneficial to achieve a deeper remission status. In our study, the addition of maintenance therapy is associated with an improved outcome in PFS and OS.

Dataset Information

The Glasgow Prognostic Score at Diagnosis Is a Predictor of Clinical Outcome in Patients with Multiple Myeloma Undergoing Autologous Haematopoietic Stem Cell Transplantation.

Publications

The Glasgow Prognostic Score at Diagnosis Is a Predictor of Clinical Outcome in Patients with Multiple Myeloma Undergoing Autologous Haematopoietic Stem Cell Transplantation.

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