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Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases - a guide for the generalist.

ABSTRACT: Autologous haematopoietic stem cell transplantation (aHSCT) is commonly used for the treatment of haematological cancers, but is increasingly used in the treatment of patients severely affected by autoimmune diseases (ADs). In fact, ADs have become the fastest growing indication for aHSCT. A wide range of diseases have been treated, but the field has focused on three areas: multiple sclerosis, diffuse cutaneous systemic sclerosis and Crohn's disease, where there are populations of patients for whom disease control remains unsatisfactory despite the advent of biological and targeted small molecule therapies. Scientific studies of immune reconstitution have provided support for a 'rebooting' of the immune system through a re-diversification of naive and regulatory immune effector cells. In addition, there may be health economic benefits from a single one-off procedure. Even so, the treatment with aHSCT is intensive with a range of toxicities and risks which, despite being routine to transplant haematologists, are less familiar to disease specialists. Close collaboration between transplant haematologists and relevant disease specialists in patient selection, clinical management and follow-up is mandatory. Ideally, patients should be treated on a clinical trial if available.

SUBMITTER: Snowden JA

PROVIDER: S-EPMC6334059 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases - a guide for the generalist.

Snowden John A JA Sharrack Basil B Akil Mohammed M Kiely David G DG Lobo Alan A Kazmi Majid M Muraro Paolo A PA Lindsay James O JO

Clinical medicine (London, England) 20180801 4

Autologous haematopoietic stem cell transplantation (aHSCT) is commonly used for the treatment of haematological cancers, but is increasingly used in the treatment of patients severely affected by autoimmune diseases (ADs). In fact, ADs have become the fastest growing indication for aHSCT. A wide range of diseases have been treated, but the field has focused on three areas: multiple sclerosis, diffuse cutaneous systemic sclerosis and Crohn's disease, where there are populations of patients for w ...[more]

PMID: 30072560

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Project description:BACKGROUND:Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS:We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score. RESULTS:In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ?9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group. CONCLUSIONS:Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530 .).

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.

Dataset Information

Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases - a guide for the generalist.

Publications

Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases - a guide for the generalist.

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