ArticlesCardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis
Introduction
Systemic sclerosis generally affects young women and is a chronic autoimmune disease of unknown cause complicated by a combination of diffuse vasculopathy, immune activation, and tissue fibrosis.1 Standard therapies are unable to reverse disease progression, although several non-randomised trials involving small numbers of patients suggest that autologous haemopoietic stem-cell transplantation (HSCT) can improve skin and stabilise or improve forced vital capacity.2, 3, 4, 5, 6, 7, 8, 9, 10, 11 In the only randomised trial published to date (the American Scleroderma Stem Cell versus Immune Suppression Trial [ASSIST]),2 autologous HSCT improved both skin and forced vital capacity, whereas disease progression was noted in patients treated with the standard therapy of monthly intravenous cyclophosphamide.
Several transplantation trials for systemic sclerosis have been complicated by treatment-related mortality.3, 4, 6, 7, 10, 12 Such mortality was 10% (eight of 79 patients) in the largest reported trial to date, the European Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial.12 For cancer13 and autoimmune diseases including systemic sclerosis,14, 15 published guidelines recommend an echocardiogram to assess cardiac reserve to establish whether a patient can safely tolerate a transplant. However, unlike other diseases for which haemopoietic transplantation is done, the usual disease-related cause of death for systemic sclerosis is cardiac complications arising from pulmonary artery hypertension and primary cardiac or pericardial involvement.16
Therefore, we analysed results from two centres that used the same mobilisation and non-myeloablative HSCT regimen without selection or manipulation of the graft to assess the causes of treatment-related mortality, whether impaired cardiac function affects outcome, and the appropriate screening method before transplantation to prevent enrolment of patients with insufficient cardiac reserve to safely tolerate the procedure.
Section snippets
Study design and patients
We undertook a retrospective analysis of all patients treated with HSCT, either as part of a study or on a compassionate basis, at Northwestern University (Chicago, IL, USA) and the University of São Paulo (Ribeirão Preto, Brazil). Patients were enrolled in institutional review board (IRB)-approved studies and retrospective IRB approval was obtained to report off-study patients. We defined duration of disease as duration from time of diagnosis of systemic sclerosis. Patients were followed up
Results
Between November, 2002, and July, 2011, we included 59 patients at Northwestern University and 31 patients at the University of São Paulo (figure 1). 59 patients were in IRB-approved studies (28 from Northwestern University and 31 from University of São Paulo) and retrospective IRB approval was obtained for 31 patients. Table 1 shows demographic characteristics of 90 patients who were offered autologous HSCT.
Median day of engraftment (absolute neutrophil count >1000 cells per μL) was day 9
Discussion
HSCT was associated with treatment-related mortality in five (6%) of 90 patients in our study, which is about half the rate (eight [10%] of 79 patients) in the European multicentre ASTIS trial.12 Treatment-related mortality in our study was predominantly related to cardiac events (four of five deaths). We attribute the reduced mortality in our study compared with ASTIS to recognition that echocardiogram and resting right heart catheterisation might be insufficient to assess cardiac risk in
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Died March 21, 2012