Safety profile of autologous hematopoietic stem cell mobilization and transplantation in patients with systemic sclerosis

Abstract

Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24–68). The median duration of disease before AHSCT was 14 months (range 2–85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg) [n = 11], melphalan (MEL; 140 mg/m2) and alemtuzumab [n = 2], CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg) [n = 4], and CY alone (n = 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24–68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0–95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.

Re-evaluating inclusion criteria for autologous hematopoietic stem cell transplantation in advanced systemic sclerosis: Three successful cases and review of the literature

“…The age limit varied between studies from the upper limit of 40 years in an Indian study 14 to the upper limit of 70 years in a Polish cohort. 15 Four studies allowed inclusion of patients who had either skin involvement with mRSS >15 or organ involvement, [15][16][17]20 while in the other three studies, patients had to have both skin involvement and involvement of at least one major organ (heart, lung, or kidneys). 14,18,19 Patients with limited cutaneous SSc were included in one study as well, if severe pulmonary fibrosis or pulmonary hypertension was present.…”

Autologous Haematopoietic Stem Cell Transplantation and Systemic Sclerosis: Focus on Interstitial Lung Disease

“…The specific effect of TBI and CYC on cardiac function needs to be better clarified to assess the contribution of each component to treatment-related outcomes. Based on the results presented by Helbig G. et al [ 22 ], the use of alemtuzumab, in association with CYC, for the conditioning phase, was associated with an increased occurrence of infections and thus it should be avoided because of high risk of developing infectious complications. Indeed, one of the main clinical unmet needs is the identification of the most effective conditioning protocol avoiding the toxicity induced by over-treatment and the concomitant increase in infection rate.…”

“…Many factors influence the outcome of transplant, and they are as follows: HSCT protocol, age of patient, disease duration before transplant, quality of life, and co-morbidities, e.g., decreased left ventricle ejection fraction (LVEF) or pulmonary arterial hypertension (PAH). The most frequent complications are viral reactivations (CMV, EBV, HSV) and opportunistic infections [ 21 , 22 , 27 , 29 ]. Reactivation may be dependent on ATG in conditioning [ 29 ] and occurs more frequently in CD34-selected patients [ 21 ] and in patients with low B cell count prior to transplant [ 29 ].…”

Life after Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis

“…Most phase I/II studies showed stabilization or slight improvement in FVC after transplantation, and DLCO stabilization. [30][31][32][33] One study showed significant improvement for both FVC and DLCO over 5 years and another study showed that FVC and DLCO improved only in the subgroup of patients with progressive lung disease as an https://doi.org/10.2147/JBM.S338077…”