ABSTRACT
BACKGROUND: HLA compatibility predicts allogeneic hematopoietic cell transplant (allo-HCT) and graft-versus-host disease (GvHD) outcomes. There is insufficient information regarding GvHD outcomes for outpatient HLA-identical and haploidentical-HCT employing reduced-intensity conditioning (RIC). RESEARCH DESIGN AND METHODS: We compare GvHD outcomes between donor types and report risk factors associated with GvHD. Stem cell source was T-cell replete peripheral blood. GvHD prophylaxis was post-transplant cyclophosphamide (PT-CY), mycophenolic acid, and calcineurin inhibitors for haploidentical (n = 107) and oral cyclosporine (CsA) plus methotrexate i.v. for HLA-identical (n = 89) recipients. RESULTS: One hundred and ninety-six HCT transplant patients were included. aGvHD and cGvHD frequency were similar between HCT types. aGvHD severity was comparable, but severe cGvHD was less frequent in the haploidentical group (p = .011). One-hundred-day cumulative incidence (CI) of aGvHD for haploidentical and HLA-identical was 31% and 33% (p = .84); 2-year CI of cGvHD was 32% and 38% (p = .6), respectively. Haploidentical recipients had less steroid-refractory cGvHD (p = .043). Patients with cGvHD had less 2-year relapse (p = .003); both aGvHD and cGvHD conferred higher OS (p = .010 and p = .001), respectively. Male sex was protective for steroid-refractory cGvHD (p = .028). CONCLUSIONS: Acute and chronic GvHD rates were comparable between HLA-identical and haploidentical transplant groups. cGvHD severity was lower in the haploidentical group.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Male , Hematopoietic Stem Cell Transplantation/adverse effects , Outpatients , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Graft vs Host Disease/epidemiology , Cyclophosphamide/therapeutic use , Steroids , Transplantation Conditioning/adverse effectsABSTRACT
BACKGROUND: Immunotherapy is emerging as an alternative treatment for Merkel cell carcinoma, but its long-term effects on response, survival, and safety are not well established. High-quality evidence is needed to estimate the efficacy of this treatment and to review the characteristics of patients and tumors that might improve outcomes. OBJECTIVE: To summarize efficacy and safety of immunotherapy in patients with Merkel cell carcinoma. METHODS: A systematic review was performed for studies published in MEDLINE, Web of Science, Scopus, and EMBASE. Two reviewers examined the literature and data extraction in duplicate. We estimated the proportions for objective responses, progression-free survival, overall survival, and treatment-related adverse events. Associations between objective response rate and immunobiologic markers were analyzed. RESULTS: Six clinical trials of 201 patients treated with immunotherapy were included. The objective response rate was 51% (95% confidence interval, 0.40-0.62; I2 = 37.1%) and grade ≥3 treatment-related adverse events were observed in 18% (95% confidence interval, 0.11-0.29; I2 = 49.5%) of patients. No significant difference was observed between response rates and immunobiologic characteristics. CONCLUSIONS: A significantly reduced tumor diameter with durable response rates and a safe profile are obtained with immunotherapy. Similar response rates achieved on either subgroup of viral status or programmed death ligand 1 expression suggests that it might act on multiple, unexplored pathways.
