ABSTRACT
T-cell replete hematopoietic stem cell transplantation (HSCT) from a haploidentical donor followed by high doses of cyclophosphamide has been demonstrated to provide the best chances of a cure for many children in need of an allograft but who lack both a sibling and an unrelated donor. In this study we retrospectively compared the outcome of pediatric patients undergoing T-replete haploidentical HSCT (Haplo) for acute leukemia with those undergoing transplantation from unrelated HLA-matched donor (MUD) and HLA mismatched unrelated donor (MMUD) from 2012 to 2017 at our Center. Both univariable and multivariable analyses showed similar 5-year overall survival rates for MUD, MMUD, and Haplo patients: 71% (95% CI 56-86), 72% (95% CI 55-90), and 75% (95% CI 54-94), respectively (p = 0.97). Haplo patients showed reduced event-free survival rates compared to MUD and MMUD patients: 30% (95% CI 12-49) versus 70% (95% CI 55-84) versus 53% (95% CI 35-73), respectively (p = 0.007), but these data were not confirmed by a multivariable analysis. Non-relapse mortality (NRM) and relapse incidence (RI) were similar for the three groups. Therefore, our data confirm that Haplo is a suitable clinical option for pediatric patients needing HSCT when lacking both an MUD and an MMUD donor.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Child , Cyclophosphamide , Humans , Retrospective Studies , Unrelated DonorsABSTRACT
BACKGROUND: A phase 2 trial was carried out to assess the antineoplastic activity of 2 courses of cyclophosphamide-etoposide in relapsed osteosarcoma patients. METHODS: Twenty-six relapsed osteosarcoma patients with a median age of 18.5 years (8.3-47.1) were enrolled. Seven patients were in first relapse (27%), 11 in second relapse (42%), 7 in third relapse (27%), and 1 in fourth relapse (4%). Eighteen patients had bone metastasis at study entry (69%). Cyclophosphamide was given at 4 g/m(2) on Day 1 followed by etoposide at 200 mg/m(2) on Days 2, 3, and 4. Second cyclophosphamide and etoposide was planned at 21 days to 28 days from the previous one. The primary endpoint of the study was the clinical benefit at 4 months measured as progression-free survival. RESULTS: Progression-free survival at 4 months was 42%. Five patients achieved responses (19%), 9 patients had stable disease (35%), and 12 had tumor progression (46%). Overall survival (OS) at 1 year was 50%. The only grade 4 extrahematological toxicities were fever (5%), acute bronchospasm (4%) and stomatitis (18%). Six patients (23%) underwent radical surgery after cyclophosphamide and etoposide x2. CONCLUSIONS: Cyclophosphamide and etoposide x2 may arrest osteosarcoma progression in a significant number of patients (54%). Osteosarcoma progression arrest after cyclophosphamide and etoposide x2 translates in a better OS. Cyclophosphamide and etoposide x2 had good tolerability and the toxicity was time-limited and resolved in all cases.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Etoposide/administration & dosage , Osteosarcoma/drug therapy , Adolescent , Adult , Child , Disease-Free Survival , Female , Hematopoietic Stem Cell Mobilization , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapyABSTRACT
First-line treatment of GVHD is based on steroids and produces sustained responses in 50-80% of patients with acute GVHD (aGVHD) and 40-50% of patients with chronic GVHD (cGVHD) depending on the initial disease severity. Non-responding children are offered second-line therapy with combinations of various agents, but currently available agents have not improved survival in these high-risk populations. In this minireview, we will focus on new agents to treat GVHD in paediatric patients.
