These results indicate the feasibility and safety of bone marrow gene therapy with a potentially therapeutic gene, the MDR gene.

The prognosis is very dismal for patients with relapsed CD20

SummaryObinutuzumab is a novel glycoengineered Type-II CD20 monoclonal antibody. CD20 is expressed in approximately 100% of children and adolescents with Burkitt lymphoma (BL) and 40% with precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL). We evaluated the anti-tumour activity of obinutuzumab versus rituximab against rituximab-resistant (Raji 4RH) and -sensitive (Raji) BL and pre-B-ALL (U698-M) cells in vitro and in human BL or Pre-B-ALL xenografted mice. We demonstrated that obinutuzumab compared to rituximab significantly enhanced cell death against Raji 35Á6 AE 3Á1% vs. 25Á1 AE 2Á0%, (P = 0Á001), Raji4RH 19Á7 AE 2Á2% vs. 7Á9 AE 1Á5% (P = 0Á001) and U-698-M 47Á3 AE 4Á9% vs. 23Á2 AE 0Á5% (P = 0Á001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody-dependent cellular cytotoxicity (ADCC) with K562-IL15-41BBL expanded NK cells against Raji 73Á8 AE 8Á1% vs. 56Á81 AE 4Á6% (P = 0Á001), Raji-4RH 40Á0 AE 1Á6% vs. 0Á5 AE 1Á1% (P = 0Á001) and U-698-M 70Á0 AE 1Á6% vs. 45Á5 AE 0Á1% (P = 0Á001), respectively. Overall survival in tumour xenografted mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to those receiving 30 mg/kg of rituximab in BL; Raji (P = 0Á05), Raji4RH (P = 0Á02) and U698-M (P = 0Á03), respectively. These preclinical data suggest obinutuzumab is significantly superior to rituximab in inducing cell death, ADCC and against rituximab-sensitive/-resistant BL and pre-B-ALL xenografted mice. Taken together, these preclinical results provide evidence to suggest that future investigation of obinutuzumab is warranted in patients with relapsed/refractory CD20 + BL and/or pre-B-ALL.

A B S T R A C T PurposeTo determine the maximum-tolerated or recommended phase II dose, dose-limiting toxicities (DLTs), pharmacokinetics (PK), and immunomodulatory effects of lenalidomide in children with recurrent or refractory solid tumors or myelodysplastic syndrome (MDS). Patients and MethodsCohorts of children with solid tumors received lenalidomide once daily for 21 days, every 28 days at dose levels of 15 to 70 mg/m 2 /dose. Children with MDS received a fixed dose of 5 mg/m 2 /dose. Specimens for PK and immune modulation were obtained in the first cycle. Results Forty ConclusionLenalidomide is well-tolerated at doses up to 70 mg/m 2 /d for 21 days in children with solid tumors. Drug clearance in children younger than 12 years is faster than in adolescents and young adults. Lenalidomide significantly upregulates cellular immunity, including NK and LAK activity.