Christine L. Phillips

Low dose decitabine in very high risk relapsed or refractory acute myeloid leukaemia in children and young adults

Low‐dose decitabine has encouraging activity and tolerability in adults with acute myeloid leukaemia (AML), but paediatric experience is lacking. We report our retrospective experience with decitabine in eight children and young adults (median age 4 years) with refractory/relapsed AML, who had failed multiple regimens or were not candidates for standard retrieval regimens due to prior toxicities. Three of eight patients (38%) had complete response (CR; 1 each of CR, CR with incomplete platelet recovery and CR with incomplete count recovery). Best responses were observed after a median of 2·5 cycles (range 1–4 cycles). Four patients received subsequent allogeneic stem cell transplant, and two remain in long‐term CR.

A phase I trial of MK‐2206 in children with refractory malignancies: A Children's Oncology Group study

We report results of a phase I trial designed to estimate the maximum tolerated dose (MTD), describe dose‐limiting toxicities (DLT), and characterize the pharmacokinetic profile of MK‐2206, an AKT inhibitor, in children with refractory or recurrent malignancies.

MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: A report from the Children's Oncology Group†

The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li–Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have 10‐fold increase resistance to topoisomerase II inhibitors in vitro.

Post-transplant lymphoproliferative disorder after solid-organ transplant in children

The post-transplant lymphoproliferative disorders (PTLD) are a diverse group of potentially life-threatening conditions affecting organ transplant recipients. PTLD arises in the setting of an attenuated host immunologic system that is manipulated to allow a foreign graft but then fails to provide adequate immune surveillance of transformed malignant or premalignant lymphocytes. The diversity of biological behavior and clinical presentation makes for a challenging clinical situation for those involved in the care of children with PTLD occurring after solid-organ transplantation. This review details a large transplant centers multidisciplinary approach to monitoring for PTLD and systematic approach to intervention, which has been essential for early recognition and successful treatment.

Viral surveillance using PCR during treatment of AML and ALL

While viral surveillance of cytomegalovirus (CMV), Epstein–Barr virus (EBV), and adenovirus using PCR is routine in patients undergoing hematopoetic stem cell transplant and solid organ transplant, the utility in the nontransplant pediatric leukemia population is unknown. Our institution screens patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) for viral DNAemia by PCR as part of clinical care.

Medulloblastoma with melanotic differentiation: case report and review of the literature

Medulloblastoma with melanotic differentiation, a rare variant of medulloblastoma, often carries a poor prognosis. We present such a case of a 4 year male with this rare, aggressive tumor. Additionally, we have reviewed the literature and report on the features important in the pathologic and radiologic diagnosis in this type of tumor, as well as review clinical outcomes. This subtype of medulloblastoma occurs more frequently in males, at a younger median age than the other subtypes of medulloblastoma. The prognosis is generally very poor. However, it is important to note, that a subset of patients with M0 disease who can achieve a gross total resection followed by radiation and platinum based chemotherapy can become long term survivors of this aggressive subtype of medulloblastoma.

A phase I trial of MK-2206 in children with refractory malignancies

We report results of a phase I trial designed to estimate the maximum tolerated dose (MTD), describe dose‐limiting toxicities (DLT), and characterize the pharmacokinetic profile of MK‐2206, an AKT inhibitor, in children with refractory or recurrent malignancies.

A phase I trial of MK-2206 in children with refractory malignancies: A Children's Oncology Group study: Pediatric Phase I Trial of MK 2206

We report results of a phase I trial designed to estimate the maximum tolerated dose (MTD), describe dose‐limiting toxicities (DLT), and characterize the pharmacokinetic profile of MK‐2206, an AKT inhibitor, in children with refractory or recurrent malignancies.