Michael J. Absalon

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.

Pulmonary nodules discovered during the initial evaluation of pediatric patients with bone and soft-tissue sarcoma

Recent technical advances in CT imaging and data processing have improved the ability to detect small pulmonary nodules in children with bone and soft‐tissue sarcoma undergoing radiologic imaging of the chest.

A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study (POE 10-03).

Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose.

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.

Limitations of HLH-2004 criteria in distinguishing malignancy-associated hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is characterized by dysregulated immune activation. Primary HLH involves hereditary deficits in cytotoxic lymphocytes while secondary HLH is triggered by extrinsic factors. The HLH‐2004 criteria are widely used for clinical diagnosis, yet their specificity for HLH or their ability to differentiate primary from secondary disease is unclear, potentially leading to inappropriate treatment. We describe several cases where fulfillment of HLH‐2004 criteria obscured the diagnoses of underlying malignancies and delayed curative management. These issues are remedied without waiting for genetic testing results through an alternative diagnostic approach using flow cytometry–based immunologic assays and a thorough investigation for malignancy.

Airway plaque presenting after alteration of immunosuppression in a pediatric patient remote from heart transplantation

Success after solid organ transplantation is dependent on the proper balance of immunosuppression to prevent rejection of the allograft while limiting the risk of developing infections and malignancy. We present a 9‐year‐old girl, remote from transplant, who presented with airway plaque after a change in immunosuppression to include the mTOR inhibitor sirolimus. Differential diagnosis included direct medication side effect, infection, and neoplasia.

Pulmonary nodules in the initial evaluation of pediatric patients with bone and soft-tissue sarcoma

8549 Background: The radiographic detection of the small pulmonary nodule during the initial metastatic workup of the pediatric oncology patient presents a significant clinical dilemma. The outcome of the decision of whether the nodule is malignant or benign often affects decisions regarding treatment, protocol enrollment, and assessment of prognosis. The incidence of this clinical situation in the era of helical computed tomography (CT) is unknown and practice guidelines pertaining to the pretherapy evaluation of the small pulmonary nodule are lacking. METHODS We performed a retrospective review of initial lung CT reports of 181 consecutive pediatric patients referred to our hospital for the primary treatment of bone or soft-tissue sarcomas from 1999-2003. The frequency, number, size, location and characteristics of nodules were documented. These lung CT findings were correlated with the histologic conclusions from lung biopsy and/or clinical outcome. RESULTS Pulmonary nodules were found on CT evaluation in 57 (31%) of patients. In approximately half of these patients, the largest nodule was less than or equal to 10 mm diameter. Twenty-two patients were coded as having pulmonary metastatic disease by the primary oncologist. Four of these patients underwent a lung biopsy to histologically confirm pulmonary metastasis. The remaining 18 patients were determined to have pulmonary metastasis without further intervention. Of the 35 patients who were coded as not having pulmonary metastasis, 12 had lung biopsies showing normal lung or granulomatous disease. Patients with osteosarcoma were more likely to have an invasive procedure (p=0.010), but size, number of nodules, and presence of calcifications were not predicative (p>0.36) of those going to biopsy. CONCLUSIONS Our findings confirm that the finding of a small pulmonary nodule during the initial workup of pediatric patients with sarcoma presents a common clinical scenario and highlights the need for a systematic approach to its evaluation. A proposal to study this problem will be offered. No significant financial relationships to disclose.