Osteosarcoma in patients with Rothmund-Thomson syndrome.

BACKGROUND: Rothmund-Thomson syndrome (RTS) is associated with an increased risk of osteosarcoma, but information about affected patients is limited. PROCEDURE: Seven patients with osteosarcoma, treated in the Cooperative Osteosarcoma Study Group-trials, had a diagnosis of RTS. Their patient-, tumor- and treatment-related variables and outcome were reviewed retrospectively. RESULTS: Median age at diagnosis of osteosarcoma was 13 years (range 7-16), five were female, two male. Tumor involved proximal tibia (n = 4), distal tibia (n = 1), distal fibula (n = 1) and proximal ulna (n = 1). Three patients had metastatic disease at diagnosis. All patients received surgery and chemotherapy. Four of seven patients required dose modifications and three of them terminated treatment prematurely. Complete resection of the primary tumor was achieved in all individuals. Two of three affected patients failed to achieve surgical clearance of their primary metastases and died. The third patient relapsed with multiple metastases and died. Two of four patients with localized disease were alive in first complete remission, a third patient in second complete remission after recurrence and a fourth patient died of acute leukemia, while still in first complete remission of osteosarcoma. CONCLUSIONS: Patients with RTS and osteosarcoma may be cured of their cancer with appropriate multimodal therapy. They should be treated like other osteosarcoma patients but preexisting disorders, needs for special support and development of toxicities have to be considered.

Kinetics of porphyrin fluorescence accumulation in pediatric brain tumor cells incubated in 5-aminolevulinic acid.

BACKGROUND: Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) enables more complete resections of tumors in adults. 5-ALA elicits accumulation of fluorescent porphyrins in various cancerous tissues, which can be visualized using a modified neurosurgical microscope with blue light. Although this technique is well established in adults, it has not been investigated systematically in pediatric brain tumors. Specifically, it is unknown how quickly, how long, and to what extent various pediatric tumors accumulate fluorescence. The purpose of this study was to determine utility and time course of 5-ALA-induced fluorescence in typical pediatric brain tumors in vitro. METHODS: Cell cultures of medulloblastoma [DAOY and UW228], cPNET [PFSK] atypical teratoid rhabdoid tumor [BT16] and ependymoma [RES196] were incubated with 5-ALA for either 60 minutes or continuously. Porphyrin fluorescence intensities were determined using a fluorescence-activated cell sorter (FACS) after 1, 3, 6, 9, 12 and 24 hours. C6 and U87 cells served as controls. RESULTS: All pediatric brain tumor cell lines displayed fluorescence compared to their respective controls without 5-ALA (p < 0.05). Sixty minutes of incubation resulted in peaks between 3 and 6 hours, whereas continuous incubation resulted in peaks at 12 hours or beyond. 60 minute incubation peak levels were between 52 and 91 % of maxima achieved with continuous incubation. Accumulation and clearance varied between cell types. CONCLUSIONS: We demonstrate that 5-ALA exposure of cell lines derived from typical pediatric central nervous system (CNS) tumors induces accumulation of fluorescent porphyrins. Differences in uptake and clearance indicate that different application modes may be necessary for fluorescence-guided resection, depending on tumor type.

Late graft failure in FA--case report and review of the literature.

Hematological disorders in patients with FA can only be cured by allogeneic HSCT. Severe infections in primary and early secondary graft failures pose a particular risk. Whereas most graft failures occur within 100 days, those observed after day +100 are infrequent. Here, we present our analysis of a secondary graft failure more than five yr after a first allogeneic HSCT. In this patient, isolated thrombocytopenia over a period of 12 months resulted in a chimerism subset analysis revealing a considerable decrease in the CD34-positive donor cell fraction. After a second fludarabine-based preparative regimen, the patient received PBSC from the same donor. Chimerism returned to full donor in all subsets. This clinical course demonstrates that isolated thrombocytopenia can precede complete graft failure for several months. Our review of the literature on late graft failures in patients with FA after day +100 reveals the absence of fludarabine in the preparative regimen as a potential risk factor. Further clinical research is necessary to identify more suitable approaches for ensuring safe and stable engraftment.