Clinical characteristics and prognosis of osteosarcoma in young children: a retrospective series of 15 cases

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma is the most common primary bone malignancy in childhood and adolescence. However, it is very rare in children under 5 years of age. Although studies in young children are limited in number, they all underline the high rate of amputation in this population, with conflicting results being recently reported regarding their prognosis.</p> <p>Methods</p> <p>To enhance knowledge on the clinical characteristics and prognosis of osteosarcoma in young children, we reviewed the medical records and histology of all children diagnosed with osteosarcoma before the age of five years and treated in SFCE (Société Française des Cancers et leucémies de l'Enfant) centers between 1980 and 2007.</p> <p>Results</p> <p>Fifteen patients from 7 centers were studied. Long bones were involved in 14 cases. Metastases were present at diagnosis in 40% of cases. The histologic type was osteoblastic in 74% of cases. Two patients had a relevant history. One child developed a second malignancy 13 years after osteosarcoma diagnosis.</p> <p>Thirteen children received preoperative chemotherapy including high-dose methotrexate, but only 36% had a good histologic response. Chemotherapy was well tolerated, apart from a case of severe late convulsive encephalopathy in a one-year-old infant. Limb salvage surgery was performed in six cases, with frequent mechanical and infectious complications and variable functional outcomes.</p> <p>Complete remission was obtained in 12 children, six of whom relapsed. With a median follow-up of 5 years, six patients were alive in remission, seven died of their disease (45%), in a broad range of 2 months to 8 years after diagnosis, two were lost to follow-up.</p> <p>Conclusions</p> <p>Osteosarcoma seems to be more aggressive in children under five years of age, and surgical management remains a challange.</p

Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms

A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45low CD33high, CD117+, CD13-/+, HLA Drhigh, CD123high, and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity

Does chemotherapy-induced neutropaenia result in a postponement of adjuvant or neoadjuvant regimens in breast cancer patients? Results of a retrospective analysis

In 2005, 224 patients received adjuvant/neoadjuvant chemotherapy for breast cancer in a single institution according to daily practices. Regimens consisted of epirubicin-based chemotherapy (FEC100, four or six cycles), or three cycles of FEC100 followed by three cycles of docetaxel. An absolute blood count was carried out every 3 weeks, 1–3 days before planned chemotherapy cycle. Overall, 1238 cycles were delivered. An absolute neutrophil count (ANC) <1.5 × 109 l−1 before planned chemotherapy was found in 171 cycles. Of these, 130 cycles (76%) were delivered as planned regardless of whether ANC levels recovered, and 41 (24%) were delayed. None of these patients developed a febrile neutropaenia. Haematopoietic support (granulocyte colony-stimulating factor (G-CSF)) was required in 12 cycles. We found that the majority of patients with an ANC <1.5 × 109 l−1 before planned chemotherapy received planned doses, without complications and need for G-CSF

Pediatric T- and NK-cell lymphomas: new biologic insights and treatment strategies

T- and natural killer (NK)-cell lymphomas are challenging childhood neoplasms. These cancers have varying presentations, vast molecular heterogeneity, and several are quite unusual in the West, creating diagnostic challenges. Over 20 distinct T- and NK-cell neoplasms are recognized by the 2008 World Health Organization classification, demonstrating the diversity and potential complexity of these cases. In pediatric populations, selection of optimal therapy poses an additional quandary, as most of these malignancies have not been studied in large randomized clinical trials. Despite their rarity, exciting molecular discoveries are yielding insights into these clinicopathologic entities, improving the accuracy of our diagnoses of these cancers, and expanding our ability to effectively treat them, including the use of new targeted therapies. Here, we summarize this fascinating group of lymphomas, with particular attention to the three most common subtypes: T-lymphoblastic lymphoma, anaplastic large cell lymphoma, and peripheral T-cell lymphoma-not otherwise specified. We highlight recent findings regarding their molecular etiologies, new biologic markers, and cutting-edge therapeutic strategies applied to this intriguing class of neoplasms

Safety Assessment of Intensive Induction Therapy in Childhood Anaplastic Large Cell Lymphoma: Report of the ALCL99 Randomised Trial

Background. ALCL99 protocol including six courses of chemotherapy derived from the NHL-BFM protocol is widely used for the treatment of paediatric anaplastic large-cell lymphoma. In the ALCL99 trial, patients were randomised to receive MTX 1 g/m2 in 24 hr with intrathecal injection (MTX1) versus MTX 3 g/m2 in 3 hr without intrathecal (MTX3); then to receive or not vinblastine (highrisk patients). The present study provides information about the acute adverse reactions (ARs) during the six courses of the ALCL99 treatment, assesses risk factors for ARs and evaluates the risk of overweight related to treatment. Methods. Data concerning ARs were assessed using CTCv2 and analysed overall and according to the type of course. Results. Between 1999 and 2005, 352 patients were recruited. Toxicity assessed after 2050 courses included grade 4 neutropaenia (70% of courses), grade 3\u20134 stomatitis (13%), grade 3\u20134 transaminase elevation (10%) and grade 3\u20134 infection (5%). Four patients (1%) died of toxicity. The toxicity profile differed between courses-A (significantly more haematological toxicity) and courses-B (significantly more stomatitis). The percentage of ARs was higher after the first course than after subsequent courses. Severe toxicity was more frequent after MTX1 than after MTX3 courses but did not differ between courses with or without vinblastine. Overall 20% of patients had a weight gain exceeding 20%. Conclusions. The high rate of acute toxicity should be considered when using the ALCL99 protocol. Chemotherapy including MTX 3 g/m2 in 3 hr was less toxic than the same regimen with MTX 1 g/m2 in 24 hr. Adding vinblastine did not increase the risk of toxicity