Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients.

Mutations in transmembrane protease, serine 6 (TMPRSS6) cause iron refractory iron deficiency anemia (IRIDA). Parenteral iron administration may slightly improve hemoglobin level but is troublesome for patients. Optimal treatment has yet to be determined.

Leukemia-initiating cells of patient-derived acute lymphoblastic leukemia xenografts are sensitive toward TRAIL.

Cancer stem cells represent the most important target cells for antitumor therapy. TRAIL (TNF-related apoptosis-inducing ligand) is a potential anticancer agent that induces apoptosis in a wide variety of tumor cells, but its ability to target cancer stem cells is currently unknown. Here we investigated whether TRAIL targets leukemia-initiating cells.

Optimized anti-tumor effects of anthracyclines plus Vinca alkaloids using a novel, mechanism-based application schedule.

Application of anthracyclines and Vinca alkaloids on the same day represents a hallmark of polychemotherapy protocols for hematopoietic malignancies. Here we show, for the first time, that both drugs might act most efficiently if they are applied on different days. Proof-of-concept studies in 18 cell lines revealed that anthracyclines inhibited cell death by Vinca alkaloids in 83% of cell lines.

The long-term impact of in vitro drug sensitivity on risk stratification and treatment outcome in acute lymphoblastic leukemia of childhood (CoALL 06-97).

Background: In a study of childhood acute lymphoblastic leukemia (CoALL 06-97 study), the in vitro sensitivity of the patients' cells to prednisolone, vincristine and asparaginase was introduced as a new additional risk parameter for treatment stratification. In parallel in vivo treatment response was assessed by determining the presence and extent of minimal residual disease in a subset of patients (n=224). Here we report the long-term impact of in vitro sensitivity-based risk stratification according to survival and compare the results of in vitro sensitivity with in vivo response.

Impact of reduction of therapy on infectious complications in childhood acute lymphoblastic leukemia.

Background: Infections are a major cause of morbidity and mortality in childhood acute lymphoblastic leukemia (ALL) and only limited information is available on infectious complications.

Patients And Methods: We investigated infectious complications in 293 children during different treatment phases of the multicenter protocol COALL-06-97. We also evaluated whether therapy reduction in prognostically good risk patients receiving either the low risk or high risk treatment arm would lead to fewer infectious complications.

Expression of the outcome predictor in acute leukemia 1 (OPAL1) gene is not an independent prognostic factor in patients treated according to COALL or St Jude protocols.

New prognostic factors may result in better risk classification and improved treatment of children with acute lymphoblastic leukemia (ALL). Recently, high expression of a gene named OPAL1 (outcome predictor in acute leukemia) was reported to be associated with favorable prognosis in ALL. Therefore, we investigated whether OPAL1 expression was of prognostic importance in 2 independent cohorts of children with ALL treated on Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92/97 (n = 180) and St Jude Total 13 protocols (n = 257).

Effective treatment of kaposiform hemangioendotheliomas associated with Kasabach-Merritt phenomenon using four-drug regimen.

We report a case of a 6-month-old girl suffering from a kaposiform hemangioendothelioma of the chest wall, associated with Kasabach-Merritt phenomenon. Despite rapid intervention with cortisone and interferon alpha the tumor led to a life-threatening clinical condition with progressive growth and consumption coagulopathy under therapy. Because therapy for kaposiform hemangioendotheliomas with a single anti-angiogenic or anti-proliferative agent has not been reported to be very successful, we administered vincristine, combined with cyclophosphamide, actinomycin D, and methotrexate in a critically ill patient.

The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (ALL) consists of various subtypes that respond differently to cytotoxic drugs and therefore have a markedly different clinical outcome. We used microarrays to investigate, in 190 children with ALL at initial diagnosis, whether 70 key apoptosis genes were differentially expressed between leukemic subgroups defined by lineage, genetic subtype, in vitro drug resistance, and clinical outcome. The expression of 44 of 70 genes was significantly different in T-versus B-lineage ALL, 22 genes differed in hyperdiploid versus nonhyperdiploid, 16 in TEL-AML1-positive versus-negative, and 13 in E2A-rearranged versus germ-line B-lineage ALL.

Laparoscopic adrenal surgery for recurrent tumours in patients with hereditary phaeochromocytoma.

Objective: To report our experience with Laparoscopic Partial Adrenalectomy (LPA) for recurrent tumours in patients with hereditary phaeochromocytoma.

Patients And Methods: Five patients with hereditary phaeochromocytoma (4 with von Hippel-Lindau disease and 1 with Multiple Endocrine Neoplasia 2B), who had undergone adrenal surgery previously, presented with recurrent adrenal tumours. One patient was pregnant at 20 weeks of gestation.

Successful antifungal combination therapy with voriconazole and caspofungin.

A 12-year-old boy in third remission of an acute lymphoblastic leukaemia developed infection of lung and paranasal sinuses with Aspergillus flavus in neutropenia. Because of the high risk of leukaemia-relapse bone marrow transplantation (BMT) from a matched unrelated donor was carried out despite invasive pulmonary aspergillosis (IPA). It is the first reported patient with IPA, who was successfully treated by the antifungal combination therapy with voriconazole and caspofungin therapy during myeloablative BMT.

Laparoscopic partial adrenalectomy for recurrent pheochromocytoma in a boy with Von Hippel-Lindau disease.

We describe a case of a boy with Von Hippel-Lindau disease who presented with recurrent right adrenal pheochromocytoma 4.5 years after laparoscopic bilateral partial adrenalectomy. The boy had a second laparoscopic adrenal-sparing removal of the tumor.

Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL: results of the randomized trial COALL-92.

The German cooperative study group for childhood acute lymphoblastic leukemia (COALL-92) was designed to examine the clinical effectiveness of thioguanine (TG) versus mercaptopurine (MP) in maintenance treatment of childhood acute lymphoblastic leukemia (ALL) in a randomized multicenter trial. TG and MP are prodrugs and have to be converted intracellularly to 6-thioguanine nucleotides (TGNs) for cytostatic activity. TG is converted into TGN in fewer steps and has been shown to be more cytotoxic in equimolar doses in vitro compared with 6-MP.

Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries.

Medulloblastoma is an embryonal childhood malignancy with poor prognosis. By screening 4 medulloblastoma cDNA expression libraries (SEREX) with autologous sera, 15 different antigens were identified. These antigens were encoded by 3 novel genes, genes of unknown function (KIAA0445, KIAA1853, KIAA0665, FLJ13942, HSPC213), a proto-oncogene (rab18), candidate tumor suppressor genes (BAP1, PRDM13) and genes encoding a motor protein (kinesin-2), a histone (H2A1.

Laparoscopic adnexectomy of a persistent ovarian tumor in a girl with acute lymphoblastic leukemia relapse.

The management of children with acute lymphoblastic leukemia (ALL) relapse and an ovarian tumor remains controversial. The authors report about a 4-year-old girl who developed a late bone marrow and cutaneous relapse of her pre-B-cell ALL and revealed an enlargement of her left ovary (4 x 3 x 2 cm). Chemotherapy (ALL-REZ-BFM pilot-protocol 2002) achieved effective remission, but the ovarian mass depicted no regression.