Golimumab in juvenile idiopathic arthritis-associated uveitis unresponsive to Adalimumab.

OBJECTIVE: To assess the efficacy of golimumab (GLM) as a treatment option for juvenile idiopathic arthritis (JIA)-associated uveitis refractory to adalimumab (ADA). METHODS: Retrospective single-centre study including patients with JIA receiving GLM for active uveitis after failing ADA. JIA- and uveitis-related data, including intraocular inflammation, best-corrected visual acuity, corticosteroid-sparing potential, and ocular complications were evaluated at start of GLM treatment, at 1 month and 3 months, and every 3 months thereafter during GLM administration. We further investigated the association of response to GLM with primary and secondary failure of ADA treatment. RESULTS: Ten patients were studied, all female (17 affected eyes, mean age 14.3 + 6.7 yrs., mean follow-up 25.2 + 21.7 mos). Two patients were switched to GLM because of primary non-response to ADA. Eight were switched because of loss of response (LOR). In 5 of the latter LOR was associated with neutralizing anti-ADA-antibodies. Response to GLM was observed in all 8 patients with LOR, while the 2 patients with primary non-response to ADA also did not respond to GLM. Three of the 8 responders experienced LOR. At the end of follow-up 4 of the 5 remaining responders had achieved complete response. One had achieved partial response. CONCLUSION: GLM is an efficacious therapeutic option in patients who experience LOR to ADA. Our data indicate that patients without primary response to ADA should be rather switched to a biologic agent with a different mode of action instead of further blocking the TNF-alpha pathway.

Successful Unrelated Stem Cell Transplantation in an Infant With Congenital Acute Myelogenous Leukemia FAB M5 Showing Massive Cutaneous Infiltrations--A Challenging Multidisciplinary Approach.

The multidisciplinary management of a male neonate presenting with congenital acute myelogenous leukemia of monoblastic phenotype is reported using conventional chemotherapy, high dose conditioning, and matched unrelated donor stem cell transplantation. These therapies were combined to add a graft versus leukemia effect to the treatment. Although chimerism studies showed a decrease of donor white blood cells, T-cells remained stable of allogeneic origin. We hypothesize that a continuous graft versus leukemia effect results in minimal residual disease negativity for now more than 18 months since stem cell transplantation.

Immune Thrombocytopenia in Two Unrelated Fanconi Anemia Patients - A Mere Coincidence?

Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical - namely immune - thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed.

Sirolimus for the treatment of children with various complicated vascular anomalies.

Vascular anomalies include a heterogeneous group of disorders that are categorized as vascular tumors or vascular malformations. Treatment options include resection, embolization, laser therapy, and sclerotherapy or medical treatment such as propranolol, steroids, interferon, and cytostatic chemotherapy. Mammalian target of rapamycin seems to play a key role in the signal pathway of angiogenesis and subsequently in the development of vascular anomalies. Recently, the successful use of sirolimus has been reported in children with lymphatic malformations and kaposiform hemangioendotheliomas. We report on six patients with different vascular anomalies (kaposiform hemangioendothelioma n = 2, combined lymphatico-venous malformation n = 2, pulmonary lymphangiectasia n = 1, and orbital lymphatic malformation n = 1) who were treated with peroral sirolimus. Three of the children initially presented with a Kasabach-Merrit phenomenon. Median duration of treatment was 10 months; two children are still on treatment. Three children each achieved complete and partial remission. Kasabach-Merrit phenomenon resolved within 1 month in all patients. Treatment with sirolimus was tolerated well; only mild reversible leukopenia was observed. CONCLUSION: Sirolimus proved to be effective in children with complicated lymphatic or lymphatico-venous malformations and kaposiform hemangioendotheliomas. Treatment was tolerated well with acceptable side effects. The optimum length of treatment and possible long-term side effects have to be evaluated. WHAT IS KNOWN: • Vascular anomalies including vascular tumors and vascular malformations may lead to life-threatening conditions.• Some patients are refractory to established treatment and/or are not available for local invasive procedures. WHAT IS NEW: • We reviewed the literature focusing treatment of vascular anomalies inc hildren and adolescents.• Our data support recent studies that sirolimus is an effective treatment option in patients with complicated vascular tumors andmalformations