Haploidentical peripheral-blood stem-cell transplantation for ALK-positive anaplastic large-cell lymphoma.
Article: Oncogenic protein tyrosine kinases[Show abstract] [Hide abstract]
ABSTRACT: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, the normal role of which remains to be completely elucidated. Although work carried out in mammals suggests a function in neural development, results from studies in Drosophila indicate an additional role in visceral muscle differentiation. The aberrant expression of full-length ALK receptor proteins has been reported in neuroblastomas and glioblastomas, while the occurrence of ALK fusion proteins in anaplastic large cell lymphoma (ALCL) has resulted in the identification of the new tumor entity, ALK-positive ALCL. ALK represents one of few examples of a receptor tyrosine kinase implicated in oncogenesis in both haematopoietic and non-haematopoietic tumors, given that ALK fusions also occur in the mesenchymal tumor known as inflammatory myofibroblastic tumor (IMT). The study of ALK fusion proteins, besides demonstrating their importance in tumor development, has also raised the possibility of new therapeutic treatments for patients with ALK-positive malignancies.Cellular and Molecular Life Sciences CMLS 11/2004; 61(23):2939-2953. DOI:10.1007/s00018-004-4275-9 · 5.86 Impact Factor
- Haematologica 04/2005; 90(3):ECR19. · 5.87 Impact Factor
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ABSTRACT: The use of allogeneic stem cell transplantation in NHL patients is not yet clearly defined, especially in children and adolescents, but this option offers the advantages of a tumor-free graft and the possible induction of a graft-vs.-tumor effect. We report the results of four consecutive pediatric patients affected by anaplastic large cell lymphoma (ALCL) and treated with allogeneic stem cell transplantation from an unrelated donor. The conditioning regimen was based on total body irradiation given in association with etoposide in three patients, and with thiotepa and cyclophoshamide in one patient. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporin, a short course of methotrexate and rabbit antithymocyte globulin. All patients had rapid engraftment within 3-4 wk for neutrophils and platelets, and achieved a stable full donor chimerism that has been maintained to the last follow-up visit. One patient later developed a restrictive pneumonopathy. This patient had been heavily pretreated during the course of the disease having suffered four relapses and had received a cumulative dose of bleomycin of 160 mg/m(2). After a follow-up of 11-42 months, all patients are alive in complete hematological and molecular remission; and three of them without any chronic GVHD. The increasing number of volunteer bone marrow donors and the reduced toxicity of unrelated stem cell transplantation, especially in children, make this therapeutic option worth more extensive investigation in the treatment of high-risk failure ALCL, although more data is needed to evaluate the long-term benefits. In this regard, the presence of factors predictive of worst outcome such as an early relapse (within 12 months from diagnosis), a refractory or relapsing ALCL and the persistent detection on blood or bone marrow of nucleophosmin-anaplastic lymphoma kinase protein (NPM-ALK) transcript may help select the patients eligible to allogeneic related or unrelated stem cell transplantation.European Journal Of Haematology 08/2005; 75(1):22-6. DOI:10.1111/j.1600-0609.2005.00422.x · 2.41 Impact Factor