CLINICAL CASE STUDY published: 20 December 2012 doi: 10.3389/fonc.2012.00195
Immune response to racotumomab in a child with relapsed neuroblastoma C. Sampor 1 , M. D. Guthmann 2 , A. Scursoni 3 , W. Cacciavillano 1 , A. Torbidoni 3,4 , L. Galluzzo 3 , S. Camarero 3 , J. Lopez 3 , M. T. G. de DĂĄvila 3 , L. Fainboim 5 and G. L. Chantada 1* 1 2 3 4 5
Department of Hemato-Oncology, Pediatric Hospital Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina Laboratorio Elea, Buenos Aires, Argentina Department of Pathology, Pediatric Hospital Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina Laboratory of Molecular Oncology, National University of Quilmes, Buenos Aires, Argentina Laboratory of Immunogenetics, Jose de San Martin Clinics Hospital, University of Buenos Aires, Buenos Aires, Argentina
Edited by: Daniel F. Alonso, National University of Quilmes, Argentina Reviewed by: Daniel F. Alonso, National University of Quilmes, Argentina Gabriela Cinat, University of Buenos Aires, Argentina *Correspondence: G. L. Chantada, Department of Hemato-Oncology, Pediatric Hospital Prof. Dr. Juan P. Garrahan, Pichincha 1850, Capital Federal, Buenos Aires, Argentina. e-mail: gchantada@yahoo.com.ar
Immunotherapy targeting ganglioside antigens is a powerful tool for the treatment of high risk neuroblastoma. However, only treatment with anti-GD2 antibodies has been used in clinical practice and other options may be pursued. We report the use of racotumomab, an anti-idiotype vaccine against N-glycolyl neuraminic acid (NeuGc)- containing gangliosides, eliciting an immune response in a child with relapsed neuroblastoma expressing the NeuGcGM3 ganglioside. Keywords: immunotherapy, monoclonal antibodies, neuroblastoma, ganglioside, racotumomab
INTRODUCTION This is a 4-year-old female patient who presented with diffuse pain in lower limbs leading to walking problems and a 1-month history of intermittent fever and generalized pallor. Physical examination showed right eye proptosis and an abdominal mass. Laboratory tests showed anemia (hemoglobin 7.5 g %) and elevated LDH. The child was hospitalized at another center for evaluation. A CT scan of the abdomen revealed a large calcified abdominal mass originating from left adrenal gland. She was referred to our Hospital for further treatment. At our hospital, neuroblastoma cells were evident at a bone marrow examination. Malignant cells were positive for 1p deletion and showed MYCN amplification. Metaiodobenzylguanidine (MIBG) scintigraphy revealed multiple tumoral foci in skull, spine, and left upper quadrant of the abdominal mass. Urinary catecholamines determination revealed elevated norepinephrine levels and vanillyl mandelic acid (VMA). Therefore, with a diagnosis of Stage 4 neuroblastoma belonging to the high risk group, chemotherapy was prescribed, including 5 cycles of a standard induction regimen (Matthay, 1999). Evaluation after induction chemotherapy showed progressive disease in the abdominal tumor and in the bone marrow. A second line regimen including 3 cycles of topotecan and carboplatin was given. A repeated response evaluation revealed persistent bone marrow infiltration, progressive disease in the orbit with intracranial extension, thoracic and lumbar vertebrae as well as a persistent left heterogeneous retroperitoneal mass 10 Ă— 8 Ă— 8 cm and high catecholamine levels. The patient had significant malaise and widespread pain. The disease was deemed
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refractory to conventional therapy and she was considered for experimental treatment.
BACKGROUND Despite advances in the treatment of pediatric malignancies, cancer is the second most common cause of death in children over 1-year-old in developed countries. In Argentina, it accounts for the third leading cause of death in children preceded by accidents and congenital malformations (Scursoni et al., 2011). Children with primary multifocal, refractory or relapsed malignant solid tumors still have a very poor prognosis. On the other hand, most therapies are associated with significant toxicity, causing long-term morbidity. Neuroblastoma is a cancer of the sympathetic nervous system accounting for about 12% of cancer-related deaths in children under 15-years old. It is a heterogeneous disease in which up to 50% of patients have a high-risk behavior characterized by widespread dissemination and poor long-term survival, even when using intensive multimodal treatments. Significant improved outcomes were published nearly a decade ago with the use of myeloablative therapy with stem-cell rescue, followed by differentiation treatment with isotretinoin (Matthay, 1999). However, over 50% of patients receiving standard therapy relapse and ultimately die from the tumor. Consequently, the major obstacle to cure, once remission is achieved, is the chemotherapy-refractory disease that eludes the current methods for its detection. This failure has led to a resurgence of interest in alternative methods of disease eradication. Immunotherapy became a particular and hopeful option.
December 2012 | Volume 2 | Article 195 | 1