Methotrexate osteopathy in infants with tumors of the central nervous system. 1994

B Meister, and I Gassner, and W Streif, and K Dengg, and F M Fink
Department of Pediatrics, University of Innsbruck, Austria.

Methotrexate osteopathy, previously reported as a complication of maintenance-therapy for acute lymphoblastic leukemia, is characterized by osteopenia, particularly involving the lower extremities, thick, dense provisional zones of calcification, growth arrest lines, and corner fractures resembling scurvy. In attempts to postpone radiotherapy in infants under three years of age, the multicentric German therapy protocol for childhood central nervous system tumors (HIT-89 protocol) has employed high cumulative methotrexate doses. Here we describe osteopathy in three patients as a toxic side effect after administration of cumulative methotrexate doses of 20 g/m2, 80 g/m2 and 135 g/m2. The high prevalence of this adverse effect in infants with tumors of the central nervous system may be attributed to the long-term therapy with high cumulative methotrexate-doses. Both factors may favor intracellular accumulation of methotrexate and formation of methotrexate-polyglutamates and may be responsible for bone toxicity. Apparently the susceptibility of the rapidly growing skeletal structures of infants under three years of age to this toxic side effect of methotrexate is remarkably high.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D008297 Male Males
D008527 Medulloblastoma A malignant neoplasm that may be classified either as a glioma or as a primitive neuroectodermal tumor of childhood (see NEUROECTODERMAL TUMOR, PRIMITIVE). The tumor occurs most frequently in the first decade of life with the most typical location being the cerebellar vermis. Histologic features include a high degree of cellularity, frequent mitotic figures, and a tendency for the cells to organize into sheets or form rosettes. Medulloblastoma have a high propensity to spread throughout the craniospinal intradural axis. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2060-1) Arachnoidal Cerebellar Sarcoma, Circumscribed,Medulloblastoma, Desmoplastic,Medullomyoblastoma,Sarcoma, Cerebellar, Circumscribed Arachnoidal,Medulloblastoma, Adult,Medulloblastoma, Childhood,Melanocytic Medulloblastoma,Adult Medulloblastoma,Adult Medulloblastomas,Childhood Medulloblastoma,Childhood Medulloblastomas,Desmoplastic Medulloblastoma,Desmoplastic Medulloblastomas,Medulloblastoma, Melanocytic,Medulloblastomas,Medulloblastomas, Adult,Medulloblastomas, Childhood,Medulloblastomas, Desmoplastic,Medulloblastomas, Melanocytic,Medullomyoblastomas,Melanocytic Medulloblastomas
D008727 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D001851 Bone Diseases, Metabolic Diseases that affect the METABOLIC PROCESSES of BONE TISSUE. Low Bone Density,Low Bone Mineral Density,Osteopenia,Metabolic Bone Diseases,Bone Density, Low,Bone Disease, Metabolic,Low Bone Densities,Metabolic Bone Disease,Osteopenias
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D002113 Calcification, Physiologic Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts. Bone Mineralization,Calcification, Physiological,Physiologic Calcification,Mineralization, Bone,Physiological Calcification
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D003131 Combined Modality Therapy The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used. Multimodal Treatment,Therapy, Combined Modality,Combined Modality Therapies,Modality Therapies, Combined,Modality Therapy, Combined,Multimodal Treatments,Therapies, Combined Modality,Treatment, Multimodal,Treatments, Multimodal
D004806 Ependymoma Glioma derived from EPENDYMOGLIAL CELLS that tend to present as malignant intracranial tumors in children and as benign intraspinal neoplasms in adults. It may arise from any level of the ventricular system or central canal of the spinal cord. Intracranial ependymomas most frequently originate in the FOURTH VENTRICLE and histologically are densely cellular tumors which may contain ependymal tubules and perivascular pseudorosettes. Spinal ependymomas are usually benign papillary or myxopapillary tumors. (From DeVita et al., Principles and Practice of Oncology, 5th ed, p2018; Escourolle et al., Manual of Basic Neuropathology, 2nd ed, pp28-9) Ependymoma, Myxopapillary,Ependymoma, Papillary,Anaplastic Ependymoma,Cellular Ependymoma,Clear Cell Ependymoma,Papillary Ependymoma,Anaplastic Ependymomas,Ependymoma, Anaplastic,Ependymomas,Ependymomas, Anaplastic,Ependymomas, Myxopapillary,Ependymomas, Papillary,Myxopapillary Ependymoma,Myxopapillary Ependymomas,Papillary Ependymomas

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