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| Year : 1999 | Volume
: 47
| Issue : 2 | Page : 142-4 |
Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphoblastic leukaemia : a case report.
Muzumdar DP, Desai K, Goel A
Departments of Neurosurgery and Neuropathology, K.E.M. Hospital, Mumbai, 12, India.
Correspondence Address:
Departments of Neurosurgery and Neuropathology, K.E.M. Hospital, Mumbai, 12, India.
A 12 year old boy with acute lymphoblastic leukaemia had received prophylactic cranial irradiation (2000 cGy/15 days) and intrathecal methotrexate. Six years later he was diagnosed to have glioblastoma in left temporoparietal region. There is a strong possibility that the glioma may have been radiation and/or chemotherapy induced.
How to cite this article:
Muzumdar D P, Desai K, Goel A. Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphoblastic leukaemia : a case report. Neurol India 1999;47:142 |
How to cite this URL:
Muzumdar D P, Desai K, Goel A. Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphoblastic leukaemia : a case report. Neurol India [serial online] 1999 [cited 2023 Jun 3];47:142. Available from: https://www.neurologyindia.com/text.asp?1999/47/2/142/1633 |
Cranial prophylaxis has greatly reduced the overt meningeal leukaemia when the leukaemic cells are low in number in the location.[1],[2] This has been shown to result in increased survival of children with acute lymphoblastic leukaemia. Although long term sequelae of cranial prophylaxis have not yet been well defined, combination therapy (cranial irradiation and intrathecal chemotherapy ) have occasionally caused both acute and delayed neurotoxicity. We encountered a child who had received such a prophylactic treatment and was harbouring a malignant glioma. The relationship of malignant glioma and prophylactic therapy has been discussed.
A 6 year old boy was admitted to a cancer hospital in 1990 with a two week history of high grade fever, listlessness, weight loss and progressive weakness. He had no prior illness. There was no family history of cancer or hereditary disease viz. Von Recklinghausen's disease. Physical findings included lymphadenopathy in the neck and hepatosplenomegaly. There was no clinical evidence of bleeding diathesis. There was no bony tenderness or joint swelling. Haematological examination and study of bone marrow aspirate confirmed acute lymphoblastic leukaemia. Induction therapy was administered with vincristine 2 mg/M2 (0.5 mg) intravenously for 6 weeks and prednisolone 25 mg/M2 orally (15 mg ) daily for 6 weeks. Remission was proved by bone marrow aspiration and physical examination a month later. Five days later, he was readmitted for central nervous system prophylaxis. [60]Cobalt irradiation was given to whole brain utilising lateral opposing fields (18x12 cm) with total dose of 2000 cGy in 10 fractions over 15 days. Intravenous adriamycin 30 mg/M2 (35 mg) was given alongwith vincristine 2 mg/M2 (1.0 mg) and cytosan, weekly for total period of 3 months. 6-mercaptopurine, 50 mg orally daily and methotrexate, 12 mg/M2 (7.5 mg) orally weekly was given as maintenance therapy. Two years later inj. Leunase 4800 IU 3 weekly was given in addition to vincristine and prednisolone for a further period of 3 weeks. He continued to be on 6-mercaptopurine and methotrexate till January 1994. All medication was stopped after 3 years and 6 months of start of treatment. Bone marrow aspiration revealed remission and since then he never had an exacerbation. He continued his schooling.
He developed generalised seizure after 2" years of stopping of the drugs. There was no postictal deficit. Two months later, he started vomiting and progressively became apathic, lethargic and developed right hemiparesis. Examination revealed presence of bilateral papilloedema. A computed tomography (CT) scan of brain revealed a large left tempero-parietal heterogenous, irregularly enhancing tumour [Figure1]. The patient underwent a left temporo-parietal craniotomy and gross total resection of the tumour was carried out. Histology showed cellular tumour composed of proliferating astrocytes with nuclear pleomorphism and hyperchromatism. There was mitosis with multinucleated tumour giant cells along with areas of necrosis and vascular endothelial proliferation [Figure 2]. Postoperatively right hemiparesis improved considerably. He was treated with 4500 cGy cranial irradiation to whole brain in 25 fractions over 40 days. Vincristine and CCNU were continued for a period of 2 months. He was in good health at 2 month followup.
The apparent induction of a second malignant neoplasm by antineoplastic therapy is well know.[3],[4],[5],[6] Although the incidence of glioblastoma of cerebrum in children is low, the tumour in the presented case may have been `spontaneous' or could be treatment-induced, either by radiation, chemotherapy or by both.
Radiation induced brain tumours are well known.[6],[7],[8] To sustain a diagnosis of neoplasia induced by radiation, the tumour must occur within the irradiated field and after a latent period sufficient to exclude its having being present at the time of radiotherapy.[9],[10] The tumour should differ histologically from the original lesion and neurocutaneous syndromes predisposing to malignancy must be excluded. Most radiation associated intracranial neoplasms have been primary sarcomas and meningiomas. Judge et al[3] reported a child who developed diffuse glioma nine years after successful treatment for acute lymphoblastic leukaemia. Few cases of radiation induced gliomas in humans have been reported.[6],[11],[12],[13] Most patients were males with an average age of 15 years (range 2-43 years). Radiation dosage ranged from 400-6000 rad with an average latent period of nine (range 1-26) years. Due to this risk, current trends have led to the reduction of radiation dosage from 24 to 18 Gy. Exact mechanism of role of radiation in carcinogenesis has not been well established in humans and experimental animals. It appears to arise through mutogenic capacity and chromosome aberration and mechanisms leading to neoplastic transformation. It is a multi-stage process rather than a single one-hit process.[14],[15]
Meadows et al[16] suggested that combination of gliomas and haematologic malignancies is non-randomly distributed in the group of patients with second malignancies and may represent a new cancer syndrome. This inference stems from the observations that outside the haematopoietic system, the brain is the most common site of second malignancy that follows leukaemia. Both these tumours have occured in the same individual even in the absence of radiation. There are families in which both tumour types have been documented; therefore, it is possible that certain patients with acute lymphoblastic leukaemia may be genetically susceptible to development of gliomas. Most radiation associated gliomas have occured after higher doses of radiation (usually more than 3000 rad) given to patients for other neoplasms.[4]
The other possible aetiological factor in the induction of patient's tumour could be combination of intrathecal methotrexate with cranial irradiation. It is known that administration of methotrexate in combination with 2000 rad or more of cranial irradiation may result in multiple necrotic areas with or without gliosis disseminated throughtout the cerebral white matter (leukoencephalopathy). There is no evidence in man or experimental animals to indicate that intrathecal methotrexate alone is carcinogenic or it enhances the carcinogenic effect of radiation.
Statistical and clinical evidence suggests that a genetic predisposition to multiple neoplasms, synergistic action of radiotherapy and intrathecal methotrexate and prolonged exposure to methotrexate could play a role in inducing these second tumours.
The authors gratefully acknowledge the support of Dr. P.M. Pai, Dean and Dr. S.K. Pandya, Professor and head of the Neurosurgery, KEM Hospital, Mumbai, for permitting us to publish this article.
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