Japanese Journal of Clinical Oncology 30:105-108 (2000)
© 2000 Foundation for Promotion of Cancer Research
Simultaneous Development of a Pineal Tumor and an Intradural Spinal Mass During Remission of Acute Lymphocytic Leukemia
Departments of 1Pediatrics and 2Radiology, School of Medicine, Sapporo Medical University, Sapporo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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A small percentage of children with acute lymphocytic leukemia experience relapse in the central nervous system in spite of prophylaxis. Diffuse leptomeningeal infiltration is common but an intracranial leukemic mass or spinal cord involvement is a rare manifestation. We report a child with acute lymphocytic leukemia who simultaneously developed a pineal tumor and an intradural spinal cord mass as her first relapse. She was successfully managed by comprehensive combined treatment including peripheral blood stem cell transplantation. She remains in continuous complete remission for more than 5 years without further evidence of neurological sequelae.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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The central nervous system (CNS) is the most common site of extramedullary relapse in children with acute lymphocytic leukemia (ALL). Diffuse leptomeningeal involvement is well known and tends to be followed by systemic relapse. An intracranial mass lesion or spinal cord involvement are rare but serious complications that cause permanent neurological sequelae if not promptly diagnosed and treated. We report a child with ALL who, after 5 years of complete remission, developed a pineal tumor with concurrent spinal cord involvement as the first manifestation of extramedullary relapse and who was successfully managed by comprehensive combined treatment including peripheral blood stem cell transplantation.
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CASE REPORT |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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A 5-year-old girl developed fever, general malaise and hepatosplenomegaly in November 1988. Her initial white blood cell (WBC) count was 9100/µl with 61% blasts, her hemoglobin was 8.2 g/dl and platelet count 20,000/µl. A bone marrow aspirate revealed replacement of the marrow with L1 lymphoblasts. Surface markers of the blasts were positive for human leukocyte antigen-DR, B4 (CD19), J5 (CD10), terminal deoxynucleotidyl transferase and cytoplasmic immunoglobulin. The karyotype was not obtained owing to poor proliferation of the blasts. The initial cerebrospinal fluid (CSF) was normal. She was treated according to the Dana–Farber Cancer Institute ALL protocol 81–01 standard risk (1). Induction therapy with methotrexate, doxorubicin, vincristine, prednisone and L-asparaginase resulted in remission. CNS prophylaxis consisted of four doses of intrathecal methotrexate and 18 Gy of cranial radiation. Intensification and continuation therapy included oral mercaptopurine, L-asparaginase, methotrexate, vincristine and oral prednisone. The intrathecal methotrexate was given every 18 weeks. She completed her entire 24 months of treatment in March 1991.
In December 1993, 33 months after finishing treatment, she developed progressive weakness of both legs and an abnormal gait. On physical examination, steppage gait and moderate leg flaccidity, more marked on the right, were noted but neither sensory nor sphincter disturbance was present. Both the patellar and Achilles tendon reflexes were decreased. Nuchal rigidity and Kernig’s sign were absent. Papilledema was present. Neither her peripheral blood count nor her bone marrow aspirates showed any evidence of leukemic relapse. A computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed a mass in the pineal gland (Fig. 1a) and an intradural spinal mass from T11 to L5 level with complete blockage of CSF flow in both the sagittal and axial view (Fig. 2a and b). Intravenous dexamethasone with glycerol every 6 h was started. After 7 days of treatment for increased intracranial pressure, a C1–C2 puncture was performed under general anesthesia for CSF cytology and characterization. So-called triple therapy consisting of methotrexate (12.5 mg), cytosine arabinoside (25 mg) and hydrocortisone (25 mg) was administered intrathecally at this time. CSF analysis revealed 8 cells/µl, all being lymphoblastoid cells. Total protein and glucose measured 14 mg and 62 mg/dl, respectively. Definitive surface marker for the CSF cells was not obtained owing to the small sample quantity. Combined steroid and glycerol therapy was continued. Two weeks later a follow-up CT scan and MRI demonstrated a marked reduction of the pineal tumor and spinal cord decompression with the appearance of CSF space. Weekly intrathecal triple therapy was started once lumbar puncture became possible. The CSF total protein increased to over 150 mg/dl with a normal cellular content. The gait disturbance improved gradually to the point where she could walk straight slowly.
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She was scheduled to continue CNS remission induction and receive systemic reinforcement therapy according to the Pediatric Oncology Group Study (2). She went into complete remission after six weekly intrathecal injections followed by craniospinal irradiation (24 and 16.5 Gy, respectively). The reinforcement therapy was then changed to a chemotherapy regimen intended for both consolidation and mobilization of peripheral blood stem cells (PBSC). The regimen consisted of five blocks of cyclic consolidation: (a) daunorubicin (45 mg/m2, day 1), VP-16 (100 mg/m2, days 1–4) and cytosine arabinoside (100 mg/m2/24 h, days 1–4), (b), (c) and (e) VP-16 (100 mg/m2, days 1–3) and cytosine arabinoside (2 g/m2, every 12 hr, days 1–5), (d) VP-16 (100 mg/m2, days 1–4) and cytosine arabinoside (100 mg/m2/24 h, days 1–4). The PBSC were collected after consolidation blocks (c), (d) and (e) when hematopoietic recovery was evident using a Haemonetics V50 apheresis system (Haemonetics, Braintree, MA).
After consolidation, both CT and MRI confirmed the disappearance of the pineal tumor (Fig. 1b) and a restored spinal region with residual adhesion and scarring of the cauda equina (Fig. 2c and d). She then received high-dose chemotherapy and PBSC transplantation in October 1994, 10 months after the CNS relapse. High-dose chemotherapy consisted of busulfan (16 mg/kg) and melphalan (210 mg/kg). The cryopreserved PBSC were rapidly thawed and infused, to a total of 6.6 x 108 mononuclear cells/kg and 8.0 x 105 CFU-GM/kg body weight. Rapid trilineage recovery of hematopoiesis was obtained and she was discharged without incident. She remains in continuous complete remission after more than 5 years without further evidence of neurological sequelae.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Isolated or combined CNS relapse occurs in <10% of patients during their first remission despite CNS prophylaxis (3). Diffuse leptomeningeal infiltration is most common. A leukemic intracranial space occupying lesion or spinal cord involvement is unusual in leukemia (4,5). Our patient simultaneously developed both a pineal mass and spinal involvement. Her initial symptoms were those of an incomplete transverse spinal cord disturbance at the lumbar level. Almost all the reported cases of spinal cord involvement (5) presented pathological features due to epidural leukemic infiltration. Such involvement was more frequent in acute myeloid leukemia than in ALL and most commonly affected the thoracic level. Spinal cord compression due to intradural infiltration is very rare in ALL and has been reported in only one adult case (6). That patient developed intraspinal cord compression due to a solitary mass at the lumbar spine level. The study of our patient emphasizes that leukemic masses may occur in various regions in the CNS.
The relationship between pineal masses and intradural spinal infiltration is not clear. However, we consider these two lesions were due to dissemination of the residual disease of primary pre-B ALL in remission. Although the CSF cytology was not definitive enough to characterize leukemic cells, the latter were sensitive to the initial administration of dexamethasone, indicating a hematopoietic origin. Two patients who had very high WBC counts at their initial diagnosis were reported to have diffuse dural thickening involving the whole brain and spine seen on MRI while in hematological remission (7). This report supports the notion that CNS infiltration may be disseminated in some leukemic patients.
An isolated CNS relapse during continuous complete remission is considered as a localized manifestation of systemic leukemia. The possibility of subsequent bone marrow relapse must be considered, regardless of intensified chemotherapy at the time of CNS relapse. The most striking prognostic factor for predicting the outcome of the initial CNS relapse was the duration of the preceding remission. The Childrens Cancer Study Group reported that the subsequent long-term survival rate was approximately three times higher (30.4%) for patients whose first CNS relapse occurred more than 1 year after their initial remission (8). The elapsed time before CNS relapse in our patient was almost 5 years.
PBSC transplantation was performed using cells which were collected 5 months after starting consolidation treatment and therefore may be less likely to be contaminated with leukemic cells. The use of PBSC rescue was effective following high-dose chemotherapy and shortened the treatment period.
CNS relapse demands comprehensive treatment both because of its associated morbidity in the regions in which it occurs and because it precedes bone marrow relapse.
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FOOTNOTES |
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+ For reprints and all correspondence: Tooru Kudoh, Department of Pediatrics, School of Medicine, Sapporo Medical University, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan. E-mail: tkudoh@sapmed.ac.jpAbbreviations: CNS, central nervous system; ALL, acute lymphocytic leukemia; WBC, white blood cell; CSF, cerebrospinal fluid; CT, computed tomography; MRI, magnetic resonance imaging; PBSC, peripheral blood stem cell
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REFERENCES |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Received August 30, 1999; accepted October 29, 1999.
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