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Spurious elevation of the cerebrospinous fluid white cell counts in three patients receiving liposomal cytarabine as part of post-remission therapy

Leukemia volume 22, pages 2277–2278 (2008)Cite this article

We report three patients treated with intrathecal depocyte as part of post-remission therapy where spurious elevation of the CSF (cerebrospinous fluid) white cell count resulted from liposomes being passed as white cells by an automated cell counter. The first patient was a 55-year-old female with Burkitt leukaemia, who was treated according to the Magrath protocol with CODOX-M/IVAC chemotherapy with the addition of rituximab. Complete remission of disease was documented after the first course of treatment. On day 27 of cycle 2 the patient received a lumbar puncture, clear CSF was sent for a cell count and cytology as would be routine in our practice and intrathecal cytarabine (depocyte 50 mg) was given as part of CNS prophylaxis. The white cell count was markedly elevated in the three samples of CSF obtained, a Gram stain was negative and routine biochemistry was normal. A cytospin revealed multiple liposomes. The previous intrathecal depocyte administration was done 27 days earlier. The second patient, a 28-year-old male, was diagnosed with HIV associated Burkitt lymphoma following presentation with a lesion in his buccal mucosa. He had multiple cranial nerve palsies and a mixed peripheral and motor sensory neuropathy and a clinical diagnosis of CNS disease was made in the absence of objective involvement on imaging or repeated CSF analysis. He was commenced on treatment with the Magrath protocol with the addition of rituximab and anti-retroviral therapy. On cycle 3, a sample of clear CSF obtained immediately prior to administration of intrathecal depocyte revealed a high white cell count and cytology revealed similar liposomes to those seen in the first patient. Similar to the first case, there was no evidence of systemic or CNS disease progression. The previous intrathecal depocyte administration had been 14 days earlier. The last patient was a 36-year-old male who presented with standard risk acute myeloid leukaemia and was treated with conventional chemotherapy upfront. After 8 months following completion of primary therapy, he relapsed with CNS involvement following presentation with peripheral blood blasts, low back pain and sensory symptoms in his lower limbs. He achieved a second complete remission with one course of salvage therapy with FLAG and aggressive CNS directed therapy, which included liposomal cytarabine. As part of post-remission therapy CSF analysis prior to depocyte injection revealed elevated white cell counts in all the three samples obtained. The previous depocyte injection had been administered 2 weeks earlier. Once again, cytology demonstrated numerous liposomes.

Neoplastic meningitis has conventionally proven a difficult condition to treat, mainly because of the difficulty delivering drugs to the CNS. Most systemic chemotherapy agents only penetrate the CNS in small quantities at conventional doses. At high doses, sufficient quantities may reach the CSF, but at the expense of considerable systemic toxicity. For most intrathecal agents, clearance from the CSF is generally too rapid to ensure adequate distribution to sites distant from the point of injection. To deliver cytocidal concentrations of these agents to the CNS, frequent intrathecal dosing is necessary, which causes inconvenience for both the patient and the clinician.

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Authors and Affiliations

  1. Department of Haematology, University College Hospital, Galway, Ireland

    R Swords

  2. Department of Haematology, St. James Hospital, Dublin, Ireland

    C O'Rafferty

  3. CTRC at the IDD, SA, TX, USA

    F Giles

  4. Department of Haematology, St James Hospital, Dublin, Ireland

    P Browne

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  1. R Swords
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  2. C O'Rafferty
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  3. F Giles
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  4. P Browne
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Correspondence to R Swords.

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Swords, R., O'Rafferty, C., Giles, F. et al. Spurious elevation of the cerebrospinous fluid white cell counts in three patients receiving liposomal cytarabine as part of post-remission therapy. Leukemia 22, 2277–2278 (2008). https://doi.org/10.1038/leu.2008.139

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