Safety of Intrathecal Rituximab as Prophylaxis or Treatment in CD20+ Acute Lymphoblastic Leukemia (ALL) and Aggressive Lymphoma (AL): Report from a Mexican Pilot Study

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 22, 2007

Presenter: Villela, L.
Presenter's Affiliation: Instituto Nacional de Ciencias Médicas y Nutrición, Mexico
Type of Session: Scientific


  • CNS involvement in acute lymphoblastic leukemia (ALL) and aggressive lymphoma (AL) is a poor prognostic indicator.
  • Systemic rituximab is a safe and effective agent in patients with B-cell neoplasms that express CD20, however, CNS penetration may be limited when given systemically.
  • External beam radiation and intrathecal chemotherapy with methotrexate and Ara-C have been used to prevent or treat CNS disease, but all of these treatments are associated with toxicity and potential for CNS relapse.
  • Intrathecal rituximab (IT-R) has been shown to be safe in animals and has been used empirically in humans with primary CNS lymphoma with leptomeningeal involvement with good outcome.
  • This study was undertaken to evaluate the safety and feasibility of IT-R in patients with AL and ALL as either prophylaxis or treatment.

Materials and Methods

  • Design: Phase I single institution, single arm study.
  • Patients:
    • 12 patients (5 AL, 7 ALL)
    • Median age was 49 years (range 14-72)
    • One patient with active CNS disease, the others were treated prophylactically.
  • Treatment: Patients received 25 mg of intrathecal rituximab (IT-R), plus the standard systemic chemotherapy protocol. 
  • Side effects were evaluated according to the NIC toxicity scale.


  • A total of 60 IT-R doses were administered (median 7, range 3-15).
  • Median follow-up was 9 months (range: 3-16 months).
  • Active disease treatment:
    • One patient had initial CNS involvement with blastic type mantle cell lymphoma; this patient received IT-R three times per week, plus two extra doses after complete CNS remission. The patient achieved a complete remission after 5 doses of IT-R which continues after autologous stem cell transplantation.
  • Prophylaxis:
    • 11 patients had risk factors that warranted prophylaxis.  All side effects were temporary and no patient has shown neither neurological nor other late toxicities.
  • Toxicity:
    • Headache 33.3%, temporally limb paresthesias 23.3%, temporally limb pain 13.3% and nausea 11.6%; the majority (98.3%) were grade I or II of NIC scale of toxicity.

Author's Conclusions

The use of rituximab as IT-R is possible. We are starting a phase II study using IT rituximab for prophylaxis and treatment, in a larger group of patients.

Clinical/Scientific Implications

  • The use of intrathecal rituximab is an appealing modality for the treatment of the thecal space for CD20+ lymphomas/leukemias.
  • The efficacy of intrathecal rituximab is an open question. Because some of the mechanisms of cell death require either complement fixation or antibody-mediated cytotoxicity, it is unclear whether it will be effective in a compartment other than intravenous. The one response observed in this study shows that IT rituximab may actually be effective, but it is difficult to separate this activity from any activity from co-administered intravenous chemotherapy.
  • The addition of a radionuclide to the anti-CD20 antibody (radioimmunotherapy) is a potential method to ensure cell killing in the absence of humoral factors.

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