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Keywords:

  • rituximab;
  • B-cell acute lymphoblastic leukaemia;
  • B-cell non-Hodgkin's lymphoma;
  • children

Rituximab (Rituxan® or Mabthera®) is a genetically engineered chimaerical murine/human anti-CD20 monoclonal antibody. This B-cell marker is expressed in all cases of mature B-cell acute lymphoblastic leukaemia (B-ALL) and Burkitt-lymphoma, a high-grade B-cell non-Hodgkin's lymphoma (B-NHL) (Maloney et al, 1997; Patte et al, 2001).

Very few data are available regarding the treatment of children with B-ALL/NHL with rituximab (Corbacioglu et al, 2003), although the drug has been used for children with other indications, such as post-transplant lymphoproliferative disease and B-cell mediated autoimmune diseases, e.g. autoimmune haemolytic anaemia (Faye et al, 2001; Zecca et al, 2003).

We here report our experiences in three children with relapsed/refractory B-ALL/NHL who were treated with rituximab on compassionate use basis.

Patient 1 was a 4-year-old boy with B-NHL with bone marrow and central nervous system (CNS) involvement. Lymphadenopathy was found in mediastinal lymph nodes, liver, spleen, pancreas, as well as kidneys. He was treated according to the Lymphome Malins de Burkitt (LMB)-96 group C protocol. He recovered from two CNS relapses at 5 and 9 months after diagnosis, but 12 months after initial diagnosis, he developed a third relapse consisting of a tumour on the thoracic wall with a pleural effusion. A fine-needle aspirate showed B-NHL with CD20 positivity in >90% of the blasts. He was treated with rituximab 375 mg/m2, and after the first infusion the thoracic wall tumour vanished. Three more infusions of rituximab (375 mg/m2, once weekly) were given, after which a complete remission (CR) was established. No side effects of rituximab have occurred. After human leucocyte antigen (HLA)-identical bone marrow transplantation, he remained in CR for almost 5 years but died of progressive respiratory failure due to chronic graft versus host disease of the lungs.

Patient 2 was a 3-year-old boy diagnosed with B-ALL with CNS involvement. Two months after completing treatment according to the LMB-96 group C protocol, he developed a rapidly growing isolated testicular relapse. A biopsy showed that more than 95% of tumour cells were CD20 positive. He was treated with four infusions of rituximab 375 mg/m2, which resulted in stable disease. Rituximab was well tolerated and no major side effects were observed in this patient. After additional chemotherapy the involved testis was surgically removed and autologous stem cell transplantation (SCT) was performed. Pathological examination of the removed testis showed no viable tumour cells. To date, he has been in CR for 4 years.

Patient 3 was a 9-year-old girl with B-NHL, showing bone marrow involvement and with localization of tumour in liver, spleen, both kidneys and synovia of right knee. The blasts were >90% CD20 positive. She was treated according to the LMB-96 protocol. She did not achieve CR, and developed CNS disease during treatment, as well as chemotherapy-resistant disease in the abdominal lymph nodes and liver. Re-induction was attempted with rituximab and repeated intrathecal triple therapy. After eight weekly infusions of rituximab (375 mg/m2 once a week), CR was achieved. She was transplanted with an HLA-identical sibling donor. Unfortunately, shortly after SCT, a CNS relapse was diagnosed, without evidence of other localizations, after which she received palliative care and died from progressive CNS leukaemia. Rituximab does penetrate into the cerebrospinal fluid, be it at low levels of approximately 0·1% of serum levels, which may explain the occurrence of a subsequent CNS relapse without evidence for systemic disease that was seen in this patient (Rubenstein et al, 2003).

In conclusion, rituximab seems able to induce responses in children with relapsed/refractory mature B-ALL/NHL. Rituximab is generally well tolerated, apart from a 10% risk of infusion-related symptoms (Maloney et al, 1997). Further studies in children are needed to clearly establish the clinical efficacy and safety of rituximab in paediatric B-ALL/NHL and to investigate its role in combination chemotherapy.

References

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  2. References
  • Corbacioglu, S., Eber, S., Gungor, T., Hummerjohann, J. & Niggli, F. (2003) Induction of long-term remission of a relapsed childhood B-acute lymphoblastic leukemia with rituximab chimeric anti-CD20 monoclonal antibody and autologous stem cell transplantation. Journal of Pediatric Hematology/Oncology, 25, 327329.
  • Faye, A., Quartier, P., Reguerre, Y., Lutz, P., Carret, A.S., Dehee, A., Rohrlich, P., Peuchmaur, M., Matthieu-Boue, A., Fischer, A. & Vilmer, E. (2001) Chimaeric anti-CD20 monoclonal antibody (rituximab) in post-transplant B-lymphoproliferative disorder following stem cell transplantation in children. British Journal of Haematology, 115, 112118.
  • Maloney, D.G., Grillo-Lopez, A.J., White, C.A., Bodkin, D., Schilder, R.J., Neidhart, J.A., Janakiraman, N., Foon, K.A., Liles, T.M., Dallaire, B.K., Wey, K., Royston, I., Davis, T. & Levy, R. (1997) IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood, 90, 21882195.
  • Patte, C., Auperin, A., Michon, J., Behrendt, H., Leverger, G., Frappaz, D., Lutz, P., Coze, C., Perel, Y., Raphaël, M. & Terrier-Lacombe, M.J. (2001) The Société Française d'Oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood, 97, 33703379.
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  • Zecca, M., Nobili, B., Ramenghi, U., Perrotta, S., Amendola, G., Rosito, P., Jankovic, M., Pierani, P., De Stefano, P., Regazzi, B.M. & Locatelli, F.W. (2003) Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood, 101, 38573861.