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Extramedullary relapse in the so-called ‘sanctuary’ sites for chemotherapy after donor lymphocyte infusion

Bone Marrow Transplantation volume 25, pages 226–227 (2000)Cite this article

Takeda et al1 recently published an interesting case report, in which three patients with existing or pre-existing intracerebral granulocytic sarcoma were successfully treated with allogeneic BMT. BMT seems to be effective for AML with existing or pre-existing intracerebral granulocytic sarcoma. They commented that a graft-versus-leukemia (GVL) effect might exist in central nervous system (CNS) lesions, because turnover of leukocytes in the CNS is very slow and the number of leukocytes increases after TBI because of damage to the blood barrier.2 However, we recently treated a patient with AML who relapsed in the CNS and testis after donor lymphocyte infusion (DLI). These organs have been called ‘sanctuary’ sites from chemotherapy, and our experience may reveal the limitation of immunotherapy in reaching these organs.

A 38-year-old male patient diagnosed with CD7-positive acute myeloid leukemia with a normal karyotype (M1 by FAB classification) received an allogeneic BMT from his sister in May 1997. The conditioning regimen consisted of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). GVHD prophylaxis was with short-term methotrexate and cyclosporine. His clinical course was uneventful until February 1998, when leukemic cells emerged in the peripheral blood. Bone marrow examination showed that 28% of the nucleated cells in the bone marrow were CD7-positive myeloblasts and he was diagnosed as having relapsed post transplant. After two courses of cytotoxic chemotherapy, complete remission was achieved in the bone marrow. To eliminate the residual leukemic cells detected by polymerase chain reaction (PCR) using Y chromosome-specific primers,3 donor lymphocytes including 4.7 X 107/kg of CD3-positive cells were infused in July 1998. After DLI, SRY PCR of the bone marrow became negative. However, 2 days after DLI, pain and paresthesia developed in the right arm. Examination of the cerebrospinal fluid (CSF) showed infiltration by myeloid leukemic cells. He was therefore diagnosed with leukemic meningitis after DLI. We repeated intrathecal methotrexate and cytarabine, after which the leukemic cells disappeared from the CSF, and the sensory disturbance improved. After DLI, cholestatic liver injury occurred and pathological examination showed hepatic involvement by GVHD. However, the AML relapsed in the left testis in September 1998. Despite intensive chemoradiotherapy, the extramedullary deposits progressed to involve the testis, CNS, conjunctiva and lymph nodes in May 1999. Since July 1998, the bone marrow has been in complete remission morphologically and of donor origin by fluorescence in situ hybridization using X chromosome probes. The extramedullary lesions are refractory to conventional chemotherapy, and we are now planning a second allogeneic BMT using the same donor.

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References

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  1. Department of Hematology and Oncology, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, Japan

    S Seo, M Kami, H Honda, T Matsumura, A Moriya, U Machida, Y Kanda, S Chiba & H Hirai

  2. Department of Pathology, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, Japan

    T Kashima

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  1. S Seo
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  2. M Kami
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Seo, S., Kami, M., Honda, H. et al. Extramedullary relapse in the so-called ‘sanctuary’ sites for chemotherapy after donor lymphocyte infusion. Bone Marrow Transplant 25, 226–227 (2000). https://doi.org/10.1038/sj.bmt.1702116

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