Abstract
Isolated extramedullary relapse is rare in patients with acute promyelocytic leukemia (APL) after allogeneic stem cell transplantation (SCT), and an optimal therapy for it has not been established. We describe a patient with APL who developed serially occurring extramedullary disease (EMD) after SCT. We confirmed that EMD had arisen from the recipient’s APL blasts by detecting t(15;17) and PML/RARα from the tumor cell suspension. The patient displayed EMD 4 times at different sites. Administration of all-trans retinoic acid with local radiotherapy and with chemotherapy for the first to third EMDs resulted in regression of the tumors. However, these regimens did not prevent the subsequent occurrence of new EMD. For the fourth EMD, intravenous administration of arsenic trioxide followed by local radiotherapy resulted in the disappearance of EMD, and no further EMD has developed to date. In the present case, the bone marrow was in morphologic and molecular remission during the course of recurrent EMD. The accumulation of detailed cases is needed to elucidate the pathogenesis, predisposing factors, and optimal therapy for EMD in APL after SCT.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Grignani F, Fagioli M, Alcalay M, et al. Acute promyelocytic leukemia: from genetics to treatment. Blood. 1994;83:10–25.
Lo Coco F, Diverio D, Falini B, Biondi A, Nervi C, Pelicci PG. Genetic diagnosis and molecular monitoring in the management of acute promyelocytic leukemia. Blood. 1999;94:12–22.
Bekassy AN, Hermans J, Gorin NC, Gratwohl A. Granulocytic sarcoma after allogeneic bone marrow transplantation: a retrospective European multicenter survey. Acute and Chronic Leukemia Working Parties of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 1996;17:801–808.
Forrest DL, Dalal BI, Naiman SC, et al. Testicular relapse of acute promyelocytic leukemia after allogeneic BMT. Bone Marrow Transplant. 1997;20:689–690.
Milone G, Inghilterra G, Li Gioi F, Peluso D, Giustolisi R. Testicular and cutaneous relapse after hematopoietic transplantation in a patient affected with APL. Bone Marrow Transplant. 1999;23:751.
Ustun C,Arat M, Celebi H, et al. Extramedullary relapse following allogeneic stem cell transplantation in acute promyelocytic leukemia: the role of ATRA. Haematologica. 2001;86:E31.
Classen CF, Debatin KM, Friedrich W, Schulz AS. Long-term remission of APL with a second allogeneic BMT after CNS relapse following HLA-identical allogeneic BMT. Bone Marrow Transplant. 2003;32:843–846.
Ammatuna E, Borza PA, Iori AP, et al. Multiple relapses and extramedullary localization with scalp and breast involvement in a case of acute promyelocytic leukaemia. Leukemia. 2005;19:479–480.
Evans GD, Grimwade DJ. Extramedullary disease in acute promyelocytic leukemia. Leuk Lymphoma. 1999;33:219–229.
Ko BS, Tang JL, Chen YC, et al. Extramedullary relapse after all-trans retinoic acid treatment in acute promyelocytic leukemia: the occurrence of retinoic acid syndrome is a risk factor. Leukemia. 1999;13:1406–1408.
Di Noto R, Lo Pardo C, Schiavone EM, et al. All-trans retinoic acid (ATRA) and the regulation of adhesion molecules in acute myeloid leukemia. Leuk Lymphoma. 1996;21:201–209.
Ito S, Ishida Y, Oyake T, et al. Clinical and biological significance of CD56 antigen expression in acute promyelocytic leukemia. Leuk Lymphoma. 2004;45:1783–1789.
Specchia G, Lo Coco F, Vignetti M, et al. Extramedullary involvement at relapse in acute promyelocytic leukemia patients treated or not with all-trans retinoic acid: a report by the Gruppo Italiano Malattie Ematologiche dell’Adulto. J Clin Oncol. 2001;19:4023–4028.
Sanz MA, Larrea L, Sanz G, et al. Cutaneous promyelocytic sarcoma at sites of vascular access and marrow aspiration: a characteristic localization of chloromas in acute promyelocytic leukemia? Haematologica. 2000;85:758–762.
Lee KH, Lee JH, Choi SJ, et al. Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course. Bone Marrow Transplant. 2003;32:835–842.
Goldberg SL, Mangan KF, Klumpp TR, Cropper TM, Schnall SF, Macdonald JS. Lack of graft-versus-leukemia effect in an immuno-logically privileged sanctuary site. Bone Marrow Transplant. 1994;14:180–181.
Au WY, Lie AK, Liang R, Kwong YL. Isolated extramedullary relapse of acute lymphoblastic leukaemia after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1999;24:1137–1140.
Shen ZX, Chen GQ, Ni JH, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL), II: clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997;89:3354–3360.
Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852–3860.
Tsimberidou AM, Estey E, Whitman GJ, et al. Extramedullary relapse in a patient with acute promyelocytic leukemia: successful treatment with arsenic trioxide, all-trans retinoic acid and gem-tuzumab ozogamicin therapies. Leuk Res. 2004;28:991–994.
Griffin RJ, Williams BW, Park HJ, Song CW. Preferential action of arsenic trioxide in solid-tumor microenvironment enhances radiation therapy. Int J Radiat Oncol Biol Phys. 2005;61:1516–1522.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Kai, T., Kimura, H., Shiga, Y. et al. Recurrent Extramedullary Relapse of Acute Promyelocytic Leukemia after Allogeneic Stem Cell Transplantation: Successful Treatment by Arsenic Trioxide in Combination with Local Radiotherapy. Int J Hematol 83, 337–340 (2006). https://doi.org/10.1532/IJH97.05167
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1532/IJH97.05167