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Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation
Cancer Genetics and Cytogenetics 137 (2002) 146–149
Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation Tonya L. Wrighta, Peter G. Bardya, Patrick Disneyb, Sarah Moorec, Noemi Horvatha,c,* a
Department of Hematology, Royal Adelaide Hospital, Adelaide, Australia Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia c SA Cancer Cytogenetics Unit, Institute of Medical and Veterinary Science, Adelaide, Australia Received 31 December 2001; received in revised form 21 February 2002; accepted 22 February 2002 b
Abstract
A 33-year-old male presented with acute lymphoblastic leukemia (ALL) characterized by translocation (11;19)(q23;p13.3). He received an allogeneic bone marrow transplant from a matched unrelated donor. Two years later his disease relapsed with an isolated intracardiac mass, presenting as right heart failure. He had no evidence of concomitant relapse in the bone marrow. Tumor cytogenetics revealed clonal evolution with the karyotype 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3), the chromosome 16 breakpoint involving the band where the genes for multidrug resistance-associated protein and CREB binding protein are known to reside. To our knowledge, this is the first report of an isolated extramedullary relapse of ALL in the heart. © 2002 Elsevier Science Inc. All rights reserved.
1. Introduction The translocation (11;19) seen in this patient has been reported to result in MLL-ENL gene fusion and is generally associated with a poor outcome [1]. Most patients with this variety of genetic lesion have M4 or M5 acute myeloid leukemia, c-acute lymphoblastic leukemia (ALL), pro-B ALL, or pre-B ALL. A smaller number are shown to have T-ALL, and it appears, from the relatively small number of patients studied, that this group has a good response to therapy with long first remissions and better survival [1,2]. For those patients who do not achieve complete remission, however, allogeneic bone marrow transplantation (BMT) may still provide a curative option, although a significant percentage of adults with ALL relapse following BMT. Relapse at an extramedullary site with sparing of the marrow is unusual. We report a patient with an isolated cardiac recurrence of ALL presenting as right heart failure, 2 years after transplant. The heart has not previously been reported in the literature as a site of extramedullary relapse, and the mechanism underlying selection of this site remains unknown. Cytogenetic analysis of our patient’s tumor revealed the t(11;19)
* Corresponding author. SA Cancer Cytogenetics Unit, Institute of Medical & Veterinary Science, Division of Hematology, PO Box 14, Rundle Mall, Adelaide 5000, Australia. Tel.: 61-8-8222-3550; fax: 61-88222- 3162. E-mail address: [email protected] (N. Horvath).
(q23;p13.3) and clonal evolution with a second translocation not previously reported in ALL. The contribution of this aberration to the pattern of relapse is unknown. The optimal treatment of isolated extramedullary relapse remains controversial. 2. Case report A 33-year-old caucasian male presented in September 1998 with cervical lymphadenopathy and leukocytosis. His total white cell count was 173109/L, with 86% circulating blasts. Bone marrow biopsy diagnosed early T precursor ALL, L2 in the French–American–British classification. Cytogenetic analysis revealed the t(11;19)(q23;p13.3) and flow cytometry demonstrated the T cell phenotype (CD3, CD4, CD5, CD7, CD8, CD34). He was treated with leukapheresis before commencing chemotherapy according to the LaLa94 protocol (unpublished observations). Since only a partial remission was achieved with induction chemotherapy, he was not a suitable candidate for autologous BMT. He subsequently received a matched unrelated donor BMT in December 1998. The conditioning regimen consisted of cyclophosphamide (total 120 mg/kg in 2 doses) and total body irradiation (13.2Gy in 8 fractions). Cyclosporin and methotrexate were given for graft-versus-host disease (GVHD) prophylaxis. Transplantation was complicated by grade 2 skin GVHD, confirmed by skin biopsy. Bone marrow biopsy 31 days after transplant confirmed tri-
0165-4608/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0165-4608(02)00 5 5 9 - 9
T.L. Wright et al. / Cancer Genetics and Cytogenetics 137 (2002) 146–149
147
Fig. 1. Transthoracic echocardiogram (short axis parasternal view) demonstrating ALL tumor mass (MASS) arising from inter-atrial septum (IAS) and occupying most of the right atrium (RA). Real time echocardiography showed interference with tricuspid valve (TV) function. LA: left atrium.
lineage engraftment and normal karyotype. He remained well for 22 months. In October 2000, he was admitted to a Surgical Unit for investigation of abdominal pain. Laparotomy was normal apart from a small amount of ascites. Analysis of the ascitic fluid revealed a high neutrophil count but no bacterial growth, suggesting spontaneous bacterial peritonitis partially treated by pre-operative antibiotics. Following surgery he developed ascites and marked peripheral edema. Clinical examination revealed an elevated JVP and a faint cardiac murmur. Right heart failure was suspected. Echocardiography revealed a large tumor in the right atrium arising from the interatrial septum, and obstructing the tricuspid valve (Fig. 1). Cardiac surgery was performed, however, complete excision was not possible due to deep invasion of the septum. Histology of the tumor was consistent with relapsed T cell ALL. Cytogenetic analysis of the tumor revealed clonal evolution, with the presence of the t(11;19) and an additional t(3;16)(q23;p13) (Fig. 2). There was no evidence of bone marrow relapse on morphologic or lymphocyte surface marker examination. Cytogenetic analysis of the bone marrow revealed the normal karyotype. Imaging did not reveal any other sites of disease relapse. Radiotherapy to the heart was commenced, and was well tolerated. Systemic treatment was not given due to his poor performance status. He remains well and free of hematopoietic relapse at 14 months.
3. Discussion Leukemic relapse can present as either hematopoietic (involving bone marrow and peripheral blood), or extramedullary (involving other sites) [3]. Extramedullary relapse of ALL in adults after allogeneic BMT rarely occurs without concomitant hematopoietic relapse [4]. The central nervous system and testes, so called sanctuary sites, are the predominant sites of isolated extramedullary disease. Only a few reports have documented relapse at other isolated sites, including liver and uterus, pancreas and retroperitoneum, pericardium and mediastinum, breast, lung, pleura, bone and soft tissue, intestine, nasopharynx, sinus, skin, ovary, eye and kidney [3–10]. No reports to our knowledge have documented an intracardiac mass as an isolated extramedullary recurrence. Savasan et al. [6] reported pericardial relapse with infiltration of myocardium and mediastinum. In this case, relapse occurred at the initial site of bulky disease, and was attributed to failure of local eradication. In our patient the mechanism of relapse is unclear. Cardiac involvement was not apparent at diagnosis, and there was no prior history of cardiac abnormality. It would seem unlikely for the heart to act as a sanctuary site, as exposure to chemotherapeutic agents is high. It has been previously suggested that the graft-versusleukemia (GVL) effect may be stronger in the marrow than in peripheral tissues, preferentially allowing extramedullary
148
T.L. Wright et al. / Cancer Genetics and Cytogenetics 137 (2002) 146–149
Fig. 2. Tumor karyotype at extramedullary relapse of ALL: 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3). Thick arrows indicate the derivative chromosomes from the t(11;19), while thin arrows indicate the chromosomes involved in the t(3;16).
relapse [10]. This differential GVL effect may be due to a lack of effector cells or cytokines capable of inducing this beneficial response in peripheral tissue [4]. The extent of GVL effect from allogeneic BMT correlates with the degree of GVHD. GVHD is not commonly reported in the myocardium, hence the heart may be a relative haven from the actions of donor T lymphocytes. If this is the case, cardiac relapse should occur much more frequently. An alternative mechanism for extramedullary relapse may be the development of a second leukemic clone, derived from either recipient or donor cells. Leukemic relapses from donor cell origin are rare, and most have occurred late after BMT, and have been attributed to total body irradiation [11]. In our patient, persistence of the initial t(11;19) (q23;p13.3) suggests recurrence of the original recipient malignant clone. Cytogenetic analysis of our patient’s cardiac tumor revealed clonal evolution with the emergence of a new t(3;16) (q23;p13). Whether the conditioning chemoradiotherapy contributes to further genetic mutation, as previously suggested, is uncertain [12]. Secondary chromosomal abnormalities in acute leukemias are not uncommon and appear to be nonrandom. This may suggest that they are responsible for important phenotypic features of the tumor cell population and promote drug resistance or disease progression [13]. Interestingly, 16p13 is the site of the multidrug resistanceassociated protein gene (MRP) and of the CREB binding protein gene. Translocation of the former gene could result in up-regulation of its expression and hence protect the
evolved clone from chemotherapy [14]. Translocation of the latter gene has previously been observed in hematologic neoplasms [15,16], some of which are secondary to chemotherapy [16]. It is still unclear as to why the myocardium was selected as the site of relapse, though it is conceivable that the secondary translocation in our patient has played a role in its selection. The optimal management of isolated extramedullary recurrence is still debated. Generally, treatment consists of local radiotherapy and/or chemotherapy [7,10]. Our patient was treated with radiotherapy alone, because of poor performance status. Chemotherapy remains a future option, as systemic relapse eventually occurs in most patients. Other options with variable success rates include salvage BMT and donor lymphocyte infusion [10–12,17]. Predictive factors for successful treatment of relapse after BMT are long interval between transplant and relapse, and isolated extramedullary disease [12]. While clonal evolution appears to be associated with shorter overall survival, it does not predict for shorter duration from relapse to death [18]. References [1] Moorman AV, Hagermeijer A, Charrin C, Rieder H. Secker-Walker LM. The translocations t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients. Leukemia 1998;12: 805–10. [2] Huret JL, Brizard A, Slater R, Charrin C, Bertheas MF, Guilhot F, Hahlen K, Kroes W, van Leeuwen E, Schoot EV, Tanzer J, Hagemeijer A. Cytogenetic heterogeneity in t(11;19) acute leukemia: clin-
T.L. Wright et al. / Cancer Genetics and Cytogenetics 137 (2002) 146–149
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
ical, hematological and cytogenetic analyses of 48 patients—updated published cases and 16 new observations. Leukemia 1993;7:152–60. Cormier MG, Armin A, Daneshgari F, Castelli M. Unusual extramedullary relapse of acute lymphoblastic leukaemia in a bone marrow transplant patient. J Surg Onc 1987;36:290–4. Au WY, Lie AKW, Liang R, Kwong YL. Isolated extramedullary relapse of acute lymphoblastic leukaemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999;24:1137–40. Facon T, Jouet JP, Fenaux P, Walter MP, Lai JL, Jabinet JL, Chambon JP, Bauters F. Isolated pericardial and mediastinal relapse following allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. Transplantation 1991;51:1125–6. Savasan S, Abella E, Karanes C, Ravindranath Y. Recurrent breast relapses in a patient with acute lymphoblastic leukaemia following allogeneic bone marrow transplantation. Acta Haematol 1998;99:95–7. Ueda S, Kanamori H, Sasaki S, Yamazaki E, Tamura T, Matsuzaki M, Motomura S, Mohri H, Okubo T. Isolated extramedullary relapse in a knee joint after allogeneic bone marrow transplantation for Ph ALL. Bone Marrow Transplant 1998;21:319–21. Lee KH, Lee JH, Kim S, Lee JS, Kim SH, Kim WK. High frequency of extramedullary relapse of acute leukaemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 2000;26:147–52. Hinkle AS, Dinndorf PA, Bulas DI, Kapur S. Relapse of acute lymphoblastic leukaemia in the inferior rectus muscle of the eye. Cancer 1994;73:1757–60. Chong G, Byrnes G, Szer J, Grigg A. Extramedullary relapse after allogeneic bone marrow transplantation for haematological malignancy. Bone Marrow Transplant 2000;26:1011–15.
149
[11] Giralt SA, Champlin RE. Leukaemia relapse after allogeneic bone marrow transplantation: a review. Blood 1994;84:3603–12. [12] Frassoni F, Barrett AJ, Granena A, Ernst P, Garthon G, Kolb HJ, Prentice HG, Vernant JP, Zwaan FE, Gratwohl A. Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the EBMT of 117 cases. Br J Haem 1986;70:317–20. [13] Johansson B, Mertens F, Mitelman F. Secondary chromosomal abnormalities in acute leukaemias. Leukemia 1996;8:953–62. [14] Viguié F. MRP (multidrug resistance-associated protein). Atlas Genet Cytogenet Oncol Haematol. 1998. Available at: http://infobiogen.fr/ services/chromcancer/Genes/MRPID106.html. Assessed December 2001. [15] Borrow J, Stanton VP Jr, Andresen JM, Becher R, Behm FG, Chaanti RS, Civiv CI, Disteche C, Dube I, Frschauf AM, Horsman D, Mitelman F, Volinia S, Watmore AE, Housman DE. The translocation t(8;16) (p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet 1996;14:34. [16] Rowley JD, Reshmi S, Sobulo O, Musvee T, Anastasi R, Raimondi S, Schneider NR, Barredo JC, Cantu ES, Schlegelgerger B, Behm F, Doggett NA, Borrow J, Zelenik-Le N. All patients with the t(11;16) (q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood 1997;90:535–41. [17] Au WY, Kwong YL, Lie AK, Ma SK, Liang R. Extramedullary relapse of leukaemia following allogeneic bone marrow transplantation. Hematol Oncol 1999;17:45–52. [18] Chucrallah AE, Stass SA, Huh YO, Albitar M, Kantarjian HM. Adult acute lymphoblastic leukaemia at relapse-cytogenetic, immunophenotypic and molecular changes. Cancer 1995;76:985–991.
Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation Tonya L. Wrighta, Peter G. Bardya, Patrick Disneyb, Sarah Moorec, Noemi Horvatha,c,* a
Department of Hematology, Royal Adelaide Hospital, Adelaide, Australia Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia c SA Cancer Cytogenetics Unit, Institute of Medical and Veterinary Science, Adelaide, Australia Received 31 December 2001; received in revised form 21 February 2002; accepted 22 February 2002 b
Abstract
A 33-year-old male presented with acute lymphoblastic leukemia (ALL) characterized by translocation (11;19)(q23;p13.3). He received an allogeneic bone marrow transplant from a matched unrelated donor. Two years later his disease relapsed with an isolated intracardiac mass, presenting as right heart failure. He had no evidence of concomitant relapse in the bone marrow. Tumor cytogenetics revealed clonal evolution with the karyotype 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3), the chromosome 16 breakpoint involving the band where the genes for multidrug resistance-associated protein and CREB binding protein are known to reside. To our knowledge, this is the first report of an isolated extramedullary relapse of ALL in the heart. © 2002 Elsevier Science Inc. All rights reserved.
1. Introduction The translocation (11;19) seen in this patient has been reported to result in MLL-ENL gene fusion and is generally associated with a poor outcome [1]. Most patients with this variety of genetic lesion have M4 or M5 acute myeloid leukemia, c-acute lymphoblastic leukemia (ALL), pro-B ALL, or pre-B ALL. A smaller number are shown to have T-ALL, and it appears, from the relatively small number of patients studied, that this group has a good response to therapy with long first remissions and better survival [1,2]. For those patients who do not achieve complete remission, however, allogeneic bone marrow transplantation (BMT) may still provide a curative option, although a significant percentage of adults with ALL relapse following BMT. Relapse at an extramedullary site with sparing of the marrow is unusual. We report a patient with an isolated cardiac recurrence of ALL presenting as right heart failure, 2 years after transplant. The heart has not previously been reported in the literature as a site of extramedullary relapse, and the mechanism underlying selection of this site remains unknown. Cytogenetic analysis of our patient’s tumor revealed the t(11;19)
* Corresponding author. SA Cancer Cytogenetics Unit, Institute of Medical & Veterinary Science, Division of Hematology, PO Box 14, Rundle Mall, Adelaide 5000, Australia. Tel.: 61-8-8222-3550; fax: 61-88222- 3162. E-mail address: [email protected] (N. Horvath).
(q23;p13.3) and clonal evolution with a second translocation not previously reported in ALL. The contribution of this aberration to the pattern of relapse is unknown. The optimal treatment of isolated extramedullary relapse remains controversial. 2. Case report A 33-year-old caucasian male presented in September 1998 with cervical lymphadenopathy and leukocytosis. His total white cell count was 173109/L, with 86% circulating blasts. Bone marrow biopsy diagnosed early T precursor ALL, L2 in the French–American–British classification. Cytogenetic analysis revealed the t(11;19)(q23;p13.3) and flow cytometry demonstrated the T cell phenotype (CD3, CD4, CD5, CD7, CD8, CD34). He was treated with leukapheresis before commencing chemotherapy according to the LaLa94 protocol (unpublished observations). Since only a partial remission was achieved with induction chemotherapy, he was not a suitable candidate for autologous BMT. He subsequently received a matched unrelated donor BMT in December 1998. The conditioning regimen consisted of cyclophosphamide (total 120 mg/kg in 2 doses) and total body irradiation (13.2Gy in 8 fractions). Cyclosporin and methotrexate were given for graft-versus-host disease (GVHD) prophylaxis. Transplantation was complicated by grade 2 skin GVHD, confirmed by skin biopsy. Bone marrow biopsy 31 days after transplant confirmed tri-
0165-4608/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0165-4608(02)00 5 5 9 - 9
T.L. Wright et al. / Cancer Genetics and Cytogenetics 137 (2002) 146–149
147
Fig. 1. Transthoracic echocardiogram (short axis parasternal view) demonstrating ALL tumor mass (MASS) arising from inter-atrial septum (IAS) and occupying most of the right atrium (RA). Real time echocardiography showed interference with tricuspid valve (TV) function. LA: left atrium.
lineage engraftment and normal karyotype. He remained well for 22 months. In October 2000, he was admitted to a Surgical Unit for investigation of abdominal pain. Laparotomy was normal apart from a small amount of ascites. Analysis of the ascitic fluid revealed a high neutrophil count but no bacterial growth, suggesting spontaneous bacterial peritonitis partially treated by pre-operative antibiotics. Following surgery he developed ascites and marked peripheral edema. Clinical examination revealed an elevated JVP and a faint cardiac murmur. Right heart failure was suspected. Echocardiography revealed a large tumor in the right atrium arising from the interatrial septum, and obstructing the tricuspid valve (Fig. 1). Cardiac surgery was performed, however, complete excision was not possible due to deep invasion of the septum. Histology of the tumor was consistent with relapsed T cell ALL. Cytogenetic analysis of the tumor revealed clonal evolution, with the presence of the t(11;19) and an additional t(3;16)(q23;p13) (Fig. 2). There was no evidence of bone marrow relapse on morphologic or lymphocyte surface marker examination. Cytogenetic analysis of the bone marrow revealed the normal karyotype. Imaging did not reveal any other sites of disease relapse. Radiotherapy to the heart was commenced, and was well tolerated. Systemic treatment was not given due to his poor performance status. He remains well and free of hematopoietic relapse at 14 months.
3. Discussion Leukemic relapse can present as either hematopoietic (involving bone marrow and peripheral blood), or extramedullary (involving other sites) [3]. Extramedullary relapse of ALL in adults after allogeneic BMT rarely occurs without concomitant hematopoietic relapse [4]. The central nervous system and testes, so called sanctuary sites, are the predominant sites of isolated extramedullary disease. Only a few reports have documented relapse at other isolated sites, including liver and uterus, pancreas and retroperitoneum, pericardium and mediastinum, breast, lung, pleura, bone and soft tissue, intestine, nasopharynx, sinus, skin, ovary, eye and kidney [3–10]. No reports to our knowledge have documented an intracardiac mass as an isolated extramedullary recurrence. Savasan et al. [6] reported pericardial relapse with infiltration of myocardium and mediastinum. In this case, relapse occurred at the initial site of bulky disease, and was attributed to failure of local eradication. In our patient the mechanism of relapse is unclear. Cardiac involvement was not apparent at diagnosis, and there was no prior history of cardiac abnormality. It would seem unlikely for the heart to act as a sanctuary site, as exposure to chemotherapeutic agents is high. It has been previously suggested that the graft-versusleukemia (GVL) effect may be stronger in the marrow than in peripheral tissues, preferentially allowing extramedullary
148
T.L. Wright et al. / Cancer Genetics and Cytogenetics 137 (2002) 146–149
Fig. 2. Tumor karyotype at extramedullary relapse of ALL: 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3). Thick arrows indicate the derivative chromosomes from the t(11;19), while thin arrows indicate the chromosomes involved in the t(3;16).
relapse [10]. This differential GVL effect may be due to a lack of effector cells or cytokines capable of inducing this beneficial response in peripheral tissue [4]. The extent of GVL effect from allogeneic BMT correlates with the degree of GVHD. GVHD is not commonly reported in the myocardium, hence the heart may be a relative haven from the actions of donor T lymphocytes. If this is the case, cardiac relapse should occur much more frequently. An alternative mechanism for extramedullary relapse may be the development of a second leukemic clone, derived from either recipient or donor cells. Leukemic relapses from donor cell origin are rare, and most have occurred late after BMT, and have been attributed to total body irradiation [11]. In our patient, persistence of the initial t(11;19) (q23;p13.3) suggests recurrence of the original recipient malignant clone. Cytogenetic analysis of our patient’s cardiac tumor revealed clonal evolution with the emergence of a new t(3;16) (q23;p13). Whether the conditioning chemoradiotherapy contributes to further genetic mutation, as previously suggested, is uncertain [12]. Secondary chromosomal abnormalities in acute leukemias are not uncommon and appear to be nonrandom. This may suggest that they are responsible for important phenotypic features of the tumor cell population and promote drug resistance or disease progression [13]. Interestingly, 16p13 is the site of the multidrug resistanceassociated protein gene (MRP) and of the CREB binding protein gene. Translocation of the former gene could result in up-regulation of its expression and hence protect the
evolved clone from chemotherapy [14]. Translocation of the latter gene has previously been observed in hematologic neoplasms [15,16], some of which are secondary to chemotherapy [16]. It is still unclear as to why the myocardium was selected as the site of relapse, though it is conceivable that the secondary translocation in our patient has played a role in its selection. The optimal management of isolated extramedullary recurrence is still debated. Generally, treatment consists of local radiotherapy and/or chemotherapy [7,10]. Our patient was treated with radiotherapy alone, because of poor performance status. Chemotherapy remains a future option, as systemic relapse eventually occurs in most patients. Other options with variable success rates include salvage BMT and donor lymphocyte infusion [10–12,17]. Predictive factors for successful treatment of relapse after BMT are long interval between transplant and relapse, and isolated extramedullary disease [12]. While clonal evolution appears to be associated with shorter overall survival, it does not predict for shorter duration from relapse to death [18]. References [1] Moorman AV, Hagermeijer A, Charrin C, Rieder H. Secker-Walker LM. The translocations t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients. Leukemia 1998;12: 805–10. [2] Huret JL, Brizard A, Slater R, Charrin C, Bertheas MF, Guilhot F, Hahlen K, Kroes W, van Leeuwen E, Schoot EV, Tanzer J, Hagemeijer A. Cytogenetic heterogeneity in t(11;19) acute leukemia: clin-
T.L. Wright et al. / Cancer Genetics and Cytogenetics 137 (2002) 146–149
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
ical, hematological and cytogenetic analyses of 48 patients—updated published cases and 16 new observations. Leukemia 1993;7:152–60. Cormier MG, Armin A, Daneshgari F, Castelli M. Unusual extramedullary relapse of acute lymphoblastic leukaemia in a bone marrow transplant patient. J Surg Onc 1987;36:290–4. Au WY, Lie AKW, Liang R, Kwong YL. Isolated extramedullary relapse of acute lymphoblastic leukaemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999;24:1137–40. Facon T, Jouet JP, Fenaux P, Walter MP, Lai JL, Jabinet JL, Chambon JP, Bauters F. Isolated pericardial and mediastinal relapse following allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. Transplantation 1991;51:1125–6. Savasan S, Abella E, Karanes C, Ravindranath Y. Recurrent breast relapses in a patient with acute lymphoblastic leukaemia following allogeneic bone marrow transplantation. Acta Haematol 1998;99:95–7. Ueda S, Kanamori H, Sasaki S, Yamazaki E, Tamura T, Matsuzaki M, Motomura S, Mohri H, Okubo T. Isolated extramedullary relapse in a knee joint after allogeneic bone marrow transplantation for Ph ALL. Bone Marrow Transplant 1998;21:319–21. Lee KH, Lee JH, Kim S, Lee JS, Kim SH, Kim WK. High frequency of extramedullary relapse of acute leukaemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 2000;26:147–52. Hinkle AS, Dinndorf PA, Bulas DI, Kapur S. Relapse of acute lymphoblastic leukaemia in the inferior rectus muscle of the eye. Cancer 1994;73:1757–60. Chong G, Byrnes G, Szer J, Grigg A. Extramedullary relapse after allogeneic bone marrow transplantation for haematological malignancy. Bone Marrow Transplant 2000;26:1011–15.
149
[11] Giralt SA, Champlin RE. Leukaemia relapse after allogeneic bone marrow transplantation: a review. Blood 1994;84:3603–12. [12] Frassoni F, Barrett AJ, Granena A, Ernst P, Garthon G, Kolb HJ, Prentice HG, Vernant JP, Zwaan FE, Gratwohl A. Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the EBMT of 117 cases. Br J Haem 1986;70:317–20. [13] Johansson B, Mertens F, Mitelman F. Secondary chromosomal abnormalities in acute leukaemias. Leukemia 1996;8:953–62. [14] Viguié F. MRP (multidrug resistance-associated protein). Atlas Genet Cytogenet Oncol Haematol. 1998. Available at: http://infobiogen.fr/ services/chromcancer/Genes/MRPID106.html. Assessed December 2001. [15] Borrow J, Stanton VP Jr, Andresen JM, Becher R, Behm FG, Chaanti RS, Civiv CI, Disteche C, Dube I, Frschauf AM, Horsman D, Mitelman F, Volinia S, Watmore AE, Housman DE. The translocation t(8;16) (p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet 1996;14:34. [16] Rowley JD, Reshmi S, Sobulo O, Musvee T, Anastasi R, Raimondi S, Schneider NR, Barredo JC, Cantu ES, Schlegelgerger B, Behm F, Doggett NA, Borrow J, Zelenik-Le N. All patients with the t(11;16) (q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood 1997;90:535–41. [17] Au WY, Kwong YL, Lie AK, Ma SK, Liang R. Extramedullary relapse of leukaemia following allogeneic bone marrow transplantation. Hematol Oncol 1999;17:45–52. [18] Chucrallah AE, Stass SA, Huh YO, Albitar M, Kantarjian HM. Adult acute lymphoblastic leukaemia at relapse-cytogenetic, immunophenotypic and molecular changes. Cancer 1995;76:985–991.