Int J Hematol DOI 10.1007/s12185-015-1824-y
CASE REPORT
Imatinib‑induced gastric antral vascular ectasia in three patients with chronic myeloid leukaemia Jeremy Ong1 · David Yeung2 · Robin Filshie1 · Timothy P. Hughes2,3,4 · Harshal Nandurkar1
Received: 13 March 2015 / Revised: 11 June 2015 / Accepted: 18 June 2015 © The Japanese Society of Hematology 2015
Abstract Imatinib is generally well tolerated, but gastric antral vascular ectasia (GAVE) remains a rare but significant complication of imatinib therapy. Whilst this complication has been described in other disease settings, only one other case of GAVE has been reported in a chronic myeloid leukaemia (CML) patient receiving imatinib. Herein, we present three CML patients with GAVE complicating imatinib therapy. In all cases, GAVE resolved only with cessation of imatinib. This confirms a causal relationship between GAVE and imatinib. GAVE should be considered as a possible cause of anaemia and upper gastrointestinal bleeding in patients receiving imatinib therapy. Keywords Chronic myeloid leukaemia · Tyrosine kinase inhibitor · Imatinib · Gastric antral vascular ectasia
Introduction Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterised by a reciprocal translocation t(9;22) (q34;q11), the Philadelphia (Ph) chromosome, in 90 % of cases. The novel fusion gene, BCR-ABL, is the target of imatinib mesylate, the first marketed tyrosine kinase inhibitor. Imatinib has revolutionised the treatment of CML, * Jeremy Ong [email protected] 1
Department of Haematology, St Vincent’s Hospital, 41 Victoria Parade, Fitzroy, VIC 3065, Australia
2
Division of Haematology, SA Pathology, Adelaide, Australia
3
University of Adelaide, South Australia, Australia
4
South Australian Health and Medical Research Institute, South Australia, Australia
allowing 98 % of patients to achieve complete haematological response and 87 % to achieve complete cytogenetic response (CCyR) at 5 years [1]. Imatinib is generally well tolerated, and adverse effects have been well documented. Gastrointestinal (GI) symptoms including nausea, vomiting, abdominal pain and diarrhoea are among the most commonly reported treatment complications [2, 3]. Gastric antral vascular ectasia (GAVE) is a rare disorder, comprising 4 % of non-variceal upper GI bleeding [4]. It is characterised by the typical endoscopic appearance of longitudinal rugal folds traversing the antrum and converging on the pylorus, giving the appearance of a “watermelon stomach” [5]. Whilst the pathogenesis remains unclear, it is commonly associated with chronic illnesses, such as liver cirrhosis, connective tissue disorders and chronic renal failure [6]. GAVE is a rarely reported, but significant adverse outcome of imatinib therapy, and has only been reported in one other patient with CML [7]. This association had previously only been described in patients receiving imatinib for gastrointestinal stromal tumour (GIST) and systemic sclerosis [8, 9]. We report three CML patients who developed GAVE whilst receiving imatinib therapy. In all cases, GAVE resolved once imatinib was ceased.
Case 1 In October 2002, a 70-year-old woman was diagnosed with chronic phase Ph-positive CML. Hydroxyurea was initially commenced but was complicated by severe pancytopaenia requiring hospital admission. In November 2002, the patient was enrolled onto a clinical trial with imatinib 400 mg/day. She achieved CCyR after 6 months of imatinib therapy.
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J. Ong et al.
In May 2003, 7 months after starting imatinib, the patient presented with severe anaemia (haemoglobin 66 g/L) but with normal neutrophil and platelet counts. An upper GI endoscopy showed linear congested antral mucosa consistent with GAVE. Due to excellent disease response, imatinib was continued. In the subsequent years, the patient required ongoing blood transfusions and multiple endoscopic argon plasma coagulation (APC) treatment for persisting GAVE. Imatinib was ceased in February 2005 for 4 months. During treatment interruption, her transfusion requirements significantly decreased and upper GI endoscopy showed resolution of GAVE. However, whilst off imatinib, the patient’s CML disease burden increased, with BCR-ABL1 quantitative polymerase chain reaction reaching 48 %. Imatinib was recommenced in June 2005. Again, the patient suffered severe transfusion-dependent anaemia, requiring imatinib to be discontinued in January 2007. The patient’s haemoglobin remained stable whilst off imatinib. The patient died of an unrelated cerebral vascular accident in February 2008.
Case 2 In May 2004, a 60-year-old man with long-standing type II diabetes was diagnosed with chronic phase Ph-positive CML. Imatinib 600 mg/day was commenced after initial cytoreduction with hydroxyurea. CCyR was documented 10 months afterwards. Imatinib was initially well tolerated, until anaemia (haemoglobin 99 g/L) was noted in August 2005, 13 months after imatinib commencement. One month later, the patient presented with melaena and a further fall in haemoglobin requiring transfusion (haemoglobin 75 g/L). Imatinib was withheld, whilst upper and lower GI endoscopies were performed. Colonoscopy identified only a polyp, whilst gastroscopy revealed the antrum to have a “watermelon stomach” appearance consistent with GAVE (Fig. 1a). Minor active bleeding was associated with these lesions. APC treatment was used to control these initial bleeding lesions and again during follow-up procedures 1 and 6 months after presentation. Imatinib was reinstituted at 400 mg/day once symptoms resolved. Anaemia and melaena recurred 13 months later in October 2006. At endoscopy, appearances consistent with GAVE were again noted in the gastric antrum. Repeat APC treatment was given to these lesions, and the patient was switched from imatinib to nilotinib, with no further recurrence of symptomatic anaemia or melaena. APC was administered at subsequent follow-up endoscopies at 6 month intervals when occasional recurrent lesions were found. Resolution was complete by April 2009 (Fig. 1b). During this period, disease response as measured by BCR-ABL improved, reaching a nadir of 0.007 % on
13
Fig. 1 a Endoscopic appearance from case 2 showing marked vascular ectasia in the gastric antrum resembling a watermelon stomach whilst on imatinib therapy. b Endoscopic resolution of GAVE after cessation of imatinib, with only minor ectatic changes now covered by scarring as a result of APC therapy
nilotinib therapy, as opposed to a previous nadir of 0.44 % on imatinib therapy.
Case 3 In September 2004, a 33-year-old man presented with massive splenomegaly, 20 cm below the costal margin. He was diagnosed with high Sokal risk chronic phase Phpositive CML. He was commenced on imatinib 400 mg/ day. His leukocytosis was slow to normalize, so imatinib was increased to 600 mg/day. A complete haematological remission was achieved after 5 months of therapy. The patient achieved a major molecular response (MMR) 2 years after diagnosis. He continued on imatinib 600 mg/ day with satisfactory control of his disease. In February 2011, 6 years after starting imatinib therapy, a routine blood count revealed iron deficiency anaemia
Imatinib-induced gastric antral vascular ectasia in three patients with chronic myeloid…
(haemoglobin 104 g/L, ferritin 8 µg/L). Lower GI endoscopy was normal, though an upper GI endoscopy showed GAVE with fresh bleeding from one ectatic area (Fig. 2a). He was commenced on a proton pump inhibitor. Repeat endoscopic investigation 2 months later showed persistent GAVE. In October 2012, imatinib was switched to nilotinib. The patient’s iron deficiency anaemia resolved on nilotinib and repeat gastroscopy in March 2013 showed complete resolution of the previous GAVE (Fig. 2b). The patient remains well on nilotinib, maintaining MMR 10 years after diagnosis.
Discussion Imatinib is generally well tolerated in CML patients, with the most frequently reported complications being oedema, nausea, diarrhoea, myalgia, fatigue and rash [2, 3]. Most adverse events are mild to moderate in severity. GI bleeding is a known but infrequent complication of imatinib therapy for GIST patients [3, 8]. However, the proposed mechanism of tumour necrosis causing GI bleeding in GIST patients is a different aetiology to the GI bleeding caused by GAVE in these three cases of imatinib therapy for CML. GAVE is a rare but significant cause of GI bleeding and anaemia in patients receiving imatinib therapy. To our knowledge, only one other case of imatinib-induced GAVE has been reported in a patient with CML [7], concerning a 57-year-old woman who presented with iron deficiency anaemia 4 years after initial treatment with imatinib. Upper GI endoscopy revealed GAVE with persistent active GI bleeding requiring cauterization and blood transfusions. The patient’s bleeding and transfusion requirements resolved only after imatinib therapy was stopped. Imatinib-induced GAVE was reported in another patient with GIST [8]. A 74-year-old woman presented with severe anaemia 8 months after commencing imatinib. An upper GI endoscopy revealed GAVE. Imatinib was withheld, and a proton pump inhibitor was commenced. Follow-up endoscopy one month later showed significant resolution of GAVE, suggesting a causal relationship between imatinib and GAVE. One other patient with systemic sclerosis developed GAVE whilst on imatinib therapy as part of a phase I/IIa open-label pilot study in systemic sclerosis-associated interstitial lung disease [9]. However, in this case, it is unclear whether GAVE was directly induced by imatinib, as there is a known association between connective tissue disorders and GAVE. In the three cases reported here, GAVE was the cause of severe anaemia and GI bleeding in CML patients treated with imatinib. In the first two cases, GAVE resolved when imatinib was withheld and recurred when the patients were
Fig. 2 a Endoscopic appearance from case 3 showing GAVE with fresh blood from one ectatic area. b Endoscopic resolution of GAVE with no signs of previous ectasia seen in the antrum after cessation of imatinib therapy
re-challenged with imatinib. Only after imatinib was ceased did the GAVE resolve. Although endoscopic treatment with APC is the usual treatment of choice for GAVE [10], in our reported patients, significant anaemia attributed to GAVE persisted despite local therapy. Cessation of imatinib and/or switching to nilotinib was required to control the GI bleeding. Additionally, it is instructive to note that endoscopic appearances of GAVE improve quickly after imatinib cessation, though minor vestiges of vascular ectasia may persist for years afterwards. The pathogenetic pathways implicated in the development of GAVE remain to be clarified. The underlying pathology is characterised by fibromuscular proliferation within the lamina propria and capillary fibrin thrombosis. One postulated theory relates to mechanical stress, where increased antral motility stimulates fibromuscular proliferation, angiogenesis and subsequent vascular ectasia [11]. Imatinib is known to increase gastrointestinal motility,
13
J. Ong et al.
leading to the common side effects of nausea, vomiting and diarrhoea. Increased motility may also contribute towards the development of imatinib-induced GAVE. These three cases strongly suggest a direct causal relationship between imatinib and GAVE. GAVE should be considered in CML patients on imatinib therapy who present with severe anaemia or upper GI bleeding. Nilotinib appears to be an alternative tyrosine kinase inhibitor not associated with GAVE. It is also noteworthy that GAVE can manifest several months to several years after commencement of imatinib. We propose that patients on imatinib developing unexplained anaemia or overt GI blood loss should be investigated with endoscopy to exclude GAVE. If GAVE is identified, imatinib should be switched to a different tyrosine kinase inhibitor since ongoing imatinib therapy may lead to persistence of GAVE. Compliance with ethical standards Conflict of interest D.Y. received research funding from Novartis and BMS and received honoraria from and participated in advisory boards of Novartis and BMS. T.H. received research funding from Ariad, CSL, Novartis and BMS and received honoraria from and participated in advisory boards of Ariad, Pfizer, Novartis and BMS. The remaining authors declare no competing financial interests.
References 1. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–17.
13
2. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCRABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031–7. 3. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347(7):472–80. 4. Dulai GS, Jensen DM, Kovacs TOG, Gralnek IM, Jutabha R. Endoscopic treatment outcomes in watermelon stomach patients with and without portal hypertension. Endoscopy. 2004;36(1):68–72. 5. Jabbari M, Cherry R, Lough JO, Daly DS, Kinnear DG, Goresky CA. Gastric antral vascular ectasia: the watermelon stomach. Gastroenterology. 1984;87(5):1165–70. 6. Liberski SM, McGarrity TJ, Hartle RJ, Varano V, Reynolds D. The watermelon stomach: long-term outcome in patients treated with Nd:YAG laser therapy. Gastrointest Endosc. 1994;40(5):584–7. 7. Alshehry NF, Kortan P, Lipton JH. Imatinib-induced gastric antral vascular ectasia in a patient with chronic myeloid leukemia. Clin Case Rep. 2014;2(3):77–8. 8. Saad Aldin E, Mourad F, Tfayli A. Gastric antral vascular ectasia in a patient with GIST after treatment with imatinib: case report and literature review. Jpn J Clin Oncol. 2012;42(5):447–50. 9. Khanna D, Saggar R, Mayes MD, Abtin F, Clements PJ, Maranian P, et al. A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosisassociated active interstitial lung disease. Arthritis Rheum. 2011;63(11):3540–6. 10. Gostout CJ, Viggiano TR, Ahlquist DA, Wang KK, Larson MV, Balm R. The clinical and endoscopic spectrum of the watermelon stomach. J Clin Gastroenterol. 1992;15(3):256–63. 11. Quintero E, Pique JM, Bombi JA, Bordas JM, Sentis J, Elena M, et al. Gastric mucosal vascular ectasias causing bleeding in cirrhosis. A distinct entity associated with hypergastrinemia and low serum levels of pepsinogen I. Gastroenterology. 1987;93(5):1054–61.
CASE REPORT
Imatinib‑induced gastric antral vascular ectasia in three patients with chronic myeloid leukaemia Jeremy Ong1 · David Yeung2 · Robin Filshie1 · Timothy P. Hughes2,3,4 · Harshal Nandurkar1
Received: 13 March 2015 / Revised: 11 June 2015 / Accepted: 18 June 2015 © The Japanese Society of Hematology 2015
Abstract Imatinib is generally well tolerated, but gastric antral vascular ectasia (GAVE) remains a rare but significant complication of imatinib therapy. Whilst this complication has been described in other disease settings, only one other case of GAVE has been reported in a chronic myeloid leukaemia (CML) patient receiving imatinib. Herein, we present three CML patients with GAVE complicating imatinib therapy. In all cases, GAVE resolved only with cessation of imatinib. This confirms a causal relationship between GAVE and imatinib. GAVE should be considered as a possible cause of anaemia and upper gastrointestinal bleeding in patients receiving imatinib therapy. Keywords Chronic myeloid leukaemia · Tyrosine kinase inhibitor · Imatinib · Gastric antral vascular ectasia
Introduction Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterised by a reciprocal translocation t(9;22) (q34;q11), the Philadelphia (Ph) chromosome, in 90 % of cases. The novel fusion gene, BCR-ABL, is the target of imatinib mesylate, the first marketed tyrosine kinase inhibitor. Imatinib has revolutionised the treatment of CML, * Jeremy Ong [email protected] 1
Department of Haematology, St Vincent’s Hospital, 41 Victoria Parade, Fitzroy, VIC 3065, Australia
2
Division of Haematology, SA Pathology, Adelaide, Australia
3
University of Adelaide, South Australia, Australia
4
South Australian Health and Medical Research Institute, South Australia, Australia
allowing 98 % of patients to achieve complete haematological response and 87 % to achieve complete cytogenetic response (CCyR) at 5 years [1]. Imatinib is generally well tolerated, and adverse effects have been well documented. Gastrointestinal (GI) symptoms including nausea, vomiting, abdominal pain and diarrhoea are among the most commonly reported treatment complications [2, 3]. Gastric antral vascular ectasia (GAVE) is a rare disorder, comprising 4 % of non-variceal upper GI bleeding [4]. It is characterised by the typical endoscopic appearance of longitudinal rugal folds traversing the antrum and converging on the pylorus, giving the appearance of a “watermelon stomach” [5]. Whilst the pathogenesis remains unclear, it is commonly associated with chronic illnesses, such as liver cirrhosis, connective tissue disorders and chronic renal failure [6]. GAVE is a rarely reported, but significant adverse outcome of imatinib therapy, and has only been reported in one other patient with CML [7]. This association had previously only been described in patients receiving imatinib for gastrointestinal stromal tumour (GIST) and systemic sclerosis [8, 9]. We report three CML patients who developed GAVE whilst receiving imatinib therapy. In all cases, GAVE resolved once imatinib was ceased.
Case 1 In October 2002, a 70-year-old woman was diagnosed with chronic phase Ph-positive CML. Hydroxyurea was initially commenced but was complicated by severe pancytopaenia requiring hospital admission. In November 2002, the patient was enrolled onto a clinical trial with imatinib 400 mg/day. She achieved CCyR after 6 months of imatinib therapy.
13
J. Ong et al.
In May 2003, 7 months after starting imatinib, the patient presented with severe anaemia (haemoglobin 66 g/L) but with normal neutrophil and platelet counts. An upper GI endoscopy showed linear congested antral mucosa consistent with GAVE. Due to excellent disease response, imatinib was continued. In the subsequent years, the patient required ongoing blood transfusions and multiple endoscopic argon plasma coagulation (APC) treatment for persisting GAVE. Imatinib was ceased in February 2005 for 4 months. During treatment interruption, her transfusion requirements significantly decreased and upper GI endoscopy showed resolution of GAVE. However, whilst off imatinib, the patient’s CML disease burden increased, with BCR-ABL1 quantitative polymerase chain reaction reaching 48 %. Imatinib was recommenced in June 2005. Again, the patient suffered severe transfusion-dependent anaemia, requiring imatinib to be discontinued in January 2007. The patient’s haemoglobin remained stable whilst off imatinib. The patient died of an unrelated cerebral vascular accident in February 2008.
Case 2 In May 2004, a 60-year-old man with long-standing type II diabetes was diagnosed with chronic phase Ph-positive CML. Imatinib 600 mg/day was commenced after initial cytoreduction with hydroxyurea. CCyR was documented 10 months afterwards. Imatinib was initially well tolerated, until anaemia (haemoglobin 99 g/L) was noted in August 2005, 13 months after imatinib commencement. One month later, the patient presented with melaena and a further fall in haemoglobin requiring transfusion (haemoglobin 75 g/L). Imatinib was withheld, whilst upper and lower GI endoscopies were performed. Colonoscopy identified only a polyp, whilst gastroscopy revealed the antrum to have a “watermelon stomach” appearance consistent with GAVE (Fig. 1a). Minor active bleeding was associated with these lesions. APC treatment was used to control these initial bleeding lesions and again during follow-up procedures 1 and 6 months after presentation. Imatinib was reinstituted at 400 mg/day once symptoms resolved. Anaemia and melaena recurred 13 months later in October 2006. At endoscopy, appearances consistent with GAVE were again noted in the gastric antrum. Repeat APC treatment was given to these lesions, and the patient was switched from imatinib to nilotinib, with no further recurrence of symptomatic anaemia or melaena. APC was administered at subsequent follow-up endoscopies at 6 month intervals when occasional recurrent lesions were found. Resolution was complete by April 2009 (Fig. 1b). During this period, disease response as measured by BCR-ABL improved, reaching a nadir of 0.007 % on
13
Fig. 1 a Endoscopic appearance from case 2 showing marked vascular ectasia in the gastric antrum resembling a watermelon stomach whilst on imatinib therapy. b Endoscopic resolution of GAVE after cessation of imatinib, with only minor ectatic changes now covered by scarring as a result of APC therapy
nilotinib therapy, as opposed to a previous nadir of 0.44 % on imatinib therapy.
Case 3 In September 2004, a 33-year-old man presented with massive splenomegaly, 20 cm below the costal margin. He was diagnosed with high Sokal risk chronic phase Phpositive CML. He was commenced on imatinib 400 mg/ day. His leukocytosis was slow to normalize, so imatinib was increased to 600 mg/day. A complete haematological remission was achieved after 5 months of therapy. The patient achieved a major molecular response (MMR) 2 years after diagnosis. He continued on imatinib 600 mg/ day with satisfactory control of his disease. In February 2011, 6 years after starting imatinib therapy, a routine blood count revealed iron deficiency anaemia
Imatinib-induced gastric antral vascular ectasia in three patients with chronic myeloid…
(haemoglobin 104 g/L, ferritin 8 µg/L). Lower GI endoscopy was normal, though an upper GI endoscopy showed GAVE with fresh bleeding from one ectatic area (Fig. 2a). He was commenced on a proton pump inhibitor. Repeat endoscopic investigation 2 months later showed persistent GAVE. In October 2012, imatinib was switched to nilotinib. The patient’s iron deficiency anaemia resolved on nilotinib and repeat gastroscopy in March 2013 showed complete resolution of the previous GAVE (Fig. 2b). The patient remains well on nilotinib, maintaining MMR 10 years after diagnosis.
Discussion Imatinib is generally well tolerated in CML patients, with the most frequently reported complications being oedema, nausea, diarrhoea, myalgia, fatigue and rash [2, 3]. Most adverse events are mild to moderate in severity. GI bleeding is a known but infrequent complication of imatinib therapy for GIST patients [3, 8]. However, the proposed mechanism of tumour necrosis causing GI bleeding in GIST patients is a different aetiology to the GI bleeding caused by GAVE in these three cases of imatinib therapy for CML. GAVE is a rare but significant cause of GI bleeding and anaemia in patients receiving imatinib therapy. To our knowledge, only one other case of imatinib-induced GAVE has been reported in a patient with CML [7], concerning a 57-year-old woman who presented with iron deficiency anaemia 4 years after initial treatment with imatinib. Upper GI endoscopy revealed GAVE with persistent active GI bleeding requiring cauterization and blood transfusions. The patient’s bleeding and transfusion requirements resolved only after imatinib therapy was stopped. Imatinib-induced GAVE was reported in another patient with GIST [8]. A 74-year-old woman presented with severe anaemia 8 months after commencing imatinib. An upper GI endoscopy revealed GAVE. Imatinib was withheld, and a proton pump inhibitor was commenced. Follow-up endoscopy one month later showed significant resolution of GAVE, suggesting a causal relationship between imatinib and GAVE. One other patient with systemic sclerosis developed GAVE whilst on imatinib therapy as part of a phase I/IIa open-label pilot study in systemic sclerosis-associated interstitial lung disease [9]. However, in this case, it is unclear whether GAVE was directly induced by imatinib, as there is a known association between connective tissue disorders and GAVE. In the three cases reported here, GAVE was the cause of severe anaemia and GI bleeding in CML patients treated with imatinib. In the first two cases, GAVE resolved when imatinib was withheld and recurred when the patients were
Fig. 2 a Endoscopic appearance from case 3 showing GAVE with fresh blood from one ectatic area. b Endoscopic resolution of GAVE with no signs of previous ectasia seen in the antrum after cessation of imatinib therapy
re-challenged with imatinib. Only after imatinib was ceased did the GAVE resolve. Although endoscopic treatment with APC is the usual treatment of choice for GAVE [10], in our reported patients, significant anaemia attributed to GAVE persisted despite local therapy. Cessation of imatinib and/or switching to nilotinib was required to control the GI bleeding. Additionally, it is instructive to note that endoscopic appearances of GAVE improve quickly after imatinib cessation, though minor vestiges of vascular ectasia may persist for years afterwards. The pathogenetic pathways implicated in the development of GAVE remain to be clarified. The underlying pathology is characterised by fibromuscular proliferation within the lamina propria and capillary fibrin thrombosis. One postulated theory relates to mechanical stress, where increased antral motility stimulates fibromuscular proliferation, angiogenesis and subsequent vascular ectasia [11]. Imatinib is known to increase gastrointestinal motility,
13
J. Ong et al.
leading to the common side effects of nausea, vomiting and diarrhoea. Increased motility may also contribute towards the development of imatinib-induced GAVE. These three cases strongly suggest a direct causal relationship between imatinib and GAVE. GAVE should be considered in CML patients on imatinib therapy who present with severe anaemia or upper GI bleeding. Nilotinib appears to be an alternative tyrosine kinase inhibitor not associated with GAVE. It is also noteworthy that GAVE can manifest several months to several years after commencement of imatinib. We propose that patients on imatinib developing unexplained anaemia or overt GI blood loss should be investigated with endoscopy to exclude GAVE. If GAVE is identified, imatinib should be switched to a different tyrosine kinase inhibitor since ongoing imatinib therapy may lead to persistence of GAVE. Compliance with ethical standards Conflict of interest D.Y. received research funding from Novartis and BMS and received honoraria from and participated in advisory boards of Novartis and BMS. T.H. received research funding from Ariad, CSL, Novartis and BMS and received honoraria from and participated in advisory boards of Ariad, Pfizer, Novartis and BMS. The remaining authors declare no competing financial interests.
References 1. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–17.
13
2. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCRABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031–7. 3. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347(7):472–80. 4. Dulai GS, Jensen DM, Kovacs TOG, Gralnek IM, Jutabha R. Endoscopic treatment outcomes in watermelon stomach patients with and without portal hypertension. Endoscopy. 2004;36(1):68–72. 5. Jabbari M, Cherry R, Lough JO, Daly DS, Kinnear DG, Goresky CA. Gastric antral vascular ectasia: the watermelon stomach. Gastroenterology. 1984;87(5):1165–70. 6. Liberski SM, McGarrity TJ, Hartle RJ, Varano V, Reynolds D. The watermelon stomach: long-term outcome in patients treated with Nd:YAG laser therapy. Gastrointest Endosc. 1994;40(5):584–7. 7. Alshehry NF, Kortan P, Lipton JH. Imatinib-induced gastric antral vascular ectasia in a patient with chronic myeloid leukemia. Clin Case Rep. 2014;2(3):77–8. 8. Saad Aldin E, Mourad F, Tfayli A. Gastric antral vascular ectasia in a patient with GIST after treatment with imatinib: case report and literature review. Jpn J Clin Oncol. 2012;42(5):447–50. 9. Khanna D, Saggar R, Mayes MD, Abtin F, Clements PJ, Maranian P, et al. A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosisassociated active interstitial lung disease. Arthritis Rheum. 2011;63(11):3540–6. 10. Gostout CJ, Viggiano TR, Ahlquist DA, Wang KK, Larson MV, Balm R. The clinical and endoscopic spectrum of the watermelon stomach. J Clin Gastroenterol. 1992;15(3):256–63. 11. Quintero E, Pique JM, Bombi JA, Bordas JM, Sentis J, Elena M, et al. Gastric mucosal vascular ectasias causing bleeding in cirrhosis. A distinct entity associated with hypergastrinemia and low serum levels of pepsinogen I. Gastroenterology. 1987;93(5):1054–61.
