- Email: [email protected]
Imatinib or transplant for chronic myeloid leukaemia?
CORRESPONDENCE
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Uzunel M, Mattsson J, Brune M, Johansson J-E, Ringden O. Kinetics of minimal residual disease and chimerism in patients with chronic myeloid leukemia after non-myeloablative conditioning and allogeneic stem cell transplantation. Blood 2003, 101: 469–72. Gratwohl A, Hermans J, Goldman JM, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Lancet 1998; 352: 1087–92. Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options. Blood 1001; 98: 2039–42.
Sir—Allogeneic stem-cell transplantation has evolved over the past two decades into a remarkably effective treatment for chronic myelogenous leukaemia and is the only curative therapy. Consequently, it is now possible to predict a long-term survival in excess of 70% for young patients with an HLA-identical sibling donor. However, only a limited number of patients with chronic myelogenous leukaemia are eligible for allogeneic transplantation. So the evidence that imatinib mesylate has the capacity to induce complete cytogenetic remissions in up to two-thirds of patients treated in the early chronic phase represents a major breakthrough in the management of this disease. However, Edward that Sausville’s recommendation1 allografting should only be undertaken in patients who fail to achieve, or lose, a significant cytogenetic response to imatinib seems premature. Although the excellent results of allografting come from studies with follow-up rates of more than 10 years, there is no evidence that responses to imatinib are durable. Indeed, experience with this agent in patients with advanced disease shows that responses in most patients are brief and last only a few months at best.2 Sustained molecular responses to imatinib seem to be rare and it is unclear whether any patients will be cured (however one seeks to define this term) by this agent. In addition, resistance to imatinib will probably become an increasingly common problem, especially with long-term use. This might be less of an issue if resistance to imatinib manifests itself as a slow and orderly relapse into chronic phase. However, there is real concern that patients may relapse abruptly into an advanced stage of the disease, in which transplantation cannot be safely or effectively done. Delaying transplantation prejudices its outcome3 and, consequently, the inevitable postponement associated with a lengthy period of imatinib therapy may compromise the efficacy of the only proven curative therapy available for
patients with this disease. It seems, therefore, prudent to retain allogeneic transplantation as an important upfront therapy in younger patients with a suitable donor, for the present at least. Advice to the contrary is based on only a limited experience with imatinib and could be judged to be overly optimistic in years to come. *C Craddock, B Augustson, S Basu *Department of Haematology, University Hospital, Birmingham B15 2TH, UK (CC, BA, SB); and Department of Haematology, Royal Wolverhampton NHS Trust, Wolverhampton, UK (SB) (e-mail: [email protected]) 1
Sausville EA. Imatinib for chronic myelogenous leukaemia: a 9 or 24 carat gold standard? Lancet 2003; 361: 1400–01. 2 Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 2002; 99: 3530–39. 3 Weisdorf DJ, Anasetti C, Antin JH, et al. Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation. Blood 2002; 99: 1971–77.
CT-guided biopsy for diagnosis of malignant disease in pleural effusions Sir—Nick Maskell and colleagues (April 19, p 1326)1 report that CTguided biopsy is better than standard pleural biopsy in patients with cytology-negative suspected malignant pleural effusions. I have, however, several questions about the general applicability of their findings. Maskell and colleagues excluded any patient with a unilateral effusion with a pleural protein concentration of less than 35 g/dL. These effusions were assumed to be transudative if the patients had heart failure or hypoalbuminaemia. One of us (DT) and colleagues2 previously noted that, in a survey of clinical practice in Bristol, 14% of unilateral malignant effusions had protein content below 35 g/dL. Furthermore, Gotsman and co-workers’ study3 of patients with heart failure and pleural effusion undergoing thoracentesis showed that two thirds had pleural fluid exudate with 10% having malignant effusions. It is exactly this type of patient that presents the greatest diagnostic challenge in clinical practice. Why did Maskell and colleagues not use the well-established Light criteria4 to ascertain whether these patients’ pleural effusions were exudative or transudative?
THE LANCET • Vol 362 • July 12, 2003 • www.thelancet.com
We are surprised at the number of patients with malignant mesothelioma in their study—20 (61%) of 33 malignant effusions were mesothelioma. This finding contrasts again with our Bristol series,2 in which six (22%) of 27 cytology-negative consecutive effusions were mesothelioma. Furthermore, Trail and colleagues5 from Oxford have suggested that abnormalities detected by thoracic CT are more accurate in the diagnosis of primary as opposed to secondary malignant disease in pleural effusions. The limited number of patients without mesothelioma in Maskell and colleagues’ study makes it difficult to generalise the findings to clinical practice with a smaller proportion of mesothelioma cases. Maskell and colleagues state that 1700 additional biopsy procedures would be avoided in the UK if CTguided biopsy was the first-line biopsy method in these patients; they also suggest that there is a potential cost saving. This interpretation of their results is rather simplistic, because most pleural interventions in malignant pleural effusion are related to the control of fluid accumulation not just to diagnosis. A CT-guided biopsy without drainage leaves patients in need of additional pleural procedures. Maskell and colleagues admit that thoracoscopy has a greater sensitivity in detection of malignant disease in pleural effusions than CT-guided biopsy. Furthermore, the ability to undertake pleurodesis at the time of thoracoscopy in patients with cancer is an important advantage in terms of reducing the number of pleural interventions that may lead to tumour seeding of the chest wall. Surely, therefore, the best approach for patients with cytology-negative suspected malignant pleural effusions is thoracoscopy with drainage and pleurodesis as part of the same intervention? Gavin D Perkins, *David Thickett Department of Medical Sciences, University of Birmingham, Birmingham B15 2TH, UK (e-mail: [email protected]) 1
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Maskell NA, Gleeson FV, Davies RJO. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361: 1326–31. Thickett DR, Armstrong L, Millar AB. Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions. Thorax 1999; 54: 707–10. Gotsman I, Fidlender Z, Meirovitz A, Dratva D, Muszkat M. The evaluation of pleural effusions in patients with heart failure. Am J Med 2001: 375–78. Light RW. Diagnostic principles in pleural disease. Eur Respir J 1997; 10: 476–81. Trail Z, Davies R, Gleeson F. Thoracic computed tomography in patients with suspected pleural effusions. Clin Radiol 2001; 56: 193–96.
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For personal use. Only reproduce with permission from The Lancet
3
4
5
Uzunel M, Mattsson J, Brune M, Johansson J-E, Ringden O. Kinetics of minimal residual disease and chimerism in patients with chronic myeloid leukemia after non-myeloablative conditioning and allogeneic stem cell transplantation. Blood 2003, 101: 469–72. Gratwohl A, Hermans J, Goldman JM, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Lancet 1998; 352: 1087–92. Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options. Blood 1001; 98: 2039–42.
Sir—Allogeneic stem-cell transplantation has evolved over the past two decades into a remarkably effective treatment for chronic myelogenous leukaemia and is the only curative therapy. Consequently, it is now possible to predict a long-term survival in excess of 70% for young patients with an HLA-identical sibling donor. However, only a limited number of patients with chronic myelogenous leukaemia are eligible for allogeneic transplantation. So the evidence that imatinib mesylate has the capacity to induce complete cytogenetic remissions in up to two-thirds of patients treated in the early chronic phase represents a major breakthrough in the management of this disease. However, Edward that Sausville’s recommendation1 allografting should only be undertaken in patients who fail to achieve, or lose, a significant cytogenetic response to imatinib seems premature. Although the excellent results of allografting come from studies with follow-up rates of more than 10 years, there is no evidence that responses to imatinib are durable. Indeed, experience with this agent in patients with advanced disease shows that responses in most patients are brief and last only a few months at best.2 Sustained molecular responses to imatinib seem to be rare and it is unclear whether any patients will be cured (however one seeks to define this term) by this agent. In addition, resistance to imatinib will probably become an increasingly common problem, especially with long-term use. This might be less of an issue if resistance to imatinib manifests itself as a slow and orderly relapse into chronic phase. However, there is real concern that patients may relapse abruptly into an advanced stage of the disease, in which transplantation cannot be safely or effectively done. Delaying transplantation prejudices its outcome3 and, consequently, the inevitable postponement associated with a lengthy period of imatinib therapy may compromise the efficacy of the only proven curative therapy available for
patients with this disease. It seems, therefore, prudent to retain allogeneic transplantation as an important upfront therapy in younger patients with a suitable donor, for the present at least. Advice to the contrary is based on only a limited experience with imatinib and could be judged to be overly optimistic in years to come. *C Craddock, B Augustson, S Basu *Department of Haematology, University Hospital, Birmingham B15 2TH, UK (CC, BA, SB); and Department of Haematology, Royal Wolverhampton NHS Trust, Wolverhampton, UK (SB) (e-mail: [email protected]) 1
Sausville EA. Imatinib for chronic myelogenous leukaemia: a 9 or 24 carat gold standard? Lancet 2003; 361: 1400–01. 2 Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 2002; 99: 3530–39. 3 Weisdorf DJ, Anasetti C, Antin JH, et al. Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation. Blood 2002; 99: 1971–77.
CT-guided biopsy for diagnosis of malignant disease in pleural effusions Sir—Nick Maskell and colleagues (April 19, p 1326)1 report that CTguided biopsy is better than standard pleural biopsy in patients with cytology-negative suspected malignant pleural effusions. I have, however, several questions about the general applicability of their findings. Maskell and colleagues excluded any patient with a unilateral effusion with a pleural protein concentration of less than 35 g/dL. These effusions were assumed to be transudative if the patients had heart failure or hypoalbuminaemia. One of us (DT) and colleagues2 previously noted that, in a survey of clinical practice in Bristol, 14% of unilateral malignant effusions had protein content below 35 g/dL. Furthermore, Gotsman and co-workers’ study3 of patients with heart failure and pleural effusion undergoing thoracentesis showed that two thirds had pleural fluid exudate with 10% having malignant effusions. It is exactly this type of patient that presents the greatest diagnostic challenge in clinical practice. Why did Maskell and colleagues not use the well-established Light criteria4 to ascertain whether these patients’ pleural effusions were exudative or transudative?
THE LANCET • Vol 362 • July 12, 2003 • www.thelancet.com
We are surprised at the number of patients with malignant mesothelioma in their study—20 (61%) of 33 malignant effusions were mesothelioma. This finding contrasts again with our Bristol series,2 in which six (22%) of 27 cytology-negative consecutive effusions were mesothelioma. Furthermore, Trail and colleagues5 from Oxford have suggested that abnormalities detected by thoracic CT are more accurate in the diagnosis of primary as opposed to secondary malignant disease in pleural effusions. The limited number of patients without mesothelioma in Maskell and colleagues’ study makes it difficult to generalise the findings to clinical practice with a smaller proportion of mesothelioma cases. Maskell and colleagues state that 1700 additional biopsy procedures would be avoided in the UK if CTguided biopsy was the first-line biopsy method in these patients; they also suggest that there is a potential cost saving. This interpretation of their results is rather simplistic, because most pleural interventions in malignant pleural effusion are related to the control of fluid accumulation not just to diagnosis. A CT-guided biopsy without drainage leaves patients in need of additional pleural procedures. Maskell and colleagues admit that thoracoscopy has a greater sensitivity in detection of malignant disease in pleural effusions than CT-guided biopsy. Furthermore, the ability to undertake pleurodesis at the time of thoracoscopy in patients with cancer is an important advantage in terms of reducing the number of pleural interventions that may lead to tumour seeding of the chest wall. Surely, therefore, the best approach for patients with cytology-negative suspected malignant pleural effusions is thoracoscopy with drainage and pleurodesis as part of the same intervention? Gavin D Perkins, *David Thickett Department of Medical Sciences, University of Birmingham, Birmingham B15 2TH, UK (e-mail: [email protected]) 1
2
3
4 5
Maskell NA, Gleeson FV, Davies RJO. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361: 1326–31. Thickett DR, Armstrong L, Millar AB. Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions. Thorax 1999; 54: 707–10. Gotsman I, Fidlender Z, Meirovitz A, Dratva D, Muszkat M. The evaluation of pleural effusions in patients with heart failure. Am J Med 2001: 375–78. Light RW. Diagnostic principles in pleural disease. Eur Respir J 1997; 10: 476–81. Trail Z, Davies R, Gleeson F. Thoracic computed tomography in patients with suspected pleural effusions. Clin Radiol 2001; 56: 193–96.
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For personal use. Only reproduce with permission from The Lancet