editorial comment
Real world data on acute myeloid leukaemia therapy from the developing world – an eye-opener Peter Hokland1 and Finbarr Cotter2 Department of Haematology, Arhus University Hospital, Arhus, Denmark, and 2Centre for Haematology-Oncology, Barts Cancer Institute, Barts and London School of Medicine and Dentistry, London, UK 1
Keywords: acute myeloid leukaemia, treatment, financial constraints.
developing world,
The international literature increasingly contains success stories about the advances in our field in developing countries, as well as in what has been coined ‘middle income’ countries. Reports cover a wide range of issues, including the implementation of aphaeresis in selected patients with hyperleucocytosis and stem cell collection in Indonesia (Triyono & Vrielink, 2014), the first successful allogeneic transplantation of a thalassaemic child in Nigeria (Bazuaye et al, 2014) and more general ventures related to improved blood banking (Berrios et al, 2013) and standardizing minimal residual disease for acute leukaemia in the setting of strained financial circumstances (Patkar et al, 2012). In a prior issue of this journal we dealt in detail with the state of haematology in developing countries (Cooper et al, 2011). While pinpointing several positive issues and highlighting the role of the practicing haematologists in improving the way our variety of diseases are diagnosed and cared for in strained economical circumstances, the contributions also outlined some problems, e.g. relating to pain medication and end-of-life care. What emerged from these papers was, however, an indication of improvments. This starkly contrasts to the paper from Vellore in Tamilnadu (India) published in this issue (Philip et al, 2015). The majority of patients diagnosed with acute myeloid leukaemia at this internationally renowned tertiary centre did not receive the proper cytoreduction due to lack of personal financial resources. This is a sobering read for at least two reasons: firstly, the mere fact that this situation occurs will be unknown to the vast majority of readers, who are accustomed to public health care and/or insurance paid medical treatments. Secondly, and just as significantly, up-to-date cytoreduction and treatment of neutropenic fever conditions was available at the institution, though the incidence of
Correspondence: Professor Peter Hokland, Department of Haematology, Aarhus University Hospital, Tage-Hansens Gade 2, Aarhus C 8000, Denmark. E-mail: [email protected]
ª 2015 John Wiley & Sons Ltd British Journal of Haematology, 2015, 170, 1–2
multi-resistant microbial agents is a daunting challenge. The latter fact is perhaps highlighted by the observation that the patients had to travel a median of 580 km to the hospital, probably reflecting the reputation and documented expertise of the department in treating promyelocytic leukaemia (Mathews et al, 2006). Although this is not, in any way, a population-based study, as previously published in this journal from Northern Sweden (Derolf et al, 2009), the referral pattern of Indian patients might be a valuable study in itself, adding even more data to those provided by the patient questionnaire used in this study. Some years ago, a noted Indian haematologist stated in conversation that that government-paid treatment of childhood leukaemia needed to wait until all Indian children had access to (i) a proper diet, (ii) a full vaccination scheme and (iii) to hygienic toilet facilities. This might not be so valid today, but the fact remains that when resources remained strained, prioritization is often the name of the game. In fact, India has, in some ways, shown the way to prioritize the costs of treatment of haematological malignancies, both in the setting of initial treatment (Chandy, 2006) and even allogeneic transplantations, where innovative solutions have been instituted for the same reason (Chandy, 2009). Add to this the results of consensus conferences, which have specified treatment in Asia according to resources, including personnel skills, available laboratory support and the financial situation [e.g. (Yeoh et al, 2013)], and we have at least a framework to present to politicians, who will then have to consider the prevalence and net result of different cancers in their country. Needless to ssay, this can change rapidly, as evidenced by the dramatic Ebola outbreak in West Africa in 2014. Abandonment of cytoreduction is nevertheless by no means unknown in the literature. Thus, a fairly recent metaanalysis in childhood acute lymphoblastic leukaemia (ALL) showed that this phenomenon was clearly more pronounced in low-income countries than in middle-income ones, once more identifying financial constraints as the major factor for treatment deferral (Bhakta et al, 2013). The data from Philip et al, in this issue are the more illustrative in terms of providing real world data, because the incidence of abandonment by patients is so high even though the treatment provision is there.
First published online 8 April 2015 doi: 10.1111/bjh.13410
Editorial Comment However, we do not need to end this editorial on a negative note. Recent literature suggests the progress in the developing World, in addition to that discussed above, is also being made on several other fronts, including the awareness of the reasons for childhood anaemia in children in Africa (Calis et al, 2008) and even the treatment of T-cell ALL in India (Abraham et al, 2014). In the meantime, and irrespective of the state of a rapidly expanding Indian economy, it is to be hoped that the paper
References Abraham, A., George, B., Ahmed, R., Viswabandya, A., Mathews, V., Lakshmi, K.M., Srivastava, V.M., Chandy, M. & Srivastava, A. (2014) Outcome of treatment with a low cost protocol in adults with T cell acute lymphoblastic leukemia in a tertiary care center in India. Leukemia & Lymphoma, 55, 947–949. Bazuaye, N., Nwogoh, B., Ikponmwen, D., Irowa, O., Okugbo, S., Isa, I., Ighodaro, E., Aina, Y.-I., Osaguona, A., Idemudia, O., Iyoha, O., Ighosewe, O., Osaghae, D. & Bucher, C. (2014) First successful allogeneic hematopoietic stem cell transplantation for a sickle cell disease patient in a low resource country (Nigeria): a case report. Annals of Transplantation: Quarterly of the Polish Transplantation Society, 19, 210–213. Berrios, R., Gonzalez, A. & Cruz, J.R. (2013) Achieving self-sufficiency of red blood cells based on universal voluntary blood donation in Latin America. The case of Nicaragua. Transfusion and Apheresis Science: Official Journal of the World Apheresis Association: Official Journal of the European Society for Haemapheresis, 49, 387– 396. Bhakta, N., Martiniuk, A.L., Gupta, S. & Howard, S.C. (2013) The cost effectiveness of treating paediatric cancer in low-income and middleincome countries: a case-study approach using acute lymphocytic leukaemia in Brazil and
2
from Philip et al, reported in this issue, will be brought to the attention of Indian politicians, haematologist and oncologists in the developed world, and those providing the resources for improving world health. We should all seriously consider the present situation highlighted by this important data set and continue to strive to improve care, even when resources are limited.
Burkitt lymphoma in Malawi. Archives of Disease in Childhood, 98, 155–160. Calis, J.C.J., Phiri, K.S., Faragher, E.B., Brabin, B.J., Bates, I., Cuevas, L.E., de Haan, R.J., Phiri, A.I., Malange, P., Khoka, M., Hulshof, P.J.M., van Lieshout, L., Beld, M.G.H.M., Teo, Y.Y., Rockett, K.A., Richardson, A., Kwiatkowski, D.P., Molyneux, M.E. & van Hensbroek, M.B. (2008) Severe anemia in Malawian children. The New England Journal of Medicine, 358, 888–899. Chandy, M. (2006) An approach to the management of leukemia in the developing world. Clinical and Laboratory Haematology, 28, 147– 153. Chandy, M. (2009) Innovative supportive care practices for stem cell transplantation in India. Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation, 15, 95–98. Cooper, N., Hart, D., Bates, I. & Cotter, F.E. (2011) The importance of developing world haematology. British Journal of Haematology, 154, 667. Derolf, A.R., Kristinsson, S.Y., Andersson, T.M.-L., Landgren, O., Dickman, P.W. & Bj€ orkholm, M. (2009) Improved patient survival for acute myeloid leukemia: a population-based study of 9729 patients diagnosed in Sweden between 1973 and 2005. Blood, 113, 3666–3672. Mathews, V., George, B., Lakshmi, K.M., Viswabandya, A., Bajel, A., Balasubramanian, P.,
Shaji, R.V., Srivastava, V.M., Srivastava, A. & Chandy, M. (2006) Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood, 107, 2627–2632. Patkar, N., Alex, A.A., Bargavi, B., Ahmed, R., Abraham, A., George, B., Vishwabandya, A., Srivastava, A. & Mathews, V. (2012) Standardizing minimal residual disease by flow cytometry for precursor B lineage acute lymphoblastic leukemia in a developing country. Cytometry Part B: Clinical Cytometry, 82, 252–258. Philip, C., George, B., Ganapule, A., Korula, A., Jain, P., Alex, A.A., Lakshmi, K.M., Sitaram, U., Abubacker, F.N., Abraham, A., Viswabandya, A., Srivastava, V.M., Srivastava, A., Balasubramanian, P. & Mathews, V. (2015) Acute myeloid leukaemia: challenges and real world data from India. British Journal of Haematology, 170, 110– 117. Triyono, T. & Vrielink, H. (2014) Therapeutic apheresis in Asia: an Indonesia single center experience. Journal of Clinical Apheresis, doi: 10.1002/jca.21350 [Epub ahead of print] Yeoh, A.E.J., Tan, D., Li, C.-K., Hori, H., Tse, E., Pui, C.-H.Asian & Summit, Oncology (2013) Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013. Lancet Oncology, 14, e508–e523.
ª 2015 John Wiley & Sons Ltd British Journal of Haematology, 2015, 170, 1–2
Real world data on acute myeloid leukaemia therapy from the developing world – an eye-opener Peter Hokland1 and Finbarr Cotter2 Department of Haematology, Arhus University Hospital, Arhus, Denmark, and 2Centre for Haematology-Oncology, Barts Cancer Institute, Barts and London School of Medicine and Dentistry, London, UK 1
Keywords: acute myeloid leukaemia, treatment, financial constraints.
developing world,
The international literature increasingly contains success stories about the advances in our field in developing countries, as well as in what has been coined ‘middle income’ countries. Reports cover a wide range of issues, including the implementation of aphaeresis in selected patients with hyperleucocytosis and stem cell collection in Indonesia (Triyono & Vrielink, 2014), the first successful allogeneic transplantation of a thalassaemic child in Nigeria (Bazuaye et al, 2014) and more general ventures related to improved blood banking (Berrios et al, 2013) and standardizing minimal residual disease for acute leukaemia in the setting of strained financial circumstances (Patkar et al, 2012). In a prior issue of this journal we dealt in detail with the state of haematology in developing countries (Cooper et al, 2011). While pinpointing several positive issues and highlighting the role of the practicing haematologists in improving the way our variety of diseases are diagnosed and cared for in strained economical circumstances, the contributions also outlined some problems, e.g. relating to pain medication and end-of-life care. What emerged from these papers was, however, an indication of improvments. This starkly contrasts to the paper from Vellore in Tamilnadu (India) published in this issue (Philip et al, 2015). The majority of patients diagnosed with acute myeloid leukaemia at this internationally renowned tertiary centre did not receive the proper cytoreduction due to lack of personal financial resources. This is a sobering read for at least two reasons: firstly, the mere fact that this situation occurs will be unknown to the vast majority of readers, who are accustomed to public health care and/or insurance paid medical treatments. Secondly, and just as significantly, up-to-date cytoreduction and treatment of neutropenic fever conditions was available at the institution, though the incidence of
Correspondence: Professor Peter Hokland, Department of Haematology, Aarhus University Hospital, Tage-Hansens Gade 2, Aarhus C 8000, Denmark. E-mail: [email protected]
ª 2015 John Wiley & Sons Ltd British Journal of Haematology, 2015, 170, 1–2
multi-resistant microbial agents is a daunting challenge. The latter fact is perhaps highlighted by the observation that the patients had to travel a median of 580 km to the hospital, probably reflecting the reputation and documented expertise of the department in treating promyelocytic leukaemia (Mathews et al, 2006). Although this is not, in any way, a population-based study, as previously published in this journal from Northern Sweden (Derolf et al, 2009), the referral pattern of Indian patients might be a valuable study in itself, adding even more data to those provided by the patient questionnaire used in this study. Some years ago, a noted Indian haematologist stated in conversation that that government-paid treatment of childhood leukaemia needed to wait until all Indian children had access to (i) a proper diet, (ii) a full vaccination scheme and (iii) to hygienic toilet facilities. This might not be so valid today, but the fact remains that when resources remained strained, prioritization is often the name of the game. In fact, India has, in some ways, shown the way to prioritize the costs of treatment of haematological malignancies, both in the setting of initial treatment (Chandy, 2006) and even allogeneic transplantations, where innovative solutions have been instituted for the same reason (Chandy, 2009). Add to this the results of consensus conferences, which have specified treatment in Asia according to resources, including personnel skills, available laboratory support and the financial situation [e.g. (Yeoh et al, 2013)], and we have at least a framework to present to politicians, who will then have to consider the prevalence and net result of different cancers in their country. Needless to ssay, this can change rapidly, as evidenced by the dramatic Ebola outbreak in West Africa in 2014. Abandonment of cytoreduction is nevertheless by no means unknown in the literature. Thus, a fairly recent metaanalysis in childhood acute lymphoblastic leukaemia (ALL) showed that this phenomenon was clearly more pronounced in low-income countries than in middle-income ones, once more identifying financial constraints as the major factor for treatment deferral (Bhakta et al, 2013). The data from Philip et al, in this issue are the more illustrative in terms of providing real world data, because the incidence of abandonment by patients is so high even though the treatment provision is there.
First published online 8 April 2015 doi: 10.1111/bjh.13410
Editorial Comment However, we do not need to end this editorial on a negative note. Recent literature suggests the progress in the developing World, in addition to that discussed above, is also being made on several other fronts, including the awareness of the reasons for childhood anaemia in children in Africa (Calis et al, 2008) and even the treatment of T-cell ALL in India (Abraham et al, 2014). In the meantime, and irrespective of the state of a rapidly expanding Indian economy, it is to be hoped that the paper
References Abraham, A., George, B., Ahmed, R., Viswabandya, A., Mathews, V., Lakshmi, K.M., Srivastava, V.M., Chandy, M. & Srivastava, A. (2014) Outcome of treatment with a low cost protocol in adults with T cell acute lymphoblastic leukemia in a tertiary care center in India. Leukemia & Lymphoma, 55, 947–949. Bazuaye, N., Nwogoh, B., Ikponmwen, D., Irowa, O., Okugbo, S., Isa, I., Ighodaro, E., Aina, Y.-I., Osaguona, A., Idemudia, O., Iyoha, O., Ighosewe, O., Osaghae, D. & Bucher, C. (2014) First successful allogeneic hematopoietic stem cell transplantation for a sickle cell disease patient in a low resource country (Nigeria): a case report. Annals of Transplantation: Quarterly of the Polish Transplantation Society, 19, 210–213. Berrios, R., Gonzalez, A. & Cruz, J.R. (2013) Achieving self-sufficiency of red blood cells based on universal voluntary blood donation in Latin America. The case of Nicaragua. Transfusion and Apheresis Science: Official Journal of the World Apheresis Association: Official Journal of the European Society for Haemapheresis, 49, 387– 396. Bhakta, N., Martiniuk, A.L., Gupta, S. & Howard, S.C. (2013) The cost effectiveness of treating paediatric cancer in low-income and middleincome countries: a case-study approach using acute lymphocytic leukaemia in Brazil and
2
from Philip et al, reported in this issue, will be brought to the attention of Indian politicians, haematologist and oncologists in the developed world, and those providing the resources for improving world health. We should all seriously consider the present situation highlighted by this important data set and continue to strive to improve care, even when resources are limited.
Burkitt lymphoma in Malawi. Archives of Disease in Childhood, 98, 155–160. Calis, J.C.J., Phiri, K.S., Faragher, E.B., Brabin, B.J., Bates, I., Cuevas, L.E., de Haan, R.J., Phiri, A.I., Malange, P., Khoka, M., Hulshof, P.J.M., van Lieshout, L., Beld, M.G.H.M., Teo, Y.Y., Rockett, K.A., Richardson, A., Kwiatkowski, D.P., Molyneux, M.E. & van Hensbroek, M.B. (2008) Severe anemia in Malawian children. The New England Journal of Medicine, 358, 888–899. Chandy, M. (2006) An approach to the management of leukemia in the developing world. Clinical and Laboratory Haematology, 28, 147– 153. Chandy, M. (2009) Innovative supportive care practices for stem cell transplantation in India. Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation, 15, 95–98. Cooper, N., Hart, D., Bates, I. & Cotter, F.E. (2011) The importance of developing world haematology. British Journal of Haematology, 154, 667. Derolf, A.R., Kristinsson, S.Y., Andersson, T.M.-L., Landgren, O., Dickman, P.W. & Bj€ orkholm, M. (2009) Improved patient survival for acute myeloid leukemia: a population-based study of 9729 patients diagnosed in Sweden between 1973 and 2005. Blood, 113, 3666–3672. Mathews, V., George, B., Lakshmi, K.M., Viswabandya, A., Bajel, A., Balasubramanian, P.,
Shaji, R.V., Srivastava, V.M., Srivastava, A. & Chandy, M. (2006) Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood, 107, 2627–2632. Patkar, N., Alex, A.A., Bargavi, B., Ahmed, R., Abraham, A., George, B., Vishwabandya, A., Srivastava, A. & Mathews, V. (2012) Standardizing minimal residual disease by flow cytometry for precursor B lineage acute lymphoblastic leukemia in a developing country. Cytometry Part B: Clinical Cytometry, 82, 252–258. Philip, C., George, B., Ganapule, A., Korula, A., Jain, P., Alex, A.A., Lakshmi, K.M., Sitaram, U., Abubacker, F.N., Abraham, A., Viswabandya, A., Srivastava, V.M., Srivastava, A., Balasubramanian, P. & Mathews, V. (2015) Acute myeloid leukaemia: challenges and real world data from India. British Journal of Haematology, 170, 110– 117. Triyono, T. & Vrielink, H. (2014) Therapeutic apheresis in Asia: an Indonesia single center experience. Journal of Clinical Apheresis, doi: 10.1002/jca.21350 [Epub ahead of print] Yeoh, A.E.J., Tan, D., Li, C.-K., Hori, H., Tse, E., Pui, C.-H.Asian & Summit, Oncology (2013) Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013. Lancet Oncology, 14, e508–e523.
ª 2015 John Wiley & Sons Ltd British Journal of Haematology, 2015, 170, 1–2
