Letter to the Editor
Acute myeloblastic leukemia, hematopoietic stem cell transplantation, clinical outcomes, prediction.
Since I am asked by the editor to prevent Dr. Gale and Dr. Moiseev from slugging it out, I would like to find positions where we can meet:
1) The informed consent for any treatment particularly with the risks for the patient will require a complete disclosure of risks and alternative treatments (Declaration of Helsinki, Belmont report). If we recommend a transplant to a patient with AML in first remission at intermediate risk, we have to tell them how they would fare with conventional treatment [1-3].
2) Knowing the dilemma of our prediction capability. Hematologists and transplanters work for more than 40 years on refinement of predictive models. The predictive model by Smith and Keating has been applied to a patient group with acute leukemia and could show a survival advantage for transplants in the high and intermediate, but not in the good risk group [4, 5].
3) The current EBMT recommendations state AML patients with good cytogenetic features are not: patients with intermediate and poor risk, are candidates for transplant in first CR [6-10].
4) Risk Assessment integrating cytogenetic and molecular profiling might improve the predictability .
5) Since the age represents one of the most adverse prognostic indicators for response to treatment and overall survival and since the results of transplant in patients older than 60 years have improved significantly, further emphasis should be directed towards elderly AML patients to sort out age risk factor versus molecular and cytogenetic markers .
6) As to the ornithological questions, how to overcome the black and white swans . I would like to point to Cocoanuts
1929, the Marx Brothers: “Why a duck?”.
7) As to the slugging it out, I would like to recommend the Bavarian method to drown the dispute in beer until everything is clear and the question forgotten.
Axel Rolf Zander, MD, Dr.h.c., FACP
Huntsman Cancer Institute, University of Utah,
Salt Lake City
1. Gale RP. Transplants for acute myeloid leukaemia in 1st remission: statisticians, magicians and the rest of us. Cell Ther Transplant (CTT). 2017; 6 (4): 10-12.
2. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Department of Health, Education and Welfare (DHEW) (30 September 1978). The Belmont report (http://videocast.nih.gov\pdf\ohrpbelmont_report.pdf) (PDF). Washington, DC: United States Government Printing Office.
3. World Medical Association (2013). “Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects” (http://jama.jamanetwork.com\article.aspx?articleid=1760318). JAMA. 310 (20): 2191-2194. doi:10.1001\jama.2013.281053 (https:\\doi.org\10.1001%2Fjama.2013.281053). PMID 24141714 (https:\\www.ncbi.nlm.nih.gov\pubmed\24141714). Retrieved July 24, 2015.
4. Murray PM, The History of Informed Consent. Iowa Orthop J. 1990; 10: 104-109.
5. Smith TL, Gehan EA, Keating MJ, et al: Prediction of remission in adult acute leukemia: Development and testing of predictive models. Cancer. 1982; 50:466-472.
6. Zander AR, Keating M, Dicke K, et al: A comparison of marrow transplantation with chemotherapy for adults with acute leukemia or poor prognosis in first complete remission. J Clin Oncol. 1988; 6(10): 1548-1557.
7. Burnett AK, Wheatley K, Goldstone AH, et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse. Results of the UK MRC AML 10 trial. Brit J Haematol. 2002; 118:385-400.
8. Zittoun RA, Madelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups. New Engl J Med. 1995; 332: 217-223.
9. Koreth J, Schlenk R, Kpoecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: Systematic review and meta-analysis of prospective clinical trials. JAMA. 2009; 301: 2349-2361.
10. Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra J, Bornhauser M, Juliusson G, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012; 9:579-590.
11. Moarii M, Papaemmanuil E. Classification and risk assessment in AML: integrating cytogenetics and molecular profiling. American Society of Hematology. 2017; 37.
12. Cornelissen JJ, Blaise D. Hematopoietic stem cell transplantation for patients with AML in first complete remission. Blood. 2016; 127:62-70.
13. Moiseev IS. Transplants for аcute myeloid leukaemia in 1st remission: standard of care or something else? Cell Ther Transplant, 2018; 7(1):67-70.
14. The Cocoanuts 1929, The Marx Brothers: “Why A Duck?” www.marx-brothers.org/whyaduck/info/.../whyaduck.htm