MDS Clearpath: An internet-based educational algorithm for the work-up, diagnosis and management of patients with myelodysplastic syndromes from the Canadian Consortium on MDS

2023 update

Authors

  • Heather A. Leitch, MD, PhD St. Paul’s Hospital; University of British Columbia, Vancouver, BC
  • Brian Leber, MD Juravinski Cancer Centre, Hamilton, ON
  • Harold J. Olney, MD Centre Hospitalier de l’Université de Montréal, Montreal, QC
  • April Shamy, MDCM Sir Mortimer B. Davis Jewish General Hospital; McGill University, Montreal, QC

DOI:

https://doi.org/10.58931/cht.2023.2S1137

Abstract

Background

Myelodysplastic Syndrome (MDS) treatments reduce transfusion dependence, delay progression to acute leukemia, and may improve survival. The Canadian Consortium on MDS (CCMDS) developed the MDS ClearPath, a comprehensive tool for the diagnosis, work-up and management of MDS of any risk category at any point during a patient’s disease course.

Methods

The draft ClearPath algorithm was revised by 60 Canadian hematologists, finalized by consensus of the Steering Committee and went live in 2013. The update went online in January 2023.

Results

An approach to the diagnosis and management of MDS is provided. Appropriate investigations are detailed, current scoring systems are included as is a prognostic calculator, and an IPSS-M calculator link is included.

Treatments (erythropoiesis-stimulating agents; lenalidomide; hypomethylating agents; immunosuppressive therapy; supportive care [transfusions; antibiotics; bleeding prevention; iron chelation]; investigational agents; links to clinical trial websites) are detailed, including dosing/administration; monitoring; dose adjustments; expected response; side effect management; and provincial reimbursement.

Added were details on luspatercept, decitabine and decitabine/cedazuridine; recommendations for mutation analysis; WHO and ICC 2022 classifications; the IPSS-M and Clinical Frailty scores; familial predisposition testing; and response assessment criteria. Recommendations are made where data are lacking.

The Treatment Wizard, a series of questions specific to clinical status, leads to treatment recommendations; the self-directed mode is the overall algorithm. References with abstract links are included, and information panels included throughout.

The ClearPath in English or French is available at www.MDSClearPath.org; a (free) iPad app is being updated.

Discussion

The CCMDS presents an internet/app-based algorithm to support MDS management, with recommendations designed to assist in the standardization of MDS care.

Author Biographies

Heather A. Leitch, MD, PhD, St. Paul’s Hospital; University of British Columbia, Vancouver, BC

Dr. Heather Leitch is a Hematologist at St. Paul’s Hospital in Vancouver, Canada and Clinical Professor in the Department of Medicine at the University of British Columbia. Dr. Leitch has a clinical and research interest in transfusional iron overload in acquired anemias such as the myelodysplastic syndromes (MDS), and a longstanding interest in lymphoproliferative and other blood disorders in the setting of HIV infection. She is Director of Hematology/Oncology Research at St. Paul’s Hospital, a reviewer of scientific papers for several medical journals, and an active member of the Canadian Consortium on MDS (CCMDS) and the UBC Department of Medicine Research Advisory Committee.

Brian Leber, MD, Juravinski Cancer Centre, Hamilton, ON

Dr. Brian Leber is a Professor of Medicine (Hematology) at McMaster University and an Attending Hematologist at the Juravinski Hosptial and Cancer Centre of Hamilton Health Sciences. He has a long‑standing interest in myeloid malignancies.

Harold J. Olney, MD, Centre Hospitalier de l’Université de Montréal, Montreal, QC

Dr. Harold Olney is the Chief of the Department of Hematology-Transfusion Medicine and the Director of the malignant cytogenetics laboratory at Centre Hospitalier de l’Université de Montréal (CHUM). He is an Assistant Clinical Professor in the Department of Medicine at the University of Montreal. Dr. Olney’s research Interests include myeloid diseases, lymphoproliferative syndrome, adrenal neoplasia, and Immune thrombocytopenia (ITP).

April Shamy, MDCM, Sir Mortimer B. Davis Jewish General Hospital; McGill University, Montreal, QC

Dr. April Shamy is an Associate Professor of Medicine at McGill University and a member of the Department of Medicine and Department of Oncology at the Jewish General Hospital. Dr. Shamy is a graduate of McGill University Medical School. She completed her Internal Medicine Residency and Hematology Fellowship at McGill University before training in Malignant Hematology at the University of Texas MD Anderson Cancer Centre. She manages a large clinical practice of patients with hematologic cancers and is actively involved in clinical research. She is an active member of the Canadian Consortium on Myelodysplastic Syndromes (CCMDS) and the Groupe des Maladies Plasmocytaires du Quebec (GMPQ). Dr. Shamy is the Medical Director of the Hematology‑Oncology‑Internal Medicine Ward at the JGH and is very involved in teaching within the McGill Medical School Curriculum and in the Internal Medicine and Hematology Residency Programs.

References

Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079‑88.

Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007 Aug 10;25(23):3503-10.

Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. [Research Support, Non-U.S. Gov’t]. 2012 Sep 20;120(12):2454-65.

Schanz J, Tuchler H, Sole F, Mallo M, Luno E, Cervera J, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. Journal of Clinical Oncology. [Research Support, Non-U.S. Gov’t]. 2012 Mar 10;30(8):820-9.

Kantarjian H, O’Brien S, Ravandi F, Cortes J, Shan J, Bennett JM, et al. Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer. 2008 Sep 15;113(6):1351-61.

Bernard E, Tuechler H, Greenberg PL, Hasserjian RP, Arango Ossa JE, Nannya Y, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evidence. 2022;1(7).

Buckstein R, Wells RA, Zhu N, Leitch HA, Nevill TJ, Yee KW, et al. Patient-related factors independently impact overall survival in patients with myelodysplastic syndromes: an MDS-CAN prospective study. British Journal of Haematology. 2016 Jul;174(1):88-101.

Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer. 2007 Apr 15;109(8):1536-42.

Dayyani F, Conley AP, Strom SS, Stevenson W, Cortes JE, Borthakur G, et al. Cause of death in patients with lower-risk myelodysplastic syndrome. Cancer. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2010 May 1;116(9):2174-9.

Statistics Canada. Life expectancy, at birth and at age 65, by sex and by province and territory 2012 [cited 2015 June 27]; Available from: http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/health72a-eng.htm.

Malcovati L, Della Porta MG, Cazzola M. Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica. 2006 Dec;91(12):1588-90.

Balducci L. Transfusion independence in patients with myelodysplastic syndromes: impact on outcomes and quality of life. Cancer. 2006 May 15;106(10):2087-94.

Buckstein R, Wells RA, Zhu N, Nevill TJ, Leitch HA, Yee KWL, et al. Paient related factors have an independent impact on overall survival in myelodysplastic syndrome patients: a report of the MDS-Can Registry. Blood. 2014;124(21):abstract 165.

Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. [Research Support, Non-U.S. Gov’t Review]. 2022 Jul;36(7):1703-19.

Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022 Sep 15;140(11):1200-28.

Bejar R. CHIP, ICUS, CCUS and other four-letter words. Leukemia. [Review]. 2017 Sep;31(9):1869-71.

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Edition ed. Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, editors. Lyon: WHO Press; 2008.

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55.

Raza A, Ravandi F, Rastogi A, Bubis J, Lim SH, Weitz I, et al. A prospective multicenter study of paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure. Cytometry B Clin Cytom. [Multicenter Study Research Support, Non-U.S. Gov’t]. 2014 May;86(3):175-82.

Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008 May 20;26(15):2505-11.

Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Perez WS, Anasetti C, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood. 2004 Jul 15;104(2):579-85.

Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005 Oct 15;106(8):2912-9.

Rose C, Brechignac S, Vassilief D, Pascal L, Stamatoullas A, Guerci A, et al. Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A Multicenter Study by the GFM. Leuk Res. 2010;34(7):864-70.

Leitch HA, Chan C, Leger CS, Foltz LM, Ramadan KM, Vickars LM. Improved survival with iron chelation therapy for red blood cell transfusion dependent lower IPSS risk MDS may be more significant in patients with a non-RARS diagnosis. Leukemia Research. [Research Support, Non-U.S. Gov’t]. 2012 Nov;36(11):1380-6.

Gattermann N, Finelli C, Della Porta M, Fenaux P, Stadler M, Guerci-Bresler A, Schmid M, Taylor K, Vassilieff D, Habr D, Marcellari A. Hematologic responses in myelodysplastic syndromes (MDS) patients treated with deferasirox: an EPIC post-hoc analysis using International Working Group (IWG) 2006 criteria. Blood. 2010 Nov 19;116(21):2912.

List AF, Baer MR, Steensma D, Raza A, Esposito B, Virkus J, et al. Deferasirox (ICL670); Exjade) reduces serum ferritin (SF) and labile plasma iron (LPI) in patients with myelodysplastic syndromes (MDS). Blood. 2008;112(11):523a.

Wells RA, Leber B, Buckstein R, Lipton JH, Hasegawa W, Grewal K, et al. Iron overload in myelodysplastic syndromes: a Canadian consensus guideline. Leuk Res. 2008 Sep;32(9):1338-53.

Leitch HA, Ezzat HM, Merkeley HL, Buckstein R, Zhu N, Nevill TJ, et al. MDS iron road: an internet based algorithm for the diagnosis, workup and management of iron overload in patients with myelodysplastic syndromes from the Canadian Consortium on MDS (CCMDS). 2020. Available from:

https://www.mdsironroad.org/.

List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006 Oct 5;355(14):1456-65.

Giagounidis A, Fenaux P, Mufti GJ, Muus P, Platzbecker U, Sanz G, et al. Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes. Annals of hematology. [Research Support, Non-U.S. Gov’t Review]. 2008 May;87(5):345-52.

Sekeres MA, Maciejewski JP, Giagounidis AA, Wride K, Knight R, Raza A, et al. Relationship of treatment-related cytopenias and response to lenalidomide in patients with lower-risk myelodysplastic syndromes. J Clin Oncol. 2008 Dec 20;26(36):5943-9.

Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. [Clinical Trial, Phase III Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2011 Oct 6;118(14):3765-76.

Sloand EM, Mainwaring L, Fuhrer M, Ramkissoon S, Risitano AM, Keyvanafar K, et al. Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome. Blood. 2005 Aug 1;106(3):841-51.

Saunthararajah Y, Nakamura R, Wesley R, Wang QJ, Barrett AJ. A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. Blood. 2003 Oct 15;102(8):3025-7.

Passweg J, Simcock M, Giagounidis A, Aul C, Dobbelstein C, Stadler M, et al. Immunosuppression for patients with low and intermediate risk myelodysplastic syndrome: a prospective randomized multicentre trial comparing antithymocyte globulin cyclosporin with best supportive care: SAKK 33/99. Haematologica. 2008 June 15;93(S1).

Nakao S, Sugimori C, Yamazaki H. Clinical significance of a small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure. International journal of hematology. [Research Support, Non-U.S. Gov’t Review]. 2006 Aug;84(2):118-22.

Lim ZY, Killick S, Germing U, Cavenagh J, Culligan D, Bacigalupo A, et al. Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin. Leukemia. [Multicenter Study]. 2007 Jul;21(7):1436-41.

Hellstrom-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J, et al. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. British Journal of Haematology. [Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 1997 Nov;99(2):344-51.

Santini V, Schemenau J, Levis A, Balleari E, Sapena R, Ades L, et al. Can the revised IPSS predict response to erythropoietic-stimulating agents in patients with classical IPSS low or intermediate-1 MDS? Blood. [Letter]. 2013 Sep 26;122(13):2286-8.

Buckstein R, Balleari E, Wells R, Santini V, Sanna A, Salvetti C, et al. ITACA: A new validated international erythropoietic stimulating agent-response score that further refines the predictive power of previous scoring systems. American Journal of Hematology. 2017 Oct;92(10):1037-46.

Jadersten M, Malcovati L, Dybedal I, Della Porta MG, Invernizzi R, Montgomery SM, et al. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol. 2008 Jul 20;26(21):3607-13.

Park S, Grabar S, Kelaidi C, Beyne-Rauzy O, Picard F, Bardet V, et al. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood. 2008 Jan 15;111(2):574‑82.

Gabrilove J, Paquette R, Lyons RM, Mushtaq C, Sekeres MA, Tomita D, et al. Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes. Br J Haematol. 2008 Jul;142(3):379-93.

Gotlib J, Lavori P, Quesada S, Stein RS, Shahnia S, Greenberg PL. A Phase II intra-patient dose-escalation trial of weight-based darbepoetin alfa with or without granulocyte-colony stimulating factor in myelodysplastic syndromes. Am J Hematol. 2009 Jan;84(1):15-20.

Mundle S, Lefebvre P, Vekeman F, Duh MS, Rastogi R, Moyo V. An assessment of erythroid response to epoetin alpha as a single agent versus in combination with granulocyte- or granulocyte-macrophage-colony-stimulating factor in myelodysplastic syndromes using a meta-analysis approach. Cancer. 2009 Feb 15;115(4):706-15.

Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. Journal of the National Cancer Institute. [Meta-Analysis Research Support, Non-U.S. Gov’t Review]. 2006 May 17;98(10):708-14.

Hellstrom-Lindberg E. Erythropoiesis-stimulating agents in myelodysplastic syndromes. Leukemia & Lymphoma. [Comment]. 2010 Jul;51(7):1155-6.

Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25.

Platzbecker U, Fenaux P, Ades L, Giagounidis A, Santini V, van de Loosdrecht AA, et al. Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials. Blood. 2019 Mar 7;133(10):1020-30.

Silverman LR, Fenaux P, Mufti GJ, Santini V, Hellstrom-Lindberg E, Gattermann N, et al. Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. Cancer. [Clinical Trial, Phase III Research Support, Non-U.S. Gov’t]. 2011 Jun 15;117(12):2697-702.

Santini V, Alessandrino PE, Angelucci E, Barosi G, Billio A, Di Maio M, et al. Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leukemia Research. [Practice Guideline Research Support, Non-U.S. Gov’t]. 2010 Dec;34(12):1576-88.

Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. [Clinical Trial, Phase III Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2009 Mar;10(3):223-32.

Itzykson R, Thepot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P, et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. [Clinical Trial Multicenter Study Research Support, Non-U.S. Gov’t]. 2011 Jan 13;117(2):403-11.

Santini V, Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Silverman LR, List A, et al. Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*. European journal of haematology. [Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2010 Aug;85(2):130-8.

Gore SD, Fenaux P, Santini V, Bennett JM, Silverman LR, Seymour JF, et al. A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial. Haematologica. [Clinical Trial, Phase III Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2013 Jul;98(7):1067-72.

List AF, Fenaux P, Mufti GJ, Hellström-Lindberg E, Gore S, Bennett JM, et al.; American Society of Clinical Oncology. Effect of azacitidine (AZA) on overall survival in higher-risk myelodysplastic syndromes (MDS) without complete remission. J Clin Oncol. [ASCO Annual Meeting Abstract] 2008;26(15_Suppl):7006.

Platzbecker U, Aul C, Ehninger G, Giagounidis A. Reduction of 5-azacitidine induced skin reactions in MDS patients with evening primrose oil. Annals of hematology. [Controlled Clinical Trial Letter]. 2010 Apr;89(4):427-8.

Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. [Clinical Trial, Phase II Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2020 Aug 6;136(6):674-83.

Fenaux P, Kantarjian H, Lyons R, Larson RA, Sekeres MA, Becker PS, et al. An open-label extension study evaluating the long-term safety and efficacy of romiplostim in thrombocytopenic patients (Pts) with myelodysplastic syndromes (MDS). Blood. 2009 Nov 16;114(22):1081.

https://clinicaltrials.gov/. 2023 [cited 2023 March 17]; A database of clinical trials conducted worldwide].

Greenberg PL, Attar E, Bennett JM, Bloomfield CD, De Castro CM, Deeg HJ, et al. NCCN Clinical practice guidelines in oncology: myelodysplastic syndromes. Journal of the National Comprehensive Cancer Network. [Practice Guideline]. 2011 Jan;9(1):30-56.

Salacz ME, Lankiewicz MW, Weissman DE. Management of thrombocytopenia in bone marrow failure: a review. J Palliat Med. [Review]. 2007 Feb;10(1):236-44.

Downloads

Published

2023-11-21

How to Cite

1.
Leitch HA, Leber B, Olney HJ, Shamy A. MDS Clearpath: An internet-based educational algorithm for the work-up, diagnosis and management of patients with myelodysplastic syndromes from the Canadian Consortium on MDS: 2023 update. Can Hematol Today [Internet]. 2023 Nov. 21 [cited 2024 Jul. 27];2(S11):2–14. Available from: https://canadianhematologytoday.com/article/view/2-s11-leitch_et_al