MULTILINEAGE DYSPLASIA IN IRAQI KURDS WITH ACUTE MYELOID LEUKEMIA: A RETROSPECTIVE STUDY ON 105 PATIENTS
Background: Acute Myeloid leukemia (AML) with multilineage dysplasia (MLD) is an important subcategory of acute myeloid leukemia, which has been reported to have prognostic importance. No studies have addressed this category of AML in Iraq Kurds, so this study was initiated.
Subject and Methods: A total of 105 patients diagnosed as Acute Myeloid leukemia over 10 years were reassessed. They have a median age of 40 and a male: female ratio of 1.02:1. The reassessment included re-evaluation of their clinical and hematological records, as well as re-evaluation of their peripheral blood and marrow smears for multilineage dysplasia. The study also included assessing any correlations between various clinical and hematological parameters and the presence of MLD.
Results: Multilineage dysplasia was documented in 35.3% of cases. The dysplasia was bilineage in 23.8% and trilineage in 11.4%. The most frequent dysplastic changes were hypogranular granulocytes, pseudo-pelger-hüet anomely, and mono-lobated megakaryocytes, seen in 46.6%, 29.5% and 20.9% respectively. The dysplasia was encountered in most frequently in M5 and M6 morphological subtypes, while it was absent in the M3 subtype, a finding which was significant (p =0.001). When the latter subtype was excluded from evaluation, it was found that patients with MLD were less likely to have organomegaly, more likely to have leukopenia, platelets < 20x109 /l, blast <20% in peripheral blood or <60% in bone marrow than those with no MLD, although none was significant.
Conclusions: Multilineage dysplasia is frequently encountered in Iraqi Kurds with AML and seen in all morphological subtypes except M3, and its presence needs to be documented in bone marrow reports on new AML cases. Further prospective studies preferably including cytogenetics to evaluate outcome in AML-MLD versus AML without it, needs to be initiated.
2- De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood cancer J. 2016; 6(7): e441.
3- Deschler B, Lübbert M. Acute myeloid leukemia: epidemiology and etiology. Cancer. 2006; 107(9): 2099-210.
4- Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002; 100:2292-2302.
5- Arber DA, Brunning RD, Orazi A, Bain BJ, Porwit A, Vardiman JW et al. Acute Myeloid Leukaemia with myelodysplasia- related change In Ed Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues, 4th Edition, International agency for research on cancer. Lyon, 2008; pp.124-126.
6- Weinberg OK, Seetharam M, Ren L, Seo K, Ma L, Merker JD, et al. Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system. Blood. 2009; 113(9): 1906-1908.
7- Pouls RK, Shamoon RP, Muhammed NS. Clinical and haematological parameters in adult AML patients: a four year experience at Nanakaly Hospital for blood diseases. Zanco J. Med. Sci. 2012; 16 (3): 199-203.
8- Al Allawi NAS, Hilmi FA, Yahya HI, Wajdi FT, Al Saleem TI, Al-Kassab F. Acute myeloid leukaemia: Morphological subtyping and hasematological findings in 214 Iraqi Adults. J. Fac .Med. Bagdad 1991; 33 (1): 59-71.
9- Hillman RS, Ault KA, Leporrier M, Rinder HM. Hematology in clinical practice. 5th edition. McGraw Hill Medical Publications. New York, 2011.
10- Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, et al. Age and acute myeloid leukemia. Blood. 2006; 107 (9): 3481-3485.
11- Strom SS, Oum R, Gbito E, Kplola Y, Garcia‐Manero G, Yamamura Y. De novo acute myeloid leukemia risk factors. Cancer. 2012; 118(18): 4589-4596.
12- Brito‐Babapulle F, Catovsky D, Galton DAG. Clinical and laboratory features of de novo acute myeloid leukaemia with trilineage myelodysplasia. British J Haematol. 1987; 66(4): 445-450.
13- Haferlach T, Schoch C, Löffler H, Gassmann W, Kern W, Schnittger S, et al. Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies. J. Clin. Oncol. 2003; 21(2): 256-265.
14- Goasguen JE, Matsuo T, Cox C, Bennett JM. Evaluation of the dysmyelopoiesis in 336 patients with de novo acute myeloid leukemia: major importance of dysgranulopoiesis for remission and survival. Leukemia. 1992; 6(6): 520-525.
15- Wakui M, Kuriyama K, Miyazaki Y, Hata T, Taniwaki M, Ohtake S, et al. Diagnosis of acute myeloid leukemia according to the WHO classification in the Japan Adult Leukemia Study Group AML-97 protocol. Int J Hematol. 2008; 87(2): 144-151.
16- Smith M, Barnett M, Bassan R, Gatta G, Tondini C, Kern W. Adult acute myeloid leukaemia. Critical reviews in oncology/hematology. 2004; 50(3): 197-222.
17- Bao L, Wang X, Ryder J, Ji M, Chen Y, Chen H, et al. Prospective study of 174 de novo acute myelogenous leukemias according to the WHO classification: subtypes, cytogenetic features and FLT3 mutations. Europ J Haematol. 2006; 77(1): 35-45.
18- Yanada M, Suzuki M, Kawashima K, Kiyoi H, Kinoshita T, Emi N, et al. Long‐term outcomes for unselected patients with acute myeloid leukemia categorized according to the World Health Organization classification: a single‐center experience. Europ J Haematol. 2005; 74(5): 418-423.
19- Arber DA, Stein AS, Carter NH, Ikle D, Forman SJ, Slovak ML. Prognostic impact of acute myeloid leukemia classification: importance of detection of recurring cytogenetic abnormalities and multilineage dysplasia on survival 2003. Am J Clin Pathol. 2003; 119(5): 672-80
20- Xu XQ, Wang JM, Gao L, Qiu HY, Chen L, Jia L, et al. Characteristics of acute myeloid leukemia with myelodysplasia‐related changes: A retrospective analysis in a cohort of Chinese patients. Am J Hematol. 2014; 89(9): 874-881.
21- Wandt H, Schäkel U, Kroschinsky F, Prange-Krex G, Mohr B, Thiede C, et al. MLD according to the WHO classification in AML has no correlation with age and no independent prognostic relevance as analyzed in 1766 patients. Blood. 2008; 111(4): 1855-1861.
22- Miesner M, Haferlach C, Bacher U, Weiss T, Macijewski K, Kohlmann A, et al . Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as “AML not otherwise specified” (AML-NOS) or “AML with myelodysplasia-related changes” (AML-MRC). Blood. 2010; 116(15): 2742-2751.
23- Kahl C, Florschütz G, Müller K, Jentsch-Ullrich M, Arland S. et al. Prognostic significance of dysplastic features of hematopoiesis in patients with de novo acute myelogenous leukemia. Ann Hematol. 1997; 75:91–94.
24- Vardiman J, Reichard K. Acute Myeloid Leukemia with myelodysplasia-related changes. Am J Clin Path. 2015; 144; 30-43.