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  Table of Contents  
Year : 2019  |  Volume : 56  |  Issue : 4  |  Page : 354-355

Atypical chronic myeloid leukemia achieving good response with azacitidine

Department of Hematology, The Fraternity Memorial Hospital, 2-1-11 Yokoami, Sumida-Ku, Tokyo, Japan

Date of Web Publication11-Oct-2019

Correspondence Address:
Atsushi Marumo
Department of Hematology, The Fraternity Memorial Hospital, 2-1-11 Yokoami, Sumida-Ku, Tokyo
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_506_18

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 » Abstract 

The prognosis of atypical chronic myeloid leukemia (aCML) patients is poor, but some patients with a suitable donor can be treated with allogeneic hematopoietic stem cell transplantation (HSCT). However, many of these patients cannot be treated with HSCT due to their age. The effectiveness of decitabine was recently indicated in case reports; however, the effectiveness of azacitidine (AZA) has not yet been reported. We report the case of a aCML patient successfully treated with AZA. A 66-year-old man with no remarkable medical history was admitted to our hospital because of leukocytosis. We diagnosed his disease as aCML and administered hydroxyurea (HU) and AZA. After four courses of AZA, his blood cell values improved, and he no longer needed transfusions and was able to stop HU. He continued receiving AZA without any severe complications. This is the first report that AZA is effective for the treatment of aCML.

Keywords: Atypical CML, azacitidine, case report, hypomethylating therapy

How to cite this article:
Marumo A, Mizuki T, Tanosaki S. Atypical chronic myeloid leukemia achieving good response with azacitidine. Indian J Cancer 2019;56:354-5

How to cite this URL:
Marumo A, Mizuki T, Tanosaki S. Atypical chronic myeloid leukemia achieving good response with azacitidine. Indian J Cancer [serial online] 2019 [cited 2020 Jun 1];56:354-5. Available from:

 » Introduction Top

Atypical chronic myeloid leukemia (aCML) was first reported in 1992 as a disease characterized by increasing numbers of granulocytes and a Philadelphia chromosome-negative status, and detailed guidelines for the diagnosis of aCML were first published in 1994.[1] No treatment for aCML has yet been established, and most patients are treated with hydroxyurea (HU) or interferon-α in order to control the number of blood cells. While the effectiveness of decitabine was indicated in a recent study, the effectiveness of azacitidine (AZA) remains to be clarified.[2],[3]

We herein report the case of a 66-year-old nontransplant aCML patient successfully treated with AZA.

 » Case History Top

A 66 year old man with no remarkable medical history visited a previous hospital because he suffered from a compression fracture after falling down. He had a blood sample, which indicated leukocytosis. He was suspected of having a hematological disease and was admitted to our hospital. A blood test revealed a white blood cell (WBC) count of 62,500/μL (blast cell 7.0%, myelocyte 6.0%, metamyelocyte 6.0%, stab cell 12.5%, segmented cell 57.0%, lymphocyte 8.5%, monocyte 4.5%, erythroblast 4.0%), hemoglobin (Hb) concentration of 9.6 g/dL, and platelet (Plt) count of 6,000/μL. In addition, his levels of reticulocytes, lactate dehydrogenase, WT1 mRNA, and vitamin B12 were high, but his neutrophil alkaline phosphatase score was low. Magnetic resonance imaging at the previous hospital revealed splenomegaly (major axis: 146 mm). A morphological examination of the bone marrow also revealed hypercellular bone marrow, 10% myeloblasts, and abnormal lobulation [Figure 1]. G-banding revealed a normal chromosome karyotype, 46, XY (20), and a fluorescence in situ hybridization study showed that the patient did not have the BCR-ABL fusion gene, PDG-FRA fusion gene, PDG-FRB fusion gene, nor FGFR1 reconstruction. Polymerase chain reaction revealed it to be JAK2 V617F- and CSF3R T618I-negative. We diagnosed the patient with aCML and started HU. Once the WBC count became controlled, the patient was discharged. He did not wish to undergo allogeneic hematopoietic stem cell transplantation (HSCT) and he was instead treated by AZA.
Figure 1: Examination of the bone marrow. (a) Hypercellular bone marrow and increasing numbers of neutrophil precursors. May–Gruenwald Giemsa strain, 100×. (b) Abnormally clumped nuclear chromatin and hyposegmented mature neutrophils; the acquired Pelger–Huet anomaly. May–Gruenwald Giemsa strain, 400×

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We started AZA (7 days, 75 mg/m [2]) without any prophylaxis medicine. He experienced no severe side effects, such as infections. After continuing AZA for four courses as an outpatient, his Hb level normalized and his WT1 mRNA titer improved. Due to the effectiveness of AZA, we were able to stop HU and platelet transfusion [Figure 2].
Figure 2: Clinical course after starting hydroxyurea and azacitidine. HU=Hydroxyurea; AZA=Azacitidine

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 » Discussion Top

aCML was incorporated into the third edition of the WHO classification in 2001. In the WHO 2016 classification, aCML was also defined as myelodysplastic/myeloproliferative neoplasams (MDS/MPN) disease. aCML is characterized by granulocytic dysplasia, showing abnormally clumped nuclear chromatin, hypersegmentation, and others. It has an annual incidence of one to two cases per 1,000,000 and an acute myeloid leukemia progression rate of ~40%. Some studies have indicated an overall survival of 14–30 months.[4],[5] Most patients are elderly men, and chromosomal aberrations, including trisomy 8, were identified in 44% of aCML patients in one study.[4] Genetic abnormalities, such as RAS (KRAS/NRAS), were identified in 35% of patients in the same study.[4]

No treatment for aCML has yet been established, and the prognosis of aCML patients is poor. Eligible patients with a suitable donor can be treated with allogeneic HSCT. However, according to the report by Onida et al. in 2017, the complete remission rate was 87%, and the 5-year relapse-free survival rate was 36% in 42 aCML patients treated with allogeneic HSCT.[6] Given this high relapse rate, the lack of an effective treatment for aCML remains a problem. Treatments for HSCT-ineligible patients include HU and interferon-α for controlling leukocytosis or stalling progressive disease, and some reports have indicated that splenectomy and radiation show efficacy with some limitations.

Several recent reports have indicated that aCML patients have more CSF3R mutations than other leukemia patients,[7] and ruxoltinib may be effective in aCML patients who are CSF3R T618I- or JAK2 V617F-positive.[8],[9] Other reports have suggested that trametinib may be effective in aCML patients positive for the RAS mutation.[10] However, the RAS mutation exists in only 30% of aCML patients,[2] and CSF3R T618I and JAK2 V617F positivity exist in even fewer patients. These findings suggest that ruxoltinib can be administered to only a limited population of patients. However, DNA hypomethylating agent, AZA, can be administered to all aCML patients, regardless of their mutation status, and the effectiveness of AZA for other MDS/MPN, such as chronic myelomonocytic leukemia, has also been reported in some articles. A few articles have additionally reported the effectiveness of decitabine in aCML patients.[2],[3]

We used AZA in the present patient, and he was able to continue using this agent without suffering any severe complications, even given his advanced age. His WBC and platelet counts, and hemoglobin concentration improved, allowing him to ultimately stop using HU.

In conclusion, the current case report revealed that AZA is effective for treating aCML.


We would like to thank clinical technologists, Department of Clinical Laboratory, the Fraternity Memorial Hospital for their excellent technical assistance. We are also indebted to the inpatient nursing teams and support staff for the excellent care they provided to our patient and his family.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick H, et al. The chronic myeloid leukaemias: Guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group. Br J Haematol 1994;87:746-54.  Back to cited text no. 1
Tong X, Li J, Zhou Z, Zheng D, Liu J, Su C, et al. Efficacy and side-effects of decitabine in treatment of atypical chronic myeloid leukemia. Leuk Lymphoma 2015;56:1911-13.  Back to cited text no. 2
Hausmann H, Bhatt VR, Yuan J, Maness LJ, Ganti AK. Activity of single-agent decitabine in atypical chronic myeloid leukemia. J Oncol Pharm Pract 2016;22:790-4.  Back to cited text no. 3
Kurzrock R, Bueso-Ramos CE, Kantarjian H, Freireich E, Tucker SL, Sicilano M, et al. BCR rearrangement-negative chronic myelogenous leukemia revisited. J Clin Oncol 2001;19:2915-26.  Back to cited text no. 4
Wang SA, Hasserjian RP, Fox PS, Rogers HJ, Geyer JT, Chabot-Richards D, et al. Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms. Blood 2014;123:2645-51.  Back to cited text no. 5
Onida F, de Wreede LC, van Biezen A, Eikema DJ, Byme JL, Iori AP, et al. Allogeneic stem cell transplantation in patients with atypical chronic myeloid leukaemia: A Retrospective study from the chronic malignancies Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol 2017;177:759-65.  Back to cited text no. 6
Maxon JE, Gotlib J, Pollyea DA, Fleischman AG, Agarwal A, Eide CA, et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. N Engl J Med 2013;368:1781-90.  Back to cited text no. 7
Fleischman AG, Maxson JE, Luty SB, Agarwal A, Royer LR, Abel ML, et al. The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition. Blood 2013;122:3628-31.  Back to cited text no. 8
Gunawan AS, McLornan DP, Wilkins B, Waghom K, Hoade Y, Cross NCP, et al. Ruxolitinib, a potent JAK1/JAK2 inhibitor, induces temporary reductions in the allelic burden of concurrent CSF3R mutations in chronic neutrophilic leukemia. Haematologica2017;102:e238-40.  Back to cited text no. 9
Khanna V, Pierce ST, Dao KH, Tognon CE, Hunt DE, Junio B, et al. Durable disease control with MEK inhibition in a patient with NRAS-mutated atypical chronic myeloid leukemia. Cureus 2015;7:e414.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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