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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 12  |  Issue : 4  |  Page : 217-219

Immature granulocyte percentage in early chronic myeloid leukemia


1 Department of Pathology, Baptist Christian Hospital, Tezpur, Assam, India
2 Department of Internal Medicine, Baptist Christian Hospital, Tezpur, Assam, India

Date of Submission21-Jan-2021
Date of Decision14-Apr-2021
Date of Acceptance17-Apr-2021
Date of Web Publication18-Jan-2022

Correspondence Address:
Dr. Mahendra Narain Mishra
Baptist Christian Hospital, Tezpur - 784 001, Assam
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joah.joah_4_21

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  Abstract 


A 38-year-old man presented with mild fatigue of recent onset to the medical outpatient department (OPD). Clinical examination showed an absence of fever, pallor, and no organomegaly. Routine complete blood count (CBC) showed mild leukocytosis (total leukocyte count 22.93 × 109/L), absence of features of sepsis but with immature granulocyte (IG) fraction of 26.6% on peripheral blood film without basophilia or eosinophilia. A diagnosis of chronic myeloid leukemia (CML) was suspected which was confirmed by conventional karyotyping and quantitative reverse transcription − polymerase chain reaction (QPCR). Following administration of imatinib for 2 weeks, a follow-up CBC showed a reduction in IG fraction to 1.5%. The patient is under follow-up in OPD for 4 months and is responding well as substantiated by follow-up QPCR. To the best of our knowledge, this is the first ever report where CML was first suspected on the basis of IG fraction and the same parameter proved useful for follow-up.

Keywords: Chronic myeloid leukemia, immature granulocytes percentage, Philadelphia chromosome


How to cite this article:
Mishra MN, Odyuo B, Webster J. Immature granulocyte percentage in early chronic myeloid leukemia. J Appl Hematol 2021;12:217-9

How to cite this URL:
Mishra MN, Odyuo B, Webster J. Immature granulocyte percentage in early chronic myeloid leukemia. J Appl Hematol [serial online] 2021 [cited 2022 Sep 25];12:217-9. Available from: https://www.jahjournal.org/text.asp?2021/12/4/217/335944




  Introduction Top


Immature granulocyte (IG) percentage as flagged by hematology cell analyzer has been used for identifying sepsis, prognostic marker for gastrointestinal hemorrhage, and as a marker of tumor-related myeloid proliferation.[1],[2],[3],[4] With slightly elevated total leukocyte count (TLC 22.93 × 109/L) and absence of features of sepsis on peripheral blood film, IG percentage provided the first clue to possible early chronic myeloid leukemia (CML) in a young patient without clinical hepatosplenomegaly. Our diagnosis was subsequently confirmed by conventional karyotyping and quantitative reverse transcription − polymerase chain reaction (RT-PCR). A second scattergram 12 days after commencing imatinib mesylate showed a significant decline in IG. It is the first-ever report in literature where IG alarm has been described to be useful for diagnosis and follow-up in a CML patient.


  Case Report Top


A 38-year-old male reported with complaints of mild fatigue for 3 days. Clinical examination was unremarkable with no fever, hepatosplenomegaly, or any localizing signs. The results of CBC done on XN350 Sysmex Hematology Cell analyzer were as follows: Hemoglobin of 131 g/L, platelets 335 × 109/L, and TLC-22.93 × 109/L with 82.5% neutrophils of which IG comprised 26.6% (reference interval 0%–1%) as seen in the left panel of the white blood cell (WBC) scattergram [Figure 1]. Eosinophils and basophils comprised 1.8% and 1.4% of the TLC, respectively. Peripheral blood film microscopy showed promyelocytes: 5%, myelocytes: 9%, metamyelocytes: 5%, neutrophils: 56%, eosinophils: 1%, basophils: 1%, lymphocytes: 19%, and monocytes: 3% (Pro5My9Me5P56E1B1 L19M3) without any toxic granules, vacuoles, or Dohle bodies. IG fraction typically includes the metamyelocytes, myelocytes, and granular promyelocytes.[5] Other relevant investigations were C-reactive protein: 6 mg/dl (normal <10) and serum lactate dehydrogenase [LDH]: 456 units/L (normal: 120–246). Ultrasonographic examination of the abdomen showed mild hepatomegaly and no splenomegaly. A possibility of CML was considered on basis of high IG percentage with the absence of inflammatory markers. Bone marrow aspiration was carried out and a portion was shipped in a heparin vacutainer for conventional karyotyping. Microscopy of the bone marrow aspirate showed normal cellularity with myeloid-to-erythroid ratio of 4.2:1, normoblastic maturation, normal megakaryocytes count, and morphology and differential count of Pro5My30Me7P36E2 L1, with 19% being erythroid precursors. A diagnosis of reactive marrow with myeloid hyperplasia was made. Chromosome analysis by conventional karyotyping showed translocation involving long arms of chromosomes 9 and 22 as the sole abnormality in all the 20 metaphases studied, thus confirming the provisional diagnosis. The patient was referred to the government oncology center of the state. Baseline quantitative RT-PCR was done on peripheral blood sample to measure the number of BCR/ABL fusion transcripts and normalized copy number and international scale conversion value BCR/ABL 1 ratio % (IS) prior to initiation of chemotherapy. The IS was 49.33% and BCR/ABL copy number was 94,500. Imatinib mesylate therapy was initiated at a dose of 400 mg per day. TLC after 12 days of treatment was 10.99 × 109/L and the differential counts were P80E3B1M2 L14 with IG percentage of 1.5 (WBC scattergram – right panel) and marginally raised serum LDH (256 u/L). Four months since initiation of treatment, the patient is doing well at the last follow-up.
Figure 1: Scattergram on diagnosis (left) and 12 days after initiation of treatment (right). The immature granulocyte fraction is indicated by a blue arrow

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  Discussion Top


Median age for diagnosis of CML is 45 years in India which is a decade earlier than in Europe.[6] Typical CBC features in chronic phase CML are as follows: absolute leukocytosis (median of 100,000/μL) with a left shift and classic “myelocyte bulge” (more myelocytes than the more mature metamyelocytes seen on the blood smear); blasts usually number <2%; and absolute basophilia is nearly universal, with absolute eosinophilia in 90% of cases.[7] Unique features of this patient include relatively young age, no hepatosplenomegaly on clinical examination, absence of typical peripheral blood findings of chronic phase CML including anemia, thrombocytosis, and those mentioned above. Splenomegaly and hepatomegaly were present in 89% and 61% of Indian CML patients, respectively, in a study of 299 patients.[8] A study from the USA mentions the presence of splenomegaly and hepatomegaly in 40%–50% and 10% of cases, respectively.[9] The first clue to possible diagnosis was provided by high absolute count of IG which was flagged by the hematology cell counter – a feature that always has to be correlated by peripheral blood smear examination. Philadelphia chromosome is usually the sole abnormality in 100% of metaphases. This is the first reported case of CML in which IG fraction provided a clue to possible diagnosis and posttreatment reduction was observed which was verified by microscopic examination. This article underlines the significance of IG fraction as a clue for the first suspicion of early CML in a young patient and its possible role in monitoring response to treatment in a resource-poor setting.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgment

The authors wish to acknowledge Cytogenetics Laboratory of Dr Lal PathLabs, National Reference Laboratory, New Delhi, for reporting on the karyotyping results, and Molecular Diagnostic Department of AmPath Central Reference Laboratory, Hyderabad, for performing the BCR/ABL International Scale Quantitative test.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801-10.  Back to cited text no. 1
    
2.
Pavare J, Grope I, Gardovska D. Assessment of immature granulocytes percentage to predict severe bacterial infection in latvian children: An analysis of secondary data. Medicina (Kaunas) 2018;54:56.  Back to cited text no. 2
    
3.
Prabu NR, Patil VP. Is immature granulocyte count a potential prognostic marker for upper gastrointestinal tract bleeding? A new road to explore. Indian J Crit Care Med 2020;24:750-2.2.  Back to cited text no. 3
    
4.
Che YQ, Shen D, Zhang SM, Qi J. Identification of immature granulocytes in cancer chemotherapy patients by cell counting vs. microscopic examination of blood smears. Mol Clin Oncol 2014;2:207-11.  Back to cited text no. 4
    
5.
The Immature Granulocyte Count – The First to Know about Inflammation Sysmex Xtra Online; November 2011. p. 1-4. Available from: http://www.sysmex-europe.com 'fileadmin ' media ' Xtra. [Last accessed on 2020 Dec 20]  Back to cited text no. 5
    
6.
Singhal MK, Sengar M, Nair R. Summary of the published Indian data on chronic myeloid leukemia. South Asian J Cancer 2016;5:162-5.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications. Blood 2011;117:5019-32.  Back to cited text no. 7
    
8.
Malhotra P, Varma N, Varma S. A short report on chronic myeloid leukemia from post graduate institute of medical education and research, Chandigarh. Indian J Med Paediatr Oncol 2013;34:186-8.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol 2018;93:442-59.  Back to cited text no. 9
    


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