|Year : 2021 | Volume
| Issue : 4 | Page : 217-219
Immature granulocyte percentage in early chronic myeloid leukemia
Mahendra Narain Mishra1, Biben Odyuo1, Jemin Webster2
1 Department of Pathology, Baptist Christian Hospital, Tezpur, Assam, India
2 Department of Internal Medicine, Baptist Christian Hospital, Tezpur, Assam, India
|Date of Submission||21-Jan-2021|
|Date of Decision||14-Apr-2021|
|Date of Acceptance||17-Apr-2021|
|Date of Web Publication||18-Jan-2022|
Dr. Mahendra Narain Mishra
Baptist Christian Hospital, Tezpur - 784 001, Assam
Source of Support: None, Conflict of Interest: None
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
| Introduction|| |
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.,,, 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|| |
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. 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|| |
Median age for diagnosis of CML is 45 years in India which is a decade earlier than in Europe. 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. 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. A study from the USA mentions the presence of splenomegaly and hepatomegaly in 40%–50% and 10% of cases, respectively. 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.
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
Conflicts of interest
There are no conflicts of interest.
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