|Year : 2022 | Volume
| Issue : 3 | Page : 373-375
Asymptomatic chronic-phase chronic myeloid leukemia BCR-ABL. (+) without splenomegaly: A case report
W Rajabto, YK Angkasa
Department of Internal Medicine, Division of Hematology.-Medical Oncology, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
|Date of Submission||07-Apr-2021|
|Date of Acceptance||30-Dec-2021|
|Date of Web Publication||16-Mar-2022|
Dr. Y K Angkasa
Jl. Pangeran Diponegoro No 71, RW 5, Kenari, Kec. Senen, Kota Jakarta Pusat, Daerah Khusus Ibukota, Jakarta - 10430
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Chronic Myeloid Leukemia (CML) is one of the myeloproliferative disorders characterized by Philadelphia chromosome presence. Contrary to Western countries, most CML patients in Indonesia present symptoms with splenomegaly as the most common finding. It is rare to find asymptomatic CML patients. We present a case of asymptomatic chronic-phase chronic myeloid leukemia BCR-ABL (+) without splenomegaly who achieved a hematologic and molecular response to imatinib.
Keywords: Asymptomatic CML, imatinib, low to intermediate risk of ELTS and Sokal score, molecular response
|How to cite this article:|
Rajabto W, Angkasa Y K. Asymptomatic chronic-phase chronic myeloid leukemia BCR-ABL. (+) without splenomegaly: A case report. Niger J Clin Pract 2022;25:373-5
|How to cite this URL:|
Rajabto W, Angkasa Y K. Asymptomatic chronic-phase chronic myeloid leukemia BCR-ABL. (+) without splenomegaly: A case report. Niger J Clin Pract [serial online] 2022 [cited 2022 Dec 3];25:373-5. Available from: https://www.njcponline.com/text.asp?2022/25/3/373/339706
| Introduction|| |
Chronic Myeloid Leukemia (CML) is one of the myeloproliferative disorders characterized by the Philadelphia chromosome resulting in the BCR-ABL fusion oncogenes. This BCR-ABL is a constitutive tyrosine kinase that activates signal transduction pathways, which affect hematopoietic cells' growth and survival.
Approximately 85% of patients with CML are diagnosed in the chronic phase. In the United States (US) and Europe, 40%–50% of patients with chronic-phase CML are asymptomatic, with the diagnosis made solely based on an abnormal blood count. Splenomegaly is the most common finding on physical examination and present in more than half of patients. Contrary to the US and Europe, the vast majority of patients with chronic phase at a national referral hospital in Indonesia were symptomatic with splenomegaly as the most common physical examination abnormality up to 80% of cases. In Indonesia, it is unusual for a patient with chronic-phase CML to present asymptomatic condition.
We therefore report a case of asymptomatic chronic-phase CML BCR-ABL (+) without splenomegaly who achieved a favorable outcome with imatinib.
| Case Presentation|| |
A 51-year-old male visited a polyclinic of hematology-medical oncology due to severe leukocytosis after a medical check-up. The patient had no presenting symptoms and co-morbidities. Physical examination showed normal, even absence of splenomegaly. Complete blood count read Hemoglobin (Hb) 12.4 g/dL (N: 13–17 g/dL), white blood cell (WBC) 133.500/μL (N: 5000-10.000/μL), Platelet 577.000/μL (N: 150.000-400.000/μL). Differential count was basophil 0%, eosinophil 1%, neutrophil band 23%, neutrophil segment 55%, lymphocyte 10%, monocyte 2%, blast 2%, myelocytes 4%, metamyelocytes 3%. We made a diagnosis of CML and performed bone marrow aspiration and RT-PCR BCR-ABL from peripheral blood [Figure 1].
|Figure 1: Bone marrow morphology showed hypercellular, blast 1%, Myeloid:Erythroid (M:E) ratio = 15:1, suppression of erythropoiesis, hyperplasia of granulopoiesis, and increased number of megakaryocytes including dwarf megakaryocyte|
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The RT-PCR BCR-ABL transcript detected with an international scale ratio was 69%. We established the diagnosis of Chronic-Phase CML BCR-ABL (+) with the Sokal score of 0.9 points (intermediate) and the EUTOS long-term survival (ELTS) score of 1.0821 (low-risk group). After the result of BCR-ABL, we administered imatinib 400 mg once daily. After 3 months, this patient achieved a complete hematologic response, and on the sixth month, the patient achieved molecular response with quantitative BCR-ABL that showed an international scale ratio of 0.05%. We planned to repeat the quantitative BCR-ABL for the next 6 months. The patient tolerated the side-effects of imatinib well and continued the treatment.
| Discussion|| |
The diagnosis of chronic-phase CML consists of documenting persistent unexplained leukocytosis (or occasionally thrombocytosis), the presence of the Philadelphia (Ph) chromosome abnormality, or the detection of BCR-ABL by RT-PCR molecular studies. In this case, the patient did not have any symptoms nor splenomegaly except severe leukocytosis. In the US, approximately 50% of patients diagnosed with CML are asymptomatic. CML's diagnosis often occurs during a routine physical examination or blood tests, just as in this case. Meanwhile, it is considered rare for a patient with chronic-phase CML at a national referral hospital in Indonesia, who presents asymptomatic without splenomegaly and visits the polyclinic due to severe leukocytosis as the result of a medical check-up.
Although CML can be diagnosed from peripheral blood examinations in conjunction with positivity for BCR-ABL, at diagnosis, a bone marrow aspirate should be performed to confirm the course of the disease. We performed a bone marrow aspirate for a morphological investigation, and the morphology of bone marrow was consistent with chronic-phase CML.
The therapeutic strategy for CML has changed radically by introducing BCR-ABL Tyrosine Kinase Inhibitors (TKIs). Till date, four TKIs include imatinib, and the second generation (2G) TKIs nilotinib, dasatinib, and bosutinib have been approved for the first-line treatment of CML in the chronic phase. Patients with CML treated with TKIs can experience a life span comparable to the non-CML population., Although 2GTKIs have demonstrated higher probabilities of molecular response than imatinib, none of the 2GTKIs has shown increased overall survival (OS) when compared to imatinib.
As all of the TKIs are indicated for treating chronic phase CML, experts recommend selecting the most appropriate TKIs based on age, risk of the disease, co-morbidities, side-effects of each TKIs, and availability.,, Based on the availability, only imatinib and nilotinib are reimbursed by Indonesia's national health insurance, while ponatinib is available, but the patients have to pay for themselves. The patient's age plays an essential role in the treatment decision. Patients younger than 50 years of age are expected to live more than 30 years. Therefore, inducing a durable complete molecular response (CMR) may potentially lead to therapy discontinuation. The second-generation TKIs induce a significantly higher rate of CMR compared with imatinib. Patients with high or intermediate ELTS or Sokal scores have demonstrated improved disease reduction with a first-line second-generation TKI. For a patient who does not have any co-morbidity, it is possible to administer imatinib or nilotinib., In conclusion, based on the patient's age, low to intermediate risk score, and cardiovascular disease risk will be high; we prefer imatinib as the first-line treatment. If the patient cannot achieve the milestone of monitoring treatment in the next future, we still have nilotinib as a second-line treatment.
Once we administer TKIs for a patient with chronic-phase CML, monitoring of treatment is crucial. According to European leukemiaNet 2020 recommendations for treating CML, the optimal response milestone determines whether the current treatment to be continued are CMR within 3 months, qBCR-ABL ≤1% on the sixth month, and qBCR-ABL ≤0.1% at 12 months. This patient reached optimal response after imatinib treatment since he achieved CHR in the third month and qBCR-ABL 0.05% in the sixth month; so that treatment with imatinib should be continued [Table 1]. This patient tolerated imatinib well and achieved a favorable outcome with it.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Hochhaus A, Saussele S, Rosti G, Mahon F-X, Janssen JJWM, Hjorth-Hansen H, et al
. Chronic myeloid leukemia: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol 2017;28(Suppl 4):iv41-51.
Granatowicz A, Piatek CI, Moschiano E, El-Hemaidi I, Armitage JD, Akhtari M. An overview and update of chronic myeloid leukemia for primary care physicians. Korean J Fam Med 2015;36:197-202.
Rajabto W, Harryanto A, Tadjoedin H, Harimurti K. Association of clinical features and hematological laboratories between Ph (+)/BCL-ABL (+) chronic myeloid leukemia and other type of Ph/BCL-ABL chronic myeloid leukemia. Jurnal Penyakit Dalam Indonesia 2018;5:11-6.
Castagnetti F, Gugliotta G, Soverini S, Baccarani M, Rosti G. Current Treatment Approaches in CML. Hemasphere Educational Updates in Hematology Book; 2019;3:p. 54-6.
Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy, and monitoring. Am J Hematol 2020;95:691-709.
Smith G, Apperley J, Milojkovic D, Cross CP N, Foroni L, Bryne J, et al
. A british society for haematology guideline on the diagnosis and management of chronic leukemoid leukemia. Br J Heamatol 2020;191:171-93.
Saglio G, Jabbour E. First-line therapy for chronic phase CML: Selecting the optimal BCR-ABL1-targeted TKI. Leuk Lymphoma 2018;59:1523-38.
Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al
. European leukemia NET 2020 recommendations for treating chronic myeloid leukemia. Leukemia 2020;34:966-84.