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ОСТРЫЙ МИЕЛОИДНЫЙ ЛЕЙКОЗ У БОЛЬНОГО ХРОНИЧЕСКИМ ЛИМФОЦИТАРНЫМ ЛЕЙКОЗОМ: ТРУДНОСТИ ДИАГНОСТИКИ (КЛИНИЧЕСКИЙ СЛУЧАЙ)
©М.С. Фернандеш1, Ж. Мартинш1, М.А. Кампуш1, К. Магаляеш1, Ю.О. Еремина12
Больница Педро Ишпану, Местное отделение здравоохранения Матозиньюша,
Матозиньюш, Португалия (1) Институт общественного здравоохранения Университета Порту, Порту, Португалия (2)
О сосуществовании хронического лимфоцитарного лейкоза (ХЛЛ) и острого миело-идного лейкоза (ОМЛ) у одного и того же пациента сообщалось редко, чаще как результат лечения химиотерапевтическими препаратами. Изменения показателей крови у онкологических больных могут быть интерпретированы как прогрессирование заболевания или ят-рогенные эффекты, связанные с агрессивным лечением, приводя к несвоевременной диагностике. В нашей статье мы хотим обратить внимание на возможность развития ОМЛ у больных ХЛЛ и сопутствующие трудности диагностики.
Ключевые слова: хронический лимфоцитарный лейкоз; острый миелоидный лейкоз; гематологические анализаторы; флаги; мазок периферической крови; разрушенные клетки; бласты.
ACUTE MYELOID LEUKEMIA IN A CHRONIC LYMPHOCYTIC LEUKEMIA PATIENT: DIAGNOSTIC CHALLENGE (CLINICAL CASE)
M.S. Fernandes1, J. Martins1, M.A. Campos1, C. Magalhaes1, Y.O. Eremina1,2
Hospital Pedro Hispano, Local Health Unit of Matosinhos, EPE, Matosinhos, Portugal (1) Institute of Public Health of the University of Porto, Porto, Portugal (2)
Chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) coexistence in the same patient has been rarely reported, more frequently due to treatment with chemotherapeutic agents. Blood parameter changes in cancer patients may be interpreted as disease progression or iatrogenic effects related to aggressive treatment, leading to delayed diagnosis. In our article, we call attention to the possibility of AML development in CLL patients and its diagnostic challenge.
Keywords: chronic lymphocytic leukemia; acute myeloid leukemia; hematology analyzers; flags; peripheral blood smear; smudge cells; blasts.
Chronic lymphocytic leukemia (CLL) is known to be associated with the increased risk of second hematological malignancies [1]. The coexistence of CLL and acute myeloid leukemia (AML) in the same patient has been rarely reported. Most cases were the result of treatment with chemotherapeutic agents for CLL [2]. Few cases describe CLL patients
who developed AML two weeks to four years after treatment. In addition, cases without previous treatment are extremely rare [3].
Modern automated blood count analyzers enable quantitative and identification analyses and flagging tangible blood components with electrical impedance, laser light scattering, and dye bonding (flow cytometry). Different
_© Eco-Vector, 2021
РОССИЙСКИЙ МЕДИКО-БИОЛОГИЧЕСКИЙ ВЕСТНИК I.P. PAVLOV RUSSIAN MEDICAL
имени академика И.П. Павлова. 2021. Т. 29. №1. С. 130-133 130 BIOLOGICAL HERALD. 2021;29(1):130-3
CLINICAL CASE
groups of detected components are presented numerically and displayed on scattergrams. Automated hematology analyzers perform complete blood count (CBC), generate algorithms-based pathology flags for all three lineages (erythrocytes, leukocytes, and platelets) to alert the clinical pathologist. As for leukocyte differentiation alterations and other morphologic abnormalities, Sysmex (Kobe, Japan) analyzers detect pathologic patterns and generate messages (flags): «Blast?» (Sysmex XE-5000) or «Blasts/Abnormal Lymphocytes?» (Sysmex XN with improved detection performance). These flags appear in acute and chronic leukemias of myeloid and lymphoid origin, myelodysplastic syndrome, plasma cell myeloma, lymphomas, left shift in granulocyte maturation, pseudo-Pelger-Huet anomaly, and in newborn children. The examination of the peripheral blood (PB) smear is routinely used as a basic step to evaluate hematological conditions and diseases suspected on analyzers flags [4-6].
In this letter, we intend to raise awareness of the possibility of AML development in CLL patients and its diagnostic challenge.
Case description. An 80-year-old man presented to the Emergency Department in
November 2019 with an acute-onset of right knee pain and edema, general weakness, and fever. His physical examination revealed skin pallor and hepatosplenomegaly.
His recent medical history included prostate cancer diagnosed in January 2018 and treated with leuprolide; clear cell renal cell carcinoma diagnosed in June 2018 with subsequent nephrectomy; small lymphocytic lymphoma diagnosed in June 2018 and treated with six cycles of complex chemotherapy (rituximab + cyclophosphamide + vincristine + prednisolone). While his initial response was positive, the patient progressed to CLL in October 2018 and started Ibrutinib with a favorable response.
His automated PB count revealed bicytopenia and leukocytosis (hemoglobin: 5.2 g/dL, platelets: 75x109/L, white blood cells: 93.73 x109/L). The Sysmex XE-5000 analyzer reported a flag «blasts?» that was already present in all the patient's CBCs since his CLL diagnosis. While anemia, leukocytosis, and thrombocytopenia could be interpreted as CLL relapse, the scattergram cytoDIFF was suspicious for the presence of blasts and required further examination (Figure 1).
Fig. 1. Sysmex 5000 - Scattergram cytoDIFF
The PB smear microscopic examination showed two distinct populations suggesting
an abnormality: small cells corresponding to mature lymphocytes (83%) with smudge cells
РОССИЙСКИЙ МЕДИКО-БИОЛОГИЧЕСКИЙ ВЕСТНИК имени академика И.П. Павлова. 2021. Т. 29. №1. С. 130-133
CLINICAL CASE
and large cells corresponding to blast cells proportion increased to 37%. (13%, Figure 2). In four weeks, the blast cells
Fig. 2. PB Smear (May-Grunwald-Giemsa staining) microscopy (500*): A - Smudge cell, B - Blast cells, C - Lymphocytes
PB immunophenotypic analysis confirmed morphological findings. CLL diagnosis was confirmed by demonstrating the expression of mature B-cell markers (CD19+, CD20dim), CD5+, and CD10-. Blast cells expressed myeloid markers (CD33+, MPO+), and «AML not otherwise specified» was diagnosed.
Conclusions Bicytopenia development in cancer patients may be interpreted as disease
progression or iatrogenic effects related to aggressive treatment, leading to delayed diagnosis. The present case highlights the need for careful PB smear revision, especially in CLL patients where the automatic analyzers routinely produce abnormal leucocytes presence alerts. Awareness of the possible development of AML in CLL patients is the key to its timely and accurate diagnosis.
Литература
1. Giri S., Bhatt V.R., Khanal S., et al. Treatment-related acute myeloid leukemia in a chronic lymphocytic leukemia patient: role of fludarabine? // Therapeutic Advances in Hematology. 2015. Vol. 6, №2. P. 88-92. doi: 10.1177/204062071 4566567
2. Al Mussaed E., Osman H., Elyamany G. Simultaneous existence of acute myeloid leukemia and chronic lymphocytic leukemia: a case report // BMC Cancer. 2016. Vol. 16, №1. P. 739. doi: 10.1186/s12885-016-2780-5
3. Dong Q., Xiu Y., Bossler A., et al. CLL dedifferentiation to clonally related myeloid cells // Blood Advances. 2020. Vol. 4, №24. P. 6169-6174. doi:10. 1182/bloodadvances.2020002726
4. Schoorl M., Schoorl M., Chevallier M., et al. Flagging performance of the Sysmex XN2000 haemato-logy analyser // International Journal of Laboratory Hematology. 2016. Vol. 38, №2. P. 160-166. doi:10.1111/ijlh. 12461
5. Furundarena J.R., Sainz M., Uranga A., et al. Com-
parison of abnormal cell flagging of the hematology analyzers Sysmex XN and Sysmex XE-5000 in oncohematologic patients // International Journal of Laboratory Hematology. 2017. Vol. 39, №1. P. 5867. doi:10.1111/ijlh. 12575
6. Eilertsen H., Saether P.C., Henriksson C.E., et al. Evaluation of the detection of blasts by Sysmex hematology instruments, CellaVision DM96, and manual microscopy using flow cytometry as the confirmatory method // International Journal of Laboratory Hematology. 2019. Vol. 41, №3. P. 338-344. doi:10. 1111/ijlh. 12980
References
1. Giri S, Bhatt VR, Khanal S, et al. Treatment-related acute myeloid leukemia in a chronic lymphocytic leukemia patient: role of fludarabine? Therapeutic Advances in Hematology. 2015;6(2):88-92. doi:10. 1177/2040620714566567
2. Al Mussaed E, Osman H, Elyamany G. Simultaneous existence of acute myeloid leukemia and chronic lymphocytic leukemia: a case report. BMC
РОССИЙСКИМ медико-биологическим вестник имени академика И.П. Павлова. 2021. Т. 29. №1. С. 130-133
Cancer. 2016;16(1):739. doi:10.1186/s12885-016-2780-5
3. Dong Q, Xiu Y, Bossler A, et al. CLL dedifferentiation to clonally related myeloid cells. Blood Advances. 2020;4(24):6169-74. doi:10.1182/blood advances.2020002726
4. Schoorl M, Schoorl M, Chevallier M, et al. Flagging performance of the Sysmex XN2000 haema-tology analyser. International Journal of Laboratory Hematology. 2016;38(2):160-6. doi:10.1111/ ijlh.12461
5. Furundarena JR, Sainz M, Uranga A, et al. Compa-
CLINICAL CASE
rison of abnormal cell flagging of the hematology analyzers Sysmex XN and Sysmex XE-5000 in oncohematologic patients. International Journal of Laboratory Hematology. 2017;39(1):58-67. doi:10. 1111/ijlh. 12575 6. Eilertsen H, Saether PC, Henriksson CE, et al. Evaluation of the detection of blasts by Sysmex hematology instruments, CellaVision DM96, and manual microscopy using flow cytometry as the confirmatory method. International Journal of Laboratory Hematology. 2019;41(3):338-44. doi:10.1111/ijlh. 12980
Дополнительная информация [Additional Info]
Конфликт интересов. Авторы заявляют, что у них нет известных конкурирующих финансовых интересов или личных отношений, которые могли бы повлиять на работу, описанную в этой статье. [Conflict of interests. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]
Участие авторов. Фернандеш М.С. - сбор и анализ материала, написание текста, изображения, Мартинш Ж., Кампуш М.А., Магаля-еш К. - анализ клинического случая и редактирование рукописи, Еремина Ю.О. - концепция статьи, сбор и анализ материала, редактирование рукописи. [Participation of authors. M.S. Fernandes - collection and analysis of material, writing the text, images, J. Martins, M.A. Campos, C. Magalhaes - case analysis and manuscript editing, Y.O. Eremina - concept of the article, collection and analysis of material, manuscript editing.]
Информация об авторах [Authors Info]
* Фернандеш Марта София - врач, магистр медицины, ординатор по клинической патологии, отделение клинической патологии, Больница Педро Ишпану, Местное отделение здравоохранения Матозиньюша, Матозиньюш, Португалия. [Marta S. Fernandes - MD, MMSc, Resident in Clinical Pathology, Department of Clinical Pathology, Hospital Pedro Hispano, Local Health Unit of Matosinhos, Matosinhos, Portugal.]
ORCID ID: 0000-0003-1900-1639. E-mail: martascf23@gmail.com
Мартинш Жуана - врач-специалист по клинической гематологии, отделение клинической гематологии, Больница Педро Ишпану, Местное отделение здравоохранения Матозиньюша, Матозиньюш, Португалия. [Joana Martins - MD, Specialist in Clinical Hematology, Department of Clinical Hematology, Hospital Pedro Hispano, Local Health Unit of Matosinhos, Matosinhos, Portugal.]
Кампуш Мария Антония - врач-консультант по клинической патологии, отделение клинической патологии, Больница Педро Ишпану, Местное отделение здравоохранения Матозиньюша, Матозиньюш, Португалия. [M. Antônia Campos - MD, Consultant in Clinical Pathology, Department of Clinical Pathology, Hospital Pedro Hispano, Local Health Unit of Matosinhos, Matosinhos, Portugal.] ORCID ID: 0000-0001-8016-8660.
Магаляеш Касилда - врач-консультант по клинической патологии, директор отделения клинической патологии, Больница Педро Ишпану, Местное отделение здравоохранения Матозиньюша, Матозиньюш, Португалия. [Cacilda Magalhaes - MD, Consultant in Clinical Pathology, Director of the Department of Clinical Pathology, Hospital Pedro Hispano, Local Health Unit of Matosinhos, Matosinhos, Portugal.] ORCID ID: 0000-0001-7407-4908.
Еремина Юлиана Олеговна - к.м.н., специалист по клинической патологии, отделение клинической патологии, Больница Педро Ишпану, Местное отделение здравоохранения Матозиньюша, Матозиньюш, Португалия; сотрудник исследовательской группы по экологической и лабораторной эпидемиологии, Департамент охраны окружающей среды, Институт общественного здравоохранения Университета Порту, Порту, Португалия. [Yuliana O. Eremina - MD, PhD, Specialist in Clinical Pathology, Department of Clinical Pathology, Hospital Pedro Hispano, Local Health Unit of Matosinhos, EPE, Matosinhos, Portugal; Collaborator of Environmental and Laboratorial Epidemiology Research Group (EPIUnit), Environmental Health Department, Institute of Public Health of the University of Porto, Porto, Portugal.] ORCID ID: 0000-0002-3656-7266, Researcher ID: ABD-8614-2020.
Цитировать: Фернандеш М.С., Мартинш Ж., Кампуш М.А., Магаляеш К., Еремина Ю.О. Острый миелоидный лейкоз у больного хроническим лимфоцитарным лейкозом: трудности диагностики (клинический случай) // Российский медико-биологический вестник имени академика И.П. Павлова. 2021. Т. 29, №1. С. 130-133. doi:10.23888/PAVLOVJ2021291130-133
To cite this article: Fernandes MS, Martins J, Campos MA, Magalhaes C, Eremina YO. Acute myeloid leukemia in a chronic lymphocytic leukemia patient: diagnostic challenge (clinical case). I.P. Pavlov Russian Medical Biological Herald. 2021;29(1):130-3. doi:10.23888/PAVLOVJ 2021291130-133
Поступила/Received: 07.06.2020 Принята в печать/Accepted: 01.03.2021
РОССИЙСКИЙ МЕДИКО-БИОЛОГИЧЕСКИЙ ВЕСТНИК имени академика И.П. Павлова. 2021. Т. 29. №1. С. 130-133
