Int J Clin Exp Med 2018;11(4):4262-4270 www.ijcem.com /ISSN:1940-5901/IJCEM0062572 Case Report Adult high-risk Burkitt’s acute lymphocytic leukemia was successfully rescued by rituximab combined with hyper-CVAD/MA regimens: two case reports and a literature review Zhiwei Chen1*, Zhanglin Zhang1*, Ping Huang1,2,3, Nan Zhong1,2, Weiping Tang1,2, Xiaojie Zhang1,2, Yunyun Wang1, Yanlin Wei1, Fei Li1,4 1Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China; 2Medical Col- lege, Nanchang University, Nanchang, China; 3Department of Nutriology, The First Affiliated Hospital of Nanchang University, Nanchang, China; 4Jiangxi Key Laboratory of Molecular Diagnosis and Precision Medicine, Nanchang, China. *Equal contributors. Received June 22, 2017; Accepted February 3, 2018; Epub April 15, 2018; Published April 30, 2018 Abstract: Objective: We report two adult cases with high-risk Burkitt’s acute lymphocytic leukemia (Burkitt’s ALL) was successfully rescued by rituximab combined with hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone)/MA (methotrexate and cytarabine) regimens. Methods: Two patients were diagnosed with high- risk Burkitt’s ALL. One had a t(8;22) chromosome translocation, respiratory failure, pulmonary infection, pleural effusion, hypoproteinemia, and his LDH was 13854 U/L; he developed central nervous system leukemia shortly thereafter. Another patient had a t(8;14) chromosome translocation and was two months pregnant, and her LDH was 5664 U/L. They both initially received low-dose prephase chemotherapy followed by rituximab combined with a hyper-CVAD chemotherapy regimen. Results: Both patients achieved complete remission after a course of che- motherapy; the cerebrospinal fluid of patient one returned to normal levels after administration of methotrexate by intrathecal injection and high-dose MA chemotherapy. His lung infection gradually improved, and multiple high-den- sity bilateral pulmonary plaques has been absorbed. The second patient safely underwent a medical abortion after her blood cell count returned to normal levels. Both patients are currently receiving an alternative chemotherapy regimen consisting of rituximab combined with hyper-CVAD/MA. Conclusion: Burkitt’s ALL is a medical emergency and should be promptly diagnosed and treated with proper chemotherapy. Rituximab combined with hyper-CVAD/ MA regimens may be an effective therapeutic strategy for patients to achieve the chance of survival. Keywords: Burkitt, acute lymphocytic leukemia, MYC arrangement, t(8;14), t(8;22) Introduction partner chromosomes, including chromosome 2 [t(2;8), 15%], chromosome 14 [t(8;14), 80%] Burkitt’s lymphoma/leukemia (BL) is a rare and and chromosome 22 [t(8;22), 5%], occur in al- aggressive mature B-cell non-Hodgkin’s lym- most all patients with BL [4]. Most cases of BL phoma (NHL) that was first diagnosed in African present with tumor masses, and bone marrow children in the late 1950s, with an incidence of (BM) involvement is common. Rarely, BL in- approximately 1% for mature NHL [1, 2]. The volves only the BM, which was previously re- three established subtypes of BL are endemic, ferred to “L3” acute lymphocytic leukemia (ALL- sporadic and AIDS-related BL. BL is more com- L3) [5]. BL patients with BM involvement are mon in whites and males than in other race classified to Ann Arbor IV stage and thought to groups and females [3]. BL also correlates with have very poor survival, the estimated median age, the incidence of BL gradually decreases progression-free survival (PFS) and overall sur- from 38% in patients aged 1-14 years old to vival (OS) were only 3 and 5 months [6]. 21% in patients aged 15-19 years and 5% in patients older than 20 years [3]. Translocations In this article, we present the two adult cases involving the MYC gene on chromosome 8 to its diagnosed with sporadic high-risk Burkitt’s ALL. Rituximab-based chemotherapy in Burkitt’s ALL One patient had a rare t(8;22) chromosome Personal history: The two patients had no his- translocation and respiratory failure, whereas tory of contact with contaminated water, no his- another female patient had a t(8;14) chromo- tory of smoking, drinking or other unhealthy some translocation and was two months preg- habits, and no history of contact with patients nant. Both patients were successfully rescued with acquired immunodeficiency syndrome by rituximab combined with Hyper-CVAD (cy- (AIDS). In addition, the family history did not clophosphamide, vincristine, doxorubicin and identify notable diseases. dexamethasone)/MA (methotrexate and cyta- rabine) regimens. We also retrospectively intro- Physical examination: Patient one exhibited duce data from the two patients and review the severe shortness of breath but a lucid mental related literature. status, moist rales in both lungs, an increased heart rate (114 beats/minute), and mild ede- Materials and methods ma in both lower extremities. Neither enlarged superficial lymph nodes nor liver and spleen History of present illness could be palpated. Patient two had enlarged lymph nodes in her left neck and an enlarged Informed consent was obtained before treat- spleen (3 cm below the left costal margin). ment, and the institutional review board ap- Cardiac and pulmonary abnormalities were not proved this case report. detected. The liver could not be palpated below the right costal margin. Case one was a 46-year-old man. He was ad- mitted to our hospital on February 7th, 2017 Adjuvant examinations due to “fever (37.7-38.5°C) and dizziness for a week, shortness of breath for one day”. The Patient one: the blood cell count showed a patient developed a slight cough with sputum. WBC of 33.84×109/L with 50% blasts, a Hb No skin hemorrhage or ecchymosis was found. level of 66 g/L, a PLT count of 20×109/L. An The blood cell count revealed the following: the albumin (ALB) level of 22.0 g/L (normal range, 9 white blood cell (WBC) count was 33.84×10 /L 40-55 g/L), a triglyceride (TG) level of 3.63 9 (normal range, 4-10×10 /L) with 50% blasts, mmol/L (normal range, 0-1.7 mmol/L), and a the hemoglobin (Hb) level was 66 g/L (normal lactate dehydrogenase (LDH) level of 13854 range, 120-160 g/L), and the platelet (PLT) U/L (normal range, 0-248 U/L). A blood gas 9 count was 20×10 /L (normal range, 100- analysis showed respiratory failure (PO 56 300×109/L). The patient was admitted due to 2 mmHg, PH 7.25, and PCO2 30 mmHg). The pro- suspected acute leukemia. Since onset, the thrombin time (PT) was 14 s (normal range, patient was in poor spirits, had poor appetite 9.8-12.1 s), the activated partial prothrombin and sleep, and had lost a significant amount of time (APTT) was 18.1 s (normal range, 21.1- weight. 36.5 s), and the thrombin time (TT) was 18.0 s Case two was a 16-year-old female who was (normal range, 14.0-21.0 s). The fibrinogen two months pregnant. She was admitted to our (Fbg) level was 7.16 g/L (normal range, 1.8-3.5 center on April 10th, 2017 due to a “neck mass g/L). The serum ferritin (SF) level was 3000 for two weeks”. Fever, cough and skin hemor- µg/L (normal range, 30-400 µg/L). The procal- rhage were absent. The blood cell count showed citonin (PCT) level was 2.25 ng/mL (< 0.5 ng/ the following: the WBC count was 29.46×109/L mL), and the C-reactive protein (CRP) level was with 65% blasts, the Hb level was 106 g/L, 84.5 mg/L (normal range, 0-8 mg/L). In addi- and the PLT count was 29×109/L. The patient tion, Epstein-Barr virus (EBV) and cytomegalovi- was admitted due to suspected acute leuke- rus (CMV) DNA serological tests, a blood cul- mia. Since onset, the patient was in normal ture (veins in both upper limbs, cultures for spirits, exhibited normal appetite and sleep, aerobic, anaerobic and fungal, three times), a and had not lost significant amounts of weight. (1-3)-Beta-D-Glucan assay (G test) and a galac- tomannan assay (GM test) were all negative. Past history: The two patients had no history of The alanine aminotransferase (ALT), aspartate hepatitis, tuberculosis or other infectious dis- aminotransferase (AST), bilirubin (BIL), and eases, no history of food or drug allergy, no his- serum creatinine (Scr) values were all normal. A tory of trauma surgery, and no history of blood computed tomography (CT) scan examination transfusion. revealed bilateral high-density plaques in the 4263 Int J Clin Exp Med 2018;11(4):4262-4270 Rituximab-based chemotherapy in Burkitt’s ALL CD3, CD7, CD34, CD117 and TDT were negative. Patient two: the blood cell count showed the following: a WBC of 29.46×109/L with 65% blasts, a Hb level of 106 g/L, a PLT level of 29×109/L. An ALT level of 99 U/L, an AST level of 92 U/L, and a LDH level of 5664 U/L. The PT, APTT, TT and Fbg were normal. In addition, the SF, PCT, CRP, EBV and CMV DNA serological tests, blood culture, G test and GM test were all negative. A color ultrasound revealed many enlarged lymph nodes throughout the body and sple- nomegaly. A CT scan examina- tion revealed normal bilateral pulmonary morphology and an enlarged spleen. ECG and ec- Figure 1. The bone marrow morphology, molecular genetic abnormalities and chromosome karyotype in patient one. A. The bone marrow morphology hocardiography results were showed acute lymphoblastic leukemia (Wright-Giemsa staining, ×1,000). normal. A BM smear showed B.