Blood Res 2018; 53(1):
Published online March 31, 2018
https://doi.org/10.5045/br.2018.53.1.92
© The Korean Society of Hematology
1Department of Molecular Pathology and Cytogenetic, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
2Department of Molecular Pathology and Cytogenetic, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
3Department of Pathology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
4Department of Hemato-Oncology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Correspondence to : Moeinadin Safavi. Department of Molecular Pathology and Cytogenetics, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, Iran. safavi_moeinadin@yahoo.com, safavi@sums.ac.ir
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
On the other hand, t(17;19)(q22;p13) is a very rare translocation in acute lymphoblastic leukemia that is associated with an extremely poor prognosis. Coexistence of t(17;19)(q22;p13) with Philadelphia chromosome has only been reported once in the literature [3].
A 41-year-old man was admitted to hospital due to bone pain and abdominal discomfort. Pallor and splenomegaly were the only two abnormal findings on physical examination. Laboratory tests showed prominent leukocytosis, anemia and thrombocytopenia (white blood cell count=170,000/µL, hemoglobin=9.2 g/dL, platelet count= 30,000/µL). Flow cytometry of bone marrow aspiration revealed 80% blast cells with B cell precursor phenotype expressing HLA-DR, CD19, CD10, CD22, tdt, CD20. Bone marrow cytogenetic study with Giemsa banding method exhibited 45XY t(9;22) (q34;q11) de(3) der(9) t(3;9)(q11;q13) del3(q10) t(17;19)(q11;p13) (Fig. 1). Reverse transcription polymerase chain reaction was performed on a bone marrow specimen which also revealed m-bcr-abl1 fusion gene (p 190).
During hospitalization, the patient had an episode of epistaxis and his coagulation tests showed prolonged prothrombin time (PT=19.2 sec, normal range, 11–13 sec), partial thromboplastin time (PTT=42.5 sec, normal range, 25–35 sec) and low fibrinogen level (fibrinogen=92 mg/dL, normal range, 200–400 mg/dL). Thus, he underwent treatment with fresh frozen plasma till the symptoms resolved and the fibrinogen level reached beyond 100 mg/dL. He also received induction chemotherapy with Hyper CVAD chemotherapy regimen including cycles A and B. During cycle A, he took 1) cyclophosphamide with Mesna 500 mg IV on the first 3 days, 2) vincristine 2 mg IV on days 4 and 11, 3) adryamycin 50 mg on day 4, and 4) dexamethasone 40 mg on days 1 to 4 and 11 to 14. Three weeks later cycle B was initiated with the following combination: 1) methotrexate IV infusion 1,600 mg on the first day, 2) folinic acid 30 mg every 6 hours for 8 doses, 3) cytarabine 3,000 mg every 12 hours for 4 doses on 2nd and 3rd days, and 3) methylprednisolone 30 mg twice daily for 6 doses on days 1, 2 and 3. Imatinib (600 mg daily) was also added to his regimen after the detection of Philadelphia chromosome. Meanwhile, the patient received 12 mg intrathecal methotrexate weekly. Unfortunately, the patient's peripheral smear showed prominent leukocytosis (white blood cell count=140,000/µL) with 80% blast cells after completion of hyper-CVAD regimen (four courses of cycle A and B). Then he became candidate for bone marrow transplantation after salvage chemotherapy but he refused to receive salvage chemotherapy regimen. Therefore, there was no remedy but to continue treatment with 6-mercaptopurine (50 mg three times daily), methotrexate (15 mg weekly), vincristine (2 mg monthly) and another tyrosine kinase inhibitor, nilotinib (400 mg daily). Subsequent peripheral blood smear showed no blast cells and complete blood count yielded the following: white blood cells=2,500/µL, hemoglobin=10 g/dL and platelets=25,000/µL.
The Philadelphia chromosome was the first chromosomal aberration found to be associated with malignancy [4]. In fact, it is a diminutive chromosome 22 derived from t(9;22)(q34;q11). This translocation can result in three differently sized fusion products: p190, p210 and rarely p230. This fusion gene has a tyrosine kinase activity and occurs in chronic myelogenous leukemia, acute biphenotypic leukemia, and acute lymphoblastic leukemia. It has recently been discovered that an intragenic deletion of the
t(17;19)(q22;p13) is an extremely rare translocation with an estimated incidence of 0.1% [4]. Among 9,000 acute lymphoblastic leukemia trial patients in the Leukemia Research Cytogenetic Group Survey, only 9 had t(17;19) (q22;p13). Their ages ranged from 5 to 18 years with a median age of 13 years. Acute lymphoblastic leukemia patients had a B-cell precursor phenotype and none of them had remarkable leukocytosis (50×109/L) [9]. It is supposed to be a variant of t(1;19)(q23;p13) and results in fusion of the
In a recent review of the literature, 21 cases with t(17;19)(q22;p13) were reported and their clinical presentation and outcome were evaluated. They were all children and teenagers with ages ranging from 3 to 16 years, and there was a slight female predominance. Nine cases showed evidence of disseminated intravascular coagulation at diagnosis or during the course of the disease. Twelve cases also demonstrated hypercalcemia in their laboratory tests. Almost all of them died due to relapse of leukemia or post-chemotherapy infection [14].
Our case had some features of both t(9;22) and t(17;19). The present case was an adult who had remarkable leukocytosis and splenomegaly which are all common in Philadelphia positive acute lymphoblastic leukemia and rare in t(17;19). On the other hand, he also had disseminated intravascular coagulation, which is a feature of t(17;19). We reviewed the literature and found only one case of Philadelphia positive adult lymphoblastic leukemia with t(17;19) whose clinical presentation was relatively similar to ours. That case was a 44-year-old woman with weakness, splenomegaly and leukocytosis [3]. These findings show that coincidence of t(17;19) and t(9;22) tends to be seen in adults rather than children and may be associated with remarkable leukocytosis and splenomegaly in addition to disseminated intravascular coagulation or hypercalcemia. Glover et al. [15] exhibited
No potential conflicts of interest relevant to this article were reported.
Bone marrow karyotype exhibited t(17;19)(q11;p13) in addition to Philadelphia chromosome and unbalanced translocation between chromosomes 3 and 9.
Blood Res 2018; 53(1): 92-94
Published online March 31, 2018 https://doi.org/10.5045/br.2018.53.1.92
Copyright © The Korean Society of Hematology.
Moeinadin Safavi1,2,3*, Akbar Safaei1, and Mahnaz Lotfi4
1Department of Molecular Pathology and Cytogenetic, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
2Department of Molecular Pathology and Cytogenetic, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
3Department of Pathology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
4Department of Hemato-Oncology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Correspondence to:Moeinadin Safavi. Department of Molecular Pathology and Cytogenetics, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, Iran. safavi_moeinadin@yahoo.com, safavi@sums.ac.ir
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
On the other hand, t(17;19)(q22;p13) is a very rare translocation in acute lymphoblastic leukemia that is associated with an extremely poor prognosis. Coexistence of t(17;19)(q22;p13) with Philadelphia chromosome has only been reported once in the literature [3].
A 41-year-old man was admitted to hospital due to bone pain and abdominal discomfort. Pallor and splenomegaly were the only two abnormal findings on physical examination. Laboratory tests showed prominent leukocytosis, anemia and thrombocytopenia (white blood cell count=170,000/µL, hemoglobin=9.2 g/dL, platelet count= 30,000/µL). Flow cytometry of bone marrow aspiration revealed 80% blast cells with B cell precursor phenotype expressing HLA-DR, CD19, CD10, CD22, tdt, CD20. Bone marrow cytogenetic study with Giemsa banding method exhibited 45XY t(9;22) (q34;q11) de(3) der(9) t(3;9)(q11;q13) del3(q10) t(17;19)(q11;p13) (Fig. 1). Reverse transcription polymerase chain reaction was performed on a bone marrow specimen which also revealed m-bcr-abl1 fusion gene (p 190).
During hospitalization, the patient had an episode of epistaxis and his coagulation tests showed prolonged prothrombin time (PT=19.2 sec, normal range, 11–13 sec), partial thromboplastin time (PTT=42.5 sec, normal range, 25–35 sec) and low fibrinogen level (fibrinogen=92 mg/dL, normal range, 200–400 mg/dL). Thus, he underwent treatment with fresh frozen plasma till the symptoms resolved and the fibrinogen level reached beyond 100 mg/dL. He also received induction chemotherapy with Hyper CVAD chemotherapy regimen including cycles A and B. During cycle A, he took 1) cyclophosphamide with Mesna 500 mg IV on the first 3 days, 2) vincristine 2 mg IV on days 4 and 11, 3) adryamycin 50 mg on day 4, and 4) dexamethasone 40 mg on days 1 to 4 and 11 to 14. Three weeks later cycle B was initiated with the following combination: 1) methotrexate IV infusion 1,600 mg on the first day, 2) folinic acid 30 mg every 6 hours for 8 doses, 3) cytarabine 3,000 mg every 12 hours for 4 doses on 2nd and 3rd days, and 3) methylprednisolone 30 mg twice daily for 6 doses on days 1, 2 and 3. Imatinib (600 mg daily) was also added to his regimen after the detection of Philadelphia chromosome. Meanwhile, the patient received 12 mg intrathecal methotrexate weekly. Unfortunately, the patient's peripheral smear showed prominent leukocytosis (white blood cell count=140,000/µL) with 80% blast cells after completion of hyper-CVAD regimen (four courses of cycle A and B). Then he became candidate for bone marrow transplantation after salvage chemotherapy but he refused to receive salvage chemotherapy regimen. Therefore, there was no remedy but to continue treatment with 6-mercaptopurine (50 mg three times daily), methotrexate (15 mg weekly), vincristine (2 mg monthly) and another tyrosine kinase inhibitor, nilotinib (400 mg daily). Subsequent peripheral blood smear showed no blast cells and complete blood count yielded the following: white blood cells=2,500/µL, hemoglobin=10 g/dL and platelets=25,000/µL.
The Philadelphia chromosome was the first chromosomal aberration found to be associated with malignancy [4]. In fact, it is a diminutive chromosome 22 derived from t(9;22)(q34;q11). This translocation can result in three differently sized fusion products: p190, p210 and rarely p230. This fusion gene has a tyrosine kinase activity and occurs in chronic myelogenous leukemia, acute biphenotypic leukemia, and acute lymphoblastic leukemia. It has recently been discovered that an intragenic deletion of the
t(17;19)(q22;p13) is an extremely rare translocation with an estimated incidence of 0.1% [4]. Among 9,000 acute lymphoblastic leukemia trial patients in the Leukemia Research Cytogenetic Group Survey, only 9 had t(17;19) (q22;p13). Their ages ranged from 5 to 18 years with a median age of 13 years. Acute lymphoblastic leukemia patients had a B-cell precursor phenotype and none of them had remarkable leukocytosis (50×109/L) [9]. It is supposed to be a variant of t(1;19)(q23;p13) and results in fusion of the
In a recent review of the literature, 21 cases with t(17;19)(q22;p13) were reported and their clinical presentation and outcome were evaluated. They were all children and teenagers with ages ranging from 3 to 16 years, and there was a slight female predominance. Nine cases showed evidence of disseminated intravascular coagulation at diagnosis or during the course of the disease. Twelve cases also demonstrated hypercalcemia in their laboratory tests. Almost all of them died due to relapse of leukemia or post-chemotherapy infection [14].
Our case had some features of both t(9;22) and t(17;19). The present case was an adult who had remarkable leukocytosis and splenomegaly which are all common in Philadelphia positive acute lymphoblastic leukemia and rare in t(17;19). On the other hand, he also had disseminated intravascular coagulation, which is a feature of t(17;19). We reviewed the literature and found only one case of Philadelphia positive adult lymphoblastic leukemia with t(17;19) whose clinical presentation was relatively similar to ours. That case was a 44-year-old woman with weakness, splenomegaly and leukocytosis [3]. These findings show that coincidence of t(17;19) and t(9;22) tends to be seen in adults rather than children and may be associated with remarkable leukocytosis and splenomegaly in addition to disseminated intravascular coagulation or hypercalcemia. Glover et al. [15] exhibited
No potential conflicts of interest relevant to this article were reported.
Bone marrow karyotype exhibited t(17;19)(q11;p13) in addition to Philadelphia chromosome and unbalanced translocation between chromosomes 3 and 9.
Bone marrow karyotype exhibited t(17;19)(q11;p13) in addition to Philadelphia chromosome and unbalanced translocation between chromosomes 3 and 9.