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Chung, Chi, Seo, Jang, Park, and Lee: Erythroleukemic Blast Crisis of Chronic Myeloid Leukemia
Original Article

Korean J Leg Med 2006;26(4):255-262.

Published online: 10 February 2006

DOI: https://doi.org/10.3343/kjlm.2006.26.4.255

Erythroleukemic Blast Crisis of Chronic Myeloid Leukemia

Hee-Jung Chung, M.D.1, Hyun-sook Chi, M.D.1, Eul Ju Seo, M.D.1, Seongsoo Jang, M.D.1, Chan Jeoung Park, M.D.1, Kyoo-Hyung Lee, M.D.2

1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea

2Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea

Received 14 March 2006       Revised 27 July 2006       Accepted 2 August 2006

Copyright © 2006 The Korean Society for Legal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Erythroleukemic blast crisis of chronic myeloid leukemia (CML) is very rare. We report two cases of erythroleukemic blast crisis of CML resistant to imatinib treatment. Both patients made a rapid progression to blast crisis 6 and 4 months after diagnosis while being treated with imatinib 400 mg/day. Bone marrow aspiration revealed predominant erythroid precursors with 65.4% and 54.8% each. There were significant proportions (more than 20%) of myeloblasts among non-erythroid cells. Immunophenotyping revealed expression of glycophorin A confirming erythroleukemic blast crisis. The karyotyping result of patient 1 was 46,XX,t(9;22)(q34;q11.2)[3]/52,idem,+8,+12,+18,+21,+22,+ der(22)t(9;22)[17] and that of patient 2 was 46,XX,inv(3)(q21q26.2),t(9;22)(q34;q11.2)[20]. Patient 1 showed no response to imatinib and BMS-354825 in the following bone marrow study. She died of septic shock as a complication of an infection after 69 days of blast crisis. Patient 2 received allogeneic bone marrow transplantation (BMT) in the cytogenetically no response state, but she also died of graft-versus-host disease 9 weeks after BMT. The poor prognosis and rapid progression of disease in both cases were correspondent to most of the reported cases. During the course of the disease of the two patients, we monitored the BCR-ABL chimeric mRNA with real-time quantitative polymerase chain reaction (RT-PCR), and it was found useful in predicting the imatinib response and progression to blast crisis of CML. Although both of our cases showed the typical bad prognosis and findings of erythroleukemic blast crisis of CML, the karyotypes were different from the expected type of t(3;21)(q26;q22). But the relationship between additional changes of EVI1 on chromosome 3q26 shown in case 2, and progression to the erythroleukemic blast crisis need further investigation.

Keywords: Chronic myeloid leukemia, Erythroleukemic blast crisis, Imatinib resistance

References

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Fig. 1.
Hematologic findings at erythroleukemic blast crisis in patient 1 [(A) PB ×1,000 Wright stain, (B) BM biopsy ×200 Hematoxylineosin stain, (C) BM smear ×1,000 Wright stain, (D) BM smear, ×1,000 Periodic acid-Schiff stain]. Leukemic blasts show large size, high N/C ratio, round nucleus with fine nuclear chromatin, 2–4 large prominent nucleoli, basophilic cytoplasm with perinuclear halo and occasional small cytoplasmic vacuoles.
kjlm-26-255f1.tif
Fig. 2.
Hematologic findings at erythroleukemic blast crisis in patient 2 [(A) PB ×1,000 Wright stain, (B) BM biopsy ×200 Hematoxylineosin stain, (C) BM smear ×1,000 Wright stain, (D) BM smear, ×1,000 Periodic acid-Schiff stain]. Leukemic blasts show large size, high N/C ratio, round nucleus with fine nuclear chromatin, 1–2 large prominent nucleoli and basophilic cytoplasm with perinuclear halo.
kjlm-26-255f2.tif
Fig. 3.
Immunophenotyping of blasts at erythroleukemic blast crisis. (A) Blasts of patient 1 express glycophorin A and coexpression of CD13 and CD7. (B) Blasts of patient 2 coexpress glycophorin A and CD33.
kjlm-26-255f3.tif
Fig. 4.
Karyotyping at Erythroleukemic Blast crisis. (A) 46,XX,t(9;22)(q34;q11.2)[3]/52,idem,+8,+12,+18,+21,+22,+der(22)t(9;22)[17] in patient 1. (B) 46,XX,inv(3)(q21q26.2),t(9;22)(q34;q11.2)[20] in patient 2.
kjlm-26-255f4.tif
Fig. 5.
Quantitation of BCR-ABL chimeric mRNA compared with percentage of total blasts of bone marrow nucleated cells in patient 1.
kjlm-26-255f5.tif
Table 1.
Laboratory data of patient on days of treatment in patient 1
Days of treatment Diagnosis PB
 BM
 BCR-ABL chimeric mRNA quantitative PCR (ratio of BCR-ABL/G6PDH) Karyotyping with BM aspirates
WBC (×109/L) Hb (g/dL) Platelet (×109/L) Meloid precursor (%) Blast (%) Cellularity (%) Blast (%)
D1 CML-CP 5.2 9.5 37 3 6     0.129 (PB) 46,XX,t(9;22)(q34;q11.2)[20]
D80   9.3 9.5 24 4 5     0.258 (PB)  
D161 CML-BC 8.8 11.6 19 5 3 95 62.4 1.409 (BM) 46,XX,t(9;22)(q34;q11.2)[3]/52,idem,+8,+12,+18,+21, +22,+der(22)t(9;22)[17]
D170   120.9 10.4 23 62 1     NT  
D198   3.6 8.5 21 5 4 70 11.8 0.361 (BM) 46,XX,t(9;22)(q34;q11.2)[2]/52,idem,+8,+12,+18,+21, +22,+der(22)t(9;22)[18]
D203 Imatinib resistant CML 2.8 11.6 14 9 3     NT  
D217 BMS-354825 resistant CML 33.7 11.1 38 53 1 70 84.8 1.182 (BM) 52,idem,+8,+12,+18,+21, +22,+der(22)t(9;22)[20]
D230 BMS-354825 resistant CML 9.9 10.7 22 35 1 40 44.4 NT 46,XX,t(9;22)(q34;q11.2)[3]/52,idem,+8,+12,+18,+21,+22,+der(22)t(9;22)[17]

Abbreviations: CML, chronic myeloid leukemia; CP, chronic phase; AP, accelerated phase; BC, blast crisis; PB, peripheral blood; BM, bone marrow; NR, no response; NT, not tested.

Table 2.
Laboratory data of patient on days of treatment in patient 2
Day of treatment Diagnosis PB
 BM
 BCR-ABL chimeric mRNA quantitative PCR Karyotyping with BM aspirates
WBC (×109/L) Hb (g/dL) Platelet (×109/L) Meloid precursor (%) Blast (%) Cellularity (%) Blast (%)
D1 CML-CP 3.8 10.5 26 0 0 35 0.4 0.148 (PB) 46,XX,inv(3)(q21q26.2),t(9;22) (q34;q11.2)[20]
D65 CML-AP 3.4 9.4 15 0 0   12.0 0.122 (PB)  
D129 CML-BC 2.3 9.0 26 1 0 35 62.4 0.131 (BM) 46,XX,inv(3)(q21q26.2),t(9;22) (q34;q11.2)[20]

Abbreviations: CML, chronic myeloid leukemia; CP, chronic phase; AP, accelerated phase; BC, blast crisis; PB, peripheral blood; BM, bone marrow; NR, no response; NT, not tested.

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