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Acute promyelocytic leukemia with tetraploid karyotype: First report in the Western hemisphere and update of previous reports
Leukemia Research 35 (2011) e93–e95
Contents lists available at ScienceDirect
Leukemia Research journal homepage: www.elsevier.com/locate/leukres
Letter to the Editor Acute promyelocytic leukemia with tetraploid karyotype: First report in the Western hemisphere and update of previous reports 1. Introduction Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21) cytogenetic abnormality in the majority of cases. Additional cytogenetic abnormalities are observed in 35–45% of cases and include +8, del (9q) and ider(17)(q10)t(15;17) [1]. Tetraploidy has only been reported in 11 cases of APL in the literature, with all cases being reported from the Far East (5 Japanese, 5 Chinese, and 1 Korean) [2–8]. To date no case has been reported in the Western hemisphere. Currently we report a case of acute promyelocytic leukemia with tetraploidy in United States and update the outcome of previously reported cases. 2. Materials and methods A literature review demonstrated 11 prior case reports of APL with tetraploidy. Two patients had died at the time of their report. We were able to update the outcomes of 4 previously reported patients (Table 2). Disease-free survival was defined as the time from attainment of a complete remission (CR) to relapse or death. Overall survival was defined as the time from APL diagnosis until death from any cause or date of last survival update. Kaplan–Meier survival curves were created using GraphPad Prism 5 (GraphPad Software, La Jolla, CA).
3. Results The patient is 48 year old man who presented with upper respiratory symptoms and fatigue for 1 month. The patient is of Eastern European descent (Polish and Czech). Upon admission the white blood count was 1700/mm3 with 63% neutrophils, 35% lymphocytes and 2% monocytes. The hemoglobin was 11.1 g/dl and the platelet count was 147,000/mm3 . The PT and PTT were 10.9 and 28.5 s and the fibrinogen was 252 mg/dl. The bone marrow was 50–60% cellular with numerous large promyelocytes (14%) that contained irregular bilobed nuclei, abundant cytoplasm with granularity and numerous Auer Rods. Erythroid precursors were relatively increased with nuclear:cytoplasmic dyssynchrony and occasional dyspoietic forms. Flow cytometry showed a population of large immature CD13+, CD33+, CD34−, CD117+, HLA-DR−, CD2−, CD56− cells that were strictly in the granulocyte gate by CD45/side scatter (i.e. moderate CD45, high SSC). Cytogenetics showed a tetraploid karyotype in 7 of 20 metaphases as follows: 92,XXYY,t(15;17) (q22;q21)X2[4]/92,XXYY,add(5)(q22),t(15;17)(q22;q21)X2[3]/46, XY[13]. The patient received idarubicin 12 mg/m2 for 3 days, cytarabine 100 mg/m2 IV over 24 h daily times 7 days and all-trans retinoic acid (ATRA) 45 mg/m2 daily until he obtained a CR. He subsequently received 2 courses of consolidation therapy with idarubicin (12 mg/m2 daily for 2 days), cytarabine (100 mg/m2 for 5 days) and ATRA (45 mg/m2 daily). He then received arsenic 0145-2126/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2011.01.028
0.15 mg/kg/day 5 days a week plus ATRA for two 5 week courses. Currently the patient is well in complete remission receiving maintenance therapy with ATRA, mercaptopurine and methotrexate eight months after his original diagnosis. The baseline characteristics and the updated treatment outcomes of the 12 reported cases are summarized in Tables 1 and 2, respectively. The median age is 49 years (range 21–68). All cases except one were male. Of the 6 patients with a reported baseline CBC, all patients presented with pancytopenia. Eleven cases reported flow cytometry results. All cases were CD33+, 9 were CD13+, 6 were CD2+, 2 were CD117+, 2 were CD34+ (both of whom were also CD2+) and 1 was HLA-DR+. Not all antigens were reported on all cases. Of the 12 total cases five cases had additional cytogenetic abnormalities [our case: add(5)(q22), one case: del(2)(q?), one case -16,-16, two cases: complex abnormalities]. Patients received a variety of regimens from ATRA alone, to combinations of ATRA plus arsenic and/or chemotherapy (Table 2). Two patients expired early (days 5 and 16, respectively) with evidence of persistent leukemia in the peripheral blood. Both of these cases were CD2+, an immunophenotype which has been associated with a poor prognosis in APL [9]. The estimated disease free survival at 60 months is 68.6%. The estimated overall survival at 60 months is 83.3% and at 120 months is 66.7%.
4. Discussion Tetraploidy is rare in acute myelogenous leukemia and is especially rare in acute promyelocytic leukemia. Although the sample size is small, there appeared to be some differences in the baseline characteristics of patients with APL and tetraploidy compared to those without tetraploidy reported in the literature. Eleven of 12 patients with tetraploidy were male in contrast to literature reports of an equal male/female distribution in non-tetraploid APL [10]. The frequency of CD2 expression (at least 6 of 12 current cases) also appeared increased compared with the literature reported incidence of 10–20% [9]. On the other hand, the incidence of secondary cytogenetic abnormalities is comparable for that reported for nontetraploid APL (32%) [1]. The estimated disease free survival at 60 months of 68.6% and the estimated overall survival at 60 months of 83.3% is comparable to that reported in patients with APL without tetraploidy [10]. In a previous CALGB trial of patients with APL who were treated with chemotherapy the presence of additional cytogenetic abnormalities was associated with a longer CR duration and event free survival, but no difference in overall survival [1]. None of the patients on that trial had tetraploidy.
Conflict of interest statement There are no relevant conflicts of interest for any of the authors.
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Letter to the Editor / Leukemia Research 35 (2011) e93–e95
Table 1 Diagnostic evaluation of cases. Case
Age/sex
W/H/P
Immunophenotype
Karyotype
Current
48/M
1.7/11.1/147
CD13+, CD33+, CD34−, CD117+, HLA-DR−, CD2−, CD56−
Morita et al. [6]
50/M
1.7/7.3/107
CD2+, CD13+, CD33+CD34+HLA-DR+
Au et al. [3]
24/M
1.6/7.9/32
CD2+, CD13+, CD33+
Kojima et al. [3] Kuyama et al. [6] Pan et al. [8]
53/M 56/M
0.5/9.3/118 NR
21/M
NR
Pan et al. [8] Pan et al. [8] Pan et al. [8] Pan et al. [8] Kaito et al. [7]
26/M 68/M 40/M 38/M 56/M
NR NR NR NR 0.8/12.0/21
Oh et al. [4]
50/F
1.7/9.3/12
NR CD2−, CD13+, CD33+, CD34−, CD56−, HLA-DR− CD2+, CD13+, CD15+CD33+, CD117+ CD2+, CD13+, CD33+ CD13+, CD33+ CD13+, CD33+ CD33+ CD2+, CD13+, CD33+, CD34+, CD56+, HLA-DR− CD2+, CD13+, CD33+, CD34-CD56−, HLA-DR−
92,XXYY,t(15;17)(q22;q21)x2[4]/ 92,XXYY,add(5)(q22),t(15;17) (q22;q21)x2[3]/46,XY[13] 45,XY,add(1)(p36),−9,der(15)t(15;17),−17, add(20)(q13),−21,+mar1,+mar2[2]/ 46,idem,+mar3[6]/45,idem,del(11) (p11),add(13)(p11),+18,+21,−mar1,−mar2[2]/ 86,XX,−Y,−Y,add(6)(p21) × 2,−8,−9,−11,−12, der(15)t(15;17) × 2,−16,−17,−17,+18,−19,+mar4, +mar5[2]/46,XY[5] 73∼89,XXY,−Y[3],−3[10],−5[9],−7[4],−9[7], −11[9],−14[10],−15[9],t(15;17)[10],t(15;17)[4], der(15)t(15;17)[4],−17[8], −18[7],−19[9],−20[3], +mar1[9],+mar2 × 2[10],+mar3[7][cp10]/46,XY[6] 92,XXYY,del(2)(q?),t(15;17)(q22;q21)x2[4]/46,XY[16] 90[1/6]/91[1/6]/92,XXYY,t(15;17)(q22;q12) × 2,-16,-16,+2mar [4/6] 46,XY,t(15;17)[3]/|92,XXYY,t(15;17)x2[6]/|46,XY[1] 92,XXYY,t(15;17)x2[10] 92,XXYY,t(15;17)x2[5]/|46,XY[5] 92,XXYY,t(15;17)x2[10] 92,XXYY,t(15;17)x2[18]/|46,XY[2] 92,XXYY,t(15;17)x2[20] 92,XXYY,t(15;17)x2[20]
W/H/P: white blood count × 103 , Hgb g/dl and platelets × 103 ; NR: not reported. Table 2 Treatment outcome and updated results of prior reportsa . Case
Age/sex
Treatment
Outcome
Current
48/M
CR 8 + months
Moritaa et al. [6]
50/M
Ida + AraC + ATRA × 3 Arsenic + ATRA × 2 6-MP + MTX + ATRA ongoing ATRA, then AraC + Mito + VP-16 ATRA + Ida then Ida, Mito ATRA + Ida Arsenic Arsenic + ATRA, then AraC + VP-16 + VDS
Aua et al. [2]
24/M
Kojimaa et al. [3] Kuyamaa et al. [6] Pan et al. [8] Pan et al. [8] Pan et al. [8] Pan et al. [8] Pan et al. [8] Kaito et al. [7] Oh et al. [4]
53/M 56/M 21/M 26/M 68/M 40/M 38/M 56/M 50/F
ATRA then Dauno + AraC ATRA + AraC + Mito JALSG-APL97 JALSG-APL97 Arsenic Arsenic + ATRA Arsenic + ATRA ATRA ATRA ATRA ATRA + AraC + Dauno
CR 10 months CR 11 + years CR 96 + months CR 101 + months CR 6 + months CR 2.5 + months CR 12 + months CR 48 + months CR 120 + months No response, expired day 5 No response, expired day 16
CR 22 months CR 13 months CR 4 months CR 16 months CR 13 months Expired in relapse 80 months from Dx
Ida: idarubicin; AraC: cytarabine; ATRA: all trans retinoic acid; 6-MP: mercaptopurine; MTX: methotrexate; Dauno: daunorubicin; Mito: mitoxantrone; VP-16: etoposide. a Results updated from original report; Dx: diagnosis.
Acknowledgements There was no financial support of this report. Contributions. PMR, DL, KK, OM, JK and WA provided data review, manuscript preparation; JW provided pathology, manuscript preparation and KS provided design of study, data review, manuscript preparation. References [1] Slack JL, Arthur DC, Lawrence D, Mrózek K, Mayer RJ, Davey FR, et al. Secondary cytogenetic changes in acute promyelocytic leukemia—prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: a Cancer and Leukemia Group B study. J Clin Oncol 1997;15:1786–95.
[2] Au WY, Ma SK, Lam CCK, Chan LC, Kwong YL. Tetraploid acute promyelocytic leukemia with large bizarre blast cell morphology. Cancer Genet Cytogenet 1999;115:52–5. [3] Kojima K, Imaoka M, Noguchi T, Narumi H, Uchida N, Sakai I, et al. Hypocellular acute promyelocytic leukemia with a tetraploid clone characterized by two t(15;17). Cancer Genet Cytogenet 2003;145:169–71. [4] Oh SH, Park TS, Kim HH, Chang CL, Lee EY, Son HC, et al. Tetraploid acute promyelocytic leukemia with double t(15;17) and PML/RARA rearrangements detected by fluorescence in situ hybridization analysis. Cancer Genet Cytogenet 2003;145:49–53. [5] Morita Y, Takahashi A, Yamamoto K, Miki T, Murakami N, Miura O. Secondary near-tetraploidy with double der(15)t(15;17) in acute promyelocytic leukemia in relapse. Cancer Genet Cytogenet 2004;149:131– 6. [6] Kuyama J, Tsumori Y, Aoyama K, Kosugi S, Take H, Matsuyama T. Tetraploid acute promyelocytic leukemia with double PML/RARA gene rearrangements successfully treated with all-trans retinoic acid. Int J Hematol 2004;79:405– 6.
Letter to the Editor / Leukemia Research 35 (2011) e93–e95 [7] Kaito K, Otsubo H, Dobashi N, Usui N, Kobayashi M. CD2+ tetraploid acute promyelocytic leukemia variant with double (15;17) translocations. Int J Hematol 2005;81:29–31. [8] Pan JI, Xue YI, Qiu H, Wu Y, Wang Y, Zhang J, et al. Tetraploid clone characterized by two t(15;17) in five cases of acute promyelocytic leukemia. Cancer Genet Cytogenet 2009;188:57–9. [9] Kaito K, Katayama T, Masuoka H, Nishiwaki K, Sano K, Sekiguchi N, et al. CD2+ acute promyelocytic leukemia is associated with leukocytosis, variant morphology and poorer prognosis. Clin Lab Haematol 2005;27:307–11. [10] Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, et al. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood 2010;116:3751–7.
Pavan Mahendra Ravella Delong Liu Department of Medicine, New York Medical College, Valhalla, NY, USA Kensuke Kojima MD Anderson Cancer Center, Houston, TX, USA James Weisberger BioReference Laboratories, Elmwood Park, NJ, USA
e95
Osamu Miura Tokyo Medical and Dental University, Tokyo, Japan Jun Kuyama KKR Otemae Hospital, Osaka, Japan Wing Au Queen Mary Hospital, Hong Kong, Hong Kong Karen Seiter ∗ Department of Medicine, New York Medical College, Valhalla, NY, USA ∗ Corresponding author at: Department of Medicine, New York Medical College, Room 250 Munger Pavilion, Valhalla, NY 10595, USA. Tel.: +1 914 493 7514; fax: +1 914 594 4420. E-mail address: karen [email protected] (K. Seiter)
3 January 2011 Available online 25 February 2011
Contents lists available at ScienceDirect
Leukemia Research journal homepage: www.elsevier.com/locate/leukres
Letter to the Editor Acute promyelocytic leukemia with tetraploid karyotype: First report in the Western hemisphere and update of previous reports 1. Introduction Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21) cytogenetic abnormality in the majority of cases. Additional cytogenetic abnormalities are observed in 35–45% of cases and include +8, del (9q) and ider(17)(q10)t(15;17) [1]. Tetraploidy has only been reported in 11 cases of APL in the literature, with all cases being reported from the Far East (5 Japanese, 5 Chinese, and 1 Korean) [2–8]. To date no case has been reported in the Western hemisphere. Currently we report a case of acute promyelocytic leukemia with tetraploidy in United States and update the outcome of previously reported cases. 2. Materials and methods A literature review demonstrated 11 prior case reports of APL with tetraploidy. Two patients had died at the time of their report. We were able to update the outcomes of 4 previously reported patients (Table 2). Disease-free survival was defined as the time from attainment of a complete remission (CR) to relapse or death. Overall survival was defined as the time from APL diagnosis until death from any cause or date of last survival update. Kaplan–Meier survival curves were created using GraphPad Prism 5 (GraphPad Software, La Jolla, CA).
3. Results The patient is 48 year old man who presented with upper respiratory symptoms and fatigue for 1 month. The patient is of Eastern European descent (Polish and Czech). Upon admission the white blood count was 1700/mm3 with 63% neutrophils, 35% lymphocytes and 2% monocytes. The hemoglobin was 11.1 g/dl and the platelet count was 147,000/mm3 . The PT and PTT were 10.9 and 28.5 s and the fibrinogen was 252 mg/dl. The bone marrow was 50–60% cellular with numerous large promyelocytes (14%) that contained irregular bilobed nuclei, abundant cytoplasm with granularity and numerous Auer Rods. Erythroid precursors were relatively increased with nuclear:cytoplasmic dyssynchrony and occasional dyspoietic forms. Flow cytometry showed a population of large immature CD13+, CD33+, CD34−, CD117+, HLA-DR−, CD2−, CD56− cells that were strictly in the granulocyte gate by CD45/side scatter (i.e. moderate CD45, high SSC). Cytogenetics showed a tetraploid karyotype in 7 of 20 metaphases as follows: 92,XXYY,t(15;17) (q22;q21)X2[4]/92,XXYY,add(5)(q22),t(15;17)(q22;q21)X2[3]/46, XY[13]. The patient received idarubicin 12 mg/m2 for 3 days, cytarabine 100 mg/m2 IV over 24 h daily times 7 days and all-trans retinoic acid (ATRA) 45 mg/m2 daily until he obtained a CR. He subsequently received 2 courses of consolidation therapy with idarubicin (12 mg/m2 daily for 2 days), cytarabine (100 mg/m2 for 5 days) and ATRA (45 mg/m2 daily). He then received arsenic 0145-2126/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2011.01.028
0.15 mg/kg/day 5 days a week plus ATRA for two 5 week courses. Currently the patient is well in complete remission receiving maintenance therapy with ATRA, mercaptopurine and methotrexate eight months after his original diagnosis. The baseline characteristics and the updated treatment outcomes of the 12 reported cases are summarized in Tables 1 and 2, respectively. The median age is 49 years (range 21–68). All cases except one were male. Of the 6 patients with a reported baseline CBC, all patients presented with pancytopenia. Eleven cases reported flow cytometry results. All cases were CD33+, 9 were CD13+, 6 were CD2+, 2 were CD117+, 2 were CD34+ (both of whom were also CD2+) and 1 was HLA-DR+. Not all antigens were reported on all cases. Of the 12 total cases five cases had additional cytogenetic abnormalities [our case: add(5)(q22), one case: del(2)(q?), one case -16,-16, two cases: complex abnormalities]. Patients received a variety of regimens from ATRA alone, to combinations of ATRA plus arsenic and/or chemotherapy (Table 2). Two patients expired early (days 5 and 16, respectively) with evidence of persistent leukemia in the peripheral blood. Both of these cases were CD2+, an immunophenotype which has been associated with a poor prognosis in APL [9]. The estimated disease free survival at 60 months is 68.6%. The estimated overall survival at 60 months is 83.3% and at 120 months is 66.7%.
4. Discussion Tetraploidy is rare in acute myelogenous leukemia and is especially rare in acute promyelocytic leukemia. Although the sample size is small, there appeared to be some differences in the baseline characteristics of patients with APL and tetraploidy compared to those without tetraploidy reported in the literature. Eleven of 12 patients with tetraploidy were male in contrast to literature reports of an equal male/female distribution in non-tetraploid APL [10]. The frequency of CD2 expression (at least 6 of 12 current cases) also appeared increased compared with the literature reported incidence of 10–20% [9]. On the other hand, the incidence of secondary cytogenetic abnormalities is comparable for that reported for nontetraploid APL (32%) [1]. The estimated disease free survival at 60 months of 68.6% and the estimated overall survival at 60 months of 83.3% is comparable to that reported in patients with APL without tetraploidy [10]. In a previous CALGB trial of patients with APL who were treated with chemotherapy the presence of additional cytogenetic abnormalities was associated with a longer CR duration and event free survival, but no difference in overall survival [1]. None of the patients on that trial had tetraploidy.
Conflict of interest statement There are no relevant conflicts of interest for any of the authors.
e94
Letter to the Editor / Leukemia Research 35 (2011) e93–e95
Table 1 Diagnostic evaluation of cases. Case
Age/sex
W/H/P
Immunophenotype
Karyotype
Current
48/M
1.7/11.1/147
CD13+, CD33+, CD34−, CD117+, HLA-DR−, CD2−, CD56−
Morita et al. [6]
50/M
1.7/7.3/107
CD2+, CD13+, CD33+CD34+HLA-DR+
Au et al. [3]
24/M
1.6/7.9/32
CD2+, CD13+, CD33+
Kojima et al. [3] Kuyama et al. [6] Pan et al. [8]
53/M 56/M
0.5/9.3/118 NR
21/M
NR
Pan et al. [8] Pan et al. [8] Pan et al. [8] Pan et al. [8] Kaito et al. [7]
26/M 68/M 40/M 38/M 56/M
NR NR NR NR 0.8/12.0/21
Oh et al. [4]
50/F
1.7/9.3/12
NR CD2−, CD13+, CD33+, CD34−, CD56−, HLA-DR− CD2+, CD13+, CD15+CD33+, CD117+ CD2+, CD13+, CD33+ CD13+, CD33+ CD13+, CD33+ CD33+ CD2+, CD13+, CD33+, CD34+, CD56+, HLA-DR− CD2+, CD13+, CD33+, CD34-CD56−, HLA-DR−
92,XXYY,t(15;17)(q22;q21)x2[4]/ 92,XXYY,add(5)(q22),t(15;17) (q22;q21)x2[3]/46,XY[13] 45,XY,add(1)(p36),−9,der(15)t(15;17),−17, add(20)(q13),−21,+mar1,+mar2[2]/ 46,idem,+mar3[6]/45,idem,del(11) (p11),add(13)(p11),+18,+21,−mar1,−mar2[2]/ 86,XX,−Y,−Y,add(6)(p21) × 2,−8,−9,−11,−12, der(15)t(15;17) × 2,−16,−17,−17,+18,−19,+mar4, +mar5[2]/46,XY[5] 73∼89,XXY,−Y[3],−3[10],−5[9],−7[4],−9[7], −11[9],−14[10],−15[9],t(15;17)[10],t(15;17)[4], der(15)t(15;17)[4],−17[8], −18[7],−19[9],−20[3], +mar1[9],+mar2 × 2[10],+mar3[7][cp10]/46,XY[6] 92,XXYY,del(2)(q?),t(15;17)(q22;q21)x2[4]/46,XY[16] 90[1/6]/91[1/6]/92,XXYY,t(15;17)(q22;q12) × 2,-16,-16,+2mar [4/6] 46,XY,t(15;17)[3]/|92,XXYY,t(15;17)x2[6]/|46,XY[1] 92,XXYY,t(15;17)x2[10] 92,XXYY,t(15;17)x2[5]/|46,XY[5] 92,XXYY,t(15;17)x2[10] 92,XXYY,t(15;17)x2[18]/|46,XY[2] 92,XXYY,t(15;17)x2[20] 92,XXYY,t(15;17)x2[20]
W/H/P: white blood count × 103 , Hgb g/dl and platelets × 103 ; NR: not reported. Table 2 Treatment outcome and updated results of prior reportsa . Case
Age/sex
Treatment
Outcome
Current
48/M
CR 8 + months
Moritaa et al. [6]
50/M
Ida + AraC + ATRA × 3 Arsenic + ATRA × 2 6-MP + MTX + ATRA ongoing ATRA, then AraC + Mito + VP-16 ATRA + Ida then Ida, Mito ATRA + Ida Arsenic Arsenic + ATRA, then AraC + VP-16 + VDS
Aua et al. [2]
24/M
Kojimaa et al. [3] Kuyamaa et al. [6] Pan et al. [8] Pan et al. [8] Pan et al. [8] Pan et al. [8] Pan et al. [8] Kaito et al. [7] Oh et al. [4]
53/M 56/M 21/M 26/M 68/M 40/M 38/M 56/M 50/F
ATRA then Dauno + AraC ATRA + AraC + Mito JALSG-APL97 JALSG-APL97 Arsenic Arsenic + ATRA Arsenic + ATRA ATRA ATRA ATRA ATRA + AraC + Dauno
CR 10 months CR 11 + years CR 96 + months CR 101 + months CR 6 + months CR 2.5 + months CR 12 + months CR 48 + months CR 120 + months No response, expired day 5 No response, expired day 16
CR 22 months CR 13 months CR 4 months CR 16 months CR 13 months Expired in relapse 80 months from Dx
Ida: idarubicin; AraC: cytarabine; ATRA: all trans retinoic acid; 6-MP: mercaptopurine; MTX: methotrexate; Dauno: daunorubicin; Mito: mitoxantrone; VP-16: etoposide. a Results updated from original report; Dx: diagnosis.
Acknowledgements There was no financial support of this report. Contributions. PMR, DL, KK, OM, JK and WA provided data review, manuscript preparation; JW provided pathology, manuscript preparation and KS provided design of study, data review, manuscript preparation. References [1] Slack JL, Arthur DC, Lawrence D, Mrózek K, Mayer RJ, Davey FR, et al. Secondary cytogenetic changes in acute promyelocytic leukemia—prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: a Cancer and Leukemia Group B study. J Clin Oncol 1997;15:1786–95.
[2] Au WY, Ma SK, Lam CCK, Chan LC, Kwong YL. Tetraploid acute promyelocytic leukemia with large bizarre blast cell morphology. Cancer Genet Cytogenet 1999;115:52–5. [3] Kojima K, Imaoka M, Noguchi T, Narumi H, Uchida N, Sakai I, et al. Hypocellular acute promyelocytic leukemia with a tetraploid clone characterized by two t(15;17). Cancer Genet Cytogenet 2003;145:169–71. [4] Oh SH, Park TS, Kim HH, Chang CL, Lee EY, Son HC, et al. Tetraploid acute promyelocytic leukemia with double t(15;17) and PML/RARA rearrangements detected by fluorescence in situ hybridization analysis. Cancer Genet Cytogenet 2003;145:49–53. [5] Morita Y, Takahashi A, Yamamoto K, Miki T, Murakami N, Miura O. Secondary near-tetraploidy with double der(15)t(15;17) in acute promyelocytic leukemia in relapse. Cancer Genet Cytogenet 2004;149:131– 6. [6] Kuyama J, Tsumori Y, Aoyama K, Kosugi S, Take H, Matsuyama T. Tetraploid acute promyelocytic leukemia with double PML/RARA gene rearrangements successfully treated with all-trans retinoic acid. Int J Hematol 2004;79:405– 6.
Letter to the Editor / Leukemia Research 35 (2011) e93–e95 [7] Kaito K, Otsubo H, Dobashi N, Usui N, Kobayashi M. CD2+ tetraploid acute promyelocytic leukemia variant with double (15;17) translocations. Int J Hematol 2005;81:29–31. [8] Pan JI, Xue YI, Qiu H, Wu Y, Wang Y, Zhang J, et al. Tetraploid clone characterized by two t(15;17) in five cases of acute promyelocytic leukemia. Cancer Genet Cytogenet 2009;188:57–9. [9] Kaito K, Katayama T, Masuoka H, Nishiwaki K, Sano K, Sekiguchi N, et al. CD2+ acute promyelocytic leukemia is associated with leukocytosis, variant morphology and poorer prognosis. Clin Lab Haematol 2005;27:307–11. [10] Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, et al. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood 2010;116:3751–7.
Pavan Mahendra Ravella Delong Liu Department of Medicine, New York Medical College, Valhalla, NY, USA Kensuke Kojima MD Anderson Cancer Center, Houston, TX, USA James Weisberger BioReference Laboratories, Elmwood Park, NJ, USA
e95
Osamu Miura Tokyo Medical and Dental University, Tokyo, Japan Jun Kuyama KKR Otemae Hospital, Osaka, Japan Wing Au Queen Mary Hospital, Hong Kong, Hong Kong Karen Seiter ∗ Department of Medicine, New York Medical College, Valhalla, NY, USA ∗ Corresponding author at: Department of Medicine, New York Medical College, Room 250 Munger Pavilion, Valhalla, NY 10595, USA. Tel.: +1 914 493 7514; fax: +1 914 594 4420. E-mail address: karen [email protected] (K. Seiter)
3 January 2011 Available online 25 February 2011