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Published in: International Journal of Hematology 3/2013

01-03-2013 | Original Article

Inclusion of hemoglobin level in prognostic score provides better prognostic stratification in patients with acute promyelocytic leukemia (APL)

Authors: Silvia Park, Su Jin Lee, Kihyun Kim, Jun Ho Jang, Dong Hwan Kim, Kyu Hyung Lee, Je Hwan Lee, Jung Hee Lee, Dae Young Kim, Dae-Young Jang, Hawk Kim, Jae Hoo Park, Hun Mo Ryoo, Sung Hwa Bae, Min Kyung Kim, Myung Soo Hyun, Young Don Joo, Won Sik Lee, Sang Min Lee, Chul Won Jung

Published in: International Journal of Hematology | Issue 3/2013

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Abstract

The clinical outcomes of acute promyelocytic leukemia (APL) have improved greatly, but treatment failure still occurs. Identification of patients with poor prognosis is fundamental, and we propose a new clinical prognostic system (CBC-score) consisting of WBC, platelet count, and hemoglobin level. Between 1995 and 2009, 156 patients with APL from seven institutes in Korea were retrospectively reviewed. In the new CBC-score system, each of the following (WBC ≥10 × 109/L, platelet <40 × 109/L, hemoglobin <8.0 g/dL) was considered as a risk factor; the sum of each was designated as the CBC-score. With a median follow-up of 8.4 years, the complete remission (CR) rate was 81.4 % (127/156), while 24 (15.4 %) were considered as treatment failures due to early death (ED). The 5-year overall survival (OS), leukemia-free survival, and cumulative incidence of relapse were 73.8, 82.8, and 13.5 %, respectively. Compared to the individual CBC parameters, combined prognostic systems such as PETHEMA or CBC-score provided better prognostic stratification. Compared to PETHEMA stratification, the proposed prognostic CBC-score system showed better stratification of APL patients in terms of CR rates (p = 0.004), OS (p = 0.004), and ED (p = 0.008). This retrospective study suggests that the proposed CBC-score may provide better prognostic stratification of APL patients.
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Literature
1.
go back to reference Douer D. The epidemiology of acute promyelocytic leukaemia. Best Pract Res Clin Haematol. 2003;16:357–67.PubMedCrossRef Douer D. The epidemiology of acute promyelocytic leukaemia. Best Pract Res Clin Haematol. 2003;16:357–67.PubMedCrossRef
2.
go back to reference Ribeiro RC, Rego E. Management of APL in developing countries: epidemiology, challenges and opportunities for international collaboration. Hematology Am Soc Hematol Educ Program. 2006:162–8. Ribeiro RC, Rego E. Management of APL in developing countries: epidemiology, challenges and opportunities for international collaboration. Hematology Am Soc Hematol Educ Program. 2006:162–8.
3.
go back to reference Sanz MA, Grimwade D, Tallman MS, Lowenberg B, Fenaux P, Estey EH, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113:1875–91.PubMedCrossRef Sanz MA, Grimwade D, Tallman MS, Lowenberg B, Fenaux P, Estey EH, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113:1875–91.PubMedCrossRef
4.
go back to reference Mistry AR, Pedersen EW, Solomon E, Grimwade D. The molecular pathogenesis of acute promyelocytic leukaemia: implications for the clinical management of the disease. Blood Rev. 2003;17:71–97.PubMedCrossRef Mistry AR, Pedersen EW, Solomon E, Grimwade D. The molecular pathogenesis of acute promyelocytic leukaemia: implications for the clinical management of the disease. Blood Rev. 2003;17:71–97.PubMedCrossRef
5.
go back to reference Pulsoni A, Pagano L, Lo Coco F, Avvisati G, Mele L, Di Bona E, et al. Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: the GIMEMA experience. Blood. 2002;100:1972–76. Pulsoni A, Pagano L, Lo Coco F, Avvisati G, Mele L, Di Bona E, et al. Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: the GIMEMA experience. Blood. 2002;100:1972–76.
6.
go back to reference Sirulnik A, Melnick A, Zelent A, Licht JD. Molecular pathogenesis of acute promyelocytic leukaemia and APL variants. Best Pract Res Clin Haematol. 2003;16:387–408.PubMedCrossRef Sirulnik A, Melnick A, Zelent A, Licht JD. Molecular pathogenesis of acute promyelocytic leukaemia and APL variants. Best Pract Res Clin Haematol. 2003;16:387–408.PubMedCrossRef
7.
go back to reference Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72:567–72.PubMed Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72:567–72.PubMed
8.
go back to reference Tallman MS, Nabhan C, Feusner JH, Rowe JM. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood. 2002;99:759–67.PubMedCrossRef Tallman MS, Nabhan C, Feusner JH, Rowe JM. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood. 2002;99:759–67.PubMedCrossRef
9.
go back to reference Sanz MA, Tallman MS, Lo-Coco F. Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia. Blood. 2005;105:3019–25.PubMedCrossRef Sanz MA, Tallman MS, Lo-Coco F. Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia. Blood. 2005;105:3019–25.PubMedCrossRef
10.
go back to reference Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337:1021–8.PubMedCrossRef Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337:1021–8.PubMedCrossRef
11.
go back to reference Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, et al. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood. 2002;100:4298–302.PubMedCrossRef Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, et al. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood. 2002;100:4298–302.PubMedCrossRef
12.
go back to reference Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999;94:1192–200.PubMed Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999;94:1192–200.PubMed
13.
go back to reference Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, et al. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell’Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups. Blood. 1997;90:1014–21. Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, et al. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell’Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups. Blood. 1997;90:1014–21.
14.
go back to reference Sanz MA, Martin G, Rayon C, Esteve J, Gonzalez M, Diaz-Mediavilla J, et al. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group. Blood. 1999;94:3015–21.PubMed Sanz MA, Martin G, Rayon C, Esteve J, Gonzalez M, Diaz-Mediavilla J, et al. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group. Blood. 1999;94:3015–21.PubMed
15.
go back to reference Di Bona E, Avvisati G, Castaman G, Luce Vegna M, De Sanctis V, Rodeghiero F, et al. Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia. Br J Haematol. 2000;108:689–95.PubMedCrossRef Di Bona E, Avvisati G, Castaman G, Luce Vegna M, De Sanctis V, Rodeghiero F, et al. Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia. Br J Haematol. 2000;108:689–95.PubMedCrossRef
16.
go back to reference de la Serna J, Montesinos P, Vellenga E, Rayon C, Parody R, Leon A, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. 2008;111:3395–402.PubMedCrossRef de la Serna J, Montesinos P, Vellenga E, Rayon C, Parody R, Leon A, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. 2008;111:3395–402.PubMedCrossRef
17.
go back to reference Sanz MA, Lo Coco F, Martin G, Avvisati G, Rayon C, Barbui T, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96:1247–53.PubMed Sanz MA, Lo Coco F, Martin G, Avvisati G, Rayon C, Barbui T, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96:1247–53.PubMed
18.
go back to reference Sanz MA, Martin G, Gonzalez M, Leon A, Rayon C, Rivas C, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004;103:1237–43.PubMedCrossRef Sanz MA, Martin G, Gonzalez M, Leon A, Rayon C, Rivas C, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004;103:1237–43.PubMedCrossRef
19.
go back to reference Sanz MA, Montesinos P, Rayon C, Holowiecka A, de la Serna J, Milone G, et al. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010;115:5137–46.PubMedCrossRef Sanz MA, Montesinos P, Rayon C, Holowiecka A, de la Serna J, Milone G, et al. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010;115:5137–46.PubMedCrossRef
20.
go back to reference Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.PubMedCrossRef Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.PubMedCrossRef
21.
go back to reference Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A, et al. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group. J Clin Oncol. 1998;16:78–85.PubMed Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A, et al. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group. J Clin Oncol. 1998;16:78–85.PubMed
22.
go back to reference Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Loffler H, et al. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group. Leukemia. 2000;14:1362–70.PubMedCrossRef Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Loffler H, et al. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group. Leukemia. 2000;14:1362–70.PubMedCrossRef
23.
go back to reference Ades L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, et al. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006;24:5703–10.PubMedCrossRef Ades L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, et al. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006;24:5703–10.PubMedCrossRef
24.
go back to reference Ades L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, et al. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008;111:1078–84.PubMedCrossRef Ades L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, et al. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008;111:1078–84.PubMedCrossRef
25.
go back to reference Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial. Blood. 1999;93:4131–43.PubMed Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial. Blood. 1999;93:4131–43.PubMed
26.
go back to reference Kelaidi C, Chevret S, De Botton S, Raffoux E, Guerci A, Thomas X, et al. Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience. J Clin Oncol. 2009;27:2668–76.PubMedCrossRef Kelaidi C, Chevret S, De Botton S, Raffoux E, Guerci A, Thomas X, et al. Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience. J Clin Oncol. 2009;27:2668–76.PubMedCrossRef
27.
go back to reference Callens C, Chevret S, Cayuela JM, Cassinat B, Raffoux E, de Botton S, et al. Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL): a retrospective study from the European APL Group. Leukemia. 2005;19:1153–60.PubMedCrossRef Callens C, Chevret S, Cayuela JM, Cassinat B, Raffoux E, de Botton S, et al. Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL): a retrospective study from the European APL Group. Leukemia. 2005;19:1153–60.PubMedCrossRef
30.
go back to reference Cook JD. Diagnosis and management of iron-deficiency anaemia. Best Pract Res Clin Haematol. 2005;18:319–32.PubMedCrossRef Cook JD. Diagnosis and management of iron-deficiency anaemia. Best Pract Res Clin Haematol. 2005;18:319–32.PubMedCrossRef
31.
go back to reference Sanz MA, Montesinos P, Vellenga E, Rayon C, de la Serna J, Parody R, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-transretinoic acid and anthracycline monochemotherapy: long term outcome of the LPA 99 multicenter study by the PETHEMA Group. Blood. 2008;112:3130–4.PubMedCrossRef Sanz MA, Montesinos P, Vellenga E, Rayon C, de la Serna J, Parody R, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-transretinoic acid and anthracycline monochemotherapy: long term outcome of the LPA 99 multicenter study by the PETHEMA Group. Blood. 2008;112:3130–4.PubMedCrossRef
Metadata
Title
Inclusion of hemoglobin level in prognostic score provides better prognostic stratification in patients with acute promyelocytic leukemia (APL)
Authors
Silvia Park
Su Jin Lee
Kihyun Kim
Jun Ho Jang
Dong Hwan Kim
Kyu Hyung Lee
Je Hwan Lee
Jung Hee Lee
Dae Young Kim
Dae-Young Jang
Hawk Kim
Jae Hoo Park
Hun Mo Ryoo
Sung Hwa Bae
Min Kyung Kim
Myung Soo Hyun
Young Don Joo
Won Sik Lee
Sang Min Lee
Chul Won Jung
Publication date
01-03-2013
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 3/2013
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-013-1276-1

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