Skip to main content

Advertisement

Log in

Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR–ABL-positive acute lymphoblastic leukemia—retrospective analysis of Polish Adult Leukemia Group (PALG)

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Patients with Philadelphia chromosome-positive (Ph+) and/or BCR–ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR–ABL+ ALL registered in Poland in 1997–2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR–ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Avivi I, Goldstone AH (2003) Bone marrow transplant in Ph+ALL patients. Bone Marrow Transplant 31:623–632

    Article  PubMed  CAS  Google Scholar 

  2. Boucheix C, David B, Sebban C, Racadot E, Bene MC, Bernard A, Campos L, Jouault H, Sigaux F, Lepage E, Herve P, Fiere D (1994) Immunophenotype of adult acute lymphoblastic leukemia, clinical parameters, and outcome: an analysis of a prospective trial including 562 tested patients (LALA 87). Blood 84:1603–1612

    PubMed  CAS  Google Scholar 

  3. Chao NJ, Blume KG, Forman SJ, Snyder DS (1995) Long-term follow-up of allogeneic bone marrow recipients for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 85:3353–3354

    PubMed  CAS  Google Scholar 

  4. Cimino G, Elia L, Mancini M, Annino L, Anaclerico B, Fazi P, Vitale A, Specchia G, Di Raimondo F, Recchia A, Cuneo A, Mecucci C, Pane F, Saglio G, Foa R, Mandelli F (2003) Clinico-biologic features and treatment outcome of adult pro-B-ALL patients enrolled in the GIMEMA 0496 study: absence of the ALL1/AF4 and of the BCR/ABL fusion genes correlates with a significantly better clinical outcome. Blood 102:2014–2020

    Article  PubMed  CAS  Google Scholar 

  5. Clavio M, Venturino C, Pierri I, Garrone A, Miglino M, Canepa L, Balleari E, Balocco M, Michelis GL, Ballerini F, Gobbi M (2004) Combination of liposomal daunorubicin (DaunoXome), fludarabine, and cytarabine (FLAD) in patients with poor-risk acute leukemia. Ann Hematol 83:696–703

    Article  PubMed  CAS  Google Scholar 

  6. Dombret H, Gabert J, Boiron JM, Rigal-Huguet F, Blaise D, Thomas X, Delannoy A, Buzyn A, Bilhou-Nabera C, Cayuela JM, Fenaux P, Bourhis JH, Fegueux N, Charrin C, Boucheix C, Lheritier V, Esperou H, MacIntyre E, Vernant JP, Fiere D (2002) Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia—results of the prospective multicenter LALA-94 trial. Blood 100:2357–2366

    Article  PubMed  CAS  Google Scholar 

  7. Faderl S, Kantarjian HM, Thomas DA, Cortes J, Giles F, Pierce S, Albitar M, Estrov Z (2000) Outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia. Leuk Lymphoma 36:263–273

    Article  PubMed  CAS  Google Scholar 

  8. Gleissner B, Gokbuget N, Bartram CR, Janssen B, Rieder H, Janssen JW, Fonatsch C, Heyll A, Voliotis D, Beck J, Lipp T, Munzert G, Maurer J, Hoelzer D, Thiel E (2002) Leading prognostic relevance of the BCR–ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 99:1536–1543

    Article  PubMed  CAS  Google Scholar 

  9. Gokbuget N, Hoelzer D (2004) Treatment with monoclonal antibodies in acute lymphoblastic leukemia: current knowledge and future prospects. Ann Hematol 83:201–205

    Article  PubMed  Google Scholar 

  10. Heerema NA, Harbott J, Galimberti S, Camitta BM, Gaynon PS, Janka-Schaub G, Kamps W, Basso G, Pui CH, Schrappe M, Auclerc MF, Carroll AJ, Conter V, Harrison CJ, Pullen J, Raimondi SC, Richards S, Riehm H, Sather HN, Shuster JJ, Silverman LB, Valsecchi MG, Arico M; Acute Lymphoblastic Leukemia Study Groups; ALL-BFM; CoALL; AIEOP; DCLSG; FRALLE; CCG; DFCI; POG; St Jude; UKALL (2004) Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome. Leukemia 18:693–702

    Article  PubMed  CAS  Google Scholar 

  11. ISCN (International System for Human Cytogenetic Nomenclature) (1991) Guidelines for cancer cytogenetics. In: Mitelman F (ed) Supplement to an International System for Human Cytogenetic Nomenclature. Karger, Basel, pp 1–53

    Google Scholar 

  12. Li S, Ilaria RL Jr, Million RP, Daley GQ, Van Etten RA (1999) The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J Exp Med 189:1399–1412

    Article  PubMed  CAS  Google Scholar 

  13. Lo Nigro L, Sainati L, Mirabile E, Lanciotti M, Poli A, Leszl A, Basso G (2004) Association of cytogenetic abnormalities with detection of BCR–ABL fusion transcripts in children with T-lineage lymphoproliferative diseases (T-ALL and T-NHL). Pediatr Blood Cancer 42:278–280

    Article  PubMed  Google Scholar 

  14. Maurer J, Janssen JW, Thiel E, van Denderen J, Ludwig WD, Aydemir U, Heinze B, Fonatsch C, Harbott J, Reiter A et al (1991) Detection of chimeric BCR–ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaction. Lancet 337:1055–1058

    Article  PubMed  CAS  Google Scholar 

  15. Pane F, Cimino G, Izzo B, Camera A, Vitale A, Quintarelli C, Picardi M, Specchia G, Mancini M, Cuneo A, Mecucci C, Martinelli G, Saglio G, Rotoli B, Mandelli F, Salvatore F, Foa R (2005) Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult Philadelphia-positive acute lymphoblastic leukemia. Leukemia 19:628–635

    PubMed  CAS  Google Scholar 

  16. Primo D, Tabernero MD, Perez JJ, Rasillo A, Sayagues JM, Espinosa AB, Lopez-Berges MC, Garcia-Sanz R, Gutierrez NC, Hernandez JM, Romero M, Osuna CS, Giralt M, Barbon M, San Miguel JF, Orfao A (2005) Genetic heterogeneity of BCR/ABL+adult B-cell precursor acute lymphoblastic leukemia: impact on the clinical, biological and immunophenotypical disease characteristics. Leukemia 19:713–720

    Article  PubMed  CAS  Google Scholar 

  17. Raanani P, Trakhtenbrot L, Rechavi G, Rosenthal E, Avigdor A, Brok-Simoni F, Leiba M, Amariglio N, Nagler A, Ben-Bassat I (2005) Philadelphia-chromosome-positive T-lymphoblastic leukemia: acute leukemia or chronic myelogenous leukemia blastic crisis. Acta Haematol 113:181–189

    Article  PubMed  Google Scholar 

  18. Robak T (2004) Acute lymphoblastic leukaemia in elderly patients. Biological characteristics and therapeutic approaches. Drugs Aging 21:779–791

    Article  PubMed  Google Scholar 

  19. Robak T, Szmigielska-Kapłon A, Wrzesień-Kuś A, Wierzbowska A, Skotnicki AB, Pitkowska-Jakubas B, Kuliczkowski K, Mazur G, Zduńczyk A, Stella-Hołowiecka B, Hołowiecki J, Dwilewicz-Trojaczek J, Mdry K, Dmoszyńska A, Cioch M (2004) Acute lymphoblastic leukemia in elderly: the Polish Adult Leukemia Group (PALG) experience. Ann Hematol 83:225–231

    Article  PubMed  CAS  Google Scholar 

  20. Specchia G, Pastore D, Carluccio P, Liso A, Mestice A, Rizzi R, Ciuffreda L, Pietrantuono G, Liso V (2005) FLAG-IDA in the treatment of refractory/relapsed adult acute lymphoblastic leukemia. Ann Hematol 84:792–795

    Article  PubMed  CAS  Google Scholar 

  21. Thomas X, Thiebaut A, Olteanu N, Danaila C, Charrin C, Archimbaud E, Fiere D (1998) Philadelphia chromosome positive adult acute lymphoblastic leukemia: characteristics, prognostic factors and treatment outcome. Hematol Cell Ther 40:119–128

    PubMed  CAS  Google Scholar 

  22. Vidarsson B, Abonour R, Williams EC, Woodson RD, Turman NJ, Kim K, Mosher DF, Wiersma SR, Longo WL (2001) Fludarabine and cytarabine as a sequential infusion regimen for treatment of adults with recurrent, refractory or poor prognosis acute leukemia. Leuk Lymphoma 41:321–331

    Article  PubMed  CAS  Google Scholar 

  23. Wetzler M, Dodge RK, Mrozek K, Stewart CC, Carroll AJ, Tantravahi R, Vardiman JW, Larson RA, Bloomfield CD (2004) Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group B. Br J Haematol 124:275–288

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The following members of the PALG were also authors of this publication and recruited five, or less, patients to the analysis or verified five, or less, karyotypes with additional abnormalities: Salamaczuk Z, (Department of Hematology, Collegium Medicum of Jagiellonian University, Kraków, Poland), Mariaska B, Nasilkowska Z., Warzocha K, (Institute of Hematology and Transfusiology, Warsaw, Poland), Kloczko J, Mazgajska K, Piszcz J, (Department of Hematology, Medical University, Bialystok, Poland), Panasiuk B, (Department of Clinical Genetics, Medical University, Bialystok), Krawczyk-Kuliś M, and Giebel S. (Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. Robak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wrzesień-Kuś, A., Robak, T., Pluta, A. et al. Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR–ABL-positive acute lymphoblastic leukemia—retrospective analysis of Polish Adult Leukemia Group (PALG). Ann Hematol 85, 366–373 (2006). https://doi.org/10.1007/s00277-006-0099-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-006-0099-z

Keywords

Navigation