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Lymphoma

Prevalence and clinical implications of bone marrow involvement in pediatric anaplastic large cell lymphoma

Leukemia volume 19, pages 1643–1647 (2005)Cite this article

Abstract

Anaplastic large cell lymphoma (ALCL) harbors the reciprocal chromosomal translocation t(2;5)(p23;q35) in approximately 80% of the cases. The genes involved are nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) and the resulting chimeric NPM–ALK protein is thought to play a key role in the pathogenesis of t(2;5) positive ALCL. Few data on bone marrow (BM) involvement in ALCL have been published and they mostly rely on morphological examination of BM smears. We studied 52 ALCL for NPM–ALK expression by RT-PCR: 47/52 biopsies were positive. In 41 of the 47 cases we obtained the BM at diagnosis and investigated the prevalence of minimal BM infiltration by RT-PCR and real-time PCR. Minimal disseminated disease was positive in 25/41 patients (61%), of whom six had morphologically infiltrated BM. Survival analysis demonstrated a 5-year progression-free survival of 41±11% for patients with molecularly positive BM vs 100% for patients with negative BM (P= 0.001). These results suggest that minimal BM involvement at diagnosis is a common event in pediatric ALCL and that minimal BM disease monitoring could identify patients at risk of relapse.

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References

  1. Falini B, Pileri S, Pizzolo G, Durkop H, Flenghi L, Stirpe F et al. CD30 (Ki-1) molecole: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood 1995; 85: 1–14.

    CAS  PubMed  Google Scholar 

  2. Stansfeld AG, Diebold J, Kapanci Y, Rilke F, Kelenyi G, Sundstrom C et al. Updated Kiel classification for lymphomas. Lancet 1988; I: 292–293.

    Article  Google Scholar 

  3. Benharroch D, Bedoyan Z, Lamant L, Amin C, Brugieres L, Terrier-Lacombe MJ et al. ALK-positive lymphoma: a single disease with a broad spectrum of morphology. Blood 1998; 91: 2076–2084.

    CAS  PubMed  Google Scholar 

  4. Rimokh R, Magaud JP, Berger F, Samarut J, Coiffier B, Germain D et al. A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma (‘Ki-1 lymphoma’). Br J Haematol 1989; 71: 31–36.

    Article  CAS  PubMed  Google Scholar 

  5. Lamant L, Meggetto F, Saati T, Brugieres L, de Paillerets BB, Dastague N et al. High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining. Blood 1996; 87: 284–291.

    CAS  PubMed  Google Scholar 

  6. Morris SW, Naeve C, Mathew P, James PL, Kirstein MN, Cui X et al. ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK). Oncogene 1997; 14: 2175–2188.

    Article  CAS  PubMed  Google Scholar 

  7. Iwahara T, Fujimoto J, Wen D, Cupples R, Bucay N, Arakawa T et al. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene 1997; 14: 439–449.

    Article  CAS  PubMed  Google Scholar 

  8. Fujimoto J, Shiota M, Iwahara T, Seki N, Satoh H, Mori S et al. Characterization of the transforming activity of p80, a hyperphosphorilated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5). Proc Natl Acad Sci USA 1996; 93: 4181–4186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kuefer MU, Look AT, Pulford K, Behm FG, Pattengale PK, Mason DY et al. Retrovirus-mediated gene transfer of NPM–ALK causes lymphoid malignancy in mice. Blood 1997; 90: 2901–2910.

    CAS  PubMed  Google Scholar 

  10. Falini B, Pileri S, Zanzini PL, Carbone A, Zagonel V, Wolf-Peeters C et al. ALK+ lymphoma: clinico-pathological findings and outcome. Blood 1999; 93: 2697–2706.

    CAS  PubMed  Google Scholar 

  11. Fraga M, Brousset P, Schlaifer D, Payen C, Robert A, Rubie H et al. Bone marrow involvement in anaplastic large cell lymphoma. Am J Clin Pathol 1995; 103: 82–89.

    Article  CAS  PubMed  Google Scholar 

  12. Seidemann K, Tiemann M, Schrappe M, Yakisan E, Simonitsch I, Janka-Schaub G et al. Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin–Frankfurt–Munster Group Trial NHL-BFM 90. Blood 2001; 97: 3699–3706.

    Article  CAS  PubMed  Google Scholar 

  13. Murphy SB . Classification, staging and end results of treatment of childhood non-Hodgkin's lymphomas: dissimilarities from lymphomas in adults. Semin Oncol 1980; 7: 332–339.

    CAS  PubMed  Google Scholar 

  14. Brugières L, Le Deley MC, Pacquement H, Meuerian-Bedoyan Z, Terrier-Lacombe MJ, Robert A et al. CD 30+ anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood 1998; 92: 3591–3598.

    PubMed  Google Scholar 

  15. Kaplan EL, Meier P . Non parametric estimation from incomplete observation. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  16. Peto R, Peto J . Asymptotically efficient rank invariant test procedures. J R Stat Soc A 1972; 135: 185–198.

    Article  Google Scholar 

  17. Cox DR . Regression models and life tables. J R Stat Soc 1972; 34: 187–220.

    Google Scholar 

  18. Stein H, Dallenbach F . Diffuse large cell lymphomas of B and T cell type. In: Knowles DM (ed). Neoplastic Hematopathology. Williams and Wilkins: Baltimore, 1992, pp 675–714.

    Google Scholar 

  19. Gerard CJ, Olsson K, Ramanathan R, Reading C, Hanania EG . Improved quantitation of minimal residual disease in multiple myeloma using real-time polymerase chain reaction and plasmid-DNA complementary determining region III standards. Cancer Res 1998; 58: 3957–3964.

    CAS  PubMed  Google Scholar 

  20. Marcucci G, Livak KJ, Bi W, Strout MP, Bloomfield CD, Caligiuri MA et al. Detection of minimal residual disease in patients with AML1/ETO-associated acute myeloid leukemia using a novel quantitative reverse transcription polymerase chain reaction assay. Leukemia 1998; 12: 1482–1489.

    Article  CAS  PubMed  Google Scholar 

  21. Mensink E, Van de Locht A, Schattenberg A, Linders E, Schaap N, Geurts van Kessel A et al. Quantitation of minimal residual disease in Philadelphia chromosome positive chronic myeloid leukaemia using real-time quantitative RT-PCR. Br J of Haematol 1998; 102: 768–774.

    Article  CAS  Google Scholar 

  22. Viehmann S, Teigler-Schlegel A, Bruch J, Langebrake C, Reinhardt D, Harbott J . Monitoring of minimal residual disease (MRD) by real-time quantitative reverse transcription PCR (RQ-RT-PCR) in childhood acute myeloid leukaemia with AML1/ETO rearrangement. Leukemia 2003; 17: 1130–1136.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Fondazione Città della Speranza, by a grant from MIUR-CNR and by AIL (Associazione Italiana contro le Leucemie). L Mussolin is a fellow of Fondazione Città della Speranza. We thank Gloria Tridello for the statistical analysis, Ilaria Zecchini for data collection and management and Angelica Zin for technical support. We are grateful to the clinicians of the Italian Association of Pediatric Hematology and Oncology (AIEOP) for providing biological samples and patient information.

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Authors and Affiliations

  1. Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Università di Padova, Padova, Italy

    L Mussolin, M Pillon, L Zanesco & A Rosolen

  2. U.O. Anatomia Patologica, Ospedale S. Bortolo, Vicenza, Italy

    E S d'Amore

  3. U.O. Pediatria, Azienda Ospedaliera-Policlinico, Bari, Italy

    N Santoro

  4. Clinica di Oncoematologia Pediatrica, Ospedale Bambino Gesù, Rome, Italy

    A Lombardi

  5. OIRM S. Anna, Torino, Italy

    F Fagioli

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  1. L Mussolin
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Correspondence to A Rosolen.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu/).

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Mussolin, L., Pillon, M., d'Amore, E. et al. Prevalence and clinical implications of bone marrow involvement in pediatric anaplastic large cell lymphoma. Leukemia 19, 1643–1647 (2005). https://doi.org/10.1038/sj.leu.2403888

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  • DOI: https://doi.org/10.1038/sj.leu.2403888

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