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In patients with BCR-ABL-positive ALL in CR peripheral blood contains less residual disease than bone marrow: Implications for autologous BMT

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Summary

Residual leukemic cells are detectable at frequencies as low as 1 in 106 normal cells in patients with Philadelphia chromosome/BCR-ABL-positive leukemias in complete remission (CR) using reverse-transcriptase polymerase chain reaction (RT-PCR) with specific nested primers. The level of minimal residual disease (MRD) in the bone marrow (BM) and the peripheral blood (PB) may favor one of the two as the source for an autologous graft. In order to quantify MRD with RT-PCR we analyzed patients ficolled cells after limiting logarithmic dilutions in normal ficolled buffy-coat cells. In six patients with BCR-ABL-pos ALL who were in CR by conventional criteria (5 in CR1 and 1 in CR2), we studied a total of nine paired BM and PB samples prior to scheduled ABMT. A positive RT-PCR signals was detectable in all samples up to dilutions ranging from 1∶101 to 1∶103 in PB, and at higher titers ranging from 1∶103 to 1∶105 in the BM. The BM titers exceeded the corresponding PB titers in all nine sample pairs by at least 1 log. The mean difference was 1.55 log (geometric mean,n=9) and is statistically significant (p<0.03). We conclude that residual leukemia in BCR-ABL-positive ALL preferentially locates in the BM compartment, and we assume that PB may yield autologous grafts with significantly less leukemic contamination.

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References

  1. Barrett AJ, Horowitz MM, Ash RC et al. (1992) Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukema. Blood 79:3067–3070

    Google Scholar 

  2. Brenner MK, Rill DR, Moen RC et al. (1993) Gene-marking to trace original of relapse after autologous bone marrow transplantation. Lancet 341:8837:85–86

    Google Scholar 

  3. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Google Scholar 

  4. Cross NCP, Feng L, Chase A, Bungey J, Hughes TP, Goldman JM (1993) Competitive polymerase chain reaction to estimate the numbers of BCR-ABL transcripts in chronic myeloid leukemia patients after bone marrow transplantation. Blood 82:1929–1936

    Google Scholar 

  5. Cross NCP, Marks DI, Goldman JM (1993) Quantitative PCR for p190 BCR-ABL in Philadelphia-positive acute lymphoblastic leukemia. Exp Hematol 212:1099 (abstr. 326)

    Google Scholar 

  6. Dhut S, Gibbons B, Chaplin T, Young BD (1991) Establishment of a lymphoblastoid cell-line, SD-1, expressing the p190 BCR-ABL chimaeric protein. Leukemia 5:49–55

    Google Scholar 

  7. Forman SJ, O'Donnell MR, Nademanee AP et al. (1987) Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 70:587–588

    Google Scholar 

  8. Gehly GB, Bryant EM, Lee AM, Kidd PG, Thomas ED (1991) Chimeric BCR-ABL messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 78:458–465

    Google Scholar 

  9. Gilmore MJ, Hamon MD, Prentice HG et al. (1991) Failure of purged autologous bone marrow transplantation in highrisk acute lymphoblastic leukaemia in first complete remission. Bone Marrow Transplant 8:19–26

    Google Scholar 

  10. Gribben JG, Freedman AS, Neuberg D et al. (1991) Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med 325:1525–1533

    Google Scholar 

  11. Hoelzer D (1989) Which factors influence the different outcome of therapy in adults and children with ALL? Bone Marrow Transplant 4 [Suppl 1]: 98–100

    Google Scholar 

  12. Hoelzer D (1993) Therapy of the newly diagnosed adult with acute lymphoblastic leukemia. Hematol Oncol Clin North Am 7:139–160

    Google Scholar 

  13. Hoelzer D, Thiel E, Löffler H et al. (1988) Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71:123–131

    Google Scholar 

  14. Hoelzer D, Thiel E, Ludwig WD et al. (1992) The German multicentre trials for treatment of acute lymphoblastic leukemia in adults. Leukemia 6 [Suppl 2]: 175–177

    Google Scholar 

  15. Kawasaki ES, Clark SS, Coyne MY et al. (1988) Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc Natl Acad Sci USA 85:5698–5702

    Google Scholar 

  16. Körbling M, Martin H, Fliedner TM (1987) Autologous blood stem cell transplantation. In: Gale RP, Champlin R (eds) 4th International UCLA Symposium on Bone Marrow Transplantation, 1986, Keystone, Co. Progress in Bone Marrow Transplantation. Alan R. Liss, New York, pp 877–888

    Google Scholar 

  17. Kurzrock R, Gutterman JU, Talpaz M (1988) The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med 319:990–998

    Google Scholar 

  18. Kvalheim G, Sorensen O, Fodstad O et al. (1988) Immunomagnetic removal of B-lymphoma cells from human bone marrow: a procedure for clinical use. Bone Marrow Transplant 3:31–41

    Google Scholar 

  19. Martin H, Atta J, Bruecher J, Claudé R, Elsner S, Hoelzer D (1993) Minimal residual disease in patients with Ph-pos acute lymphoblastic leukemia before and after autologous bone marrow transplantation. Exp Hematol 21:1065 (abstr. 205)

    Google Scholar 

  20. Martin H, Claudé R, Schardt C et al. (1992) Autologous BMT in Ph'-positive ALL: cell line BV-173 as a model for in vitro purging. Ann Hematol 64 [Suppl]: A94 (Abstr. 88)

    Google Scholar 

  21. Maurer J, Jannsen JWG, Thiel E et al. (1991) Detection of chimeric BCR-ABL genes in acute lmyphoblastic leukemia by the polymerase chain reaction. Lancet 337:1055–1058

    Google Scholar 

  22. Miyamura K, Tanimoto M, Morishima Y et al. (1992) Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation. Blood 79:1366–1370

    Google Scholar 

  23. Pegoraro L, Matera L, Ritz J, Levis A, Palumbo A, Biagini G (1983) Establishment of a Ph'-positive human cell line (BV173). J Natl Cancer Inst 70:447–451

    Google Scholar 

  24. Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV (1990) Philadelphia-positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia 5:196–199

    Google Scholar 

  25. Stadler M, Martin H, Schardt C et al. (1992) Evaluation by reverse transcriptase polymerase chain reaction (RT-PCR) of immunomagnetic bead purging in Philadelphia chromosome (Ph')-positive acute lymphoblastic leukemia. Ann Hematol 65 [Suppl]: A36 (Abstr. 29)

    Google Scholar 

  26. Yokata S, Hansen-Hagge TE, Ludwig WD et al. (1991) Use of polymerase chain reactions to monitor minimal residual disease in acute lymphoblastic leukemia patients. Blood 77:331

    Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Johann-Wolfgang-Goethe-University, Theodor-Stern-Kai 7, D-60590, Frankfurt/Main, Germany

    H. Martin, J. Atta, J. Bruecher, S. Elsner, C. Schardt, M. Stadler, H. v. Melchner & D. Hoelzer

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  1. H. Martin
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  2. J. Atta
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  3. J. Bruecher
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  4. S. Elsner
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  5. C. Schardt
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  6. M. Stadler
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  7. H. v. Melchner
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  8. D. Hoelzer
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This work was supported by theDeutsche Forschungsgemeinschaft

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Martin, H., Atta, J., Bruecher, J. et al. In patients with BCR-ABL-positive ALL in CR peripheral blood contains less residual disease than bone marrow: Implications for autologous BMT. Ann Hematol 68, 85–87 (1994). https://doi.org/10.1007/BF01715137

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  • DOI: https://doi.org/10.1007/BF01715137

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