Induction of Complete Remission of Hypoplastic Leukemia with Antithymocyte Globulin


A 13-year-old boy was admitted to a local hospital because of pancytopenia. A bone marrow aspiration and biopsy revealed severely hypocellular marrow with no obvious leukemic cells. The diagnosis was severe aplastic anemia, and the patient was treated with antithymocyte globulin and cyclosporin A. A trilineage response was obtained, and the patient became transfusion-independent within 2 weeks. Two months later, the peripheral blood count normalized with an increased bone marrow cellularity. However, the patient was readmitted 5 months later for recurrence of the pancytopenia. A bone marrow aspiration revealed hypocellular marrow with morphologically blastoid cells. A surface marker study revealed the presence of a single clone that was positive for CD7, CD33, CD34, and HLA-DR. A diagnosis of hypoplastic leukemia was made on the basis of morphology and the surface marker studies. Retrospectively, the laboratory findings were the same as those seen at the onset of the disease. The patient did not respond to combination chemotherapy consisting of vincristine, prednisolone, cyclophosphamide, L-asparaginase, and doxorubicin, but administration of etoposide resulted in complete remission. An in vitro study revealed that >95% of the leukemic cells of this patient could be lysed after an incubation with antithymocyte globulin and human AB serum or baby rabbit serum. These findings suggest the efficacy of antithymocyte globulin in treating certain hypoplastic leukemias.

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  1. 1.

    Camitta B, O’Reilly RJ, Sensenbrenner L, et al. Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia.Blood. 1983;62:883–888.

    PubMed  PubMed Central  CAS  Google Scholar 

  2. 2.

    Champlin R, Ho W, Gale RP. Antithymocyte globulin treatment in patients with aplastic anemia: a prospective randomized trial.N Engl J Med. 1983;308:113–118.

    Article  PubMed  CAS  Google Scholar 

  3. 3.

    Bonnefoy-Berard N, Revillard JP. Mechanisms of immunosuppression induced by antithymocyte globulins and OKT3.J Heart Lung Transplant. 1996;15:435–442.

    PubMed  CAS  Google Scholar 

  4. 4.

    Genestier L, Fournel S, Flacher M, et al. Induction of Fas (Apo-1, CD95)-mediated apoptosis of activated lymphocytes by polyclonal antithymocyte globulins.Blood. 1998;91:2360–2368.

    PubMed  PubMed Central  CAS  Google Scholar 

  5. 5.

    Raefsky EL, Gascon P, Gratwohl A, Speck B, Young NS. Biological and immunological characterization of ATG and ALG.Blood. 1986;68:712–719.

    PubMed  CAS  Google Scholar 

  6. 6.

    Bonnefoy-Berard N, Vincent C, Revillard JP. Antibodies against functional leukocyte surface molecules in polyclonal antilymphocyte and antithymocyte globulins.Transplantation. 1991;51:669–6733.

    Article  PubMed  CAS  Google Scholar 

  7. 7.

    Tsuge I, Kojima S. Comparison of antibody specificities of four anti-thymocyte/anti-lymphocyte globulin products.Curr Ther Res. 1995;56:671–677.

    Article  Google Scholar 

  8. 8.

    Fisher RI, Silver BA, Vanhaelen CP, Jaffe ES, Cossman J. Objective regressions of T-and B-cell lymphomas in patients following treatment with anti-thymocyte globulin.Cancer Res. 1982;42:2465–2469.

    PubMed  CAS  Google Scholar 

  9. 9.

    Kojima S, Hibi S, Kosaka Y, et al. Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia.Blood. 2000;96:2049–2054.

    PubMed  PubMed Central  CAS  Google Scholar 

  10. 10.

    Greco B, Bielory L, Stephany D, et al. Antithymocyte globulin reacts with many normal human cell types.Blood. 1983;62:1047–10544.

    PubMed  CAS  Google Scholar 

  11. 11.

    Bonnefoy-Berard N, Genestier L, Flacher M, et al. Apoptosis induced by polyclonal antilymphocyte globulins in human B-cell lines.Blood. 1994;83:1051–1059.

    PubMed  CAS  Google Scholar 

  12. 12.

    Baum W, Steininger H, Bair HJ, et al. Therapy with CD7 monoclonal antibody TH-69 is highly effective for xenografted human T-cell acute lymphoblastic leukemia.Br J Haematol. 1996;95:327–3388.

    Article  PubMed  CAS  Google Scholar 

  13. 13.

    Drenou B, Blancheteau V, Burgess DH, Fauchet R, Charron DJ, Mooney NA. A caspase-independent pathway of MHC class II antigen-mediated apoptosis of human B lymphocytes.J Immunol. 1999;163:4115–4124.

    PubMed  CAS  Google Scholar 

  14. 14.

    Vidovic D, Toral JI. Selective apoptosis of neoplastic cells by the HLA-DR-specific monoclonal antibody.Cancer Lett. 1998;128:127–1355.

    Article  PubMed  CAS  Google Scholar 

  15. 15.

    Leveille C, Zekki H, Al-Daccak R, Mourad W. CD40- and HLADR- mediated cell death pathways share a lot of similarities but differ in their use of ADP-ribosyltransferase activities.Int Immunol. 1999;11:719–730.

    Article  PubMed  CAS  Google Scholar 

  16. 16.

    Killick SB, Marsh JCW, Gordon-Smith EC, Sorlin L, Gibson FM. Effects of antithymocyte globulin on bone marrow CD34+ cells in aplastic anemia and myelodysplasia.Br J Haematol. 2000;108:582–5922.

    Article  PubMed  CAS  Google Scholar 

  17. 17.

    Faille A, Barrett AJ, Balitrand N, Ketels F, Gluckman E, Najean Y. Effect of antilymphocyte globulin on granulocyte precursors in aplastic anaemia.Br J Haematol. 1979;42:371–380.

    Article  PubMed  CAS  Google Scholar 

  18. 18.

    Mangan KF, D’Alessandro L, Mullaney MT. Action of antithymocyte globulin on normal human erythroid progenitor cell proliferation in vitro: erythropoietic growth-enhancing factors are released from marrow accessory cells.J Lab Clin Med. 1986;107:353–3644.

    PubMed  CAS  Google Scholar 

  19. 19.

    Hunter RF, Mold NG, Mitchell RB, Huang AT. Differentiation of normal marrow and HL60 cells induced by antithymocyte globulin.Proc Natl Acad Sci U S A. 1985;82:4823–4827.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. 20.

    Gascon P, Zoumbos NC, Scala G, Djeu JY, Moore JG, Young NS. Lymphokine abnormalities in aplastic anemia: implications for the mechanism of action of antithymocyte globulin.Blood. 1985;65:407–4133.

    PubMed  CAS  Google Scholar 

  21. 21.

    Kawano Y, Nissen C, Gratwohl A, Speck B. Immunostimulatory effects of different antilymphocyte globulin preparations: a possible clue to their clinical effect.Br J Haematol. 1988;68:115–119.

    Article  PubMed  CAS  Google Scholar 

  22. 22.

    Hatta Y, Iwata T, Takeuchi J, Ohshima T, Horie T. Complete remission in a patient with hypoplastic acute lymphoblastic leukemia induced by granulocyte-colony-stimulating factor.Acta Haematol. 1995;94:39–43.

    Article  PubMed  CAS  Google Scholar 

  23. 23.

    Yanagisawa K, Yano A, Takada K, Yasukawa M, Fujita S. Increase of erythropoiesis and thrombopoiesis, and induction of remission by granulocyte colony-stimulating factor (G-CSF) in a patient with hypoplastic leukemia [letter].Leukemia. 1994;8:1249–12511.

    PubMed  CAS  Google Scholar 

  24. 24.

    Maloney DG, Liles TM, Czerwinski DK, et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma.Blood. 1994;84:2457–2466.

    PubMed  PubMed Central  CAS  Google Scholar 

  25. 25.

    McLaughlin P, Grillo-Lopez AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.J Clin Oncol. 1998;16:2825–2833.

    Article  PubMed  CAS  Google Scholar 

  26. 26.

    Hale G, Dyer MJ, Clark MR, et al. Remission induction in non- Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H.Lancet. 1988;2:1394–1399.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ayami Yoshimi or Chikako Nakamoto or Yoichi Nakamura or Koji Kato or Takaharu Matsuyama or Kazuko Kudo or Seiji Kojima.

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Yoshimi, A., Nakamoto, C., Nakamura, Y. et al. Induction of Complete Remission of Hypoplastic Leukemia with Antithymocyte Globulin. Int J Hematol 77, 277–281 (2003).

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Key words

  • Antithymocyte globulin
  • Hypoplastic leukemia
  • Complement-mediated cytolysis
  • Apoptosis