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Therapy of acute lymphocytic leukemia in childhood with intermediate dose methotrexate and CNS irradiation

A report of the ALL 77-02 study group

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Summary

One hundred and eight children with acute lymphocytic leukemia (ALL) were admitted to a prospective therapeutic regime. Remission induction was achieved in 94% of the cases with vincristine, L-asparaginase, adriamycine and prednisone. One hundred and one patients received three intermediate dose methotrexate (MTX) infusions combined with intrathecal MTX, followed by L-asparaginase 24 h later. High risk (HR) patients (n=50) were treated in addition with high dose cyclophosphamide and Ara-C over 3 weeks.

One hundred and one patients received cranial irradiation (1,800 rads standard risk (SR)-patients, 2,400 rads HR-patients) and intrathecal MTX. Maintenance therapy was performed with the usual two drug combination of daily 6 mercaptopurine (6 MP) and weekly MTX orally.

Based on phenotyping 67% of patients had common type ALL, and pre-T or T-cell type in 18%. Six per cent of the patients had leukemic blasts expressing both common ALL and T-cell markers (c/T-type); 9% had acute undifferentiated leukemia (AUL). Out of 108, 101 achieved a complete remission, 6 patients died during induction therapy, 1 was a non-responder and 9 patients relapsed. Of these 6 had haematological relapses, 2 had CNS relapse and 1 had a testicular relapse. Four patients died in continuous complete remission (CCR).

For 101 patients the 30 months probability of CCR is 0.85 (± 0.05). For 51 patients with standard risk CCR probability is 0.98 (± 0.03), for 50 patients with high risk indices it is 0.65 (±0.11). Patients with c-ALL have a CCR survival of 0.85 (±0.07), those with T- or pre-T-ALL 0.88 (±0.09), all 5 patients with c/T-ALL alive in CCR. In our study pediatric AUL patients have the most unfavourable prognosis.

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References

  1. Aur RJA, Simone JV, Verzosa HO, Hustu HO (1978) Childhood acute lymphocytic leukemia study VIII. Cancer 42: 2123–2129

    Google Scholar 

  2. Bleyer WA (1978) The clinical pharmacology of methotrexate. Cancer 41: 36–43

    Google Scholar 

  3. Cutler S, Ederer F (1965) Maximum utilization of the life table method in analyzing survival. J Chronic Dis 8: 699–705

    Google Scholar 

  4. Drexler HG, Gaedicke G (1983a) Isoenzyme studies in human leukemia — II. Carboxylic Esterase (E.C.3.1.1.1.) Leuk Res, in press

  5. Drexler HG, Gaedicke G (1983 b) Isoenzyme studies in human leukemia — III. β-hexosaminidase (E.C.3.2.1.30) Leuk Res, in press

  6. Freeman AI, Wang JJ, Sinks LF (1977) High-dose methotrexate in acute lymphocytic leukemia. Cancer Treat Rep 61: 727–731

    Google Scholar 

  7. Freeman AI, Brecher ML, Wang JJ, Sinks LF (1979) Intermediate dose methotrexate (IDM) in childhood acute lymphocytic leukemia (ALL). In: Neth R (ed) Modern trends in human leukemia III. New results in clinical and biologic research. Springer, Berlin Heidelberg New York. Blut (Suppl.) 23: 115–123

    Google Scholar 

  8. Freeman AI, Weinberg V, Brecher ML, et al. (1983) Comparison of intermediate dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children. N Engl J Med 308: 477–484

    Google Scholar 

  9. Frei E, Sallan SE (1978) Acute lymphoblastic leukemia: Treatment. Cancer 42: 828–838

    Google Scholar 

  10. Gaedicke G, Winkler K, Petersen N, Stein H, Landbeck G (1977) Das maligne mediastinale lymphoblastische Lymphom mit leukämischem Verlauf. Klin Paediatr 189: 31–36

    Google Scholar 

  11. Green DM, Brecher ML, Blumenson LE, Grossi M, Freeman AI (1982) The use of intermediate dose methotrexate in increased risk childhood acute lymphoblastic leukemia. Cancer 50: 2711–2727

    Google Scholar 

  12. Haas RJ, Netzel B, Janka GE, Rodt H, Thiel E, Thierfelder S (1978) Diagnostischer Einsatz spezifischer Antiseren bei der akuten lymphatischen Leukämie im Kindesalter. Klin Paediatr 191: 446–452

    Google Scholar 

  13. Haas RJ, Helmig M, Prentl E (1980) Effektivität intramuskulär verabreichten Cytosin-Arabinosids bei der ambulanten Behandlung von Kindern mit akuter Leukämie. Onkologie 3: 53–59

    Google Scholar 

  14. Haas RJ, Janka GE, Netzel B, Helmig M, für die Mitglieder der Studie (1981) Münchner Studie zur Behandlung der akuten lymphoblastischen Leukämie im Kindesalter (ALL 77-01). Klin Paediatr 193: 137–144

    Google Scholar 

  15. Henze G, Langermann HJ, Brämswig J, Breu H, Gadner H, Schellong G, Welte K, Riehm H (1981) Ergebnisse der Studie BFM 76/79 zur Behandlung der akuten lymphoblastischen Leukämie bei Kindern und Jugendlichen. Klin Paediatr 193: 145–154

    Google Scholar 

  16. Killmann SA (1972) Kinetics of leukemic blast cells in man. Clin Haematol 1: 95–111

    Google Scholar 

  17. Lobel JS, O'Brien RT, Mc Intosh S, Aspnes GT, Capizzi RL (1979) Methotrexate and asparaginase combination chemotherapy in refractory acute lymphoblastic leukemia of childhood. Cancer 43: 1089–1094

    Google Scholar 

  18. Netzel B, Rodt H, Thiel E, Haas RJ, Thierfelder S (1979) Use of specific antisera against leukemia-associated antigens in the diagnosis of childhood lymphoblastic leukemia. Acta Haematol 61: 177–183

    Google Scholar 

  19. Pinkel D (1979) The Ninth Annual David Karnofsky Lecture. Treatment of acute lymphocytic leukemia. Cancer 43: 1128–1137

    Google Scholar 

  20. Riehm H, Gadner H, Welte (1977) Die West-Berliner Studie zur Behandlung der akuten lymphoblastischen Leukämie des Kindes. Erfahrungsbericht nach 6 Jahren. Klin Paediatr 189: 89–102

    Google Scholar 

  21. Sinks LF, Wang JJ, Freeman AI (1981) The treatment of primary childhood acute lymphocytic leukemia with intermediate dose methotrexate. In: Neth, Gallo, Graf, Mannweiler, Winkler (eds) Haematology and blood Transfusion, Vol. 26. Modern trends in human leukemia IV. Springer, Berlin Heidelberg, pp 18–26

    Google Scholar 

  22. Thiel E, Rodt H, Huhn D, Netzel B, Grosse-Wilde H, Ganeshaguru K, Thierfelder S (1980) Multimarker classification of acute lymphoblastic leukemia: evidence for further T subgroups and evaluation of their clinical significance. Blood 56: 759–772

    Google Scholar 

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Authors and Affiliations

  1. Abteilung Hämatologie und Onkologie, Kinderklinik der Universität München, Lindwurmstraße 4, D-8000, München 2, Federal Republic of Germany

    R. J. Haas, G. Janka & B. Netzel

  2. Abteilung Pädiatrie II, Kinderklinik der Universität Ulm, Prittwitzstraße 43, D-7900, Ulm/Donau, Federal Republic of Germany

    G. Gaedicke & E. Kohne

Authors
  1. R. J. Haas
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  2. G. Janka
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  3. G. Gaedicke
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  4. E. Kohne
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  5. B. Netzel
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Additional information

In cooperation with E. Kleihauer, I. Eick-Prinz (Ulm), V. Schöck (Bielefeld), F. J. Knust (Hamm), O. Sauer (Mannheim), M. Keuth (Neunkirchen), E. Pongratz (Augsburg), P. Klose (München-Harlaching), R. Dickerhoff, U. Graubner, M. Helmig (München), H. Rodt, E. Thiel (Institut für Hämatologie, München), and D. Hölzel (Institut für Statistik und Dokumentation, München)

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Haas, R.J., Janka, G., Gaedicke, G. et al. Therapy of acute lymphocytic leukemia in childhood with intermediate dose methotrexate and CNS irradiation. Blut 47, 321–331 (1983). https://doi.org/10.1007/BF00320346

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  • DOI: https://doi.org/10.1007/BF00320346

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