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Intensification of remission induction therapy for acute nonlymphocytic leukemia (ANLL)

I. Response and toxicity in four different regimens

Intensivierte Induktionstherapie der akuten nichtlymphoblastischen Leukämie (ANLL)

I. Therapeutische Resultate und Toxizität von 4 verschiedenen Protokollen

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Zusammenfassung

Cytosin-Arabinosid (ARA-C) und Daunorubicin (DNR) (7+3-Schema) führten bei 16 von 31 erwachsenen Patienten mit ANLL zu einer kompletten Remission (C.R.) (Regime A). Das identische Schema erweitert durch Vincristin (VCR) und Ifosfamid (IF) ergab eine C.R. bei 5 von 11 Patienten (Regime B). Dosissteigerung für ARA-C und DNR sowie Ergänzungen durch Thioguanin (TG) (T.A.D.-Schema) ergab C.R. bei 5 von 9 Patienten, wenn ARA-C kontinuierlich infundiert wurde (Regime D) und bei 8 von 10 Patienten wenn ARA-C als Bolus-Injektionen gegeben wurde (Regime F).

Eine adäquate Blastenreduktion im Knochenmark bereits nach dem ersten Kurs zeigten bei den T.A.D.-Schemata D und F 11 von 14 Patienten gegenüber 15/38 bei A und B (p<0,05). Die Erholungszeit der Neutrophilen und Thrombozyten war nach einem D- oder F-Kurs nicht länger als nach einem A- oder B-Kurs, sofern eine adäquate Blastenreduktion erzielt wurde.

Erhöhte Dosis von ARA-C als Dauerinfusion (D) statt Bolusinjektion (F) verursachte inakzeptable gastro-intestinale Nebenwirkungen.

Nach dem am längsten verfolgten Regime A betrug die mediane Remissionsdauer 11,5 (1-31+) Monate, und zwar bei Patienten mit adäquater Blastenreduktion durch den ersten Kurs 19 (5-31+) Monate vs. 2,5 (1–6) Monate bei Patienten mit verzögerter Blastenreduktion (p<0,001).

Bei Patienten unter 60 Jahren erreichten 11/11 bei den Regimen D und F eine C.R. gegenüber 18/34 in A und B (p<0,025). Bei den Patienten ohne Dosisreduktion erreichten 12/14 bei den Regimen D und F und 13/36 bei A und B eine C.R. (p<0,1).

Summary

Cytosine arabinoside (ARA-C) and daunorubicin (DNR) (7+3 regimen) produced complete remission (C.R.) in 16 of 31 adult patients with ANLL (regimen A). Addition of vincristine (VCR) and ifosfamide (IF) revealed C.R. in 5 of 11 patients (regimen B). Dosage escalation for ARA-C and DNR and additional thioguanine (T.A.D. regimen) produced C.R. in 5 of 9 patients when ARA-C was given by continuous infusion (regimen D) and in 8 of 10 patients when given by bolus injections (regimen F).

Clearance of blasts from the bone marrow by the first course was achieved in 11 of 14 patients by the T.A.D. regimens D and F vs. 15 of 38 patients by regimens A and B (p<0.05). Time to recovery of neutrophils and platelets after one course of D or F was not prolonged as compared to A and B provided that clearance of bone marrow blasts was adequate. Increased dose of ARA-C by continuous infusion (D) instead of bolus injections (F) induced unacceptable gastrointestinal toxicity.

In (only evaluable) regimen A median remission duration was 11.5 (1-31+) months. In patients with adequate blast clearance by the first course median remission duration was 19 (5-31+) months vs. 2.5 (1–6) months in the delayed blast clearance group (p<0.001).

In patients under 60 years of age in regimens D and F 11 of 11 achieved C.R. vs. 18 of 34 in A and B (p<0.025). In patients receiving chemotherapy at original dosage 12 of 14 in regimens D and F achieved C.R. vs. 13 of 26 in A and B (p<0.1).

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Authors and Affiliations

  1. Medizinische Universitätsklinik und Poliklinik und Institut für Arterioskleroseforschung an der Universität Münster, Westring 3, D-4400, Münster i. Westf., Federal Republic of Germany

    Th. Büchner, D. Urbanitz, W. Hiddemann, D. Kamanabroo, R. Meister, L. Balleisen, U. Delvos, E. -M. Lagrèze, U. Schmitz-Huebner, H. Schulte & J. van de Loo

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  1. Th. Büchner
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  2. D. Urbanitz
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  3. W. Hiddemann
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  4. D. Kamanabroo
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  5. R. Meister
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  6. L. Balleisen
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  7. U. Delvos
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  8. E. -M. Lagrèze
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  9. U. Schmitz-Huebner
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  10. H. Schulte
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  11. J. van de Loo
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Büchner, T., Urbanitz, D., Hiddemann, W. et al. Intensification of remission induction therapy for acute nonlymphocytic leukemia (ANLL). Blut 39, 133–140 (1979). https://doi.org/10.1007/BF01008088

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