Dietzfelbinger, H.

Emmerich, B.

Knauf, W. U.

Langenmayer, Irmgard

Mausbach, P.

Nerl, C.

Thiel, E.

Ziegler-Heitbrock, H. W.

English

Universität München: Elektronischen Publikationen

15-1-92 
ISSN 0378-584 Χ 
1992; 15:1-76 
Β 4308 F 
CA Internationale Zeitschrift für 
Krebsforschung und -behandlung 
Aus dem Inhalt • From the Contents 
UBERSICHTSARBEITEN · REVIEW ARTICLES 
Regional Chemotherapy of Malignant Liver Tumors 
ORIGINALARBEITEN - ORIGINAL PAPERS 
Idarubicin in Relapsed and Refractory AML 12 
Primary Gastrointestinal Sarcomas 20 
Goals of Treatment in Metastatic Breast Cancer 25 
TNFoc Modulation for Prophylaxis of aGvHD 31 
Prognostic Value of S-Phase Fraction \ 36 
\ 
LXuraräDE KLINISCHE STUDIEN • ONGOING dLINICALTRIALS 
All Trans Retinoic Acid in APLTherapy 42 
G-CSF in High-Grade Malignant NHL 46 
lnterferon-alpha2b for Early Phase 
Chronic Lymphocytic Leukemia 55 
INFORMATIONEN FÜR DIE KLINIK . CLINICAL INFORMATION 
Empfehlungen für onkologische Prüfinstitutionen 
der Phase I und Phase IIa 58 
Ausführliches Autoren- und Inhaltsverzeichnis siehe Seite 2 
Complete Author Index and Contents on Page 2 
S. Karger 
Verlag für Medizin und 
Naturwissenschaften GmbH 
Basel · München 
Paris · London 
New York · New Delhi 
Bangkok · Singapore ^^^^p^^^^^^^f Suuauuao f£08 ΌντΗΗΛ aaOHVM s 
Onkologie 1992;15:55-57 
WKnauf" 
I.Langenmayerb 
Ctierl0 
H: Dietzfelbinger d 
P/Ua\ibäche 
HML Ziegler-Heitbrockf 
B. Emmerich* 
a Abt. Hämatologie/Onkologie, Klinikum 
Steglitz der Freien Universität Berlin 
b Abt. Hämatologie, Klinikum Innenstadt der 
Universität München 
c I . Medizinische Klinik, Städtisches Kranken­
haus München-Schwabing 
d Abt. Hämatologie/Onkologie, Klinikum 
rechts der Isar der Technischen Universität 
München 
e I . Medizinische Klinik Ingolstadt 
f Institut für Immunologie der Universität 
München 
lnterferon-alpha2b for Early Phase 
Chronic Lymphocytic Leukemia 
with High Risk for Progression -
First Results of a Randomized 
Multicenter AlO-Study1 
Key Words 
Interferon-alpha2b 
Chronic lymphocytic leukemia 
Early phase 
Summary 
Background: In prior pilot studies Interferon-alpha2b (IFN-alpha) was shown to be 
effective in B-cell type chronic lymphocytic leukemia (B-CLL). Therefore, the bene­
fit of an IFN-alpha-therapy in early phase B-CLL is assessed with respect to freedom 
from progression and long term survival in a randomized multicenter study. Material 
and methods: Patients with early phase B-CLL (Binet A) and high risk for progres­
sion (diffuse bone marrow infiltration plus serum level of thymidinkinase >5 U/l 
plus/or lymphocyte doubling time < 12 months) are randomized into an IFN-treat-
ment group (arm A) or a watch and wait group (arm B). Patients who do not share 
the risk parameters are documented in another watch and wait arm C. Dosage of 
IFN-alpha is 3 χ 5 Mill. IE per week. Results: Out of 14 evaluable patients im arm A 
two patients achieved a complete remission (normalization of blood cell counts, no 
lymph nodes palpable) and three patients attained a partial remission. Three patients 
have stable disease, and one out of four patients with progressive disease was in need 
of chemotherapy. Ten out of 15 evaluable patients in arm Β have stable disease, but 
five others had progressive disease with four patients in need of chemotherapy. None 
of the 24 evaluable patients in arm C had progressive disease with need of chemo­
therapy. Conclusion: These preliminary results seem to prove the validity of the risk 
parameters and show the possible benefit of an IFN-treatment in early phase B-CLL 
at high risk for progression. 
1 Presented as Actual Contribution' at the Common Meeting of German and Austrian Societies of 
Hematology and Oncology, Innsbruck, October 10 -13,1991 
Dr. W. Knauf © 1992 S. Karger GmbH, 
Abt. Hämatologie München 
Klinikum Steglitz der FU 
Hindenburgdamm 30 
D-1000 Berlin 45 (FRG) 
Schlüsselwörter Zusammenfassung 
Interferon-alpha2b Hintergrund: In Pilotstudien hat sich Interferon-alpha2b (IFN-alpha) als effektiv in 
Chronische lymphatische Leukämie der Behandlung der chronischen lymphatischen Leukämie vom B-Zelltyp (B-CLL) 
Frühphase erwiesen. In einer randomisierten multizentrischen Studie wird deshalb der Nutzen 
einer Interferonbehandlung bezüglich Progressionsfreiheit und Langzeitüberleben 
geprüft. Material und Methodik: Patienten mit einer unbehandelten B-CLL im Früh­
stadium (Binet A) und hohem Progressionsrisiko (diffuse Knochenmarkinfiltration 
plus Serumspiegel der Thymidinkinase >5 U/1 plus/oder Lymphozytenverdopplungs-
zeit < 12 Monate) werden einer IFN-Behandlungsgruppe (Arm A) oder einer Beob­
achtungsgruppe (Arm B) zugeteilt. Patienten, die das Risikoprofil nicht erfüllen, 
werden in einem weiteren Beobachtungsarm C dokumentiert. Die Dosierung von 
IFN-alpha besteht aus 3x5 Mill. IE pro Woche. Ergebnisse: Von 14 auswertbaren 
Patienten im Arm Α haben zwei Patienten eine klinische komplette Remission (Nor­
malisierung des Blutbildes, keine Lymphadenopathie) und drei Patienten eine parti­
elle Remission erreicht. Drei Patienten sind in einer stabilen Phase und vier Patien­
ten waren progredient, wovon jedoch nur ein Patient zytostatisch behandelt werden 
mußte. Bei zwei weiteren Patienten wurde die Therapie wegen Nebenwirkungen vor­
zeitig abgebrochen. In Arm Β sind zehn von 15 auswertbaren Patienten in einer 
stabilen Phase, und vier von fünf progredienten Patienten mußten zytostatisch be­
handelt werden. Von 24 evaluierbaren Patienten im Arm C erlitt keiner eine thera­
piepflichtige Progression. Schlußfolgerung: Diese vorläufigen Daten unterstützen 
nicht nur das Stratifizierungskonzept, sondern weisen auch auf einen therapeuti­
schen Nutzen des IFN-alpha in der Frühphase der B-CLL hin. 
Introduction 
The majority of previously untreated patients with early phase 
B-cell chronic lymphocytic leukemia (B-CLL, stage Binet A) 
expects a long-lasting indolent course of the disease. Long 
time survival of these patients does not differ from that of an 
age and sex matched control population [1]. However, approxi­
mately 30% of the patients will have progressive disease within 
two years after establishment of diagnosis. Diffuse bone mar­
row infiltration [2], lymphocyte doubling time > 12 months [3], 
and serum levels of thymidine kinase >5 U/l [4] have been iden­
tified as risk factors for progression. In pilot studies, inter-
feron-alpha2b (IFN-cc) has been shown to be efficient for 
B-CLL [5,6]. In Binet stage A disease a decrease of circulating 
malignant B-lymphocytes was achieved. In addition, IFN-cc 
treatment induced an increase in serum immunoglobulin levels 
[7]. The possible benefit of an IFN-oc treatment of Binet stage 
A B-CLL at high risk for progression is therefore being exam­
ined in an ongoing randomized multicenter study. The goals of 
the study are freedom from progression and from chemothera­
py, and overall survival. 
Material and Methods 
Inclusion criteria and study design: Patients who are not older than 75 
years and having a morphologically and immunophenotypically proven, 
previously untreated B - C L L in stage Binet A were included into the study. 
The lymphocyte count to had be below 100,000/μ1. The patients had to 
give their written informed consent. Patients with a diffuse bone marrow 
involvement and a lymphocyte doubling time <12 months, and/or a serum 
thymidine kinase level > 5 U/ l were allocated to the high risk group. They 
were randomized into study arm A (IFN-a therapy) or study arm Β (wait 
and watch). Patients with diffuse bone marrow involvement but without an 
additional risk factor as well as all patients with nodular bone marrow infil­
tration are allocated to the low risk group receiving no treatment (study 
arm C, wait and watch). 
Patient characteristics: Until September 1,1991,100 patients were enrolled 
into the study. Risk factors were known from 63 patients. Sixteen patients 
were randomized into arm A , and 19 patients into arm B. Twenty-eight pa­
tients did not fulfill the criteria for being at high risk for progression and 
were therefore included in arm C. In the high risk group, the mean lym­
phocyte doubling time was 4.1 months compared to 27.4 months in the low 
risk group. The mean serum level of thymidine kinase was 11.0 U/l in the 
high risk and 4.6 U/ l in the low risk patients. 
Therapy: High risk patients randomized into study arm A are treated with 
IFN-α (Intron A®) subcutaneously. The planned dosage per week is 3x5 
Mio I E IFN-α. Dose modification for individual reasons like toxic side ef­
fects is possible. In case of increasing lymphocyte counts during IFN-α 
treatment, dose escalation up to 3x8 Mio I E IFN-α is planned. 
Results 
Two out of 14 evaluable patients of the IFN-treatment group 
achieved a complete remission defined as normalization of pe­
ripheral blood counts and absence of enlarged lymphnodes. 
Three patients attained a partial remission and three other pa­
tients had stable disease. In four patients progression occurred 
and one of them was in need of chemotherapy. Due to toxic 
side effects (fever, nausea, depression) the treatment was 
56 Knauf/Langenmayer/Nerl/Dietzfelbinger/ Interferon-alpha2b for Early Phase Chronic 
Maubach/Ziegler-Heitbrock/Emmerich/Thiel Lymphocytic Leukemia 
Table 1. Treatment P P i l i ! ^ ^ 
r e s u j t s - High risk/ High risk/ Low risk/ 
IFN-ot treatment (n = 16) no treatment (n = 19) no treatment (n = 28) 
Evaluable 14 15 24 
Complete remission 2 
Partial remission 3 
Stable disease 3 10 21 
Progression1 4 5 3 
Need for chemotherapy 1 4 0 
Off study due to toxicity 2 
1 Progression is defined as increase of lymphocytes over 100,000/μ1, or occurrance of new enlarged lymphnodes, or increase of 
prior enlarged liver/spleen/lymphnodes 
Table 2. Toxicity of IFN-α (WHO grading > II ) 
η 
Fever 2 
Arthralgia/myalgia 1 ' . 
Diarrhea 1 
Nausea/vomiting 0 
Weight loss 1 
Hair loss •0 
Depression 2 
stopped in two patients. Ten out of 15 evaluable patients of the 
high risk group without IFN-α treatment have stable disease, 
whereas five patients had progressive disease, with four of 
them in need of chemotherapy. In contrast, none of the 24 pa­
tients in the low risk group was in need of chemotherapy. 
The treatment results and toxicities of IFN-α are summarized 
in tables 1 and 2, respectively. 
Discussion 
These preliminary results seem to show the benefit of an IFN-α 
treatment of early stage B-CLL at high risk for progression. 
Antileucemic effects of IFN-α had been reported earlier in pi­
lot studies on B-CLL [5,6,7]. It has been shown, that IFN-α is 
more effective in early stage than in late stage disease [8]. In 
this still ongoing randomized trial the effectiveness of IFN-α 
appears to become evident. While four out of 14 patients treat­
ed with IFN-α had progressive disease, only one of them was in 
need of chemotherapy. In the high risk group, however, five out 
of 15 patients had progressive disease and four of them needed 
chemotherapy. Moreover, the randomization concept seems to 
be confirmed as none of the patients without risk factors were 
in fact in need of specific therapy. These preliminary data sup­
port the validity of the risk factors, i.e. diffuse bone marrow in­
filtration, short lymphocyte doubling time, and high levels of 
serum thymidine kinase. Whether IFN-α could decrease the 
use of chemotherapy and prolong overall survival requires a 
greater number of patients and follow-up investigation of this 
ongoing trial. 
References 
1 French cooperative group on chronic lymphocytic 
leukemia: Effects of chlorambucil and therapeutic de­
cision in initial forms of chronic lymphocytic leuke­
mia (stage A): Results of a randomized clinical trial 
on 612 patients. Blood 1991;75:1414-1421. 
2Rozman C, Hernandez-Nieto L, Montserrat E , Bru-
gues R: Prognostic significance of bone marrow pat­
terns in chronic lymphocytic leukaemia. Brit J Hae­
matol 1981;47:529-537. 
3 Montserrat E , Sanchez-Bisono J, Vinolas N, Rozman 
C: Lymphocyte doubling time in chronic lymphocytic 
leukaemia: Analysis of its prognostic significance. 
Brit J Haematol 1986;62:567-575. 
4 Källander CFR, Simonsson B, Hagberg H, Grono-
witz JS: Serum deoxythymidine kinase gives progno- · 
stic information in chronic lymphocytic leukemia. 
Cancer 1984;54:2450-2455. 
5 Thiel Ε, Schlag R, Hill W, Kettner G, Flieger D, Zieg­
ler HWL: B-CLL in early phase responds to recom­
binant alpha-2b interferon therapy as determined in a 
pilot study. Blut 1987;55:243A. 
6 Pangalis GA, Griva E: Recombinant alpha-2b-inter-
feron therapy in untreated stages A and Β chronic 
lymphocytic leukemia. Cancer 1988;61:869-872. 
7 Ziegler-Heitbrock HWL, Schlag R, Flieger D, Thiel 
Ε: Favorable response of early stage B-CLL patients 
to treatment with IFN-alpha2. Blood 1989; 
73:1426-1430. 
8 Leavitt RD, Ratanatharathorn V, Ozer H, Ultmann 
JE, Portlock C, Myers JW, Kisner D, Norred S, Spie­
gel J, Bonnern EM: Alpha-2b interferon in the treat­
ment of Hodgkin's disease and non-Hodgkin's lym­
phoma. Semin Oncol 1987;14(suppl 2):18-23. 
57 


Interferon-alpha 2b early phase chronic Lymphocytic Leukemia with high risk for progression-first results of a randomized multicenter AIO-Study

Open Access LMU

15-1-92 ISSN 0378-584 Χ 1992; 15:1-76 Β 4308 F CA Internationale Zeitschrift für Krebsforschung und -behandlung Aus dem Inhalt • From the Contents UBERSICHTSARBEITEN · REVIEW ARTICLES Regional Chemotherapy of Malignant Liver Tumors ORIGINALARBEITEN - ORIGINAL PAPERS Idarubicin in Relapsed and Refractory AML 12 Primary Gastrointestinal Sarcomas 20 Goals of Treatment in Metastatic Breast Cancer 25 TNFoc Modulation for Prophylaxis of aGvHD 31 Prognostic Value of S-Phase Fraction \ 36 \ LXuraräDE KLINISCHE STUDIEN • ONGOING dLINICALTRIALS All Trans Retinoic Acid in APLTherapy 42 G-CSF in High-Grade Malignant NHL 46 lnterferon-alpha2b for Early Phase Chronic Lymphocytic Leukemia 55 INFORMATIONEN FÜR DIE KLINIK . CLINICAL INFORMATION Empfehlungen für onkologische Prüfinstitutionen der Phase I und Phase IIa 58 Ausführliches Autoren- und Inhaltsverzeichnis siehe Seite 2 Complete Author Index and Contents on Page 2 S. Karger Verlag für Medizin und Naturwissenschaften GmbH Basel · München Paris · London New York · New Delhi Bangkok · Singapore ^^^^p^^^^^^^f Suuauuao f£08 ΌντΗΗΛ aaOHVM s Onkologie 1992;15:55-57 WKnauf" I.Langenmayerb Ctierl0 H: Dietzfelbinger d P/Ua\ibäche HML Ziegler-Heitbrockf B. Emmerich* a Abt. Hämatologie/Onkologie, Klinikum Steglitz der Freien Universität Berlin b Abt. Hämatologie, Klinikum Innenstadt der Universität München c I . Medizinische Klinik, Städtisches Kranken­haus München-Schwabing d Abt. Hämatologie/Onkologie, Klinikum rechts der Isar der Technischen Universität München e I . Medizinische Klinik Ingolstadt f Institut für Immunologie der Universität München lnterferon-alpha2b for Early Phase Chronic Lymphocytic Leukemia with High Risk for Progression -First Results of a Randomized Multicenter AlO-Study1 Key Words Interferon-alpha2b Chronic lymphocytic leukemia Early phase Summary Background: In prior pilot studies Interferon-alpha2b (IFN-alpha) was shown to be effective in B-cell type chronic lymphocytic leukemia (B-CLL). Therefore, the bene­fit of an IFN-alpha-therapy in early phase B-CLL is assessed with respect to freedom from progression and long term survival in a randomized multicenter study. Material and methods: Patients with early phase B-CLL (Binet A) and high risk for progres­sion (diffuse bone marrow infiltration plus serum level of thymidinkinase >5 U/l plus/or lymphocyte doubling time < 12 months) are randomized into an IFN-treat-ment group (arm A) or a watch and wait group (arm B). Patients who do not share the risk parameters are documented in another watch and wait arm C. Dosage of IFN-alpha is 3 χ 5 Mill. IE per week. Results: Out of 14 evaluable patients im arm A two patients achieved a complete remission (normalization of blood cell counts, no lymph nodes palpable) and three patients attained a partial remission. Three patients have stable disease, and one out of four patients with progressive disease was in need of chemotherapy. Ten out of 15 evaluable patients in arm Β have stable disease, but five others had progressive disease with four patients in need of chemotherapy. None of the 24 evaluable patients in arm C had progressive disease with need of chemo­therapy. Conclusion: These preliminary results seem to prove the validity of the risk parameters and show the possible benefit of an IFN-treatment in early phase B-CLL at high risk for progression. 1 Presented as Actual Contribution' at the Common Meeting of German and Austrian Societies of Hematology and Oncology, Innsbruck, October 10 -13,1991 Dr. W. Knauf © 1992 S. Karger GmbH, Abt. Hämatologie München Klinikum Steglitz der FU Hindenburgdamm 30 D-1000 Berlin 45 (FRG) Schlüsselwörter Zusammenfassung Interferon-alpha2b Hintergrund: In Pilotstudien hat sich Interferon-alpha2b (IFN-alpha) als effektiv in Chronische lymphatische Leukämie der Behandlung der chronischen lymphatischen Leukämie vom B-Zelltyp (B-CLL) Frühphase erwiesen. In einer randomisierten multizentrischen Studie wird deshalb der Nutzen einer Interferonbehandlung bezüglich Progressionsfreiheit und Langzeitüberleben geprüft. Material und Methodik: Patienten mit einer unbehandelten B-CLL im Früh­stadium (Binet A) und hohem Progressionsrisiko (diffuse Knochenmarkinfiltration plus Serumspiegel der Thymidinkinase >5 U/1 plus/oder Lymphozytenverdopplungs-zeit < 12 Monate) werden einer IFN-Behandlungsgruppe (Arm A) oder einer Beob­achtungsgruppe (Arm B) zugeteilt. Patienten, die das Risikoprofil nicht erfüllen, werden in einem weiteren Beobachtungsarm C dokumentiert. Die Dosierung von IFN-alpha besteht aus 3x5 Mill. IE pro Woche. Ergebnisse: Von 14 auswertbaren Patienten im Arm Α haben zwei Patienten eine klinische komplette Remission (Nor­malisierung des Blutbildes, keine Lymphadenopathie) und drei Patienten eine parti­elle Remission erreicht. Drei Patienten sind in einer stabilen Phase und vier Patien­ten waren progredient, wovon jedoch nur ein Patient zytostatisch behandelt werden mußte. Bei zwei weiteren Patienten wurde die Therapie wegen Nebenwirkungen vor­zeitig abgebrochen. In Arm Β sind zehn von 15 auswertbaren Patienten in einer stabilen Phase, und vier von fünf progredienten Patienten mußten zytostatisch be­handelt werden. Von 24 evaluierbaren Patienten im Arm C erlitt keiner eine thera­piepflichtige Progression. Schlußfolgerung: Diese vorläufigen Daten unterstützen nicht nur das Stratifizierungskonzept, sondern weisen auch auf einen therapeuti­schen Nutzen des IFN-alpha in der Frühphase der B-CLL hin. Introduction The majority of previously untreated patients with early phase B-cell chronic lymphocytic leukemia (B-CLL, stage Binet A) expects a long-lasting indolent course of the disease. Long time survival of these patients does not differ from that of an age and sex matched control population [1]. However, approxi­mately 30% of the patients will have progressive disease within two years after establishment of diagnosis. Diffuse bone mar­row infiltration [2], lymphocyte doubling time > 12 months [3], and serum levels of thymidine kinase >5 U/l [4] have been iden­tified as risk factors for progression. In pilot studies, inter-feron-alpha2b (IFN-cc) has been shown to be efficient for B-CLL [5,6]. In Binet stage A disease a decrease of circulating malignant B-lymphocytes was achieved. In addition, IFN-cc treatment induced an increase in serum immunoglobulin levels [7]. The possible benefit of an IFN-oc treatment of Binet stage A B-CLL at high risk for progression is therefore being exam­ined in an ongoing randomized multicenter study. The goals of the study are freedom from progression and from chemothera­py, and overall survival. Material and Methods Inclusion criteria and study design: Patients who are not older than 75 years and having a morphologically and immunophenotypically proven, previously untreated B - C L L in stage Binet A were included into the study. The lymphocyte count to had be below 100,000/μ1. The patients had to give their written informed consent. Patients with a diffuse bone marrow involvement and a lymphocyte doubling time <12 months, and/or a serum thymidine kinase level > 5 U/ l were allocated to the high risk group. They were randomized into study arm A (IFN-a therapy) or study arm Β (wait and watch). Patients with diffuse bone marrow involvement but without an additional risk factor as well as all patients with nodular bone marrow infil­tration are allocated to the low risk group receiving no treatment (study arm C, wait and watch). Patient characteristics: Until September 1,1991,100 patients were enrolled into the study. Risk factors were known from 63 patients. Sixteen patients were randomized into arm A , and 19 patients into arm B. Twenty-eight pa­tients did not fulfill the criteria for being at high risk for progression and were therefore included in arm C. In the high risk group, the mean lym­phocyte doubling time was 4.1 months compared to 27.4 months in the low risk group. The mean serum level of thymidine kinase was 11.0 U/l in the high risk and 4.6 U/ l in the low risk patients. Therapy: High risk patients randomized into study arm A are treated with IFN-α (Intron A®) subcutaneously. The planned dosage per week is 3x5 Mio I E IFN-α. Dose modification for individual reasons like toxic side ef­fects is possible. In case of increasing lymphocyte counts during IFN-α treatment, dose escalation up to 3x8 Mio I E IFN-α is planned. Results Two out of 14 evaluable patients of the IFN-treatment group achieved a complete remission defined as normalization of pe­ripheral blood counts and absence of enlarged lymphnodes. Three patients attained a partial remission and three other pa­tients had stable disease. In four patients progression occurred and one of them was in need of chemotherapy. Due to toxic side effects (fever, nausea, depression) the treatment was 56 Knauf/Langenmayer/Nerl/Dietzfelbinger/ Interferon-alpha2b for Early Phase Chronic Maubach/Ziegler-Heitbrock/Emmerich/Thiel Lymphocytic Leukemia Table 1. Treatment P P i l i ! ^ ^ r e s u j t s - High risk/ High risk/ Low risk/ IFN-ot treatment (n = 16) no treatment (n = 19) no treatment (n = 28) Evaluable 14 15 24 Complete remission 2 Partial remission 3 Stable disease 3 10 21 Progression1 4 5 3 Need for chemotherapy 1 4 0 Off study due to toxicity 2 1 Progression is defined as increase of lymphocytes over 100,000/μ1, or occurrance of new enlarged lymphnodes, or increase of prior enlarged liver/spleen/lymphnodes Table 2. Toxicity of IFN-α (WHO grading > II ) η Fever 2 Arthralgia/myalgia 1 ' . Diarrhea 1 Nausea/vomiting 0 Weight loss 1 Hair loss •0 Depression 2 stopped in two patients. Ten out of 15 evaluable patients of the high risk group without IFN-α treatment have stable disease, whereas five patients had progressive disease, with four of them in need of chemotherapy. In contrast, none of the 24 pa­tients in the low risk group was in need of chemotherapy. The treatment results and toxicities of IFN-α are summarized in tables 1 and 2, respectively. Discussion These preliminary results seem to show the benefit of an IFN-α treatment of early stage B-CLL at high risk for progression. Antileucemic effects of IFN-α had been reported earlier in pi­lot studies on B-CLL [5,6,7]. It has been shown, that IFN-α is more effective in early stage than in late stage disease [8]. In this still ongoing randomized trial the effectiveness of IFN-α appears to become evident. While four out of 14 patients treat­ed with IFN-α had progressive disease, only one of them was in need of chemotherapy. In the high risk group, however, five out of 15 patients had progressive disease and four of them needed chemotherapy. Moreover, the randomization concept seems to be confirmed as none of the patients without risk factors were in fact in need of specific therapy. These preliminary data sup­port the validity of the risk factors, i.e. diffuse bone marrow in­filtration, short lymphocyte doubling time, and high levels of serum thymidine kinase. Whether IFN-α could decrease the use of chemotherapy and prolong overall survival requires a greater number of patients and follow-up investigation of this ongoing trial. References 1 French cooperative group on chronic lymphocytic leukemia: Effects of chlorambucil and therapeutic de­cision in initial forms of chronic lymphocytic leuke­mia (stage A): Results of a randomized clinical trial on 612 patients. Blood 1991;75:1414-1421. 2Rozman C, Hernandez-Nieto L, Montserrat E , Bru-gues R: Prognostic significance of bone marrow pat­terns in chronic lymphocytic leukaemia. Brit J Hae­matol 1981;47:529-537. 3 Montserrat E , Sanchez-Bisono J, Vinolas N, Rozman C: Lymphocyte doubling time in chronic lymphocytic leukaemia: Analysis of its prognostic significance. Brit J Haematol 1986;62:567-575. 4 Källander CFR, Simonsson B, Hagberg H, Grono-witz JS: Serum deoxythymidine kinase gives progno- · stic information in chronic lymphocytic leukemia. Cancer 1984;54:2450-2455. 5 Thiel Ε, Schlag R, Hill W, Kettner G, Flieger D, Zieg­ler HWL: B-CLL in early phase responds to recom­binant alpha-2b interferon therapy as determined in a pilot study. Blut 1987;55:243A. 6 Pangalis GA, Griva E: Recombinant alpha-2b-inter-feron therapy in untreated stages A and Β chronic lymphocytic leukemia. Cancer 1988;61:869-872. 7 Ziegler-Heitbrock HWL, Schlag R, Flieger D, Thiel Ε: Favorable response of early stage B-CLL patients to treatment with IFN-alpha2. Blood 1989; 73:1426-1430. 8 Leavitt RD, Ratanatharathorn V, Ozer H, Ultmann JE, Portlock C, Myers JW, Kisner D, Norred S, Spie­gel J, Bonnern EM: Alpha-2b interferon in the treat­ment of Hodgkin's disease and non-Hodgkin's lym­phoma. Semin Oncol 1987;14(suppl 2):18-23. 57 

Favorable response of early stage B-CLL patients to treatment with IFN-alpha2. Blood

French cooperative group on chronic lymphocytic leukemia: Effects of chlorambucil and therapeutic de cision in initial forms of chronic lymphocytic leuke mia (stage A): Results of a randomized clinical trial on 612 patients.

Griva E: Recombinant alpha-2b-interferon therapy in untreated stages A and Β chronic lymphocytic leukemia.

Gronowitz JS: Serum deoxythymidine kinase gives progno- · stic information in chronic lymphocytic leukemia.

Lymphocyte doubling time in chronic lymphocytic leukaemia: Analysis of its prognostic significance.

Prognostic significance of bone marrow pat terns in chronic lymphocytic leukaemia.

Zieg ler HWL: B-CLL in early phase responds to recom binant alpha-2b interferon therapy as determined in a pilot study. Blut

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Interferon-alpha 2b early phase chronic Lymphocytic Leukemia with high risk for progression-first results of a randomized multicenter AIO-Study

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