1. ORIGINAL ARTICLE
Altered treatment of chronic lymphocytic leukemia in Germany
during the last decade
Anna-Katharina Zoellner1
& Thomas Höhler2
& Stefan Fries3
& Angelika Böhme4
&
Philipp Kiewe5
& Lenka Kellermann6
& Martin Dreyling1
Received: 28 July 2015 /Accepted: 9 March 2016
# Springer-Verlag Berlin Heidelberg 2016
Abstract Chronic lymphocytic leukemia (CLL) is the most
common subtype of adult leukemia in the western world. We
here report a nationwide survey monitoring the treatment de-
cisions concerning CLL patients in Germany in 2011 and
compare treatment trends to sequential surveys performed pre-
viously during the last decade. The rate of patients diagnosed
in early stages (Binet A/B) notably increased (2006: 66 %,
2009: 71 %, 2011: 77 %) over the years. From 2006 to
2009, the most frequent applied regime switched from
chlorambucil to fludarabine containing regimes (2006
chlorambucil: 32 %, 2009: 14 %, fludarabine 2006: 23 %,
2009: 37 %). In 2011, the combination of rituximab with
bendamustine (31 %) was most frequent used followed by
the rituximab-fludarabine-cyclophosphamide (22 %) regime.
Further, immune-chemotherapies were administered signifi-
cantly more often over the observation period (2006: 15 %,
2011: 73 %). Taken together, this data reflects the change of
treatment strategies over the last decade in clinical reality.
Keywords CLL . Clinical practice .
Rituximab-bendamustine .
Rituximab-fludarabine-cyclophosphamide
Introduction
Chronic lymphocytic leukemia (CLL) is the most common
subtype of adult leukemia in the western world [1].
Treatment strategies vary from watch and wait to various
immuno-chemotherapy regimens.
Monotherapy with alkylating agents such as chlorambucil
was used as standard front line drug in CLL patients for de-
cades [2] but treatment options have significantly improved
with the introduction of purine analogons like fludarabine and
the development of monoclonal antibodies in the last 20 years
[3, 4]. Also, through the availability of flow cytometry and
more frequent blood testing CLL may be detected at earlier
stages and more frequent in younger patients [5, 6].
In Germany, hematologic care is offered by office-based
hematologist [OH], non-university hospitals and university
hospitals. Since patients often have significant comorbidities,
individual treatment approaches are needed.
Clinical treatment guidelines have been established
through several working groups and provide valuable support
in treatment decisions [7, 8]. Still, previous studies have sug-
gested that the patient population treated in clinical trials may
not be consistent with the clinical reality [9, 10]. We therefore
here report an analysis of a nationwide survey monitoring the
treatment decisions concerning CLL patients in Germany
2011. Further, data was descriptively compared to sequential
surveys performed previously [10, 11].
Electronic supplementary material The online version of this article
(doi:10.1007/s00277-016-2640-z) contains supplementary material,
which is available to authorized users.
* Anna-Katharina Zoellner
anna.zoellner@med.lmu.de
1
Department of Internal Medicine III, University Hospital
Munich-Großhadern, Marchioninistr. 15, 81377 Munich, Germany
2
Medizinische Klinik I - Hämatologie/Onkologie, Prosper-Hospital,
Recklinghausen, Germany
3
Onkologischen Schwerpunktpraxis, Bamberg, Germany
4
Onkologikum Frankfurt am Museumsufer, Frankfurt, Germany
5
Onkologische Praxis, Berlin, Germany
6
Oncology Information Service, Freiburg, Germany
Ann Hematol
DOI 10.1007/s00277-016-2640-z

2. Methods
Data of four nationwide health care surveys which were conduct-
ed sequentially in 2006, 2009, 2010, and 2011 in Germany in-
cluded cohorts of patients with CLL with treatment decision (start
or watch and wait, change or end of therapy) in a defined time
period. The retrospective surveys in 2009–2011 represent an up-
date of the survey in 2006 and are based on the same methodol-
ogy. In a structural analysis of CLL prevalence ∼900 centers
involved in the treatment of CLL including university hospitals
(UH), non-university hospitals (CH), and office-based hematolo-
gists (OH) were contacted, 11–16 % of identified centers provid-
ed an information on their patient load (corresponding to >10 %
of the expected national prevalence) prior to patient documenta-
tion. The consistency of the sample regarding the type of treat-
ment institution (UH, CH, and OH) was defined according to the
established distribution of treated prevalence. The online and
external monitoring systems assessed plausibility and complete-
ness of the data after checking data for completeness and plausi-
bility, data on 164 pts. (2006), 207 pts. (2009), 338 pts. (2010),
and 417 pts. (2011) with a treatment decision during a distinct 3-
month period in 2006, 2009, 2010, or 2011 (diagnosis, initiation,
change, or end of therapy) were included in this analysis.
Eight hundred seventeen centers involved in the treatment of
CLL including university hospitals, non-university hospitals,
and office-based hematologist were contacted. Fifteen percent
of identified centers provided information on 1227 patients
corresponding to 13 % of the expected national prevalence.
Detailed data on 417 unselected patients with treatment deci-
sion in the first and second quarter of 2011 (start, change, or
end of therapy) of 48 representative centers (15 university hos-
pitals, 9 non-university hospitals, and 24 office-based hematol-
ogist) were included in this analysis. The distribution of pa-
tients by institution was 16 % university hospital, 26 % non-
university hospital, and 59 % office-based hematologist.
Demographics and clinical data
Patients’ baseline characteristics (demographics, medical history
including comorbidity status and CLL stage in initial diagnosis)
and clinical data were retrospectively extracted from chart re-
views. All variables were reported by the treating physician
pseudonymized according to the available information in the
patient chart. To descriptively assess diagnostic, prognostic,
and treatment patterns according to age, information on cytoge-
netic testing (yes/no, results), and treatment including its objec-
tive and reasons for starting therapy was analyzed for all patients.
Statistics
Data presented in this article were analyzed using descriptive
and explorative methods. Diagnostic and treatment patterns
were reported with absolute and relative frequencies. For
exploratory analyses, subgroup comparisons were performed.
Differences in treatment patterns between subgroups were an-
alyzed using chi-square test and Fisher’s exact test. All p
values are given as two-sided p values, and a p value of
<0.05 was considered statistically significant. The Statistical
Package for the Social Sciences (SPSS), version 20 (SPSS,
Chicago, IL, USA), was used for analysis.
Patients characteristics and clinical presentation
Consistent with the published data [1, 12–14], male sex
(67 %) was predominant. Median age at first diagnosis of
the population was 67 years with range from 32 to 94 years.
Seventy-six percent of the patients were 60 years or older,
while 5 % were younger than 50 years (Table 1). Fatigue
was the most common symptom at initial diagnosis (38 %),
followed by lymphadenopathy (29 %) and night sweats in
17 %. Interestingly, 24 % of the patients did not suffer from
any symptoms at initial diagnosis (Table 2). As expected,
symptomatic disease increased with Binet stage (Table 3).
Performance status at initial diagnosis classified by ECOG
score [15] was 0–1 in 78 % of the patients with 16 % quali-
fying for ECOG 2 and only 6 % for ECOG score 3 or 4
Table 1 Patient characteristics
Median age (n = 402) 67 years
>80 years 12 %
70–79 years 30 %
60–69 % years 34 %
50–50 % years 18 %
<50 years 5 %
Sex (male/female) (n = 402) 67 %/33 %
Performance status at initial diagnosis (n = 387)
ECOG 0–1 78 %
ECOG 2 16 %
ECOG 3–4 6 %
Fitness at initial diagnosis (n = 402)
Go-go 58 %
Slow-go 26 %
No-go 7 %
Unknown 9 %
Fitness at initial diagnosis >67 years (n = 222)
Go-go 48 %
Slow-go 34 %
No-go 10 %
Unknown 8 %
Fitness at initial diagnosis <67 years (n = 180)
Go-go 71 %
Slow-go 16 %
No-go 3 %
Unknown 10 %
Ann Hematol

3. (Table 1). Significantly, patients younger than 67 years scored
ECOG score 0–1 (88 %) more often than patients older than
67 years (70 %) (data not shown). Thus, at initial diagnosis,
71 % of the patients younger than 67 years were classified as
fit or Bgo-go^ patients according to comorbidities and fitness
[16, 17] in comparison to only 48 % of the older patients
(Table 1). Patients younger than 67 years were in 16 % rated
as slow-go and 3 % as no-go respectively, in comparison to
older patients (34 and 10 %) (Table 1).
The majority of the patients (66 %) had significant comor-
bidities with arterial hypertension being the most common
(41 %), followed by coronary heart disease (18 %) and diabe-
tes mellitus (14 %) (Supplement 1). As expected, comorbidi-
ties were more frequent in older patients (77 %) than in youn-
ger patients (51 %) (Fig. 1).
The patient population of university, non-university hospi-
tals, and office-based hematologists was comparable in age,
performance status, and Binet stage (p=0.565). However, the
rate of significant renal (p = 0.002) and heart failure
(p<0.001) was higher in the population treated by office-
based hematologists (Fig. 2).
Histological diagnosis and staging procedures
Genetic analysis at initial diagnosis was performed in half of
the patients (50 %), in 48 % with conventional cytogenetic
proceedings; in 30 % fluorescent in situ hybridisation was
performed. Prognostic markers (ß-Microglobulin,
Thymidinkinase, ZAP 70 expression, and others) were ana-
lyzed at initial diagnosis in 49 % of the patients. Interestingly,
parameters were analyzed in younger patients significantly
more often (52 %) than in older patients (32 %) (p<0.001)
(data not shown).
According to the Binet classification [18], 44, 33, and 22 % of
the patients presented in Binet A, B, C, with 1 % of patients not
evaluable at initial diagnosis. In detail, contribution of Binet status
A, B, C in the institutions was as follows: University medical
centers: 40 %–23 %–36 %–unknown 1 %; non-university hos-
pitals: 39 %–35 %–25 %–unknown 1%, office-based hematolo-
gists: 51 %–33 %–14 %–unknown 2 % (Table 4).
First-line therapy
The majority of the patients (64 %) was primary observed
(watch and wait strategy). Therapy at initial diagnosis was
immediately started in 36 % of the patients. As expected, only
Table 2 Symptoms at
diagnosis (n = 400) Fatigue 38 %
Lymphadenopathy 29 %
Night sweats 17 %
Cytopenia 13 %
Splenomegaly 12 %
Pain 12 %
Infection 12 %
Weight loss 11 %
Asymptomatic 24 %
Table 3 Symptomatic disease/Binet (n = 400)
Binet stage Symptomatic disease (%) Non-symptomatic disease (%)
A 71 29
B 92 8
C 100 0
28%
11%
8% 8%
51%
23%
16%
19%
0%
10%
20%
30%
40%
50%
60%
arterial
hypertension
coronary heart
disease
heart failure diabetes
mellitus
< 67 years
≥ 67 years
p= 0.000
p= 0.001
p= 0.002
p= 0.002
(n=401)
Fig. 1 Comorbidities
4% 6%
47%
73%
13%
24%
50%
72%
0%
20%
40%
60%
80%
significant renal
disease
significant heart
failure
age > 68 years Karnofsky Index >90
p= 0.002
p= 0.000
p= 0.839
p= 0.735
(n=402)
Office- based hematologist
University / non-
University hospital
Fig. 2 Population/institution
Ann Hematol

4. 4 % of patients in stage Binet A received therapy at initial
diagnosis, whereas 86 % of the patients in stage Binet C were
initially treated (Fig. 3a, b). Patients with Binet stage C who
did not receive immediate therapy were significantly more
often treated at office-based hematologists (p = 0.048,
Fig. 3c). Several predictors for therapy initiation could be
identified (Fig. 4). Symptomatic disease at initial diagnosis
did trigger a rapid treatment start (p<0.001). However, only
42 % symptomatic patients were treated at initial diagnosis,
and 46 % of the initial symptomatic patients received therapy
only after progression. Significantly (p<0.001), 58 % of pa-
tients with elevated B2-Microglobuline at initial diagnosis re-
ceived primarily a therapy and only 14 % with normal B2-
Microglobuline at diagnosis were immediately treated.
Performance status was also a predictor for the start of therapy.
Patients with ECOG performance status ≥2 received in 57 %
immediate treatment, in comparison to 20 % in ECOG 0. In
contrast, age was not correlated to immediate therapy; 40 % in
patients >67 years were treated primarily and 32 % age <66
(p=0.139). Also, the presence of significant comorbidities did
not influence the initiation of therapy—33 % of the patients
without comorbidities and 38 % of the comorbid patients were
treated (p=0.446). Notably, patients treated at a university or
non-university hospitals were significantly (p=0.003) more
often treated immediately (47 %, 41 %) than by office-based
hematologists (26 %) (Fig. 4).
Therapy regimes
Overall, the most frequent therapies in the first line were
immuno-chemotherapies (73 %). The majority of the
immune-chemotherapies consisted of rituximab (93 %) while
alemtuzumab was used in 3 %, and others including 2 %,
whereas 1 % was not evaluable (data not shown).
Overall, rituximab in combination with bendamustine
(31 %) was most frequent used, followed by rituximab in
combination with fludarabine and cyclophosphamide [R-FC]
(22 %) and chlorambucil containing regimes (Fig. 5).
Significantly, rituximab in combination with bendamustine
Table 4 Binet stage (n = 402)
Stage at diagnosis All patients (%)
Binet A 44
Binet B 33
Binet C 22
Binet stage by
institution
University
hospital (%)
Non-university
hospital (%)
Office-based
hematologist (%)
Binet A 40 39 51
Binet B 23 35 33
Binet C 36 25 14
Stage
unknown
1 1 2
36%
64%
Therapy at iniƟal
diagnosis
Watch and Wait at iniƟal
diagnosis
96%
55%
14%
4%
45%
86%
0% 20% 40% 60% 80% 100%
Binet A
Binet B
Binet C
Binet / iniƟal therapy
(n=396)
All paƟents
(n=396) BA
C
Hospital,
63. 72%
23; 27%
OH;
[WERT];
[PROZENT
SATZ]
unknown,
1. 1%
Binet C paƟents (87 pts.)
immediate
therapy
89%
w & w
11%
IniƟal treatment
hospitals
immediate
therapy
78%
w & w
22%
IniƟal treatment
OH
p: 0.048
Fig. 3 Twenty three patients
equals 27 %
Ann Hematol

5. (34 %) or with fludarabine and cyclophosphamide (31 %) was
most frequent used in Bgo-go^ patients. In patients considered
to be Bslow-go/go-go^ rituximab in combination with
bendamustine (31 %) was most frequent used, followed by
chlorambucil containing regimes (26 %) and bendamustine
monotherapy (16 %) (Fig. 5).
Therapy regimes differed significantly by institutions;
office-based hematologists applied antibody containing re-
gimes less often than university medical centers and non-
university hospitals (64 % vs 74 % vs 87 %) (Fig. 6). In
addition, office-based hematologists applied bendamustine
containing regimes most frequently; rituximab in combination
with bendamustine 36 %, bendamustine monotherapy 19 %
while R-FC and chlorambucil containing regimes were less
frequent (13 and 16 %) (Fig. 6). In contrast, mainly rituximab
in combination with bendamustine (31 %) and rituximab in
combination with fludarabine and cyclophosphamide (26 %)
were used at university medical centers. Interestingly, rituxi-
mab in combination with fludarabine and cyclophosphamide
(36 %) was used more often than rituximab with
bendamustine (24 %) at non-university hospitals (Fig. 6).
Historically, this data taken together with previous surveys
[10, 11] shows an inverse use of bendamustine and
fludarabine from 2006 to 2011 (Fig. 7).
Watch and Wait at initial
diagnosis
Initiation of therapy at diagnosis
Stage A %4%69
Stage B %54%55
Stage C %68%41
Go-go %23%86
Slow-go %64%45
No-go %65%44
ECOG 0 %02%08
ECOG 1 %14%95
ECOG ≥2 %75%34
age < 67 years %23%86
age >= 67 years %04%06
b Microglobuline normal %41%78
b Microglobuline elevated %85%24
Non symptomatic disease %5%69
symptomatic disease %24%85
relevant comorbidities %83%26
no comorbidities %33%76
University Medical Center %74%35
Non- University hospital %14%95
Office-based hematologist %62%48
< 0.001
< 0.001
< 0.001
0.003
0.46
< 0.001
< 0.001
0.139
Fig. 4 Predictors of therapy
initiation (n = 396)
31% 34% 29%
22%
31%
13%
15%
6%
26%
12% 9% 16%
2% 2%
3%
4% 2%
6%
14% 16%
6%
0%
20%
40%
60%
80%
100%
(n= 172, 11 pts with missing data)
All paƟents go-go slow-go / no-go
(172pts) (91 pts) (70 pts)
Other
Rituximab
Fludarabine +/-
Cyclophosphamide
BendamusƟne
Chlorambucil +/-
other
R-FC
BendamusƟne-
Rituximab
Fig. 5 Initial treatment
Ann Hematol

6. Supportive care
Supportive therapies were applied in first-line therapy in 70 %
of the patients. The most common therapies were antibiotics
(61 %), followed by red cell transfusions (54 %) and anti-viral
medication (33 %) (Supplement 2).
Discussion
In this survey, male sex was predominant and consistent with
published data median age at diagnosis was 67. The distribution
of Binet stages at diagnosis was A 44 %, B 33 %, C 22 %. In
recent published data, the rate of Binet stages at initial diagnosis
for stage A vary significantly between 60 and 80 % [19, 20]
within Europe. A recent population-based survey of the inci-
dence of CLL in the years 2000–2010 in a US County reports
a Rai stage distribution 0 43 %, I–II 49 %, III–IV 8 %, a survey
from the Czech Republic a 51, 39, 9 % respectively. Generally, a
trend towards diagnosis in earlier stages has been described by
several studies [21, 22]. As stated before [5, 6, 21, 23], the more
frequent use and availability of flow cytometry as well as more
frequent routine blood testing may increase the diagnosis in ear-
lier stages. In our surveys, the use of flow cytometry from pe-
ripheral blood/bone marrow inclined at initial diagnosis (2009:
16 %; 2011: 80 %) while the performance of bone marrow
punctures significantly declined (2006: 80 %, 2009: 60 %; data
not shown). Accordingly, over the observation period of our
surveys, the rate of patients diagnosed in early stages (Binet A/
B) notably increased (2006: 66 %, 2009: 71 %, 2011: 77 %) and
a trend towards younger median age was detected (2006: 69 y.,
2009: 71 y., 2010: 67.5 y., and 2011: 67 y.) [10, 11].
The rate of patients with significant concomitant diseases
(2006: 63 %, 2009: 58 %, 2010: 64 %, 2011: 66 %) and
performance status 0–1 (2006: 85.6 %, 2009: 90.8 %, 2010:
87.4 %, 2011: 89.5 %) remained comparable [10, 11].
In this survey, the contribution in detail between the insti-
tutions was as follows: University medical hospitals/non-
university hospitals Binet A 40 %–B 29 %–C 31 %–unknown
1 %, office-based hematologists A 51 %–B 33 %–C 14 %–
unknown 2 %. Notably, patients presented more frequently in
Binet stage A in an outpatient setting. Accordingly, the
amount of stage C patients was significantly higher in a hos-
pital. This underlines the hypothesis, due to more frequent
routine blood tests, patients in earlier stages are diagnosed in
outpatient settings. This may explain the relatively different
distribution in our survey compared to the published data.
However, patient distribution was comparable concerning per-
formance status and age between institutions, with significant-
ly more frequent renal and heart insufficiency in patients di-
agnosed at office-based hematologists. In historical compari-
son, the amount of patients immediately treated after diagnosis
decreased substantially in the observation period (2006: 57 %,
2009: 39 %, 2010: 36 %, 2011: 36 %) (Supplement 3),
reflecting a careful evaluation of therapy initiation, reflected
31%
24%
36%
26% 36% 13%
17% 11%
16%
7%
2%
19%
12% 4%
2%
9%
3%
5%
18%
9%
0%
20%
40%
60%
80%
100%
(n=172, 7 pts with missing data)
University non- University office-based
hospital hospital hematologist
(42 pts) (45 pts) (78 pts)
Other
Rituximab
Fludarabine +/-
Cyclophosphamide
BendamusƟne
Chlorambucil +/-
other
R-FC
BendamusƟne-
Rituximab
Fig. 6 Therapy/institution
3
26
33
43
32
14
17
15
23
37 38
34
0
10
20
30
40
50
2006 2007 2008 2009 2010 2011
%ofpaƟents
BendamusƟne +/- AB
Chlorambucil +/- AB
Fludarabine +/- AB
Fig. 7 Initial therapy in Germany
2006–2011
Ann Hematol

7. in guideline recommendations [7, 24]. Still, 14 % of patients
diagnosed in stage Binet C did not receive immediate therapy.
Further analysis (Fig. 3c) detected a significant higher amount
of non-treated stage Binet C patients at office-based hematol-
ogists. Even though the presence of concomitant disease was
not an independent predictor of therapy initiation (Fig. 4), the
amount of patients with significant renal and heart disease was
higher at office-based hematologists and, as hypothesized by
others [25, 26], physicians may withhold immediate therapy
expecting the occurrence of therapy related toxicity.
Immune-chemotherapies were administered significantly
more often in the course of the observation period. In 2006,
only 15 % received immune-chemotherapy [11] while in
2011, the majority (73 %) of patients was treated with
immuno-chemotherapy. This may hint to the swift adaption
of the favorable results of several studies, including a random-
ized phase 3 trial showing a benefit [3, 27, 28] for rituximab in
combination with chemotherapy. Yet, the administration of
antibody consisting regimes was more frequently applied in
hospitals rather than by office-based hematologists. This
might be explained by the relatively long infusion time and
potential infusion-related effects of monoclonal antibodies,
which complicate treatment in an outpatient setting.
Interestingly, the combination of rituximab with bendamustine
was most frequent used as first-line therapy in this survey, follow-
ed by the R-FC regime. This is in contrast to our previous surveys;
from 2006 to 2009, the most frequent applied regime switched
from chlorambucil to fludarabine containing regimes [10, 11]
(Fig. 7). Whereas the rate of rituximab containing regimes further
increased in this current survey, bendamustine has been
established as the favorable chemotherapy backbone in CLL.
This reflects that bendamustine has been a well-known anti-
neoplastic drug in the former Eastern Germany and several clin-
ical trials have shown a favorable toxicity profile in indolent
NHL [29, 30]. Further, it is reported as effective and well-
tolerated first-line treatment in advanced indolent NHL and
mantle-cell lymphoma in German routine clinical practice [31].
Also, in CLL, superior outcomes over chlorambucil [32] as well
as feasibility in combination regimes with rituximab [33] were
demonstrated. Fludarabine in combination with cyclophospha-
mide and rituximab [3, 27, 34, 35] has shown efficacy in several
studies and is especially recommended in physical fit patients [8].
Furthermore, the German CLL study group initiated the CLL-
10 study in 2008 comparing R-Bendamustine versus R-FC in
first-line treatment of CLL, which further underlined the accep-
tance of these immuno-chemotherapies treatment schedules.
First results of this trial have been demonstrated in the meet-
ings of the American Society of hematology and show a signif-
icant difference in response and toxicity. While R-FC achieves
higher and prolonged response rates, it also induces higher tox-
icity than R-Bendamustine [36, 37]. According to this, young
and fit patients benefit from R-FC while for older and comorbid
patients R-Bendamustine shows a favorable toxicity profile.
Reflecting the undecided standard of first-line therapies in
CLL in 2011, physical fit (Bgo-go^) patients were mostly treat-
ed with rituximab with bendamustine (34 %) or R-FC (31 %).
Notably, patient classified concerning physical performance
as Bslow-go/no-go^ were most often treated with rituximab
with bendamustine (29 %) followed by chlorambucil (with or
without rituximab; 26 %) and bendamustine monotherapy
(16 %). This reflects the acceptance of the immune-
chemotherapy regime even in frail patients and is consistent
with a real-life practice report concerning CLL patients
>65 years treated with rituximab and bendamustine in Italian
hematology departments [38]. Consistently with current rec-
ommendation, national and international guidelines for patients
with significant comorbidities the second most frequent thera-
pies in patients considered as Bslow-go/no-go^ were
chlorambucil containing regimes [8, 17].
Unexpectedly, in second-line treatment, the application of
antibody consisting regimes decreased to 57 %, with rituxi-
mab being still the most common used antibody (99 %, 1 %
Alemtuzumab, data not shown). This decline of antibody us-
age in second-line therapy illustrates the clinical reality differ-
ing from guidelines and academic approaches. Again, espe-
cially office-based hematologists applied antibody consisting
regimes only in 36 %, which alike to first-line therapy, may be
due to caution towards antibody specific reaction or specific
toxicity. Only 30 % of the patient treated in relapse had re-
ceived a monoclonal antibody before. Given the reported an-
tibody use in first-line treatment in previous surveys 20 %
(2006) and 53 % (2009) [10, 11], the need for second-line
treatment 2011 for an amount of patients from that time period
seems consistent with the clinical course of CLL. Lately, the
molecular targeted therapies ibrutinib and idealisib [39, 40],
were approved for relapsed CLL by the responsible authori-
ties. To the date of our survey, they were only available in few
clinical studies and are therefore not reflected in this survey.
Interestingly, predominantly red blood transfusions and anti-
biotics were used as supportive therapy. In comparison with pre-
vious data on indolent lymphoma [11], the rate on applied G-
CSF decreased significantly from 34 % in 2009 to 18 % in 2011,
underlining the suggested considered use and the often regressive
neutropenia under chemotherapy in CLL patients [7, 26, 31].
In conclusion, this survey shows the clinical reality of CLL
therapy in Germany reflecting the adaption of evolving thera-
py concepts, but also differences between published guide-
lines and clinical practice were detected. This underlines the
need to consider comorbidities in current therapeutic strate-
gies and illustrates the requirement of such surveys.
Compliance with ethical standards
Conflict of interest The co-author M. Dreyling declares COI for
Roche: Support of clinical studies (Institution) and speaker’s honoraria
as well as Mundipharma: speaker’s honoraria. The co-author L.
Kellermann declares COI Honorary for project management and data
Ann Hematol

8. analysis for Janssen, Celgene, Mundipharma and Genzyme. All other
authors have no COI to declare.
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