Characteristics of Pericardial Effusions in Patients with Leukemia.

Keeran R. Sampat, Adriana Rossi, Valentin Garcia-Gutierrez, Jorge Cortes, Sherry Pierce, Hagop Kantarjian, and Guillermo Garcia-Manero.
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX

Abstract #7067

Abstract

Patients & Methods

Purpose Little information exists regarding the prevalence

and natural history of pericardial disease in patients with
leukemia. Recently, it has been reported that the use of
histone deacytelase inhibitors (HDACi) is associated with an
increased incidence of pericardial effusions (PEfs). To study
the characteristics and treatment relationships of PEfs in
patients with leukemia, we retrospectively analyzed a cohort
of patients with leukemia evaluated at a single center.

We reviewed the electronic medical records (EMRs) of 2592

patients evaluated in the Leukemia Department at MD Anderson
Cancer Center (MDACC)

EMR for each patient with a PEf was reviewed for all prior
treatment history, leukemia characteristics, survival, PEf size,
and evolution of the PEfs
A numerical score was assigned to grade the size of the PEf
based on the echocardiogram report: minimal (1), small (2),
moderate (3), large (4)

Survival curves determined by Kaplan and Meier method

Table 1: Patient Characteristics
MDS

p (indiv. Rx vs no rx) overall p

0.44
0.57
0.82
0.62
1
0.83
0.72
1
0.23
1
0.7
0.81

PEf >=3
4
2
3
1
2
8
1
3
1
1
2
2

p (indiv. Rx vs no rx) overall p

1
0.29
0.64
1
1
0.67
0.72
0.46
0.08
0.43
0.37
0.62

Anthracyclines
Monoclonal Antibodies
Alkylating Agents
Antimetabolites
TKIs
Aparaginase
Vinca alkaloids
Other Chemotherapy
No Treatment

51
16
49
47
13
14
51
5
17

13
4
12
12
5
2
13
3
6

0.53
0.71
0.53
0.53
1
0.24
0.53
0.61

4
0
4
4
1
0
4
1
1

1
1
1
1
1
1
1
0.41

Anthracyclines
HDAC inhibitors
Hypomethylating Agents
Monoclonal Antibodies
Alkylating Agents
Antimetabolites
Topoisomerase Inhibitors
Other Chemotherapy
No Treatment

21
8
33
7
22
31
7
20
11

9
2
10
1
7
7
0
8
1

0.1
0.54
0.24
1
0.22
0.66
1
0.11

3
1
4
0
2
2
0
2
0

0.53
0.42
0.56
n/a
0.54
1
n/a
0.53

0.72

0.35

No single type of therapy, including HDACi, was found to

correlate with larger sized PEfs with any statistical
significance (Table 2).
Evolution of PEfs
The initial PEf detected was on average the largest one
(Figure 2).
Follow-up echocardiograms revealed a decrease in size
across all disease types
Relationship with Ascites or Pleural Effusions

0.84

Figure 3: Survival Curves

A.

84.7

75% of patients (n = 244) had a pleural effusion based on

chest imaging studies
Concurrent ascites, pleural effusion, and a PEf were found
in 23% of the patients (n = 75)
Clinical Management of PEfs
0.82

10 patients (3%) required pericardiocentesis due to

tamponade at the time of the initial PEf.
B.

67.6

Patients who had an echocardiogram had a median

survival of 60 weeks versus 53 weeks for those without an
echocardiogram (Figure 3B).

73.5
60.0

70.0
Percentage of Pts.

Percentage of Pts with PEfs

75.0

60.0
50.0
40.0
30.0

26.5

25.0

20.0

50.0
40.0
30.0

10.0

0.0
AML

Conclusions

25.4
20.6

18.1

20.0

15.3

10.0

ALL

2.9 4.4

4.9
0.5

4.2 2.8

0.0

MDS

ALL

No Prior
Treatment
Post-Treatment

Disease Type

AML
Disease Type

MDS

(3) Moderate PEf

D
90.0
81.8

A: Distribution of PEfs by Timing of

Occurrence: Before or After
Treatment.

A: Survival in Pts with or without a PEf

B: Survival in Pts with or without an
echocardiogram.

(1) Minimal PEf

(2) Small PEf
(4) Large PEf

B: Overall Distribution of PEfs by

Size and Disease Type
C: Distribution of PEf Sizes Found
at Initial Presentation

Results

D: Distribution of PEf Sizes Found

After Therapy

A PEf was detected in 325 patients (20%) of the 1600

patients evaluated: 21% in AML (n = 185), 23% in ALL (n =
68), and 18% in MDS (n = 72) patients

Frequency and Sizes of PEfs in Leukemia

80.0

Percentage of Pts

70.0
60.0

65.3
58.8

50.0
40.0
30.0

Most effusions occurred after receiving some form of therapy

(Figure 1A)

30.6

29.4

9.1

5.9

10.0

4.1
0.0

0.0
ALL

AML
Type of Disease

Analysis of the pericardial fluid revealed that 4 patients

(40%) had leukemic blasts present.

Both patients with or without a PEf had a median survival

of 60 weeks (Figure 3A)

73.6

70.6
70.0

80.0

23% of patients (n = 75) were found to have ascites at the

time of a PEf based on abdominal imaging studies

Impact on Survival

20.0

Identification of a new class specific toxicity could have

significant implications for the further development of
HDACi

PEf >=2
24
8
11
8
18
36
4
8
3
2
11
17

B
90.0

Increased incidence of PEfs in patients treated with

histone deacetylase inhibitor (HDACi), MGCD0103, was
recently reported

QT interval prolongation is the only known cardiac toxicity

of HDACi

Total Pts
86
18
35
30
49
117
11
15
10
8
28
49

80.0

Leukemia is a systemic disorder and can frequently

involve the hepatic, renal, circulatory, and cardiopulmonary
systems

MGCD0103 is a novel small molecule that is being

studied as a single-agent or in combination chemotherapy
regimens for solid tumors, lymphoma, and leukemia.

Treatment/no rx
Anthracyclines
HDAC inhibitors
Hypomethylating Agents
Monocolonal Antibodies
Akylating Agents
Antimetabolites
TKIs
Topoisomerase Inhibitors
ATRA
Arsenic Trioxide
Other Chemotherapy
No Treatment

Figure 1: Distribution of PEfs

A

Background

Pericardial effusions (PEfs) are part of the leukemic

disease process, arising secondary to hemorrhagic,
infectious, or leukemic infiltrates

ALL

Concomitant ascites and pleural effusions were found based on

imaging studies

Results PEfs were detected in 325 (20%) of the patients

who had echocardiograms: 21% in AML, 23% in ALL, and
18% in MDS patients. Only a small portion of PEfs were
detected prior to the initiation of therapy: 26% in AML, 25%
ALL, and 15% in MDS. Most PEfs were of minimal size
(70%) overall. No significant differences in effusion
characteristics, including severity, were observed among
different types of therapies. The presence of PEfs had no
impact on the survival of patients evaluated.
Conclusions- PEfs are relatively common in patients with
leukemia and do not appear to be related to specific types of
therapy or to survival.

Effect of Therapy on PEf development

1600 patients (62%) had at least one echocardiogram

performed at some point during their treatment course. (Table 1)

Patients & Methods We reviewed 2592 patients with

acute myeloid leukemia (AML, N= 1282, 49%), acute
lymphocytic leukemia (ALL, N= 336, 13%), or
myelodysplastic syndrome (MDS, N=974, 38%), who were
evaluated from 8/2003 to 7/2008. Electronic medical
records were reviewed to select patients that had undergone
at least one echocardiographic evaluation. Data regarding
diagnosis, timing, effusion size, survival, and prior therapy
was collected in the patients that had echocardiographic
evidence of PEfs.

Figure 2: Evolution of PEfs Over Time

Table 2: Frequency of PEfs by Treatment Type

Disease
AML

MDS

(1) Minimal PEfs

(2) Small PEfs
(3/4) Moderate
and Large PEfs

Majority of the PEfs in leukemia were of minimal or trace size

(Figure 1B).
The size of PEfs were not significantly different for the three
leukemias prior to therapy or after therapy (Figure 1C & 1D)

Most PEfs in leukemia are found after some therapy is

given.
Most PEFs in leukemia are small (70%) and clinically
insignificant. Less than 10% of patients with PEfs had
effusions classified as moderate or large.
The distribution of PEfs is similar between diseases either
before or after therapy.
Most PEfs in leukemia get smaller over time but rarely
completely resolve.
No particular class of treatment agents is associated with
larger PEfs, including HDACi
Most patients with PEfs have evidence of other effusions
including pleural effusions and ascites.
The presence of a PEf does not impact survival in patients
with leukemia. Having an echocardiogram does not impact
survival as well.