Conclusions: SCT is increasingly applied to MF patients.
Though a small with pt and disease characteristics, cytogenetics (CG) and molecular ge-
cohort our data indicate that reduced intensity Treo/Flud conditioning is
feasible. Infections following SCT are common causes of death.
Disclosure: No conflict of interest disclosed.
P519
Specific treatment significantly influences outcome in 32
pregnancies in polycythemia vera (PV) patients
Wille K.1, Sadjadian P.1, Horstmann A.1, Kolatzki V.1, Griesshammer M.1
1
Johannes Wesling Klinikum Minden, Universittsklinik fr Hmatologie und
Onkologie, RUB Bochum, Minden, Germany
Very limited data are available regarding pregnancy (preg) outcomes in
patients with PV, less than 40 pregs being reported in the whole literature.
Within a European Leukemia Net project we collected 32 pregs in 14 PV
patients in our center since 2006. Pregs were categorized in two groups.
Group 1 consisted of pregs receiving treatment according to a suggested
algorithm (M. Griesshammer et al., Blood Rev. 2008) (n = 18). Group 2
(n = 14) included all pregs without a specific treatment. Most patients in
group 1 received low dose aspirin during preg and low molecular weight
heparin after delivery until the 6th week postpartum. The target hematocrit
during preg was 40% and therapeutic phlebotomy was performed, if need-
ed. Iron supplementation was not advised during preg.
Median age at diagnosis of PV was 28.5 yrs (range 1934), median age
at delivery 33 yrs (2439). Four out of 14 patients (28.6%) had high-risk
PV due to severe thromboembolic complications either at the time of di-
agnosis or during follow up. These included 2 Budd Chiari syndromes, 1
portal vein thrombosis and 1 pulmonary embolism. Overall live birth rate
was 47% (15/32). In group 1 live birth was recorded in 13/18 pregs (72%),
while 5 pregs were unsuccessful due to spontaneous abortion. In contrast,
outcome was significantly worse in group 2 with 2 live births out of 14
pregs (14%) [chi square, p = 0,001]. In group 2 we observed 8 (67%) spon-
taneous abortions, and 4 (33%) stillbirths. Interferon alpha was used in 4
cases with 3 live births (75%) and one spontaneous abortion. Concerning
maternal complications, no thromboembolic events were observed. How-
ever, 5 bleedings occurred (4 minor and 1 major), all of them in group 1
which was probably due to the treatment with aspirin and/or low molec-
ular weight heparin. Most PV patients hematocrit values spontaneously
decreased during preg, thus phlebotomies were mainly performed
during the first trimester.
This is the largest series of PV pregs reported in a single center experience
so far. The success rate of pregs was significantly better (72% versus 14%,
respectively) for patients with appropriate management performed ac-
cording to current guidelines. No thrombotic events were seen, however,
an increased bleeding rate was observed.
Disclosure: No conflict of interest disclosed.
P520
Assessment of CD30 expression on mast cells in
systemic mastocytosis by immunohistochemistry versus
multiparameter flow cytometry and correlation to clinical
parameters
Bellos F.1, Sotlar K.2, Jeromin S.1, Haferlach C.1, Haferlach T.1, Kern W.1
1
MLL Mnchner Leukmielabor GmbH, Mnchen, Germany, 2Pathologisches
Institut, Ludwig-Maximilians-Universitt Mnchen, Mnchen, Germany
Introduction: Systemic mastocytosis (SM) is a rare disease with variable
clinics, from indolent to aggressive clinical courses. Immunhistochemi-
cal staining (IH) has detected CD30 expression (CD30exp) on neoplastic
mast cells (MC) as potential indicator for aggressive disease. CD30exp de-
tected by multiparameter flow cytometry (MFC) might improve diagnos-
tics and help correlate CD30exp with clinical parameters giving insights
into disease biology. We compared CD30exp detected by MFC vs IH on
bone marrow (BM) MC of patients (pt) with SM and correlated results
Abstracts
netics (MG).
Methods: Expression of CD30 was analyzed in BM samples by MFC us-
ing antibodies against CD30, CD45, CD117, CD2 and CD25. MC were
identified as CD45 positive with bright CD117 expression. Coexpression
of CD2 and/or CD25 defined neoplastic MC, median fluorescence inten-
sities (medFI) of CD30 were determined and related to CD30 medFI in
lymphocytes to derive CD30 index. MC infiltration and CD30exp by IH
was assessed in 22 pt. CG and MG for KITD816V mutation were done in
44 and 80 pt, respectively. CD30exp detected by MFC was correlated to
IH-detected CD30exp and to CG and MG.
Results: Pt were 51 female, 42 male, median age 59 years (2087), karyo-
types: 41 normal, 3 aberrant, KITD816V mutation was positive in 74/80
pt. 14/93 pt had concurrent hematological non-mast cell disease (AHN-
MD). Mean (SD) MC infiltration was 20%26% (range, 1.5%-85%) by
IH and 0.4%1.8% (range, 0.01%-17%) by MFC. Mean (SD) CD30 index
was 19 20 (range, 3154), mean (SD) CD30exp by IH was 9%17%
(range, 0%-70%). MC infiltration by IH and MFC correlated significantly
(p = 0.002, r = 0.819), also KITD816V mutation ratio and MC infiltration
by IH and MFC (p = 0.006, r = 0.669 and p < 0.001, r = 0.554, respective-
ly). No correlation of MFC CD30 index with age, sex, AHNMD, KIT-
D816V mutation ratio, grade of MC infiltration or %CD30+ MC by IH
was found. Pt with normal vs aberrant karyotype had higher CD30 index
(12.2 6.2 vs 6.3 2.7, p = 0.037). A trend to higher CD30 index in pt
with KITD816V mutation was seen (23.9 89.1 vs 10.0 5.8, n.s.).
Conclusions: Neoplastic MC harbouring aberrant karyotypes displayed
stronger CD30 expression, being by trend also stronger on MC from pt
with KITD816V mutations. CD30 expression on MC should be analyzed
by both IH and MFC in a high number of pt to substantiate our findings
and to better enable correlation with clinical outcome.
Disclosure: Frauke Bellos: Employment or Leadership Position: angestellt im
Mnchener Leukmielabor
Wolfgang Kern: Employment or Leadership Position: Teilhaber Mnchner Leu-
kmielabor
P521
Two different coagulation factor VIII gene mutations in
brothers with hemophilia A: an unexpected and rare finding
Krammer-Steiner B.1, Nimtz-Talaska A.2, Toenges R.3, Friday D.3, Steiner M.4
1
Klinikum Sdstadt Rostock, Klinik fr Innere Medizin III, Rostock, Germany,
2
Praxis fr Kinder- und Jugendmedizin, Frankfurt/O., Germany, 3Diagenom
GmbH, Rostock, Germany, 4Medizinisches Labor, Rostock, Germany
Introduction and Objectives: Inherited hemophilia A in females is rare
and female hemophilia A patients are at risk of being misdiagnosed as
acquired hemophilia A or as von Willebrand disease type 2N. Here we
report a female patient with moderate factor VIII deficiency due to com-
pound heterozygosity for two different coagulation factor VIII gene mu-
tations.
Material and methods: A 41-year-old mother presented her three sons
aged 5, 8, and 12 years with moderately decreased factor VIII activity (20
to 24%) for genetic counseling and testing. Genomic DNA was obtained
from anticoagulated blood. All factor VIII gene exons and flanking re-
gions were amplified and PCR products were purified and sequenced.
Results: Initial mutational screening identified the previously identified
hemizygous factor VIII gene mutation p.Met2183Val (p.Met2164Val) lo-
cated in exon 23 in the 12-year-old first son. Unexpectedly, the mutation
could not be demonstrated in his two brothers prompting further full se-
quencing studies. A hemizygous mutation p.Arg2016Gln (p.Arg1997Gln)
in exon 19 was identified in the 8-year-old and in the 5-year-old boys.
Investigation of both mutations was conducted in the mother and con-
firmed the rare diagnosis of a compound heterozygous female hemophilia
A patient. Her residual factor VIII activity was similar to that of her sons
(23%) leading to the diagnosis of mild hemophilia A.
Conclusions: Female cases of hemophilia A are rare. Among the potential
genetic mechanisms leading to hemophilia A in females, compound hete-
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rozygosity affecting both factor VIII alleles has been demonstrated only in
a few cases. Here we report a female patient mother to three hemophilia
A sons displaying two different missense mutations in exon 19 and exon
23, respectively. Compound heterozygosity was confirmed in the mother
causing mild hemophilia A.
Disclosure: No conflict of interest disclosed.
P522
Haemophilia care: Which outcomes should be determined in
clinical routine care and are adequate for access requirements
Berger K.1, Eichler H.2, Escuriola-Ettinghausen C.3, Holstein K.4,
Klamroth R.5, Knigs C.6, Kurnik K.7, Oldenburg J.8, Scholz U.9,
Schramm W.10, Tiede A.11
1
Klinikum der Universitt Mnchen Campus Grosshadern, Medizinische Klinik
und Poliklinik III, Mnchen, Germany, 2Universitt und Universittsklinikum des
Saarlands, Institut fr Klinische Hmostaseologie und Transfusionsmedizin,
Homburg / Saar, Germany, 3HZRM Hmophilie Zentrum Rhein Main GmbH,
Mrfelden-Walldorf, Germany, 4Universittsklinikum Hamburg-Eppendorf,
Gerinnungsambulanz und Hmophiliezentrum, Hamburg, Germany, 5Vivantes
Klinikum im Friedrichshain, Zentrum fr Hmophilie und Hmostaseologie,
Berlin, Germany, 6Universittsklinikum Frankfurt, Goethe-Universitt Frankfurt,
Klinik fr Kinder- und Jugendmedizin, Schwerpunkt Hmatologie, Onkologie
und Hmostaseologie, Frankfurt am Main, Germany, 7Klinikum der Universitt
Mnchen, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen
Kinderspital, Mnchen, Germany, 8Universittsklinikum Bonn, Institut fr
experimentelle Hmatologie und Transfusionsmedizin, Bonn, Germany,
9 pts were diagnosed with haematological diseases. In total 5 adverse events
Zentrum fr Blutgerinnungsstrungen, MVZ Labor Dr. Reising-Ackermann und
Kollegen, Leipzig, Germany, 10Ludwig-Maximilians Universitt Mnchen, Rudolf-
Marx-Stiftung, Mnchen, Germany, 11Medizinische Hochschule Hannover, Klinik
fr Hmatologie, Hmostaseologie, Onkologie und Stammzelltransplantation,
Germany
Background: Stakeholders like the Institute of Quality and Efficiency in
Health Care (IQWiG), the Gemeinsame Bundesausschuss (G-BA) and
payers are increasingly demanding quality oriented patient care. Clinical
and patient reported outcomes are in the centre of this context. Therefore
the working group Outcomes of the GTH-Panel Haemophilia reached
out to determine relevant outcome parameters in clinical praxis and re-
search to meet and evaluate the best possible patient care and meet the
payers requirements. This also included assessment clinical routine care
and how they could be made assessable for future research initiatives.
Methods: Literature and desk researches to identify evidence require-
ments from different stakeholders perspectives; Development of a pilot
questionnaire to prioritize clinical and patient reported outcomes (unim-
portant to very important); Questioning of physicians treating haemo-
philia patients (children and adults).
Results: 14 physicians gave feedback on the questionnaire. Focus of the
first evaluation was on clinical outcomes. Highly prioritized clinical out-
comes were target joints (4 bleeds in one joint during 6 months), inhib-
itor development (influenced by the duration of treatment and intensity,
kind of clotting factor concentrates, mutations), mortality and bleeds.
All interviewees scored the aforementioned first three clinical outcomes
as very important, 12 physicians graded bleeds (frequency, localization,
severity) as very important, 1 as important. Arthropathy determined by
clinical joint status, Haemophilia Joint Health Score (HJHS), WFH Phys-
ical Examination Score (Gilbert Score) has been graded as important by 6
and as very important by 8 interviewees. Determination of arthropathy by
radiological joint scores eg Petterson score, magnetic resonance imaging
and ultrasound were scored of moderate importance, therapy associated
infections as important (n = 2), very important (n = 10), missing (n = 1).
Osteoporosis has been indicated as an unimportant clinical outcome by 9
interviewees, 1 moderate important, 2 important.
Conclusions: In a next step the working group outcomes will prioritize
the patient reported outcomes to be collected. The groups next objective is
to develop a concept how to improve longitudinal outcome data collection
in Germany.
Disclosure: No conflict of interest disclosed.
153 Oncol Res Treat 2016;39(suppl 3):1160
P523
Platelet transfusion in oncology/hematology patients in
routine clinical practice in of a tertiary hospital
Berger K.1, Wittmann G.2, Henschler R.3, Rieger C.1, Ostermann H.1
1
Klinikum der Universitt Mnchen Campus Grosshadern, Medizinische Klinik
und Poliklinik III, Mnchen, Germany, 2Klinikum der Universitt Mnchen,
Abteilung fr Transfusionsmedizin, Zelltherapeutika und Hmostaseologie,
Mnchen, Germany, 3Schweizerisches Rotes Kreuz SRK, Blutspende Zrich,
Zrich, Switzerland
Introduction: There is little information on real life patient data prior and
post transfusion of blood components of clinical hematology and oncol-
ogy. The objective of this study is to describe patient demographics, indi-
cation of platelet transfusion, to compare actively collected hemovigilance
data and to determine adherence to transfusion guidelines and relative
effectiveness for patients transfused with platelet components in routine
mostly prophylactic use.
Methods: Prospective open label, single-center, observational study. In-
clusion of platelet transfusions was consecutive. During the observation
period the platelet concentrates (plt) transfused were either pathogen in-
activated (PI) or produced conventionally (CON).
Results: Between March and May 2015 126 patients (pts) received 1207
platelet units (586 PI plts, 621 CON plts). 105 patients (pts) signed con-
sent, 11 pts were not able to give informed consent. Subsequently data
for 464 PI plt and 482 CON plt could be documented. Mean age was 53.8
years. 39% pts were younger than 50 years. 63% of pts were male, 80% of
were documented: 1 AE following PI, mild severity not requiring further
medical invervention,4 AEs following CON platelet transfusion of moder-
ate severity which required further medical intervention. 10% of pts with
underlying haematological diseases received more than 30 transfusions
(36% of all transfused plt). In this group approx. 69% plts were transfused
at a transfusion trigger > 10 G/I. 6% of pts received 20 -30 transfusions
(14% of all transfused plt) 18% of pts received 1020 transfusions (24% of
all transfused plt), 66% of pts received less than 10 plt transfusions (26%
of all transfused plt).
Conclusions: The majority of all platelet concentrates in this study was
transfused in a small number of patients. Only a limited number of trans-
fusion reactions were documented. We found a trend to a reduced inci-
dence of adverse events for the PI treated platelet concentrates. Platelets
were mostly transfused according to current treatment guidelines.
Disclosure: Karin Berger: Expert Testimony: Research Grant CERUs
Helmut Ostermann: Expert Testimony: Research Grant CERUS
Posterdiskussion
Aggressive Non-Hodgkin-Lymphome
P524
High efficiency of the pan-PI3K/mTOR inhibitor, PQR-309, in
MCL
Kvint R.1, Zimmermann Y.1, Hutter G.1, Hiddemann W.1, Dreyling M.1
1
Medizinische Klinik III, Klinikum der Universitt Mnchen, Mnchen, Germany
Introduction: Mantle cell lymphoma (MCL) comprises about 6% of all
non-Hodgkins lymphoma with a median survival of 35 years. New
emerging strategies especially include inhibitors of the PI3K/mTOR sig-
nalling pathway (PI3K, Akt, mTOR) which is constitutively activated in
MCL and plays a critical role in tumor growth and survival. In this study
we evaluated the efficiency and mode of action of the dual PI3K/mTOR
(c1+c2)-Inhibitor, PQR-309, in MCL cell lines, as a single agent but also in
combination with others molecular Inhibitors.
Methods: MCL cell lines (Granta 519, Jeko-1, Rec-1 and Mino) were
exposed to the panPI3K/ double mTOR inhibitor (PQR-309) as well as
to combination of PQR-309 with PIM- (AZD-199), BET- (JQ1), MEK-
(PD-0325901); BCL2- (ABT199); BTK-(Ibrutinib); RSK-(BI-D1870);
33.62.66 - 1/30/2017 9:53:02 PM
Abstracts
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