12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
scan revealed multiple deep enlarged nodes. A trephine bone marrow
biopsy showed histological and immunohistochemical findings of a classic
HL arising in CLL, so that a rare variant of Richter syndrome with HL
features was diagnosed (Figure 1). The patient was unsuitable for any
treatment and died two weeks after the HL diagnosis.
Figure 1. Hodgkin lymphoma in CLL: histological features.
Discussion and Conclusions. Richter syndrome with HL features is an
uncommon event, occurring in 0.4% CLL patients and portraying a very
poor clinical course with a reported median overall survival (OS) and a
progression-free survival (PFS) of 0.8 and 0.4 years, respectively. Most
HL transformations of CLL developed in patients who have received previous
treatments, mainly fludarabine or other purine analogs and rituximab
(Tsimberidou AM et al., Cancer 2006). So, treatments given for
CLL represent a crucial risk factor for the development of the secondary
HL. This severe complication, paradoxically, occurs only in CLL
patients with clinically most favourable biological features, such as the
IgVH mutated status and the lack of ZAP-70 expression, which have
been strongly associated with longer PFS and OS compared to unmutated
and ZAP-70 positive CLL patients (Del Pricipe et al., Blood 2006),
among which HL transformation has not been reported until now.
Indeed, HL, which doesn’t express ZAP-70, originates from IgVH mutated
and ZAP-70 negative B-cells, thereby, the progression to HL may
occur only in patients with a mutated ZAP-70 negative CLL, which is
provided by itself of a favourable course and a long survival, as observed
in our case. Therefore, given the poor clinical outlook of the HL transformation
occurring in an otherwise good prognosis CLL, and the key
role of the treatments in its development, the decision to treat a ZAP-
70 negative patient should be carefully evaluated, avoiding any early
and not mandatory interventions, taking into account the potential
occurrence of this rare but devastating complication.
1228
WHICH PARAMETERS OF NUTRITIONAL STATUS SHOULD WE CHOOSE FOR NUTRITIONAL
ASSESSMENT DURING HEMATOPOIETIC STEM CELL TRANSPLANTATIONS?- SINGLE
CENTRE EXPERIENCE
P. Rzepecki, T.S. Sarosiek, J.B. Barzal, C.S. Szczylik
Military Institute of Health Services, WARSAW, Poland
Aim. Haematopoietic stem cell transplantation (HSCT) is being used
increasingly in attempt to cure many hematological disorders, solid
tumours and autoimmune diseases. One of the major challenges in the
posttransplant period is nutrition Because nutritional changes after
HSCT have not been well studied there is no common knowledge if and
how changes of biochemical indices` levels can be useful. We probably
can use them as the risk factor of the development of malnutrition, for
establishing optimal candidates and also for determining the most appro-
448 | haematologica/the hematology journal | 2007; 92(s1)
priate time to start total parenteral nutrition. The best indices have to
be inexpensive for estimation, easy for evaluation and they should be
independent from parameters of inflammation like increased levels of
acute phase proteins. Methods. The purpose of this investigation was an
assessment of changes in parameters of nutritional status, acute phase
proteins’ levels and usefulness of investigated parameters for qualifications
for total parenteral nutrition. Patients’ informed consent was
obtained. Nutritional status was assessed in 54 patients during autologous
(30 cases) and allogeneic (24 cases) transplantations. Fifteen patients
had to be treated with total parenteral nutrition (TPN), eight of them
needed prolonged hospitalization. Biochemical (prealbumin, transferrin,
retinol binding protein and albumin) and anthropometric indices
(body weight, triceps skinfold thickness, midarm circumference) of
nutritional status as well as body fat and resting energy expenditure
were assessed. The levels of acute phase proteins (C- reactive protein,
α1- antitrypsin, α2- macroglobulin and serum precursor of amyloid A)
were estimated at the same time. All nutritional indices and acute phase
proteins` levels were evaluated during the day before the beginning of
conditioning regimen, after chemotherapy completion, and every 7 days
until engraftment, at least three times after stem cells infusion. Wilcoxon
test and canonical analysis served statistical analyses. Results and Conclusions.
The measurement of body weight, midarm circumference can
be useful for nutritional assessment during autologous and allogeneic
HSCT from sibling donors. In patients treated with autologous HSCT
high negative correlation was not observed only between retinol binding
protein level and acute phase proteins. Thus, estimation of retinol
binding protein can be useful for nutritional assessment during autologous
haematopoietic stem cell transplantations. Similar observation was
done during allogeneic haematopoietic stem cell transplantations from
sibling donors. It applied for transferrin (TRF). We found that the estimation
of TRF levels can be useful for nutritional assessment during this
kind of treatment. Prealbumin level, being measured eight days after
conditioning regimen showed in the best way the difference between
patients who required or not the prolonged hospitalization and it can
helpful to make a decision for TPN treatment.
1229
HEREDITARY SYSTEMIC AMYLOIDOSIS CAUSED BY A NEW VARIANT LYSOZYME (D67G)
IN A ROMANIAN FAMILY
D. Coriu, 1 C. Wooliver, 2 C. Murphy, 2 D. Kestler, 2 S. Wang, 2 D. Weiss, 2
G. Becheanu, 1 A. Solomon2 1 University of Medicine „Carol Davila„, BUCHAREST, Romania; 2 University
of Tennessee, KNOXVILLE, USA
Lysozyme- related amyloidosis (ALys) has been associated with mutations
in the second exon encoding the amyloidogenic precursor protein.
To date, four different variants have been identified (I56T, D67H, W64R,
F57I), all of which were deemed capable of reducing protein stability and
enhancing fibrilogenesis. We now report another case of ALys in a 52year-old
male who had predominant hepatic involvement (as well as a
family history indicating that other members had the same disorder)
and in whom we found a hitherto unreported mutation in the lysozyme
gene. Examination under polarized light of Congo red-stained sections
of liver biopsies obtained from the proband (and 2 brothers) revealed
extensive green birefringent interstitial deposits, characteristic for amyloid.
This material was extracted from 4mm-thick sections cut from formalin-fixed
paraffin embedded blocks, purified by reverse phase HPLC
and subjected, after trypsin digestion, to chemical analyses by tandem
mass spectrometry (MS/MS). These studies identified 109 of the 130
amino acids comprising wild-type lysozyme (peptides encompassing
residues 11-15, 63-69, and 114 - 122 were not found). To obtain the
complete primary structure of this protein, genomic DNA was isolated
from the proband’s peripheral blood leukocytes and the PCR products
of the 3 functional exons were synthesized. Nucleotide sequence analysis
revealed that exon 2 contained (in addition to the unmutated gene)
a GAT to GGT transition in codon 85, which would result in the substitution
of glycine for aspartic acid at position 67. Based on X-ray crystallographic
data, we posit that the resultant profound modification in
tertiary structure included by the D67G mutation would render the molecule
unstable and thus amyloidogenic. Our findings add to the known
variants of lysozyme involved in familial systemic ALys amyloidosis.