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

12 th Congress of the European Hematology Association
1457
EFFECTIVENESS OF MEGACHOP PLUS G-CSF AS A PERIPHERAL BLOOD STEM CELLS
(PBSC) MOBILIZATION AND HARVESTS SCHEME. COMPARATIVE ANALYSIS
OF TWO DIFFERENT G-CSF DOSE SCHEDULES
M.J. Rodriguez Salazar, 1 R.F. Rodríguez Sánchez, 1 B.J. González-
González, 1 M.T. Hernández-García, 1 J.V. Govantes, 2 M. Tapia, 2
G. González-Brito, 1 J.M. Raya, 1 T. Martín, 1 L. Hernández-Nieto1 1 2 Hospital Universitario de Canarias, LA LAGUNA.TENERIFE; Hospital General,
LA PALMA., Spain
Aims. 1) To assess the effectiveness in mobilizing and harvesting
peripheral blood stem cells (PBSC), using Mega-CHOP scheme and G-
CSF (filgrastrim), in the autologous stem cell transplantation setting. 2)
To analyze two different G-CSF schedule (low dose vs. high dose). Methods.
We retrospectively studied the results obtained in the PBSC mobilization
of 159 patients (87 men and 72 women) with previous diagnosis
of: Non Hodgkin Lymphoma (82), Multiple Myeloma (39), Hodgkin´s
Lymphoma (13), Breast Cancer (8), Acute Leukemia (6), Sarcoma (4),
Chronic Lymphocytic Leukemia (4), Waldenström Disease (2) and
POEMS Syndrome (1). Mobilizing chemotherapy regimen was as follows:
Cyclophosphamide 1000 mg/m 2 , Doxorrubicin 50 mg/m 2 , Vincristin
1,4 mg/m 2 (max. 2 mg), given one day. G-CSF was administred
subcutaneously, starting on +10 day, either at 7,5 µg/kg/day (Group 1)
or 10 µg/kg/12 hours (Group 2) until the completion of the apheresis or
mobilization failure evidence. Our aim was to obtain: a) A minimum of
4×10 6 cells CD34 + /Kg product, which secondarily underwent ex-vivo
purging with an immunomagnetic selection procedure, before the final
cryopreservation, or b) A minimum of 2 x 106 cells CD34 + /Kg in unmanipulated
products. Results. The average total CD34 + cells ×10 6 /kg were
8,07 (0,10 - 24,09). Five patients (3,14%) did not reach the CD34 + cells
minimum required. From those who achieved the mobilization objectives
(150 patients, 93,34%), a unique apheresis process was necessary
in 99 cases (66%), two apheresis in 43 cases (27,77%), three processes
in 7 cases (4,58%), and four apheresis in just one case (0,65%). Comparing
both G-CSF dose schedules, we observed the following results: 1)
Day of apheresis starting: Group 1: 12,37 (11-14) vs. Group 2:12,14 (11-
14) [p= 0.368]. 2) CD34 + ×10 6 cells/kg obtained: Group 1: 6,59 (0,19-21,12)
vs. Group 2: 8,98 (1.03-24,09) [p= 0.045] Conclusions. In our experience,
the Mega-CHOP scheme plus G-CSF is a highly effective strategy to
perform peripheral blood stem cells (PBSC) mobilization and harvests.
Although the first day of apheresis was in both groups +12 day, a higher
performance was reached using a G-CSF high dose schedule and there
were statistically significant differences between both groups.
1458
KIKUCHI-FUJIMOTO DISEASE (KFD) DIAGNOSED SIMULTANEOUSLY WITH SYSTEMIC
LUPUS ERYTHEMATOSUS: A CASE REPORT
A. Syrigou, A. Asimaki, M. Katsounaros, N. Neokleous, C. Lalayanni,
G. Bamihas, A. Anagnostopoulos
G. Papanicolaou Hospital, THESSALONIKI, Greece
Background. Histiocytic necrotizing lymphadenitis (HNL) or Kikuchi-
Fujimoto disease (KFD) is a benign and self-limited disorder, characterized
by tender lymphadenopathy and is usually accompanied by mild
fever and night sweats. The clinical, histopathological and immunohistochemical
features appear to point at viral etiology, a hypothesis that
still has not been proven. KFD is generally diagnosed on the basis of a
biopsy of affected lymph nodes, which shows fragmentation, necrosis
and karyorrhexis. The disease mimics, and is associated with, many
other diseases, like lymphoma, metastatic carcinoma, systemic lupus
erythematosus (SLE), and psoriasis, who can precede, postdate or coincide
with the diagnosis of KFD. Material. A young woman, aged 25 years
presented with prolonged fever, cervical lymphadenopathy and night
sweats. Clinical examination revealed cervical lymph nodes with a size
ranging from 0,5 to 5 cm, smaller nodes in both axillary areas, and liver
and spleen palpable. Laboratory examinations were normal or nonspecific.
Complete blood counts showed anemia and raised erythrocyte
sedimentation rates. Liver function test were normal but renal function
was affected and subsequently progressed, in a couple of days, to
nephrotic syndrome with proteinuria and hematuria. The biopsy of the
excised lymph node was characteristic of histiocytic necrotizing lymphadenitis
with architectural effacement, due to the presence of pale
nodular lymphohistiocytic foci with nuclei debris, a few lymphocytes,
CD4 and CD8 positive, plasmatocytoid cells, large lymphoid cells
(immunoblasts) and absence of granulocytic infiltration. There were no
520 | haematologica/the hematology journal | 2007; 92(s1)
elements of tuberculus lymphadenitis or lymphoma. Serological examinations
revealed positivity to antinuclear antibodies and decreased C3
and C4 characteristic for the diagnosis of SLE. The patient was successfully
managed with immunosuppressive therapy. Conclusions: Although
KFD is considered very uncommon, this disorder must be included in the
differential diagnosis of lymph node enlargement since its course and treatment
differs from those of lymphoma, tuberculosis and SLE. The histological
differential diagnosis of KFD mainly includes reactive lesions as
lymphadenitis associated with SLE, or herpes simplex, non-Hodgkin’s
lymphoma, plasmacytoid T-cell leukemia, Kawasaki’s disease, myeloid
tumor and even metastatic adenocarcinoma.
1459
A NEW P.K404E BCR-ABL MUTATION IN AN PH1 POSITIVE ALL PATIENT
F. Torres1 , A. Ivanova1 , M. Pereira1 , F. Ferreira2 , A. Lopes1 , H. Gabriel1 ,
P. Tavares1 , A. Fernandes1 1 CGC, PORTO, Portugal; 2 Serviço de Hematologia, HSJ, PORTO, Portugal
Background. In patients with Philadelphia acute lymphoblastic leukemia
(Ph1ALL), treatment with Imatinib (IM) results in an overall hematologic
response rate of about 60%. These results are considerable inferior to
those observed in patients with chronic myeloid leukemia (CML)-in fact
the responses in Ph1ALL are not sustained and the overwhelming of
patients become refractory to treatment after a median of only two
months due to the development of resistance. 1 Mutations in BCR-ABL
tyrosine kinase (TK) are the most common mechanism of IM resistance.
Addition of IM to intensive chemotherapy can produce high-quality complete
remission to a majority of newly diagnosed patients, providing
them a better chance to receive an allogeneic transplant. 2 More recently,
the new TK inhibitors Dasatinib and Nilotinib have produced, in phase
I/II clinical trials, very promising hematological and cytogenetic responses
in CML and Ph1ALL patients, offering a new tool to circumvent IM
resistance. 3 Aims. To ascertain if the BCR-ABL variations p.K404E and
p.I432I were acquired, and therefore more likely to cause IM resistance,
or are constitutional alterations characteristic of the studied patient. Methods.
BCR-ABL transcript identification and quantification were done
according BIOMED-1 and EAC protocols, 4,5 respectively. Mutation
screening was done by automatic sequencing of a RT-PCR nested segment
including the BCR-ABL TK domain or by automatic sequencing of
a PCR segment including the exon of interest. Results. A 34 years old
female was diagnosed in May 2006 with a Ph1ALL (E1A2 transcript).
She began chemotherapy in May 2006, according to hyper-C-VAD protocol,
receiving IM in days 1 and 15 of each cycle. She has completed the
fourth cycle last December and is now waiting for allogeneic transplant
in morphologic, immunologic and cytogenetic remission, although without
molecular remission. Table 1 summarizes her follow-up and the
molecular studies performed.
Table 1.
Summary/Conclusions. To our knowledge, this is the first time that alterations
affecting BCR-ABL amino-acid residues 404 and 432 are described.
To ascertain if they were acquired or constitutional, we have sequenced
the DNA extracted from the patient oral swab. The absence of p.K404E
and the presence of p.I432I in heterozigosity were observed. Therefore,
p.K404E (c.1591A>G), which changes the basic lysine (K) to the acidic
glutamate (E), is not a constitutional alteration, and is, most probably, an