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

12 th Congress of the European Hematology Association
1274
INTRAVENOUS (IV) BUSULPHAN IN CHILDREAN PRIOR TO AUTOLOGOUS
OR ALLOGENEIC STEM CELL TRANSPLANTATION: EARLY CLINICAL OUTCOMES TOXICITY
AND COMPLIANCE
A. Prete, 1 C. Castellini, 1 F. Fagioli, 1 R. Rondelli, 1 F. Melchionda, 1
W. Morello, 1A. Pession2 1 2 Azienda Ospedaliera S. Orsola-Malpighi, BOLOGNA; Università degli Studi
di Bologna, BOLOGNA, Italy
Background. High dose BUS is an important component of pre-transplant
conditioning regimen in children with advanced hematological
malignancies or solid tumor undergoing allogeneic or autologous stem
cell transplantation. Variable intra and inter systemic drug exposure as
measured by area under curve (AUC), can occur following oral administration
and my be influenced by age, body weight, absorption variability
and, particularly in infants, by difficulties to assumption. Aims. to
evaluate the clinical outcomes, the toxicity and the compliance to iv
BUS in children undergoing to pre-transplant conditioning regimen.
Methods. Thirty patients (pts), median age 37 (7-177) m, body weight 6-
69 kg, affected by AML (5 in I CR), ALL (7; 2 in I CR, 3 in II CR, 2 in RR),
NB (8; 2 in I CR, 6 in I PR), LCH (2), Ewing sarcoma (8; 2 in I CR, 4 in I
PR, 2 in SR) underwent to autoSCT (18) or alloSCT (12; 1 haploidentical,
2 mismatched cord, 3 mismatched unrelated, 6 matched related),
from December 204 through December 2006 and received i.v busulfan
every 6 h for a total of 16 doses, as part of their conditioning regimen.
Busulfan doses were based on accrual patient weight: 34 kg, 0,8 mg/kg/dose. Development of hepatic veno
occlusive disease (HVOD; modified Baltimore criteria) and engraftment
(absolute neutrophil count >0.5×10 9 /L and platelet count >50×10 9 /L were
evaluated. In 9 patients busulfan was followed by cyclophosphamide 21
h after the initiation of the last busulfan dose. No HVOD prophylaxis
was given. To prevent busulfan-induced seizures, all patients received
sodium valproate. 20 mg/kg/die 24 h before the first busulfan dose and
continued until 6 h after last busulfan dose. Results. Only 1 (3%) patient
developed HVOD, resolved after defibrotide and C-protein treatment.
One patient evidenced seizures 24 h after last dose of busulfan and 16
h after the last dose of sodium valproate. One patient, that received an
mismatched unrelated graft, died before engraftment for DIC. 29/30
patient demonstrated engraftment. Median time to neutrophil engraftment
was 15 d (range, 10-19 d). Median time to platelet engraftment was
22 d (range, 12-25 d). Overall survival at day +100 was 94% (28/30).
Regarding the alloSCT procedure, all the 11 valuable patient evidenced
a Donor Complete Chimerism since day +30. After a median follow up
of 12 m (range, 1-26 m), 23 patients (77%), are alive and well. Conclusions.
Intravenous busulfan in children, administered on accrual patient
weight, is safe and feasible. There was very limited toxicity and a rapid
and sustained bone marrow function recovery. No patient underwent
to alloSCT rejected nor evidenced primary or secondary graft failure.
Moreover allows to avoid assumption difficulties in younger patients.
1275
TRASLOCATION (11;14) IN TWO CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA
OF T-CELL ORIGIN
N. Marra, 1 R. Parasole, 1 G. Menna, 1 A. Mangione, 1 L. Vicari, 2
G. Maisto, 1 F. Pane, 3 V. Poggi1 1 „Santobono-Pausilipon„ Hospital, NAPLES, Italy; 2 Cardarelli Hospital,
NAPLES, Italy; 3 Federico II University, NAPLES, Italy
Background. Cytogenetic analyses of acute lymphoblastic leukaemia
(ALL) are sometimes used to define specific subgroups of patients with
poor prognosis such as t(9;22) or t(4;11). For this reason, the patients
with unfavourable cytogenetic pattern are treated with more aggressive
protocols associated with bone marrow transplantation (BMT). At the
moment, are not known the prognostic meaning of all abnormal karyotypic
finding. In this study, we investigated the clinical course of two
patients with T-ALL and t(11;14) at karyotype. Patients and Results.
Between June 2000 and January 2007, 192 patients, with ALL, were
enrolled in AIEOP ALL 2000 protocol in our Institution and 10 cases, 6
B-precursor ALL and 4 T-ALL presented a precocious relapse. Two of
relapsed T-ALL showed a particular karyotype for t(11;14) (p13;q11).
The characteristics of these 2 patients were very similar : both males
with hyperleukocytosis at diagnosis, age respectively of 8 and 3 years,
T-early immunophenotype, treated with the same protocol at high risk
(HR) for poor prednisone response (PPR) at day 8. At diagnosis both
462 | haematologica/the hematology journal | 2007; 92(s1)
patients showed large splenomegaly. Table 1 resume the characteristics
of patients. All patients achieved a complete haematological remission
(CR) at day 33 and 78, and negativity of minimal residual disease (MRD)
at molecular biology.
Table 1. Characteristic of patients.
Unfortunately, both children precociously presented a bone marrow
(BM) relapse associated with extramedullar localization (spleen in the
first patient and central nervous system (CNS) with optic nerve infiltration
in the second). The time from diagnosis to relapse was 13 and 9
months, respectively. Both were enrolled in relapsed- ALL AIEOP protocol,
followed by unrelated transplant. Patient 1 (Pts 1) showed resistance
to treatment and died at + 2 months from relapse in progression
disease (PD); Pts 2 was in CR at + 3 months and are to be undergoing a
mismatch unrelated donor (MUD) transplant. Conclusions. The description
of these similar cases suggest that a more aggressive therapeutic
approach should be recommended in T-ALL with t(11;14) at karyotype.
At the best of our knowledge, few cases of paediatric T-ALL with this
particular translocation are described but no study reports the prognostic
significance of this cytogenetic pattern. A larger series of cases is
needed to confirm this finding but we believe that these patients, for the
high risk of precocious relapse, must be treated with a more intensive
protocol followed by familial or unrelated BMT in first CR, independently
by MRD response.
1276
VON WILLEBRAND FACTOR AND PROPHYLAXIS OF THROMBOEMBOLISM IN PATIENTS
WITH MULTIPLE MYELOMA
P kubisz, 1 E. Flochova, 2 M. Dobrotova, 3 J. Ivankova, 2 J. Stasko1 1 Jessenius Medical School, Comenius Univ, MARTIN; 2 Dept.Hematology, University
Hospital, MARTIN; 3 Dept. Hematology, University Hospital, MAR-
TIN, Slovak Republic
Background. There is an increased risk of thrombotic complications in
patients with multiple myeloma. Following risk factors play role in
aetiopathogenesis: a) the presence of monoclonal immunoglobulin and
related hyperviscosity syndrome with fibrine structures, b) production
of pro-coagulation acting antibodies, c) effect of inflammatory cytokines
to endothelium, d) frequent incidence of aquired activated protein-C
resistance /Zangari 2002/, high level of both vWF:Ag /Minnema,2003//
and FVIII /Zangari 2002/. The treatment with thalidomide especially in
combination with dexamethasone and doxorubicine as well as therapeutic
regimens containing high dose dexamethazone significantly increase
the risk of thromboembolism. Prophylactic administration of LMWH in
the risk groups of patients with multiple myeloma decreases the risk of
thromboembolism by 50%. Aims. Evaluation of selected haemocoagulation
parametres (vWF:Ag, F VIII:c) in patients in various stage of multiple
myeloma and their possible relation with the prediction of thromboembolic
risk. Methods. We examined 18 patients with multiple myeloma
in clinical stage I.-III.(Durie, Salmon) for both vWF:Ag and F VIII
and compared with group of 25 healthy controls. Results. The level of
vWF:Ag was significantly increased in patients with multiple myeloma
compared to control healthy group (p=0.00086). The level of F VIII:c
was significantly higher (p=0.00020) in patients as well. Summary. Our