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

12 th Congress of the European Hematology Association
Stem cell transplantation II
0421
GRAFT-VERSUS-LEUKEMIA INDUCED BY GRAFT-VERSUS-HOST DISEASE EARLY AFTER
ALLOGENEIC BONE MARROW TRANSPLANTATION IN CHILDREN WITH DETECTABLE
LEVELS OF RESIDUAL ACUTE LYMPHOBLASTIC LEUKEMIA PRIOR TO TRANSPLANTATION
M. Bierings, 1 A. Lankester, 2 V.J.V. van der Velden, 3 E. van Wering, 4
T. Revesz, 1 A. Wijkhuis, 3 J.J.M. van Dongen, 3 M. Van Tol, 2 M. Egeler, 2
M.W. Schilham2 1 Wilhelmina Children's Hospital, UTRECHT; 2 Leiden University Hospital, LEI-
DEN; 3 Erasmus University, ROTTERDAM; 4 Dutch Childhood Oncology
Group, THE HAGUE, Netherlands
Children with high risk acute lymphoblastic leukemia who receive an
allogeneic stem cell transplantation (SCT) nevertheless have a high
chance of relapse (40%). It has been reported that the presence of minimal
residual disease (MRD) detected by sensitive molecular techniques
immediately prior to SCT predicts a very high probability of relapse
(80%). This criterion was used to select patients for an intervention
study. In patients with MRD levels > 1×10 –4 in their bone marrow pretransplantation,
we have attempted to induce a graft-versus-leukemia
effect by early tapering of cyclosporin A (CsA, 4-5 weeks post-SCT) followed,
if needed, by infusion of incremental doses of donor lymphocytes
(DLI). Dosage varied between 1×10 5 and 4×10 6 CD3 + cells/kg
depending on transplantation characteristics. When GVHD grade II
occurred, therapy was initiated to suppress GVHD. Patients with low
( 1×10 –4 . In 11 of these patients CsA was
tapered 4-5 weeks after SCT. Four patients developed GVHD, grade II
after tapering of CsA, which was controlled by treatment. Two relapsed,
the other two are still in remission. The remaining 7 MRD-positive
patients received DLI, and did not develop GVHD. Of those 7 patients,
5 had a relapse and 2 are in remission as of to date. Of the 7 relapses 4
were extramedullary. Of the remaining 29 patients in whom MRD was
either below the cut-off level of 1×10 –4 , positive but not quantifiable, or
undetectable, 9 relapsed (31%) with GVHD greater than grade I, in 2
patients. As no transplant related mortality was seen, due to induction
of GVHD, these data indicate that early reduction of immunosuppression
and low dosis DLI can safely be performed following SCT. The
timing of (mostly) extramedullary relapses in the MRD high group suggests
an antileukemic effect of the intervention.
0422
A PROSPECTIVE RANDOMIZED TRIAL OF TWO DOSE-INTENSIVE MELPHALAN REGIMENS
(100 VS 200 MG/MQ) IN NEWLY DIAGNOSED MYELOMA PATIENTS
A. Palumbo, 1 S. Bringhen, 1 M.T. Petrucci, 2 A. Falcone, 3 A.M. Liberati, 4
M. Grasso, 5 F. Pisani, 6 C. Cangialosi, 7 T. Caravita, 8 F. D'Agostino, 1
F. Cavallo, 1 P. Omedè, 1 P. Musto, 9 R. Foà, 2 M. Boccadoro1 1 Az. Osp. S. Giovanni Battista, TORINO; 2 Università La Sapienza, ROMA;
3 IRCCS Casa Sollievo della Sofferenza, SAN GIOVANNI ROTONDO (FG);
4 Policlinico Monteluce, PERUGIA; 5 Az. Osp. S. Croce e Carle, CUNEO; 6 Istituto
Regina Elena, ROMA; 7 Az. Osp. Cervello, PALERMO; 8 Università Tor
Vergata, ROMA; 9 Centro Riferimento Oncologico Basilicata, RIONERO IN
VULTURE (PZ), Italy
Background. Several trials have shown the superiority of high-dose
melphalan (usually 200 mg/m 2 , MEL200) versus standard therapy in
myeloma patients. Intermediate-dose melphalan (100 mg/m 2 , MEL100)
is also superior to the standard dose, but has not been clinically compared
with MEL200 in a randomized study. In this prospective, randomized,
phase III trial, we compared MEL200 with MEL100. Aims. The primary
end points were complete remission (CR) rate, event-free survival
(EFS) and incidence of gastrointestinal toxicity, infections and early
deaths. Methods. Between January 2002 and July 2006, 298 patients were
enrolled. Inclusion criteria were previously untreated myeloma, age < 65
and Durie and Salmon stage II or III. Exclusion criteria were prior treatment
for myeloma, abnormal cardiac function (systolic ejection fraction
3
mg/dL), HBV, HCV, or HIV positivity, concomitant cancer or psychi-
156 | haematologica/the hematology journal | 2007; 92(s1)
atric disease. The institutional review board approved the protocol and
written informed consent was obtained from all patients. All patients
received: 2 DAV debulking courses (dexamethasone-doxorubicin-vincristine),
2 cycles of cyclophosphamide (4 mg/m 2 ) plus G-CSF followed
by stem cell harvest. The MEL200 group was conditioned with 2 cycles
of melphalan 200 mg/m 2 . The MEL100 group was conditioned with 2
courses of melphalan 100 mg/m 2 . All MEL courses were followed by
stem cell infusion. Results. Two-hundred and forty-six patients (median
age 57) were evaluable: 124 in the MEL200 arm and 122 in the MEL100.
Patient characteristics were similar in both groups. In intention-to-treat
analysis, the very good partial response rate was higher in MEL200 arm
(38% versus 22%, p=0.011), but CR was 17% in the MEL200 group and
10% in the MEL100 group (p=0.2). The median follow-up for censored
patients was 26.5 months. The 3-years EFS was 48% in the MEL200 and
31% in the MEL100 arm (p=0.31). The 3-years overall survival was 86%
in the MEL200 and 71% in the MEL100 group (p=0.51). Forty-six
patients did not complete tandem MEL200; 36 did not complete tandem
MEL100. Severe hematologic toxicity was comparable in two arms, but
84% of MEL200 patients received more than 4×10 6 CD34 + /Kg compared
with 52% of MEL100 (p=0.0001). Grade 3-4 non-hematologic adverse
events were more frequent in the MEL200 (52% versus 34%, p=0.01 in
the 1st cycle and 39% versus 31%, p=0.9 in the 2nd cycle). The incidence
of severe gastrointestinal toxicity was 51% after MEL200 and 21% after
MEL100 (p