Haematologica 2003 - Supplements

268
High Dose Therapy (HDT) supported with Autologous
Blood Stem Cell (ABSC) transplantation: long term
follow-up of 3 prospective studies including 455
patients with Multiple Myeloma (MM)
V.Levy, S.Katsahian, V.Leblond, M.Divine, M.Macro,
D.Bouscary, X.Mariette, A.Jaccard, and J.P. Fermand
For the group "Myélome-Autogreffe", Caen, Créteil, Limoges,
Paris, France.
Between 1986 and 1995, we initiated 3 prospective studies
designed to assess the interest of HDT and ABSC transplantation
in the treatment of MM:
The first one was a phase II study in which 63 young patients
(median age 44 yrs) with stage III or stage II MM were included
(Blood, 1993, 82, 2005-9)
Thereafter, patients up to 56 years of age with successful ABSC
collection (185 out of 202 initially enrolled patients) were
randomly assigned to receive HDT and ABSC transplantation or
conventional chemotherapy (CCT). In the later group, HDT and
ABSC transplantation was intended to be systematically
performed in case of primary resistance to CCT or at relapse in
responders (Blood, 1998; 92, 3131-36).
The third study randomly compared HDT and ABSC
transplantation with CCT in 190 patients aged between 55 and 66
years (Blood, 1999; 94, 396a, abst. 1754). In this study, HDT
protocol consisted of melphalan (MLP) 200 mg/m2 (or MLP140
+ busulfan) whereas HDT included a 12 Gy total body irradiation
(TBI) in the 2 other studies.
At the reference date of 01/01/2003, median follow-up of all 455
patients enrolled in the 3 studies reached 13.8, 10.3 and 8.2 years,
respectively. Considering the rate of long-term survival as crucial
in evaluating the treatment, we up-dated all data aiming to precise
the rate and characteristics of long-term survivors. Results of the
analysis will be presented at the meeting.
269
High-Dose Melphalan (MEL) 280mg/m2 plus Amifostine
Cytoprotection and ASCT as Part of Initial Therapy in
Patients with Multiple Myeloma
Donna E. Reece,1 David Vesole,2 Neal Flomenberg,3
Ashraf Badros,4 Joanne Filicko,3 Roger Herzig,5 Dianna S.
Howard,5 Victoria Johnson,2 Barry Meisenberg,4 Aaron
Rapoport,4 C.Q. Xun,5 Gordon L. Phillips,4.
1University Health Network, Princess Margaret Hospital, Toronto,
ON, Canada; 2Blood and Marrow Transplantation, Medical College
of Wisconsin, Milwaukee, WI, USA; 3Blood and Marrow
Transplantation, Thomas Jefferson Unviersity Medical College,
Philadelphia, PA, USA; 4Greenebaum Cancer Center, University of
Maryland, Baltimore, MD, USA; 5Blood and Marrow
Transplantation, University of Kentucky, Lexington, KY, USA.
Recurrent multiple myeloma (MM) after ASCT remains a
significant problem in the treatment of this malignancy. One
approach has been to administer a cytotoxic regimen more
intensive than the usual melphalan (MEL) 200mg/m2 given
before a single ASCT. The use of tandem transplant represents
one effort in this regard that has produced encouraging results.
We have evaluated a different strategy in which we increased the
dose of MEL to 280mg/m2 before a single ASCT; this dose has
previously been shown to be well tolerated when given with
amisfostine (AF) to reduce non-hematopoietic toxicity (Proc
ASCO, 2001:24). The current study was performed to evaluate
this regimen in MM patients (pts) undergoing ASCT as part of
initial therapy. Between 05/99 and 12/02, 43 pts received AF
740mg/m2 IV over 5-15 min 24 hr and 15min before MEL
280mg/m2 (given IV over 15 min); stem cells were reinfused 24
hrs after MEL. Median age was 58 yrs (32-65 yrs); 28 were
male. Ig subtypes were as follows: IgG (24 pts), IgA (13 pts),
light chain (4 pts) and non-secretory (2 pts). Median pre-ASCT
beta 2-microglobulin level was 1.64 mg/L. Thirty-nine were in
CR/PR. Priming therapy for blood stem cell collection included
G-CSF alone in 6, cyclophosphamide (CY)+G-SCF +/-GM-CSF
in 12 and CY+etoposide +G-CSF in 25. Median CD34+cell dose
was 6.97x106/kg. No significant hypotension, but occasional
hypocalcemia and nausea/vomiting, were noted with AF. The
median day to recovery of an ANC of 0.5 x 109/L was 12 (range
6-28) and day of the last platelet transfusion was 16 (range 4-34)
post-ASCT; 2 pts had delayed engraftment. Median
hospitalization was 19 days (range 8-34 days). Using the Seattle
criteria for regimen-related toxicity (RRT), grade (gr) I mucosal
toxicity was seen in 14 and gr II (requirement for continuous IV
narcotics) in 12 pts evaluable to date. In addition, reversible gr II
cardiac (2 pts), bladder (2 pts), CNS (1 pt) and renal (1 pt) RRT
were seen, but no gr III or fatal toxicity was observed. One pt
with bacteremia needed temporary hemodialysis. Best post-
ASCT response in evaluable pts includes CR in 25/40 (63%), PR
in 8, stable disease in 4 and progression in 1. Thirteen pts
received maintenance therapy with thalidomide (6),
dexamethasone (3), both (3) or interferon (1). Median follow-up
is 12 mos (range 1-45 mos); 29 are alive without progression,
while 13 have progressed at median of 10 mos (range 3-20 mos)
after ASCT; five pts have died of MM. The actuarial PFS is 40%
(95% confidence intervals [C.I.] 20-87%) while the overall
survival is 71% (95% C.I. 40-100%). We conclude that 1) the
toxicity of MEL 280mg/m2 plus AF cytoprotection is acceptable;
2) the CR rate is high in pts autografted as part of initial therapy;
3) longer follow-up is required to determine durability of these
responses; 4) the possibility of performing tandem ASCT with
MEL 280mg/m2 + AF may be considered in the future.
270
AUTOLOGOUS PERIPHERAL BLOOD STEM CELL
TRANSPLANTATION FOR MULTIPLE MYELOMA:
CLINICAL RESULTS FROM A SINGLE CENTER.
L Palomera, O Gavin, JM Domingo*, V Dourdil, MT Olave,
MA Fuertes, G Azaceta, MT Calvo, M López, M Gutiérrez
Clinic University Hospital, Zaragoza and * Reina Sofía Hospital,
Tudela. SPAIN
Background: Autologous peripheral blood stem cell
transplantation (APBSCT) has become a routine treatment for
symptomatic patients with multiple myeloma (MM). We have
retrospectively analized our center experience.
Patients and methods: Between June 1995 and May 2002, 30
patients with symptomatic MM (22 males/8 females), median age
was 63,8 years (46-72), were treated with high-dose therapy
rescued with APBSCT. The median time from diagnosis to
transplant was 19,3 months (5-72). Fourteen (46,2%) patients had
IgG, 9 (29,7%) IgA, 6 (19,8%) Bence-Jones and 1 (3,3%) IgM
monoclonal component. Stage according Durie-Salmon was: I in
2 patients (6,6%), II in 11patients (36,3%)and III in 17 patients
(56,1%). Prior to APBSCT 21 (69,3%) cases had received only
one line of chemotherapy and 9 (29,7%) two o more lines. At the
time of transplant 3 patients (10%) patients were in complete
remission (CR), 23(75,9%) in partial remission (PR), 3(10%) in
minor response and 1 (3,3%) was non responding. Mobilization
of stem cells was performed with chemotherapy + G-CSF 5
µg/Kg/day in 18 procedures, G-CSF 10 µg/Kg/day in 11
procedures and G-CSF 10 g/Kg twice a day in 11 procedures,
S207