Haematologica 2003 - Supplements

yielding a median of 3x106/kg CD34 cells and 35,3x104/Kg
CFU-GM. The conditioning regimen was melphalan 200 in 26
cases(86,8%) and busulfan plus melphalan in 4 (13,2%).
Results: The median days to recovery of neutrophils (>
0,5x109/L) was 11,2 days (10-13), to recovery of neutrophils
(>1x109/L) was 11,9 days (10-14), to recovery of platelets
(>20x109/L) was 13,1 days (10-36) and to recovery of platelets
(>50x109/L) was 15,2 days (12-50). Transplant related mortality
ocurred in 1 patient (3,3%). Following the autograft 12 patients
(41,2%) were in CR, 14 (48,1%) in PR and 3 (10,3%) in
progression status. Three months after APBSCT 18 (62%)
patients received recombinant alpha interferon and steroid as
maintenance therapy. With a median follow-up of 69,6 months
(96-13),16 patients (53,3%) remain alive and 8 (26,6%) are free
of progression. The overall survival (OS) of all patients was 41,9
months (SE ,CI 95% 29-54) and the median duration of
progression free survival (PFS) was 24,8 months (SE 3,9 CI
95% 17-32).
Comments: We conclude that APBSCT is a safe and effective
therapy in MM patients. Our results are similar to obtained by
other groups in terms of mortality, overall survival and event-free
survival.
271
Long term survival after high dose chemotherapy and
stem cell transplantation for multiple myeloma - two
case reports
R. Reisner 1, A. Seebacher 1, E. Krömer 1, M. Fillitz 1, H.
Mühlberger 1, A. Nader 2, J. Drach 3, N. Worel 4, M.
Bernhart 1, M. Pfeilstöcker 1
(1)3rd Medical Dept. and Ludwig Boltzmann Institute for Leukemia
Research & Hematology, Hanusch Hospital, (2) Institute of
Pathology, Hanusch Hospital, Vienna, (3) Dept. of Internal
Medicine I, University of Vienna, (4) Inst. of Blood Group Serology
and Transfusion Medicine, University of Vienna, Austria
Multiple myeloma is not considered curable with standard
chemotherapy. High dose chemotherapy (HD-CT) followed by
stem cell transplantation (SCT) improves survival in selected
patients (pts.). After SCT 50-60% of myeloma pts. achieve
remission, minimal residual disease causes relapse in most pts,
predictors for long term survivors are not yet clear.
Among 18 pts (12 male, 6 female, median age 56 years, range 35-
62) transplanted for myeloma in our institution 2 pts with long
term remission can be identified: we report two female patients,
age at diagnosis 35 and 57 years, both presenting with stage IIIB
disease and elevated serum creatinine (3.5 mg/dl and 5.6 mg/dl);
multiple bone lesions were apparent in one case at time of
diagnosis, in the other at time of progression. Both patients had
Bence-Jones proteinuria, paraprotein was IgG lambda in one
case, light chain kappa in the other, in whom disease was
complicated by amyloidosis of the tongue apparent at time of
diagnosis (at progression also in the gut). FISH analysis at
diagnosis found no 13q14 chormosomal abnormality in both
cases. Therapy before stem cell mobilization was 1 cycle VAD /
3 cycles VID in one case and 6 cycles VAD followed by
interferon alpha maintenance treatment until progression which
was treated by further 3 cycles of VAD in the other. Time from
diagnosis to transplantation was 7 and 74 months. Both patients
received a single transplant with 5.22x10^6/kg and 3.85x10^6/kg
CD34+ cells. Both pts. are still alive in remission at 57 months
and 117 months after diagnosis, 50 and 43 months after SCT,
respectively.
We compared these two patients with the other 16 patients
transplanted in our institution: paraprotein type was IgA in 5 pts
and IgG in 11, 10 pts had stage 3 at diagnosis. There was no
difference in pretreatment (VAD/VID), mobilization therapy
(cyclophosphamide and G-CSF) and stem cell yield. All pts
received melphalan 140/200mg/m2 ± TBI as pretransplant
regimen. 10/16 pts had a tandem SCT. 10/16 pts are still alive
with an overall survival of 24.5 (8-84) months, time from
diagnosis to mobilization 6 (3-72) months, time after 1st SCT
11.5 (1-42) months. In 11 pts cytogenetic findings are available,
in 9/11 chromosomal abnormalities could be detected - in 5 pts.
aberrations on chromosome 13.
In concordance with published data our case reports confirm that
a subgroup of myeloma patients benefits from HD-CT followed
by autologous stem cell rescue achieving prolonged disease free
survival. Long time survival was observed despite stage IIIB
disease at diagnosis (as in most other pts progressing after
transplant), presence of amyloidosis or long time to transplant (in
one case) and the fact that only a single transplant was carried
out. Our data confirm the prognostic value of the absence of
chromosome 13 aberrations for a good outcome after SCT.
Evaluation of further predictive factors beside cytogenetics as
expression of genes of growth and apoptotic signaling cascades,
factors of the bone marrow microenvironment and human
herpesvirus-8 infection is warranted to identify patients at risk for
relapse after SCT.
272
A Multi-Center Randomized Phase Two Trial of
Thalidomide and Prednisone as Maintenance Therapy
For Multiple Myeloma Following Autologous Stem Cell
Transplant.
A.K. Stewart1, C. Chen1, K. Howson-Jan2, D. White3, D.
Roy4, M. Kovacs2, C. Shustik6, A. Sadura7, L. Shepherd7,
Q. Ding7, R. Meyer8, A. Belch9
1Princess Margaret Hospital, Toronto; 8Hamilton Regional Cancer
Center, Hamilton; 2London Health Sciences Center,London and
7National Cancer Institute of Canada Clinical Trials Group,
Kingston, Ontario; 3Nova Scotia Cancer Center Halifax, Nova
Scotia; 4Maisonneuve-Rosemont Hospital, 6McGill Oncology
Group, Montreal, Quebec; 9Cross Cancer Institute, Edmonton,
Aberta
Purpose: Multiple myeloma (MM) patients benefit from high dose
chemotherapy however relapse is inevitable and novel means of
maintaining remission are required. A multi-center, randomized
phase II trial was therefore conducted to assess the tolerability of
combined thalidomide and prednisone maintenance in MM.
Patients and Methods: Eligibility required transplant within one
year of treatment onset and maintenance commenced 60-100 days
post stem cell infusion. All patients received prednisone 50mg
p.o. on alternate days and thalidomide at a starting dose of either
200 mg or 400mg p.o. daily. The primary endpoint was the
incidence of dropout or dose reduction due to treatment toxicity
within 6 months.
Results: 67 patients were enrolled. Median follow-up is 9.6
months. The primary endpoint was reached by 14 of 45 patients
on the thalidomide 200mg arm (31%: C.I. 20 - 47%), and 14 of
22 patients on the thalidomide 400mg arm (63%: C.I. 45% -
83%). Allowing for dose reduction, 76% (34/45) of patients
assigned to thalidomide 200mg and 41% (9/22) of patients
assigned to thalidomide 400mg remained on maintenance therapy
17.8 months after registration. Common toxicities included
neuropathy 54%, constipation 42%, fatigue 37%, dizziness 34%,
infection 30%, sedation 22%, mouth dryness 22%, skin rash 20%
and edema 19%. Symptomatic DVT was observed in 7.5% of
patients.
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