Haematologica 2003 - Supplements

with cyclosporine A and methotrexate. Of the 38 patients enrolled,
37 proceeded to allotransplant within 6 weeks following
cyclophosphamide. The median age was 47 years (range: 31 - 55),
68% were male. The median survival from study enrollment is 31
months with 22 deaths, but 6-year survival is 42%. Of the 16
patients evaluable for response, 11 achieved complete remission
(normal marrow; no paraprotein; negative immunofixation) or very
good partial response (normal marrow; > 90% decrease in serum
paraprotein; negative BJ proteinuria) and response (> 50% decrease
in marrow plasmacytosis; > 75% decrease in serum paraproteins; >
90% decrease in BJ proteinuria). Seven patients relapsed during the
first 3 years, with a 2-year estimate of relapse of 20%. Ten patients
are event-free now for more than 5 years, with a 6-year projection
of 26%. The major cause of failure, however, was transplantrelated
mortality (TRM), with 13 deaths within 6 months (1-year
estimate of 36%), resulting in closure of the enrollment to this arm
in 1997. Of the transplant-related deaths, infection (n = 8) was the
most common cause and was associated with acute GVHD. No
further events after 5 years post-transplant were observed
suggesting the possibility of long-term disease control, but at the
expense of high initial TRM.
100%
80%
60%
40%
20%
0%
Overall Survival
Event-Free Survival
Events / N
22 / 38
28 / 38
0 2 4 6 8
Years After Transplant
6-Year
Estimate
42%
26%
304
Chronic but not acute Graft versus host disease
improves outcome in multiple myeloma patients after
nonmyeloablative allogeneic transplantation
Pérez-Simón JA(*), Martino R, Alegre A, Tomás JF, De
Leon A, Caballero D, Sureda A, Sierra J, San Miguel JF
Spanish Collaborative Group for Non-myeloablative
Transplantation.
A graft versus myeloma effect (GVM) has been observed in MM
patients after allogeneic transplantation. This effect has been used
to design less toxic regimens such as non-myeloablative
transplants (NMT) maintaining antitumor efficacy through the
GVM effect. In the present study we have evaluated the outcome
of 29 MM patients receiving fludarabine and melphalan-based
NMT. Event free survival (EFS) at 24 months was 33% being
significantly higher for patients who developed cGVHD as
compared to those who did not (51% vs 0% respectively, p=0.02;
Hazard Rate (HR) = 3.16 (95% CI=1.09-9.15, p=0.03)) as well as
for patients transplanted in response (CR/PR) or stable disease
(SD) as compared to those with refractory/progressive disease at
transplant (43% vs 0% respectively, p=0.02). Overall survival
(OS) at 24 months was 60% ranging from 72% vs 42% for
patients who did and did not develop cGVHD, respectively
(p=0.1) and 63% vs 41% for patients in CR/PR or SD vs
refractory/progressive disease at transplant, respectively
(p=0.013). After a median follow up of 366 days 13 patients are
in complete or partial remission (45% overall response rate). Nine
patients have died, 3 of them due to disease progression and 6
(21%) due to transplant related mortality (TRM). Actuarial
incidence of TRM was 37% for patients who developed aGVHD
vs 13% for those who did not (log rank p=0.04). Among patients
evaluable for cGVHD, these figures were 13% and 33% for
patients with and without cGVHD, respectively (log rank
p=0.22). The present study suggests that graft versus myeloma
(GVM) effect is the main weapon for disease control after NMT
in MM patients and the efficacy of this immune effect depends on
tumor burden before transplant.
(Supported by Grant from Spanish FIS G03/136)
305
Results of Reduced Intensity Conditioning Allogeneic
Transplantation in Myeloma – A report from the EBMT
C. Crawley, R.Szydlo, M. Lalancette, G.Juliusson, A.
Shimoni, A. Nagler, T Ruutu, M.Michallet, J Boiron,
K.Peggs, J. Sierra, H.Einsele, R.Chopra, A. Carella, A.
Zander, A. Gratwohl, H. Greinix, J. Cavenagh, F. Garban,
D. Caballero, D.Niederwieser, G. Gahrton and J.Apperley
For the Chronic Leukaemia Working Party of the EBMT.
The more widespread use of conventional allogeneic transplant
for myeloma has been limited by the substantial procedure related
mortality. Reduced intensity conditioning has been widely
adopted with the demonstration of its feasibility and apparent
lower mortality. Evidence for efficacy is limited, as the majority
of series are small and frequently diagnostically heterogeneous.
Data were collected for myeloma patients from 38 EBMT centres
on a total of 256 transplants performed between 11/97 and 07/00.
The median age was 52 years (32-66), 61% were male of whom
43% received stem cells from a female donor. 70% had stage III
disease at diagnosis. 194 were matched siblings, 40 were
unrelated and 9 were from mismatched or other related donors.
73% were CMV IgG positive. At the time of transplant 7.5%
were in CR, 54% PR and 29% had progressive disease. The
median time to transplant was 20 months (2 months – 11 years).
Conditioning regimens varied but included fludarabine in 95%.
The most frequent regimens were Fludarabine + TBI,
Fludarabine, Busulphan + ATG and Fludarabine, Melphalan ±
Campath. The cell source was peripheral blood stem cells (PBSC)
in 205 and bone marrow (BM) in 51 patients. The time to
neutrophil and platelet engraftment was faster for PBSC
recipients (14 and 13 days vs 17 and 21 days respectively). Acute
GvHD (grade II-IV) occurred in 31% and cGvHD in 49% of 195
assessable patients (extensive in 25%).
The 1 and 2 year the TRM was 23.5% and 26%. Factors
associated with an increased TRM were more than one prior
transplant (RR 1.9), > 1 year from diagnosis (RR2.7) and male
patients with a female donor (RR 2.3). At 2 years the overall and
progression free survival was 50% and 39%. Patients in remission
prior to transplant had a better 2 year overall survival (1st CR/PR
74%, >1st CR/PR 49%, no remission 38% p=0.006). 2 year
survival was worse in male patients receiving cells from a female
donor (36% vs 54%) and in patients who had had more than one
prior transplant (28% vs 54%). Similar factors were predictive for
progression free survival at 2 years namely > 1 prior transplant
(20% vs 45% p< 0.001) and remission status at conditioning (1st
remission 62% vs no remission 35% p=0.003)
Disease progression and treatment related mortality remain
challenges in allogeneic transplants for myeloma even with
reduced intensity conditioning. It is, however, possible to identify
patients where the risk may be acceptable and who may derive
real benefit.
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