Haematologica 2003 - Supplements

294
SECOND TRANSPLANT AS TREATMENT OF RELAPSE
AFTER A FIRST AUTOLOGOUS TRANSPLANT IN
MULTIPLE MYELOMA. RESULTS OF THE SPANISH
REGISTRY
J. García-Laraña, A. Alegre, R. Martínez, J.J. Lahuerta,
J.C. García-Ruiz, R. García-Sanz, A. Leon, J. De la Rubia,
F. de Arriba, A. Sureda, K. Pérez de Equiza, T. Molero, J.L.
Díez, J.L. Bello, R. Cabrera, M.J. Terol, J. Ojanguren, J.
Besalduch, P. Giraldo, L. Palomera, J.J. Marin, R. Parody,
J.M. Ribera, A. Escudero, F. Prosper, M.J. Peñarrubia, J.
Bladé and J. San Miguel
GEM: Grupo Español de Mieloma (PETHEMA, GETH, GELTAMO)
Objective To evaluate the results of hemopoietic stem cells
transplantation (HSCT) as treatment of relapse after a first
autologous transplantation in patients included in the Spanish
Registry of HSCT in multiple myeloma.
Patients The registry included 1287 patients. 80 have received
some modality of HSCT as treatment of relapse after a first
autologous transplant. Median age at second transplant was 52
years (25-70). Interval between 1º y 2º HSCT: 28,5 months (3-
103). Clinical status at 2º HSCT was CR (13%), PR (36%),
Minimal response (7%), stable disease (3%) and progression
(41%).
Autologous HSCT: Stem cell source was peripheral blood in 57
patients, bone marrow in 5 and both in 1. Peripheral blood stem
cells were mobilized with G-CSF (47%), Cyclophosphamide+G-
CSF (45%) and Cyclophosphamide+GM-CSF (8%). Median
number of apheresis was 3 (1–8), CD34 harvested 2,87 x 106/kg
(0,56–16,7). Conditioning treatment was Melphalan 200 (27%),
Busulfan/Melphalan (23%), CBV (20%), BUCY (10%),
Melphalan 140/TBI (7%), Cyclophosphamide/TBI (5%), and
others (8%).
Alogeneic HSCT: Stem cell source was marrow in 9 patients, and
peripheral blood in 8. 14 were conventional allogeneic
transplantations and 3 received a nonmyeloablative conditioning.
Median number of CD34 cells infused was 3,59 x 106/kg (0,33–
12,5). Conditioning treatment was Cyclophosphamide/TBI
(27%), Fludarabine/Melphalan (20%), Melphalan 200 (13%),
Melphalan 140/TBI (13%), BUCY (13%), CBV (7%), others
(7%).
Results Autologous HSCT: 85% of patients recovered neutrophils
> 500/mm3 in 11 days (7-40) and platelets > 20.000/mm3 in 14
days (8-214). Response to HSCT was CR (33%), PR (28%),
Minimal response (9%), stable disease (10%), progression (12%)
and early death (8%). Median survival from the second transplant
is 23 months (CI 95% 14,8-31,2) with 30% of patients alive at 3
years.
Allogeneic HSCT: 71 % of patients recovered neutrophils >
500/mm3 in 16 days (7-24) and platelets > 20.000/mm3 in 14
days (7-32). Response to HSCT was CR (13%), PR (31%),
Minimal response (12%), stable disease (6%) and early death
(38%). Median survival from the second transplant is 5 months
(CI 95% 0,4-9,6) with 17% of patients alive at 3 years
Conclusions Autologous HSCT as treatment of relapse after a
first transplantation is feasible and has an acceptable toxicity. A
significative fraction of patients (30%) are alive at 3 years.
Allogeneic transplantation, most of them with conventional
conditioning treatment, has shown a high toxic mortality and
short survival.
10.4 Transplantation in other plasma cells
disorders
295
Reducing the dose of melphalan used for stem cell
transplantation in amyloidosis is associated with a
lower response rate
Morie A. Gertz, Martha Q. Lacy, Angela Dispenzieri,
Stephen M. Ansell, Michelle A. Elliott, Dennis A. Gastineau,
David J. Inwards, Ivana N. Micallef, Luis Porrata, Mark R.
Litzow
Mayo Clinic, Rochester, MN
High dose chemotherapy with stem cell transplantation is
increasingly being used for eligible patients with immunoglobulin
light chain amyloidosis (AL). Morbidity and mortality in this
patient group with multiorgan dysfunction is high and mortality
hovers at 15%. In an attempt to render more patients eligible for
stem cell transplantation, a risk adapted strategy has been
developed to categorize patients into those eligible for full dose
chemotherapy and to treat those patients who would be at
inordinate risk for complications with lower doses. An important
issue revolves around whether de-escalation of the conditioning
dose for patients with poor performance status, multiorgan AL
involvement, mild renal insufficiency and cardiomyopathy results
in a reduction in overall response. A total of 125 patients
received high dose therapy with stem cell reconstitution for AL.
Patients who received melphalan 140/m2 plus total body
radiation 1,200 cGy and those receiving melphalan 200 mg/m2
were considered a higher dose group. Those receiving melphalan
140 mg/m2 or melphalan 100 mg/m2 were considered a lower
dose group. Patients who died as a direct result of complications
of transplant were considered non-responders. Responses were
categorized as hematologic responses with criteria identical to
those for patients with multiple myeloma who undergo stem cell
transplantation and organ which requires direct evidence of
improved organ function. The table gives the patients categorized
based on their conditioning pre-transplant and whether they
achieved a hematologic response and organ-based response both
or no response.
Conditioning
Death
Before
D100
Hematologic
Response
Organ
Response
Both
No
Response
n
Mel-TBI 17 3 3 4 7 3
Mel-200 66 7 15 7 24 20
Mel-140 31 5 7 1 6 17
Mel-100 11 3 2 - 4 5
Statistical analysis showed that there were significant differences
between the four groups with the Mel-TBI, Mel-200 and Mel-
140, Mel-100 showing response rates of 72% and 48%
respectively. Treatment related mortality was not different
among the four groups. When the groups were categorized as
high dose therapy (N=83) and lower dose therapy (N=42) the
response rate was significantly higher in the higher dose group
(P=.01). We conclude that reducing the dose of Melphalan
renders more patients with amyloidosis eligible for stem cell
transplant, but their response rate is significantly lower. Efforts
to reduce treatment-related toxicity to permit a greater proportion
of patients to receive a full dose of conditioning chemotherapy
are warranted.
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