Haematologica 2003 - Supplements

stage of myeloma, response to initial chemotherapy and number
of courses of prior chemotherapy. The parameters observed were:
number of mononuclear cells(MNC) and CD34+ cells, number of
CFU-GM , number of leukaphereses and side effects.
Results: The median number of MNC x108/Kg were 5,6 (range
1,5-11,6) for the A group, 8,6 (range 1,8-13,4) for the B group
and 13,9 (range 10,2-22) for the C group. The median number of
CD34+ cellsx106/Kg collected were 2 (range 0,1-5,3) for the A
group, 2,1 (range 0,01-7) for the B group and 4,9 (range 2,6-7,6)
for the C group. The median number of CFU-GM x104/Kg were
23,1 (range 1,3-56) for the A group, 17,5 (range 6,4-28) for the B
group and 65,5 (range 31-132) for the C group. There were no
statistically significant differences in number of leukaphereses
between all the groups. No major side effectes were observed in
the A and B groups. In C group pain bone were observed in 4
cases. Significantly more CD34+ cells and CFU-GM cells were
harvested in group C than A and B. There was no significant
difference in the engraftment parameters.
Conclusion: We conclude that mobilization of peripheral blood
stem cell with G-CSF at dose of 10 g/Kg twice a day results in
significantly more CD34+ and CFU-GM than the other groups;
the three regimens are similar in terms of hematologic recovery
after infusion.
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Individual quality assessment of autografting by
probability evaluation: Models estimated from analysis
of graft related end points in 522 patients with newly
diagnosed Multiple Myeloma.
Roer O*, Huang T*, Hammerstrøm J#, Lenhoff S¤, Johnsen
HE*
For the Nordic Myeloma Study Group∇. The Department of
Haematology, Herlev University Hospital, Denmark *,∇; Trondheim
University Hospital, Norway #,∇, Lund University Hospital,
Sweden¤,∇.
Pretransplant quality assessment of autografts is an important step
in prediction of posttransplant support, complications and safety.
Previously, disease and therapy related variables and the impact
of graft related factors have been described by weighty end points
as delayed engraftment, graft failure, regimen related death etc.
However, in actual clinical practice these observations are rare.
Today, haematological toxicity is considered one of the more
secondary end points important for graft evaluation – which in
todays practice focuses primary on health economic end points.
Such end points graded binary as acceptable or unacceptable has
allowed us to estimate clinically relevant prognostic models for
quality assessment of autografting as a whole.
In the Nordic area 522 newly diagnosed, symptomatic MM
patients were enrolled into a prospective, population based
registration study of high dose therapy and autologous
transplantation. Data from this cohorde of patients were analysed
to illustrate the benefit of combining demographic, disease and
graft related variables in predictive models for individual quality
assessment of autografting by help of clinical end point
describing short-term efficacy, toxicity and safety.
The model which estimated efficacy of autografting by graded
posttransplant primary end points (time on antibiotics and use of
transfusions) contained six independent variables including age,
sex, WHO performance status, length of priming, days of harvest
and graft CD34+ cell number. The model which estimated
toxicity by graded secondary end points (time to blood cell
recovery) included six independent variables at diagnosis
(marrow plasmacell percentage, serum creatinine, M component
isotype and WHO performance status), following therapy
(response to induction therapy) and graft CD34+ cell number.
The model evaluating safety by graded tertiary end points (early
disease recurrence or death) included known prognostic variables
at diagnosis (haemoglobin, serum beta-2 microglobulin, Durie-
Samon staging) and length of priming but not CD34+ cell
number.
In conclusion binary graded clinical end points of supportive
care, complications and safety related to autografting depends
upon pretransplant variables of which only the number of CD34+
cells may be improved by increasing the numbers of apheresis.
However, this needs to be confirmed in future prospective
multicenter studies, including strict clinical guidelines, before
recommendations for intervention can be established.
Acknowledgement: This study is supported by research grants
from the Nordic Cancer Union (grant no 56-9350/56-9351 and
56 100 02-9101/9102 95) and Danish Cancer Society (grant no
945 100-15).
Clinical data were based on the NMSG database (study NMSG
#5/94 and #7/98) from Onkologi Centrum in Lund, Sweden.
283
PRELIMINARY RESULTS FROM A PHASE I/II STUDY
OF HIGH DOSE 153-SAMARIUM EDTMP (153-
SMEDMTP) WITH FIXED DOSE MELPHALAN
PERIPHERAL STEM CELL TRANSPLANTATION
(PBSCT) FOR MULTIPLE MYELOMA (MM)
Dispenzieri, A.; Wiseman, G.A; Lacy, M.Q; Geyer, S;
Litzow, M.R; Tefferi, A.; Inwards, D.J; Micallef, I.N;
Gastineau, D.A; Ansell, S.; Gertz, M.A
Mayo Clinic, Rochester, MN, USA
Abstract: Background: High dose chemoradiotherapy improves
the quality of life, prolongs the time to progression, and prolongs
survival of patients with myeloma (MM). 153-Sm EDTMP is a
therapeutic radioisotope linked to a diphosphonate compound that
binds tightly to bone. It has a short range beta emission, a 1.9 day
half-life and very rapid clearance from non-osseous tissues.
Methods: MM patients who were candidates for autologous
PBSCT were eligible. For the phase I portion of the trial, patients
were treated with a fixed dose of melphalan (200 mg/m2) and an
escalating dose of the 153-Sm EDTMP. The original four dose
levels were 6, 12, 19.8, and 30 mCi/kg. Because of variability of
bone uptake of 153-Sm EDTMP noted after the first 12 patients,
the protocol was modified to include a trace dose of 153-Sm
EDTMP with a 24-hour whole body uptake measurement. For an
additional 6 Phase I patients and all Phase II patients, the 153-Sm
EDTMP administered activity was calculated to deliver 40 Gy to
the marrow. The 53-Sm EDTMP was given on day -11 and
Melphalan was given day -1. The goal of the Phase II study was
to achieve a combined CR and VGPR rate of at least 50%.
Results: Fifty-five patients have been treated. Median age at
PBSCT was 55, range 38-74. Forty-one (75%) were treated with
upfront transplant and 25% at relapse. Response categories pretransplant
were: primary responsive (33; 60%); primary
refractory (8; 15%); resistant relapse (5; 9%); and sensitive or
untested relapse (9; 16%). Thirteen and twenty-four patients,
respectively, had a PCLI >= 1 and a B2M > 2.7 prior to PBSC
mobilization/transplant. At the Phase II dose level, median days
to ANC > 0.5 platelet > 20 and platelet > 50 x 10(9)/L were 13
(95% CI 12-14), 13 (95% CI 11-18) and 25 (95% CI 16-53) days,
respectively. There was one death due to peri-engraftment
syndrome; the patient refused to be intubated and expired despite
treatment with high dose corticosteroids. All patients engrafted
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