Haematologica 2003 - Supplements

25 Gy to marrow. The tracer dose was followed by a therapeutic
dose of 166Ho-DOTMP. Patients received a median dose of 674
mCi/m2 (range 551-860), followed, 6 days later (range 4 to 8) by
melphalan 200 mg/m2. Autologous stem cells were reinfused two
days later. Engraftment was prompt with recovery of neutrophils
at a median of 12 days ( range 9-15) and platelets to 20,000 /ul at
10 days (range 6-15). No grade 4 adverse events were noted.
Two episodes of grade 3 mucositis and 1 episode of grade 3
neutropenic fever were seen. Six other serious adverse events
occurred, none related to holmium.
Gamma camera imaging confirmed skeletal localization of
166Ho-DOTMP, ranging from 19% to 39% of the injected dose.
The highest calculated doses to bone surfaces, red marrow and
bladder wall were 4608 cGy, 2522 cGy and 1498 cGy
respectively. PK and dosimetry were reproducible within 15%
between the 2 tracer doses. Skeletal uptake did not appear to be
affected by disease status. Kidney dosimetry was difficult to
measure reproducibly because of low activity in kidneys;
however, the median dose to kidneys was estimated to be about
0.9 cGy/mCi.
Assessment of response after transplant is ongoing at this time.
166Ho-DOTMP is a promising therapy for patients with multiple
myeloma and merits further evaluation. A prospective
randomized trial comparing high dose melphalan alone with the
combination of 166Ho-DOTMP + melphalan is planned.
10.3 Double ASCT
288
LONG-TERM FOLLOW-UP OF A SINGLE CENTRE
POPULATION OF AUTOTRANSPLANTED MULTIPLE
MYELOMA PATIENTS: LOW INCIDENCE OF TOXICITY
AND NO ADVANTAGE FOR DOUBLE
TRANSPLANTATION OR PURGED GRAFT.
Francesca Patriarca, Alessandra Sperotto, Simonetta
Prosdocimo, Carla Fili’, Antonella Geromin, Francesco
Zaja, Cristina Skert, Teresa Michelutti, Renato Fanin.
Division of Haematology and Department of Bone Marrow
Transplantation, University Hospital, Udine, Italy
Between January ’96 and December ’02 84 patients with
multiple myeloma (MM) received one or two courses of highdose
therapy in our Centre. Median age was 55 years (range 31-
65), 42 were female and 42 male, 14 patients (17%) were in stage
IA, 7 (8%) in stage IIA, 54 (64%) in stage IIIA and 9 cases (11%)
in stage IIIB. M-Component (MC) was IgG in forty-seven
patients (56%) , IgA in 15 patients (18%) , IgM in 2 (2%),
Bence Jones in 16 cases (19%) whereas 4 patients (5%) were
non-secretory. Nine patients (11%) were pretreated with at least
two lines of conventional therapy whereas the other 75 cases
proceeded directly to high-dose therapy after 4 courses of VAD
induction therapy. PBSC were collected after Cyclophosphamide
+ G-CSF at the dose of 7g/m2 (65 patients) or 4 g/m2 (19
patients); in 49 patients (58%)the leukapheresis products were
processed to positively select CD34+ cells using an avidin-biotin
immunoaffinity device (CEPRATE, CellPro).The first course of
myeloablative treatment was 12mg/Kg Busulfan plus 120 mg/m2
Melphalan, the second course was administered in 24 patients
with melphalan 200 mg/m2. Median time between diagnosis and
the autotransplantation was 10 months (6-68) for the the first
course and 16 months for the second course, median number of
CD 34 positive cells reinfused was respectively 2,7 x106/Kg and
3,2 x 106/Kg. Median time to 1 x 106 neutrophils was 13 days
(10-31) and to 50 x 106 platelets was 26 days (12-210). Fortyeight
patients (57%) had a WHO grade I-II mucositis, 22 patients
(26%) had a WHO grade III-IV mucositis, 44 (52%) a febrile
episode with evidence of bacteriemia in 9 cases. Two patients
(2%) were dead 32 days and 95 days after transplantation for
graft failure and mycotic infection respectively. Long-term
complications included 1 deep venous thrombosis, 5 herpes
zosters, 3 bacterial pneumonias, 1 pseudomembranous colitis and
3 myocardial infarctions, all but the heart complications
occurring within 10 months after ASCT. Haematologic
engrafment and extraematologic toxicity did not differ
significantly after the first procedure in comparison with the
second one and after reinfusion of positively selected CD 34+
cells in comparison with unselected PBSC. Forty-six objective
responses (55%), all partial, were achieved after the induction
therapy, 53 partial responses (64%) and 15 complete responses
(18%) were obtained after the first ASCT, 14 partial responses
(58%) and 6 (25%) complete responses were achieved among
the 24 patients undergoing the second procedure.
After a median follow-up of 37 months (86-102) after ASCT,
PFS and OS for the whole population were respectively
38% (95%CI: 22% - 53%) and 40% (95%: 10% - 72%), without
any significant difference between one or two courses of
myeloablative treatment and between selected and unselected
PBSC reinfused.
We conclude that ASCT was a safe and effective procedure after
a long-term follow-up of a single centre population mainly
constituted by newly diagnosed MM and no clear advantage
emerged for a double ASCT or reinfusion of positively selected
PBSC.
289
Statistical Analysis of EBMT Registry Data of Single Vs
Double Peripheral Stem Cell Transplantation (pbsc) in
Myeloma and its timing; clinical findings and
methodological limitations
TCM. Morris, S. Iacobelli, R. Brand, B. Bjorkstrand, G.
Gahrton
Haematology Department, Belfast City Hospital; University Medical
Centre, Leiden, Netherlands; Huddinge Hospital, Huddinge,
Sweden on behalf of the Chronic Leukaemia Working Party
Myeloma Subcommittee
EBMT registry data show that double pbsc transplantation is
common therapeutic strategy in myeloma with over 40% of 7452
transplant patients having received or planned to receive a second
transplant between January 1993 and March 2002. Of these
patients 2665 were described as “planned” (to receive a second
transplant) and this group was compared with the remaining
patients on an intention to treat basis. This approach was chosen
because a direct comparison of patients actually receiving one
transplant against those receiving two transplants is not
methodologically (statistically) valid: in order to receive a double
transplant patients must first of all survive sufficiently long.
Even though the transplant rate in the planned group failed to
reach 60% (55% of planned had the 2nd SCT before their relapse,
while 58% of the planned group had a 2nd SCT in any case) the
median survival from transplantation was 60 months for the
planned compared to 51 months for the remainder group.
However while the Hazard Ratio (HR) of the planned group is
0.89 (CI 0.79-1.00 p=0.05) before 70 months the position is
reversed after 70 months with the HR being 3.01 (1.07-8.46
p=0.04). Using a separate approach we ignored the information
on “planning” and instead described the data in terms of hazard
ratios for the main outcomes of interest (Relapsed, Treatment
Related Mortality and Overall Survival) with respect to the
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