Haematologica 2003 - Supplements

disease. The lack of response to initial induction therapy does not
appear to prevent these patients from obtaining a meaningful
response to the SCT. Longer follow-up will be needed to
ascertain if the responses in the refractory patients are durable.
Meanwhile, patients refractory to initial therapy should be offered
early SCT.
266
Autologous stem cell transplantation for multiple
myeloma – a 12 year single centre experience
AD Wechalekar, KH Orchard, AS Duncombe, D Teal and
AG Smith
Dept of Haematology, Southampton University Hospitals,
Southampton, UK
We present the results of a single centre experience with
autologous stem cell transplantation (ASCT) for multiple
myeloma.
Methods and Results: EBMT registry data was reviewed for
patients with multiple myeloma who underwent autologous stem
cell transplantation at Southampton bone marrow transplant unit,
UK, from 1990 to 2001, receiving melphalan 200mg/m2 (day –1)
and intravenous methylprednisone 1.5g (day +1 to +5) as the
conditioning regime. A total of 75 patients were identified. The
patient characteristics were: males - 43(57%), females - 32(43%),
IgG - 36(48%), IgA - 20(26.6%), Light chains -18(24%) and
Non-secretory – 1(1.3%). The median age at transplantation was
57.9 years (29.5 –63.5 yrs). 74(98%) patients received peripheral
blood stem cells and one patient (2%) received bone marrow. All
patients received a single autograft. Median time to neutrophil
engraftment was 15 days (8-40days). The transplant related
mortality was 2.6% (2 patients) due to infection(s) in the
immediate post transplant period. The response to ASCT was:
complete remission (CR)-19(25%), partial remission (PR)-
53(71%) and unknown in 3(4%) patients.
The median follow up was 5.07yrs. The median overall survival
(OS) of patients in PR was 6.7yrs(0.5 - 12.4 yrs) while it has not
yet been reached for the whole series and for patients in CR. The
mean OS was: all patients - 8.8yrs(0.5-12.4 yrs) and patients in
CR - 8.7yrs(0.6-9.4yrs). There was no statistical difference
between the OS of patients in CR vs. PS (log rank p = 0.08).
48(64%) patients are still in remission, 25(33%) have relapsed
and the status of 2(3%) remains unknown. There was no
significant difference in OS in patients with: IgG vs. IgA; kappa
vs. lambda; or presence or absence of light chain disease.
Conclusion: The present findings appear to be in keeping with
the published literature though the OS appears to be superior
compared to studies using single agent high dose melphalan as
conditioning. The use of methylprednisone in the conditioning
regime does not appear cause any additional toxicity. There
appears to be a trend for superior OS in patients achieving a CR
though this was not statistically significant. There also appears to
be a small cohort of long term survivors, irrespective of the
remission status (CR or PR), supporting a concept of “functional
cure”. These findings may suggest a role for addition of
methylprednisone to the standard melphalan conditioning.
Further studies are needed to clarify the disease biology of the
patients with a “functional cure”.
267
A Multicentre Randomised Study of High Dose or
Intermediate Dose Melphalan Consolidation of Initial
VAD / VAMP Therapy of Myeloma.
CRJ Singer*, J Cavenagh, S Kelsey, A Eden, M Mills, E
Rhodes, A Kruger, S Smith, S Rule, A Brownell, D Lewis, A
Hughes, I Grant, N Akhtar, R Evely, M Hamon, C
Krajniewski, S Curtis, N McBride, H Oakervee & J
Woodhouse
for the Southern England Collaborative Trials Group. *Royal United
Hospital, Bath, BA1 3NG, UK. Tel (44) 1225-824488, Fax (44)
1225-461044, email charles.singer@ruh-bath.swest.nhs.uk
Introduction: VAD plus high dose melphalan has become the
standard treatment for younger patients with myeloma but is not
curative and has significant toxicity. More therapy is always
required subsequently and few patients are able to tolerate several
intensive regimens. This study compares high dose melphalan
(HDM) and intermediate dose melphalan (IDM) as consolidation
after an initial response to VAMP/VAD.
Methods: 59 newly diagnosed patients with myeloma, aged < 65
years treated with 4-6 cycles of VAMP or VAD were randomised
to HDM or IDM after cyclophosphamide (CTX; 1.5 - 4g/m2) and
peripheral blood stem cell (PBSC) harvest. Patients then received
HDM (200mg/m2) plus PBSC re-infusion or IDM (80 mg/m2)
plus G-CSF (Lenograstim, Chugai). Maintenance interferonalpha
(Intron-A, 3MU/m three times weekly, Schering-Plough)
was given to both arms.
Results: 39 patients were male; median age 55 (39-64); 37 had
IgG, 12 IgA, 1 IgD serum paraproteins; 5 LC & 4 NS. 11
received VAD rather than VAMP. 10 received < 4g/m2 CTX. 29
received HDM, 30 IDM. CTX had no major therapeutic effect
and paraproteins were 87% (0-295) of the pre-CTX level.
Serum -2-microglobulin was comparable in both arms: HDM
3.6 (1.2-17.4) & IDM 4.3 (1.0 – 16.1) µg/ml. There was no
difference in inpatient days (24 vs 23) or febrile days (6 vs 6).
Neutropenia was shorter with HDM (10 vs 13 days). There were
8 CR’s in the HDM arm (4 achieved by HDM) and 5 in the IDM
(1 achieved by IDM).
Maintenance IFN- was commenced in 22 of the HDM arm and
19 of the IDM arm. In each group 50% were ultimately
intolerant. 7 of the HDM arm continue and 3 of the IDM arm.
Follow-up: HDM: progression in 13/30 (43%) at a median 22 (2-
43) mo from HDM; 21/30 (70%) are alive; median overall
survival 30 (2-87) mo from HDM; 6/9 deaths were due to
myeloma.
IDM: progression in 20/29 (69%) at a median 17 (4-84) mo from
IDM; 18/29 (62%) are alive; median overall survival 40 (5-98)
mo from IDM; all 11 deaths were due to myeloma.
Conclusions: HDM offers a higher chance of achieving CR and a
more prolonged response but there is no clear evidence of
superior survival to IDM (80 mg/m2). IDM is a reasonable
alternative for those patients in whom PBSC harvest is
unsuccessful.
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