Haematologica 2003 - Supplements

peripheral blood stem cell transplantation in the UK. In
previously untreated patients the complete response (CR) rate as
assessed at that time approached 50% 1 . The strategy which
emerged was initial conventional dose anthracycline–containing
infusional chemotherapy followed by high dose melphalan
(HDM) at 200mg/m 2 or HDM at 140mg/m 2 with the addition of
total body irradiation (TBI). Although the depth of remission
was evidently greater than with purely conventional dose therapy
the remissions were not enduring. The concept of maintaining
longer remissions was introduced with the use of interferon-alpha
(IFN-α) in a maintenance role. At the time of the initiation of
MRC Myeloma VII in 1993 there was a clear need for outcome
data on HDT in comparison with conventional dose
chemotherapy in the large randomised trial setting. In the series
of MRC trials leading up to Myeloma VII, the most effective
conventional dose regimen was ABCM 2 and this was chosen as
the standard treatment: doxorubicin 30mg/m 2 i.v., carmustine
30mg/m 2 i.v. short infusion d1; cyclophosphamide 100mg/m 2 /d
orally and melphalan 6mg/m 2 /d orally d22-25; cycle repeating
every 6 weeks to maximal response (plateau) maximum 12
cycles. Patients could switch to cyclophosphamide 300mg/m 2
i.v. weekly in the event of undue myelosuppression. Planned
maintenance was IFN-α (Roferon A) initially at 3 megaunits
3x/week. The intensive regimen was C-VAMP: doxorubicin
9mg/m 2 /d and vincristine 0.4mg/d continuous infusion d1-4;
methylprednisolone 1mg/m 2 i.v. or orally (max 1.5g) d1-5;
cyclophosphamide 500mg i.v. d1, 8 and 15; cycle repeating every
21 days to maximal response with minimum of 3 cycles before
stem cell harvesting. Adjustments for cytopenias/renal
dysfunction were applied. Stem cells were mobilised using
cyclophosphamide 2-4g/m 2 and G-CSF d5-12. The HDT
comprised HDM at 200mg/m 2 followed by the infusion of PBSCs
at 24hrs. Bone marrow autograft and TBI + melphalan
140mg/m 2 were permissible options. Methylprednisolone 1.5g/d
was given i.v. for the first 4 days following HDM. The
melphalan dose was modified according to creatinine clearance.
The planned maintenance in this treatment arm was also IFN-α.
The EMBT/IBMTR response criteria were used whereby CR
required paraprotein negative by immunofixation. A total of 407
previously untreated patients under 65 years of age were
randomised to receive “Standard” or “Intensive” treatments. Only
30 (15 percent) patients in the Standard group went on to receive
an autograft and 4 (2 percent) an allograft, outside protocol. In
the 401 evaluable patients, response rates for the Intensive group
were higher than in the Standard group: CR 44.3% v 8.5%
(p