Haematologica 2003 - Supplements

non-CR after the first transplant and highlights the importance of
obtaining CR as strictly defined by immunofixation.
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Prospects of the currents protocol of the Spanish
Myeloma
Group (GEM-Grupo Español Mieloma)
Juan José Lahuerta, Rafael Martínez, Joan Bladé, Javier de la
Rubia, José García-Laraña, Adrián Alegre, Felipe Prosper, Felipe
Arribas, Anna Sureda, Dolores Carrera, Joan Bargay, Joaquín
Díaz-Mediavilla and Jesús San Miguel
For the GEM Group Grupo Español de Mieloma
The GEM group is the result of integration of the PETHEMA and
the Stem Cell transplant Myeloma / GEL-TAMO study groups.
The current national protocol was activated in January 2000 and
the design was based on the previous experience of both
supporting groups. For this reason we used VBMCP/VBAD (x 6
cycles) as induction therapy, because in previous PETHEMA
studies this resulted in an optional debulking chemotherapy (1st
aim: to determine the response rate to this induction regimen).
Stem cells have been collected after 4th cycle (2nd aim: to see if
the use of short courses of alkylating agents hampers stem cell
collection). After this, all patients received high dose
chemotherapy followed by PB stem cell support. Conditioning
consisted of Busulphan-Melphalan (BUMEL), because it was
superior to Melphalan 200 in our previous retrospective study
(Br. J. H. 2002) (3rd aim: to confirm the efficacy and toxicity of
BUMEL). Patients that achieved CR went into maintenance
therapy, reserving the second potential transplant for relapse.
Among CR patients we will compare the outcome of those with
both EF- and immunofixation- (CR1) versus CR2 patients (EFbut
IF+) (4th aim). Patients in PR or mR will receive a second
transplant, either autologous (conditioned with CBV) or miniallogeneic
(conditioned with Fluda-Melphalan), based on the
availability of an HLA-identical donor (5th aim: to compare the
efficacy and toxicity of these two procedures). In all patients,
cytogenetic/FISH studies have been performed at diagnosis.
Moreover in patients in CR after TRx, MRD investigation is
being carried out.
So far, 732 patients have entered into the study. The overall
response rate to induction chemotherapy is 93% (14% CR1, 18%
CR2, 61% PR, 7% stable or progressive disease). Following the
first transplant, 57% of patients have achieved CR (39% CR1 and
18% CR2) while 34% were in PR. After the initial 200 patients
were transplanted an alarm emerged about a possible increase in
VOD toxicity associated with BUMEL (5 out of 12 deaths), and
accordingly, the conditioning regimen was switched to Melphalan
200. Data about this adverse event as well as stem cell collection
efficacy (93% success with a median of 3.6 x 106 CD34 cells/ kg
and 5.3 x 106 CD34 cells/kg for percentil 75) after chemotherapy,
including low doses of melphalan, will be presented.
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T2 model - a pilot study for the evaluation of the
experimental therapy of multiple myeloma relapsing
after the first autologous stem cell transplantation.
Report of the prospective non-randomized pilot study
of the Czech Myeloma Group
M. Krejci (1), A. Krivanova (1), R. Hajek (1), V. Scudla (2),
K. Indrak (2), J. Bacovsky (3), T. Buchler (1), L. Pour (1), A.
Svobodnik (4), Z. Adam (1), J.Mayer (1), J. Vorlicek (1) for
the Czech Myeloma Group
(1) Dpt of Internal Medicine - Hematooncology, University Hospital
Brno - Bohunice, (2) 3rd Dpt of Internal Medicine, University
Hospital Olomouc, (3) Dpt of Hematooncology, University Hospital
Olomouc, (4) Masaryk University Oncological Center, Brno, Czech
Republic
Background: High doses of chemotherapy followed by
autologous transplantation became widespreadly indicated as
upfront therapy for patients with multiple myeloma (MM) in the
last decade, with very good tolerance and low mortality (2-3%).
Therapy of relapsing MM is still considered to be experimental.
Design of study: The principle of T2 model is repeated
transplantation therapy with testing different experimental
approaches in patients with MM relapsing/progressing after the
1st autologous transplantation (AT). The patients (pts) are treated
with the same + something more - same or very similar induction
and reinduction treatment, same myeloablative regimen in the 1st
and the 2nd AT and a different maintenance, experimental
therapy after the 2nd transplantation. The evaluation of the results
of each therapeutic approach uses intra-individual analysis - the
comparison of event free survival I (EFS I) (after the 1st AT) and
EFS II (after the 2nd AT) in one patient. In T2 model both EFS I
and EFS II are compared in one patient, therefore the interindividual
differences are excluded.
Subjects: 32 pts with relapsing/progressing MM after the 1st AT
were included in the pilot study between January 1997 and
January 2003, median follow-up was 75,2 months.
Methods and results: Pts were matched to the following groups of
experimental therapy: autologous transplantation with IL-2
activated PBSC - 10 pts (31,2 %), pamidronate- 4 pts (12,5 %),
thalidomide -15pts (46,9 %), consolidation chemotherapy CED -
3 pt (9,4%). A sensitivity to reinduction chemotherapy C-VAD (4
cycles) was more than 90 %, the response to the 2nd
transplantation according to the 1st one was in 23 % better (7
pts), in 50 % same (16 pts) and in 27 % worse (9 pts). The
toxicity of the 1st and second transplantation was similar and
usually did not exceed grade II (SWOG criteria), there were no
significant differences instead of clinically irrelevant
hematological toxicity. Transplant-related mortality was 3 %
(1/32). EFS II is known in 22 pts. Total of 8 pts have achieved
prolongation of EFS II versus EFS I, 2 in IL-2 activated graft
group, 1 in pamidronate group, 1 in consolidation chemotherapy
CED group and 4 in thalidomide group. In the whole group
median of EFS I was 15,7 months, median of EFS II was 12,9
months, median of overall survival (OS) was 79,1 months, 63 %
pts (20/32) were alive (till 31st January 2003).
Conclusions:Repeated transplantation is one of the most powerful
approaches in treatment of relapsing MM; toxicity is acceptable,
also engraftment is similar to the 1st AT. Testing of new
perspective approaches by T2 model may bring a fundamental
benefit.
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