Haematologica 2003 - Supplements

Patient 1 (IgG/κ);IgG – 16.5 days, free κ - 5 days
Patient 2 (IgG/λ; IgG – 10 days, free λ - 5 days
Patient 3 (IgA/κ); IgA - 2.5 days, free κ5days
Patient 4 (IgA/ λ;IgA – 3.5 days, free λ - 1.5 days
The estimated half-lives for the free light chain were always
shorter than for the intact immunoglobulin. This difference was
greatest for the IgG monoclonal proteins in accordance with the
known serum half lives in normal individuals (IgG1,IgG2 &
IgG4, 12 -21 days; IgG3, 7–8 days; IgA, 6 days and free light
chain 2-6 hours). The shorter half-life of the free light chains
should provide a more accurate estimation of the rate of tumour
kill. Half-life estimates were quite different between the 4
patients but the relationship to prognosis has yet to be
established. In two patients, the melphalan treatment produced no
reduction in the concentration of the alternate (non-tumour) light
chain while in a third, the concentrations of both light chains
decreased at the same rate. By monitoring the concentrations of
both light chain types, it should be possible to gain an estimate of
the differential killing rates of the tumour and non-tumour
plasma cells.
It was notable that the flc half lives in the patients producing IgG
monoclonal proteins were considerably longer than in the patients
with IgA monoclonal proteins. Further patients need to be
examined to determine whether this is chance or a consistent
finding.
172
Prognostic significance of immuneparesis in
progression of solitary bone plasmacytoma
Rabin N, Kyriakou C, Peggs K, Ardeshna K, Yong K, D’Sa
S.
Department of Haematology, Mount Vernon Hospital,
Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK, and
Department of Haematology, University College London Hospitals,
Grafton Way, London, WC1E 3BG, UK.
Prognostic factors for patients with plasmacytoma are not fully
understood. This study aims to further define factors predicting
outcome for patients diagnosed with a solitary plasmacytoma.
Twenty -nine patients were studied retrospectively, including 23
with solitary bone plasmacytoma (SBP) and 6 with solitary
extramedullary plasmacytoma (SEP). Median age was 54 years
(range 21 to 81) and 70 years (range 52 to 88) respectively.
Thirteen patients with SBP had axial disease (56 %).
All patients with SBP received radiotherapy (median dose 40 Gy
range 20 to 50 Gy), 10 had prior surgery and 4 prior VAD
chemotherapy. Five of 6 SEP patients received radiotherapy
(median dose 48 Gy; range 27 – 50 Gy) and 1 had oral melphalan
chemotherapy.
Results: SBP patients: Serum paraprotein was present in 16 of 22,
BJP in 4 of 16 and immuneparesis in 5 of 21 evaluable patients.
β2 microglobulin was normal in 14 of 15 patients, and raised in 1.
Local relapse occurred in 2 patients at 8 and 31 months.
Radiotherapy dose, diagnostic paraprotein level, disappearance of
paraprotein at 1 year, and immuneparesis at diagnosis did not
predict relapse.
Eight patients progressed to MM at a median of 18 months (range
6 to 48 months), including one patient with a distant relapse at 18
months, progressing to MM at 4 years. Median follow up from
progression to MM is 20 months.
Immuneparesis at diagnosis predicted progression to MM
(p=0.0112). Of 5 patients with immuneparesis 4 progressed to
MM the other to amyloidosis. Paraprotein disappeared at one
year following treatment in 3 patients, none of whom developed
MM (not significant). Axial site of disease, radiotherapy dose,
serum paraprotein at diagnosis and β2 microglobulin did not
predict progression to MM.
Twenty-one of 23 patients remain alive at a median of 3 years
(range 2 months to 11 years). Two patients died. One died of
unrelated causes. One progressed to MM (at 6 months, died at 10
months).
SEP patients: M protein was present in 2 patients (1 serum, 1
BJP), 3 were non-secretory, and 1 not assessed. None were
immuneparesed. BJP disappeared in 1 patient; follow up
paraproteins were not recorded in the other patients.
Three died of unrelated causes. Three patients are alive at a
median of 18 years (range 2 to 22 years). Relapse occurred in 2
patients. One had local relapse at 15 years (treated with
radiotherapy), and remains alive at 18 years after diagnosis. The
other patient relapsed with multifocal plasmacytomas, spanning 2
to 13 years following diagnosis and remains alive at 22 years
(treated with radiotherapy and chemotherapy). Neither has
evidence of MM, and both are disease free.
Conclusion: Results support immuneparesis at diagnosis as
predicting progression to MM. Site of disease (axial skeleton),
radiotherapy dose, level of serum paraprotein, disappearance of
paraprotein and beta 2 microglobulin did not predict disease
progression. The long overall survival of this group of patients,
including those with disease relapse or progression to MM
underscores the responsiveness to treatment and indolent nature
of SBP and SEP.
173
CYCLIN D1 OVEREXPRESSION IS NOT AN ADVERSE
PROGNOSTIC VARIABLE FOR NEWLY DIAGNOSED
MULTIPLE MYELOMA PATIENTS TREATED WITH
HIGH-DOSE CHEMOTHERAPY
Simona Soverini, Michele Cavo, Carolina Terragna,
Deborah Ruggeri, Nicoletta Testoni, Claudia Cellini,
Antonio de Vivo, Antonino Neri,* Sonia Fabris,* Marilina
Amabile, Tiziana Grafone, Emanuela Ottaviani, Barbara
Giannini, Patrizia Tosi, Elena Zamagni, Francesca Bonifazi,
Delia Cangini, Sante Tura, Michele Baccarani, Giovanni
Martinelli.
Institute of Hematology and Medical Oncology “Seragnoli”,
University of Bologna, Bologna, Italy;* Ospedale Maggiore IRCCS,
University of Milan, Milan, Italy.
In the present study we analyzed the frequency and the clinical
and prognostic relevance of cyclin D1 expression, as evaluated by
a real-time RT-PCR assay, in a series of 74 patients with de novo
multiple myeloma (MM) who were randomized to receive either
single (Tx-1) or double (Tx-2) PBSC autotransplants (see Cavo et
al, IX International Workshop on MM) as primary therapy for
their malignancy. In 46 patients for whom sufficient material was
available, conventional cytogenetic and/or FISH analyses were
performed in an attempt to investigate the presence of
chromosome 11 and 13 abnormalities. Patients harboring the
t(11;14) had significantly higher cyclin D1 mRNA levels than
those with trisomy 11 (P=0.001). Both these subgroups
significantly overexpressed cyclin D1 in comparison to patients
with no evidence of 11q abnormalities ( P