Haematologica 2003 - Supplements

pt (8%). Partial response (50-74% reduction of MP) was observes
in 5 pts (42%). Minor response (25-49% reduction of MP) was
observed in one pt (8%). In five patients complete remission was
consolidated by a stem cell transplantation (one non
myeloablative-transplant and 4 auto PBSC). A majority of pts
(10/12-83%) had taper one of the drugs due to intolerance. In 3
cases the treatment was stopped for toxicity (1 ischemic acute
vascular injury and 2 neurotoxicity), all this pts progressed and
required another treatment. Another 3 pts progressed (2 after
reduction of DXM or/and thalidomide): 50% (n=6) of pts are still
in remission after 10.1 months of median follow-up (range 4-16
months).
Conclusions: combination of thalidomide-DXM-clarithromycin is
an effective regimen for relapsed and heavily pretreated MM pts.
However, this treatment has side effects in this old population
and cannot be maintained for a long time at full doses. Patients in
good response can thus be consolidated by transplantation.
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DT-PACE is highly effective in plasma cell leukemia
Andrzej J. Jakubowiak, Joseph Uberti, Christopher
Reynolds
The University of Michigan Comprehensive Cancer Center, Ann
Arbor, MI
Plasma cell leukemia (PCL) is a rare form of plasma cell
neoplasm with poor prognosis. PCL evolving from long standing
multiple myeloma (MM) is considered a terminal event for
refractory/relapsed MM and is characterized by a fulminant
course and is frequently not responsive to any treatment modality.
The optimal regimens for the treatment of PCL have not been
firmly established. Recently, combination therapy DT-PACE has
been shown to be highly effective in patients with
relapsed/refractory multiple myeloma1. We report here two cases
of PCL treated successfully with DT-PACE. In both cases, PCL
developed during the course of treatment of advanced MM, #1
with 4 cycles of VAD (first line therapy) and #2 with 5 cycles of
thalidomide and Decadron (third line therapy), to which both
patients had initial at least partial response. Prior to the treatment
with DT-PACE, patients showed progressive disease with
circulating plasma cells meeting criteria for PCL, chromosome 13
abnormalities, and elevated beta2-microglobulin. In both cases,
patients cleared circulating plasma cells within 2 weeks of the
first cycle of DT-PACE. Both patients achieved near CR after 2
cycles of DT-PACE. Overall, the treatment was well tolerated.
Patient # 1, who presented with high LDH, pneumonia, large
bilateral plural effusions, and profound cytopenias developed
early tumor lysis syndrome during the first cycle of therapy.
Subsequent therapies consisted of allogeneic stem cell transplant
(case #1) and autologous stem cell transplant. Both patients
remain in remission. These results suggest that TD-PACE, which
has established high efficacy in aggressive/refractory multiple
myeloma, appears very effective in PCL. Moreover, the results
support further previous promising outcomes of treatment of PCL
with intensive chemotherapy.
1Zangari M, Siegel E, Barolgie B, Anaissie E, Saghafifar F,
Fassas A, Morris C, Fink L, Tricot G. Thrombogenic activity of
doxorubicin in myeloma patients receiving thalidomide:
implications for therapy. Blood. 2002:100:1168-1171
343
Combination of Thalidomide, Cyclophosphamide, and
Dexamethasone in refractory-relapsed multiple
myeloma
F. Di Raimondo, A. Pennisi, D. Buglio, P. Fiumara, GA
Palumbo, R. Giustolisi
Dept. of Medical Sciences – Section of Hematology – University of
Catania, Italy
Cyclophosphamide (CTX) is a drug with activity against
myeloma and, when used at low doses, it has anti-angiogenic
activity (Browder T, Cancer Res 2000; 60: 1878). For these
reasons we elected this drug for a combination with Thalidomide
(THAL) and Dexamethasone (DEX) in refractory multiple
myeloma. Forty consecutive patients were included in this study.
Seven were relapsing and 33 were resistant or progressing after
previous treatment. Time elapsed between diagnosis and entering
this study was 23 months (range 2-70). At time of starting this
protocol, five patients were at stage I, 3 at stage II and 32 at stage
III. Median percentage of bone marrow plasma cells infiltration
was 50% (range 10-100), median Hb value was 10.2 g/dl (range
6,6-13,7), median WBC count 2,9 x10e9/l (range 0,6-7.2),
median PLT count 159 x10e9/l (range 48-347). DEX was given
at the fixed dose of 40 mg/die for 4 days every month, while
THAL at 200 mg every evening and CTX 100 mg every morning
continuously. Eight patients did not received DEXA because of
diabetes and in 6 additional patients it was discontinued because
of side effects. Nine patients discontinued treatment with THAL
(five of them definitely) because of skin rush, peripheral
neuropathy (4 patients), poor compliance in a patient affected by
Alzheimer’s disease, pneumonia, FUO, dizziness. CTX was
temporarily discontinued in 23 patients for leukopenia (20
patients), nausea, hematuria, Alzheimer’s disease. Other side
effects of the combination included constipation, nausea,
somnolence, asthenia, fever diarrhoea. Response to treatment was
evaluated by the percentage of reduction of the monoclonal
component (MC). Two patients were not evaluable: one died for
progression of disease a few days after starting treatment, and the
other refused treatment because developed a skin reaction to
THAL two days after starting treatment. Among the remaining 38
patients, 3 (8%) were considered as non responsive. Eight
patients (21%) had a reduction of MC < 50 %, 8 patients (21 %)
< 75 %, and 19 patients (50 %) > 75%). Of the latter, 8 (21 %)
achieved a complete response (100 % reduction of MC) and in
these patients bone marrow evaluation showed the disappearance
of plasma cells infiltration. Median time between start of
treatment and evaluation of response was 7 months (range 2-26).
No differences of response were observed among different Ig
isotypes. After a median follow up time of 13 months, 12 of the
responding patients (32 %) have experienced a relapse after a
median time of 5 months (range 2-19) from evaluation of
response. In conclusion, the combination of THAL-CTX-DEX
seems to be a very active and well tolerated scheme against
refractory myeloma. The high rate of discontinuation of CTX
should be evaluated in the light of the poor bone marrow reserve
of patients included in this study (median WBC 2.9). The
duration of treatment seems to be a crucial point, since some
patients have relapsed soon after stopping treatment. Future
studies are also necessary to evaluate the weight of CTX in this
combination and to explore the possibility of using this treatment
as first line therapy.
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