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FEBRUARY 1999
LOW-GRADE
NON-HODGKIN'S LYMPHOMA (NHL)
Treatment with anti-CD20
monoclonal antibody and CHOP chemotherapy. Myron Czuczman and colleagues conducted a phase
II study in which 40 patients (31 previously untreated) with low-grade or
follicular B-cell (CD20+) NHL were treated with a combination of a chimeric
anti-CD20 monoclonal antibody, RituxanŽ (IDEC Pharmaceuticals), and CHOP
chemotherapy. Patients received a total of 6 intravenous infusions of
RituxanŽ (375 mg/m2/dose) and 6 cycles of CHOP given every 3 weeks. The
response rate was 95% (55% CR and 40% PR) and median time to progression had
not been reached after a median observation time of 29+ months. Furthermore,
in a subset of 18 patients tested, 8 patients were bcl-2+ and 7 of these
patients had CRs and converted to PCR negativity after trial therapy. The
most common adverse events associated with Rituxan were infusion-related
(fever, chills). These findings suggest that RituxanŽ may add therapeutic
benefit to CHOP in the treatment of indolent B-cell NHL patients without
adding toxicity. (Czuczman MS, et al. J Clin Oncol 1999; 17: 268-275)
MALIGNANT PLEURAL
MESOTHELIOMA (MPM)
Intrapleural
administration of interleukin-2 (IL-2). Phillippe Astoul and coworkers treated 22 MPM patients
in a phase II study of IL-2 (Roussel-Uclaf) administered intrapleurally
(21X106 IU/m2/day x 5 days). Intrapleural administration of IL-2 has been
found to activate lymphokine-activated killer cells and natural killer cells
and has been associated with antitumor responses in previous studies. IL-2
immunotherapy resulted in 11 PRs and 1 CR in this current study. The median
survival of responders was 28 months compared to 8 months for nonresponders
(P<0.01). IL-2 therapy was tolerated well and all patients completed their
treatments as planned. These results show that intrapleural IL-2 has
antitumor activity in patients with MPM. (Astoul P, et al. Cancer 1998; 83:
2099-2104)
GRAFT-VERSUS-HOST
DISEASE (GVHD)
Use of CD52 moncolonal
antibodies (MoAbs) to prevent GVHD. Geoff Hale and associates investigated the use of two
CD52 MoAbs to eliminate T cells from both the donor marrow (by in vitro
CAMPATH-1M, an IgM MoAb, treatments) and the recipient host (by in vivo
CAMPATH -1G, an IgG MoAb, infusions prior to graft infusion) to prevent both
GVHD and graft rejection. They compared their results of this combination
CD52 MoAb therapy (without posttranplant immunosuppression treatments) in 70
acute myelogenous leukemia patients in first remission receiving HLA
identical sibling transplants with two historical controls: 50 patients
(investigator database) who had received bone marrow depleted with CAMPATH-1M
but who had not received in vivo MoAb therapy and 459 patients (International
Bone Marrow Transplant Registry database) who had received conventional GVHD
prophylaxis with cyclosporin A (CyA) and methotrexate (MTX). The study group
had a lower risk of graft rejection than the CAMPATH-1M group (P=0.0003) but
a higher risk than the CyA/MTX group (P=0.03). The incidences of both acute
and chronic GVHD were less in the study group than in the CyA/MTX group
(P<0.001) while there was no difference in the 5-year leukemia relapse rates.
Thus, 5-year transplant-related mortality was lower in the study group
compared to the CyA/MTX group (P=0.04). These data show that CD52 MoAb T-cell
depletion can be a useful strategy to prevent GVHD. (Hale G, et al. Blood
1998; 92: 4581-4590)
DENDRITIC CELLS (DCS)
Effects of vascular
endothelial growth factor (VEGF). Dmitry Gabrilovich et al studied the effects of
long-term (up to 28 days) continuous infusion of recombinant VEGF in mice to
investigate if clinically relevant serum concentrations of VEGF alone alter
DC development in healthy animals (BALB/c and CBA mice). Serum VEGF levels as
low as 120-160 pg/ml resulted in inhibition of DC differentiation which was
associated with decreases in functional activity of lymph node and splenic
DCs. An expansion of immature myeloid cells and an inhibition of the
transcription factor NF-kB in marrow progenitor cells also resulted from the
VEGF infusion. These data suggest DC development can be effected by
clinically relevant concentrations of VEGF. Further, VEGF effects on
pluripotent stem cells may arrest DC development. (Gabrilovich D, et al.
Blood 1998; 92: 4150-4166)
Effects of interleukin-6 (IL-6) and macrophage
colony-stimulating factor (M-CSF). C. Menetrier-Caux and colleagues isolated CD34+
progenitors from umbilical cord blood samples, expanded this progenitor cell
population in a cytokine enriched medium for 6 days, and seeded the resulting
cells with or without renal cell carcinoma (RCC) conditioned media (CM) for 6
more days to investigate the effects of soluble factors on DC development.
RCC CM inhibited the development of DCs by redirecting CD34+ cell
differentiation toward the monocyte-macrophage lineage. This inhibition of DC
differentiation was found to be mediated by IL-6 and M-CSF while VEGF had no
effect. The authors concluded that RCC cells inhibit DC development through
IL-6/M-CSF dependent mechanisms and that the lack of a VEGF effect in this
model may be because VEGF acts at an earlier stage of CD34+ progenitor
differentiation than day 6. (Menetier-Caux C, et al. Blood 1998; 92:
4778-4791)
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