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march 1999
MARROW TRANSPLANTATION
Effects of 131I
-anti-CD45 antibody in murine transplant models. Dana Matthews and colleagues
studied the use of 131I-anti-CD45 antibody, which delivers irradiation
selectively to lymphohematopoietic tissues, as a preparative regimen in two
models of murine transplantation. Recipient B6-Ly5a mice were treated with
131I-anti-CD45 antibody and were subsequently transplanted with marrow from
congenic Ly5b mice to measure marrow ablation or with marrow from
H2-mismatched BALB/c mice to test the immunosuppressive effects. Engraftment
was achieved with 131I-anti-CD45 antibody treatments alone in the Ly5
congenic model, but the H2-mismatched setting required the addition of
low-dose external total body irradiation (TBI) to allow engraftment. Their
results demonstrate that targeted radiation can enable engraftment of
congenic marrow and can partially replace TBI in the H2-mismatched setting.
(Matthews DC, et al. Blood 1999; 93:737-745)
METASTATIC MELANOMA
Combination of
chemotherapy with interleukin-2 (IL-2) and interferon alfa (IFNa). Jon Richards et al. evaluated
the therapeutic potential of combining multiagent chemohormonal therapy
(cisplatin, dacarbazine, carmustine, tamoxifen) with IL-2 and IFNa (both
provided by Roche Laboratories) to treat 84 metastatic melanoma patients. A
55% response rate (12 CR and 34 PR) was achieved and after a median follow-up
of 51 months the median time to disease progression was 7 months and the
median survival was 12.2 months with an apparent plateau of 10.7% survival
after 52 months. No patient developed grade 4 clinical toxicity (Richards JM,
et al. J Clin Oncol 1999; 17: 651-657). These results are contrasted with
those of a previous study that showed no statistically significant difference
in overall survival with the combination of IL-2 and IFNa vs. each cytokine
independently in patients with metastatic renal cell carcinoma (Negrier S, et
al. N Engl J Med 1998; 338:1272-1278). Further investigation is needed to
confirm the clinical benefit of chemoimmunotherapy vs. chemotherapy alone for
the treatment of melanoma patients.
CHRONIC MYELOGENOUS
LEUKEMIA (CML)
T-cell-depleted (TCD)
vs. non-T-cell depleted allogeneic bone marrow transplantation (BMT). Laurie Sehn and coworkers
retrospectively analyzed the outcomes of stable-phase CML patients who underwent
TCD allogeneic BMT (46 patients) vs. those who underwent non-TCD allogeneic
BMT (40 patients) from HLA-identical sibling donors during a period when
donor lymphocyte infusion (DLI) was available. The TCD group had a lower
incidence of grade 2-4 acute (P=0.026) and chronic (P=0.024) GVHD. However,
the 3 year probability of relapse was higher for the TCD patients (P=0.0003)
than for non-TCD patients. Twenty TCD patients received DLI therapy vs. 3
patients in the non-TCD group. The high complete remission rate associated
with DLI resulted in a similar estimated 3 year overall survival for the TCD
and non-TCD groups (72% vs. 68%, respectively, P=0.38). These data suggest
that post-BMT DLI allows TCD to be a viable BMT treatment option for CML
patients. (Sehn LH, et al. J Clin Oncol 1999; 17: 561-568)
Treatment with
interferon alpha (IFN-a) and low-dose cytarabine (ara-C). Because both INF-a and ara-C
induce cytogenetic responses in CML patients, Hagop Kantarjian and colleagues
evaluated the effects of combining daily IFN-a therapy (5MU/M2 subcutaneously
[SC]) with daily low-dose ara-C treatments (10 mg SC) in the treatment of 140
Ph-positive early (< 1 year) chronic phase CML patients. Their results
were retrospectively compared with two other cohorts of patients treated with
either IFN-a alone or with IFN-a plus intermittent ara-C in previous studies.
The IFN-a plus daily ara-C was tolerated with acceptable toxicity and was
associated with a higher incidence of cytogenetic response (P=0.003) than
that achieved with the previous IFN studies. Their data suggest that the
combination of daily IFN-a and SC low-dose ara-C is a promising treatment for
chronic phase CML patients. (Kantarjian HM, et al. J Clin Oncol 1999; 17:
284-292)
DENDRITIC
CELLS (DC)
DC derived from acute
myelogenous leukemia (AML) cells. Choudhury and associates recently generated DC in vitro
from cells obtained from 19 AML patients using granulocyte-macrophage
colony-stimulating factor plus interleukin-4 in combination with either tumor
necrosis factor-a or CD40 ligand. Autologous lymphocytes cultured with these
AML-derived DC demonstrated a potent ability to lyse autologous leukemia
cells in vitro while causing little cytotoxicity to autologous normal cells.
Leukemia derived DC may be effective immunotherapy for AML patients.
(Choudhury A, et al. Blood 1999; 93: 780-786)
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