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JUNE 1999
BONE MARROW
TRANSPLANTATION (BMT)
Allospecific T-cell
depletion.
Daniela Montagna et al. investigated whether in vitro allospecific T-cell
depletion by an anti-CD25-ricin immunotoxin (IT) directed against the a chain
of the human interleukin-2 receptor could affect the ability the spared
(non-alloreactive) T-cells to kill leukemic blasts or virus-infected cells.
Studies of antileukemic activity were done with peripheral blood mononuclear
cells from 3 patients with acute myeloid leukemia and demonstrated that the
frequency of cytotoxic T-lymphocyte precursors (CTLp) directed against
leukemic blasts was not affected by the IT. In addition, data obtained from 4
healthy donors showed that the spared T-cells maintained a high frequency of
CTLp directed against CMV and EBV infected cells. These data indicate that
T-cell allodepletion resulting from the anti-interleukin-2 receptor IT
effectively removes alloreactive cells and spares antileukemic and antiviral
CTLp. (Montagna D, et al. Blood 1999; 93: 3550-3557)
Improved outcome with
T-cell depletion.
Franco Aversa and colleagues enhanced pretransplant immunosuppression and
myeloablation by adding antithymocyte globulin and thiotepa to standard
TBI/cyclophosphamide conditioning for 54 consecutive patients with acute
leukemia. These patients received T-cell-depleted BMTs from HLA-identical
sibling donors (or from family donors mismatched at D-Dr in 2 cases) to lower
the risk of rejection and relapse after T-cell depletion. Graft rejection and
GVHD did not occur in any of the patients. Event-free survival for patients
in remission after a median follow-up of 6.9 years (minimum follow-up of 4.9
years) was .74 (95% CI. 54 to .93) for acute myeloid leukemia patients and
.59 (95% CI .35 to .82) for acute lymphoblastic leukemia patients. These
results show that the addition of antithymocytic globulin and thiotepa
prevented the rejection of the T-cell-depleted marrow and that the leukemia
relapse rate was not increased compared to unmanipulated transplants even in
the absence of GVHD. (Aversa F, et al. J Clin Oncol 1999; 17: 1545-1550)
GRAFT VS TUMOR (GVT)
INDUCTION
Donor leukocyte
infusion (DLI).
In a phase I trial, David Porter and coworkers administered interferon
alfa-2b followed by allogeneic DLIs as primary cancer therapy to 18 patients
with various malignancies. Donor cells were detected in blood in 14 of 16
evaluable patients within 1 hour of DLI and in 5 patients 5 to 16 weeks after
DLI. Four patients (all had received prior autologous transplantation)
developed acute GVHD and 3 of these patients responded to primary DLI
therapy. Thus, allogeneic adoptive immunotherapy can result in sustained
chimerism, acute GVHD, and a GVT response in heavily pretreated patients
without the need for intensive therapy immediately prior to DLI. (Porter DL,
et al. J Clin Oncol 1999; 17: 1234-1243)
BREAST CANCER
Effects of soluble
recombinant human CD40 ligand (srhCD40L). Akio Hirano and colleagues assessed the effects
of a srhCD40L (Immunex Inc, Seattle, WA) on human breast carcinoma cell
lines. They found that srhCD40L inhibited proliferation and increased
apoptosis of CD40+ breast cancer cells lines. In addition, srhCD40L treatment
of tumor-bearing SCID mice resulted in significant increases in survival.
These results show that human breast carcinoma cells are inhibited through
CD40 stimulation by its ligand. (Hirano A, et al. Blood 1999; 93: 2999-3007)
HEPATOCELLULAR
CARCINOMA (HCC)
Incidence in chronic
hepatitis C virus (HCV). Michiko Shindo et al. retrospectively analyzed 250 chronic HCV
patients treated with interferon-a (IFN) to determine if IFN therapy reduces
the incidence of HCC and hepatic cirrhosis. The chronic HCV patients were
classified into 3 groups (long term responders, n=93; short-term responders,
n=70; nonresponders, n=87) based on the serum aminotransferase response to
IFN therapy. The control group consisted of 89 untreated patients and the
follow-up period was 4 years. One long-term responder, 1 short-term
responder, and 3 control patients developed HCC while 14 (16%) nonresponder
developed HCC. Similar results were observed in the development of cirrhosis
in these patients. Multivariate analysis identified lack of response to IFN
as a significant factor for the development of HCC and cirrhosis. Thus,
chronic HCV patients who are nonresponders to IFN therapy are assumed to be
at high risk for HCC and cirrhosis. (Shindo M, et al. Cancer 1999; 85:
1943-1950)
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