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SEPTEMBER 1999
CHRONIC MYELOGENOUS
LEUKEMIA (CML)
T-cell depletion
(TCD) combined with donor leukocyte infusion (DLI) therapy. TCD of donor marrow reduces the
severity of GVHD in chronic phase CML patients undergoing allogeneic bone
marrow transplantation. However, TCD is also associated with a reduction in
the graft vs. leukemia effect while DLI has been shown to be effective
antileukemic salvage therapy. William Drobyski et al. Combined TCD with DLI
at the time of relapse in 25 chronic phase CML patients undergoing allogenic
bone marrow transplantation Engraftment was achieved in all 25 patients,
grade II to IV GVHD occurred in only 8% of patients, and the probability of
overall 5 year survival was 80%. TCD followed by DLI for recurrent disease
may be an effective strategy in chronic phase CML. (Drobyski WE, et al. Blood
1999; 94: 434-441)
MULTIPLE MYELOMA
Idiotype Vaccination. Massino Massaia and colleagues
administered a vaccine using idiotype (Id) specific proteins conjugated to
keyhole limpet hemocyanin (KLH) to 12 multiple myeloma (MM) patients in first
remission following high dose chemotherapy and peripheral blood progenitor
cell (PBPC) transplantation. An Id specific delayed hypersensitivity reaction
was observed in 8 of 10 patients studied, an Id specific T-cell proliferative
response was documented in 2 patients, and soluble and cellular immune
responses to KLH were observed in 100% (12/12) and 80% (8/10) of patients,
respectively. Thus, MM patients can generate specific immune responses after
high dose chemotherapy and PBPC transplantation. (Massaia M, et al. Blood
1999; 94: 673-683)
CUTANEOUS T CELL
LYMPHOMA (CTCL)
Interleukin-12
(IL-12) therapy.
Alain Rook et al. conducted a phase I trial of recombinant human (rh) IL-12
in patients with CTCL. Subcutaneous dosing resulted in a response (CR or PR)
in 5 of 9 patients (56%) and intralesional dosing resulted in tumor regression
in 2 of 2 patients. The rh IL-12 was well tolerated and these results
indicate that rh IL-12 is a potentially effective therapy for CTCL. (Rook AH,
et al. Blood 1999; 94: 902-908)
IMMUNE ANTITUMOR
RESPONSE
Synergy of fms-like
tyrosine kinase 3 ligand (Flt3L) and CD40 ligand (CD40L). It has previously been
demonstrated that Flt3L treatment of mice increases the number of dendritic
cells (DCs) and induces antitumor immunity. Luis Borges and coworkers showed
that mice treated with a combination of Flt3L and CD40L have significantly
more DCs than mice treated with either cytokine alone. Additionally, this
cytokine combination was found to synergistically generate an antitumor
response (56% tumor rejection rate) in mice bearing poorly immunogenic tumors
(either the B10.5 or 87 sarcomas) and rechallenge with tumor resulted in a
complete inhibition of tumor growth. These results indicate that cytokine
therapy that promotes the proliferation and survival of DCs can induce immune
responses against tumors that do not express known tumor antigens. Cytokine
combination therapy represents a potential means to enhance the antigen
presenting capacity of the immune system. (Borges L, et al. J Immunol 1999;
163: 1289-1297)
HEPATOCELLULAR
CARCINOMA (HCC)
Escape from immune
surveillance. The
Fas receptor (Fas)/ligand (Fas L) system plays an important role in B and T
lymphocyte development and alteration of the Fas/Fas L system can cause the
immune system to fail to recognize tumor cells. Nagao et al. studied the
relationship between tissue expression of Fas, Fas L, and p53 and
clinicopathological features in 44 HCC patients. Fas expression was positive
in 15 patients (34.1%) and these patients had fewer intrahepatic metastatic
foci (P=0.034), longer disease free survival (P=0.004) and a higher tumor
cell apoptotic index (P=0.004) than the Fas negative (<10% of cancer cells
positive) HCC patients. Complete loss of Fas expression was observed in 14 of
the 29 Fas negative cases. In addition, all P53 positive cases (n=12) were Fas
negative. The involvement of the Fas/Fas L system may provide new therapeutic
approaches for HCC. (Nagao M, et al. Hepatology 1999; 30: 413-421)
GRAFT
VERSUS HOST DISEASE (GVHD)
Immune reconstitution. Immunologic memory after stem
cell transplantation is conferred by the expansion of donor postthymic T
cells. This process is impaired by GVHD through an unknown mechanism. Sylvie
Brochu and colleagues induced GVHD in mice (B6AF1 or B6.SAF1) by injecting T
lymphocytes obtained from the spleens of differing strains of mice (C57BL/6
or B6.SJL) to determine the fate of grafted postthymic T cells. They showed
that: 1) alloreactive antihost T cells underwent a massive activation-induced
cell death (AICD) in which the Fas pathway plays a major role and 2) non-host-reactive
donor T cells showed increased membrane Fas expression and apoptosis when
coinjected with host-reactive T cells. These data indicate that future
efforts to avoid this GVHD-induced bystander lysis of post-thymic T cells
will be important to maintain immune reconstitution in GVHD patients. (Brochu
S, et al. Blood 1999; 94: 390-400)
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