Low-dose natural interleukin-2 and recombinant interferon-gamma following autologous bone marrow grafts in pediatric patients with high-risk acute leukemia.
Twenty-two patients with high risk hematologic malignancies (13 c-ALL, two B-ALL/NHL, four T-ALL, two AML M2, one pre-pre B-ALL) entered a phase I/II trial with cyclic administration of low dose natural interleukin-2/recombinant interferon-gamma (nIL-2/rIFN-gamma) following autologous bone marrow transplantation (ABMT), in order to induce a cytotoxic antileukemic effect. Eighteen patients subsequently relapsed, corresponding to a Kaplan-Meier estimate of disease-free survival (DFS) of 18%. Compared with a historical group of autologous bone marrow recipients who have not received immunotherapy, there is no significant difference according to DFS. Immunophenotyping of peripheral lymphocytes at the onset and end of therapy cycles revealed the most significant mean increase among the NK cell population (262/microliters +/- 51 vs. 354/microliters +/- 36, p = 0.004). However, even CD3 positive T cells rose significantly (591/microliters vs. 689/microliters, p = 0.04). In vitro NK cell activity tested against the NK sensitive myeloid leukemic cell line K562, and LAK cell activity tested against the LAK sensitive Burkitt lymphoma cell line Raji, was only low. An additional in vitro stimulus with nIL2, however, led to a therapy-dependent increase of cytotoxicity which was significant against Raji cells (25% +/- 4 vs. 41% +/- 5, p = 0.0124) indicating that low dose nIL2/rIFN-gamma enhances precursors of potentially cytotoxic cells in vivo.
Baumgarten
E
E
Universitätsklinikum Rudolf Virchow, Wedding, Kinderklinik, Abt. Hämatologie/Onkologie, Berlin, Germany.
Schmid
H
H
Pohl
U
U
Brzoska
J
J
Linderkamp
C
C
Siegert
W
W
Henze
G
G
D000208:Acute Disease; D000293:Adolescent; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016131:Lymphocyte Subsets; D008297:Male; D011994:Recombinant Proteins; D012307:Risk Factors; D015996:Survival Rate; D014182:Transplantation, Autologous
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma