Immune mobilization of autologous blood progenitor cells: direct influence on the cellular subsets collected.
OBJECTIVE
A phase I trial examined the ability of immunotherapy to mobilize progenitor and activated T cells.


METHODS
Interleukin (IL)-2 was administered subcutaneously for 11 days, with granulocyte (G)-colony-stimulating factor (CSF) (5 mcg/kg/day) and granulocyte-macrophage (GM)-CSF (7.5 mcg/kg/day) added for the last 5 days. Leukapheresis was initiated on day 11. Thirteen patients were treated (myeloma n = 11, non-Hodgkin's lymphoma n = 2).


RESULTS
Toxicities were minimal. IL-2 was stopped in two patients because of capillary leak (n = 1) and diarrhea (n = 1). Each patient required 2.5 leukaphereses (median; range 1-3) to collect 3.2 x 10⁶ CD34+ cells/kg (median; range 1.9-6.6 x 10⁶/kg). Immune mobilization increased the number of CD3+ CD8+ T cells (P = 0.002), CD56+ natural killer (NK) cells (P = 0.0001), CD8+ CD56+ T cells (P = 0.002) and CD4+ CD25+ cells (P = 0.0001) compared with cancer patients mobilized with G-CSF alone. There was increased lysis of myeloma cells after 7 days (P = 0.03) or 11 days (P = 0.02). The maximum tolerated dose of IL-2 was 1 x 10⁶ IU/m²/day.


CONCLUSIONS
Immune mobilization is well tolerated with normal subsequent marrow engraftment. As cells within the graft influence lymphocyte recovery, an increased number of functional lymphocytes may result in more rapid immune reconstitution.
Meehan
Kenneth R
KR
Blood and Marrow Transplant Program, Section of Hematology and Oncology, 1 Medical Center Drive, Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, NH 03756, USA. Kenneth.R.Meehan@hitchcock.org
Talebian
Laleh
L
Wu
Jillian
J
Hill
John M
JM
Szczepiorkowski
Zbigniew M
ZM
Sentman
Charles L
CL
Ernstoff
Marc S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D019559:Capillary Leak Syndrome / Q000209:etiology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D019337:Hematologic Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D007937:Leukapheresis; D008213:Lymphocyte Activation; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014182:Transplantation, Autologous
D007376:Interleukin-2; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor