Interleukin-2-activated autologous bone marrow and peripheral blood stem cells in the treatment of acute leukemia and lymphoma.
In this pilot trial of interleukin (IL)-2-treated autologous bone marrow (BM) and peripheral stem cell (PSC)-supported high-dose chemoradiotherapy, we report 36 patients with poor-prognosis leukemia and lymphoma who received BM and/or granulocyte colony-stimulating factor (G-CSF)-mobilized autologous PSCs that had been exposed to IL-2 for 24 hours ex vivo. Patients then received IL-2 by low-dose continuous intravenous (i.v.) infusion until hematologic reconstitution and then by intermediate-dose continuous i.v. infusion for six 2-week maintenance cycles given at 1-month intervals. The median Day to neutrophils over 500/microL was 22 with BM and 10 with PSCs (p = 0.01). The median Day to platelets >20,000/microL was 50 for BM and 25 for PSCs, and to platelets >50,000/microL was 138 for BM and 34 for PSCs (p not significant). After the first three patients received IL-2 at 2 mIU x m(-2) x day(-1) and had slow reconstitution, four patients were treated without IL-2 until the maintenance phase following reconstitution. The remaining 29 patients received the initial "post-infusion" IL-2 at 1 mIU x m(-2) x day(-1). Toxicities associated with the infusion of IL-2-activated cells consisted of chills and fever in about one-half of the patients and transient hypotension in 12%. Low-dose IL-2 by continuous i.v. infusion in the early posttransplant period was associated with exacerbation of fever, diarrhea, and altered mental status in a minority of patients. The major dose-limiting toxicities of maintenance IL-2 were fever, fatigue, gastrointestinal symptoms, skin rash, and dyspnea. Among 24 lymphoma patients, nine are in continuous complete remission (CCR) from 18-48 months, and 15 have died (12 due to relapse and three of therapy-related toxicities). Of 12 acute leukemia patients, two with acute lymphoblastic leukemia (ALL) are in CCR at 38 and 43 months, and one patient who was in cytogenetic but not molecular remission of Philadelphia chromosome-positive ALL died of progressive leukemia at Day 108. Three of nine with myeloid leukemia are in CCR at 21, 46, and 53 months; one is in hematologic and cytogenetic remission of acute promyelocytic leukemia at 55 months with multiple new cytogenetic abnormalities; one is alive at 54 months with pancytopenia after incomplete hematologic recovery followed by multiple new cytogenetic abnormalities (myelodysplasia); and one had an unrelated donor transplant after relapsing 4 months following protocol therapy. One myeloid leukemia patient remains without evidence of relapse, but is transfusion-dependent at 15 months following transplant.
Margolin
K A
KA
Department of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
Van Besien
K
K
Wright
C
C
Niland
J
J
Champlin
R
R
Fung
H C
HC
Kashyap
A
A
Molina
A
A
Nademanee
A P
AP
O'Donnell
M R
MR
Parker
P
P
Smith
E
E
Spielberger
R
R
Somlo
G
G
Snyder
D
D
Stein
A
A
Woo
D
D
Thomas
M
M
Sniecinski
I
I
Forman
S J
SJ
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use*; D007938:Leukemia / Q000628:therapy*; D008223:Lymphoma / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D007376:Interleukin-2