Transplantation of patients with high risk acute myeloid leukemia in first remission with autologous marrow cultured in interleukin-2 followed by interleukin-2 administration.
Relapse rates in patients after autologous bone marrow transplantation (BMT) for acute myeloid leukemia (AML) continue to be high despite the use of aggressive conditioning regimens. Based on studies in the murine system a clinical protocol was developed that utilizes immunotherapy to obtain a graft-versus-leukemia (GVL) effect both pre-BMT (to purge leukemic cells from the autograft) and post-BMT (to eradicate residual leukemia in the patient). As part of a phase I study, 10 consecutive patients (median age 41 years, range 15-60 years) with 'high risk' AML (i.e. any of the following: FAB M5, WBC of > or = 50 x 10(9)/l at diagnosis or 'unfavorable' cytogenetic abnormalities) were transplanted at a median of 32 days (range 13-128 days) after achieving first remission. Marrow cells to be autografted were first cultured for 8 days at 37 degrees C in standard long-term culture medium (containing 12.5% horse serum, 12.5% fetal calf serum and 10(-6) M hydrocortisone) to which 1000 U/ml of interleukin-2 (IL-2) was also added. During this time patients received busulfan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg for 2 days). On the day of transplantation (day 0), the cultured marrow cells were collected from the flasks and infused over 1 h. Between days 0 and 7 patients were given escalating doses of subcutaneous IL-2 (2, 4 and 6 x 10(5) U/m2/day, 3-4 patients/dose level). Side-effects attributable to IL-2 were generally mild, dose-dependent and consisted of fever and malaise.(ABSTRACT TRUNCATED AT 250 WORDS)
Klingemann
H G
HG
Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver General Hospital, Canada.
Eaves
C J
CJ
Barnett
M J
MJ
Eaves
A C
AC
Hogge
D E
DE
Nantel
S H
SH
Reece
E
E
Shepherd
J D
JD
Sutherland
H J
HJ
Phillips
G L
GL
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D014182:Transplantation, Autologous
D007376:Interleukin-2