Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study.
The success of autologous stem cell transplantation (ASCT) for hematologic malignancy is limited largely by a high relapse rate. It is postulated that IL-2 administered after ASCT may eliminate minimal residual disease and thereby reduce relapses. A phase I/II study was performed to identify a regimen of IL-2 (Chiron) that could be given early after ASCT in phase III trials. In the phase I study, beginning a median of 46 days after ASCT for hematologic malignancy, cohorts of three to four patients received escalating doses of 'induction' IL-2 of 9, 10, or 12 x 10(6) IU/m2/day for 4 or 5 days by continuous i.v. infusion (CIV), followed by a 4-day rest period, and then 1.6 x 10(6) IU/m2/day of maintenance IL-2 by CIV for 10 days. The maximum tolerated dose (MTD) of induction IL-2 was 9 x 10(6) IU/m2/day x 4. In the phase II study, 52 patients received the MTD. Eighty percent of patients completed induction IL-2. Most patients exhibited some degree of capillary leak. One patient died of CMV pneumonia and one died of ARDS. Maintenance IL-2 was well tolerated. In the phase I/II study, 16 of 31 patients with non-Hodgkin lymphoma (NHL), 3/8 with Hodgkin disease (HD), 4/17 with AML, and 4/5 with ALL remain in CR. Two of six multiple myeloma (MM) patients remain in PR. Although the regimen of IL-2 identified had significant side-effects in some patients, it was well tolerated in the majority of patients. Phase III prospectively randomized clinical trials are in progress to determine if this IL-2 regimen will decrease the relapse rate after ASCT for AML and NHL.
Robinson
N
N
Department of Medicine, University of Washington, the Fred Hutchinson Cancer Research Center, Seattle 98195, USA.
Benyunes
M C
MC
Thompson
J A
JA
York
A
A
Petersdorf
S
S
Press
O
O
Lindgren
C
C
Chauncey
T
T
Buckner
C D
CD
Bensinger
W I
WI
Appelbaum
F R
FR
Fefer
A
A
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning
D000276:Adjuvants, Immunologic; D007376:Interleukin-2