       Document 0939
 DOCN  M9620939
 TI    Prolonged administration of low-dose interleukin-2 in human
       immunodeficiency virus-associated malignancy results in selective
       expansion of innate immune effectors without significant clinical
       toxicity.
 DT    9602
 AU    Bernstein ZP; Porter MM; Gould M; Lipman B; Bluman EM; Stewart CC;
       Hewitt RG; Fyfe G; Poiesz B; Caligiuri MA; Department of Hematologic
       Oncology, Roswell Park Cancer; Institute, Buffalo, NY 14263, USA.
 SO    Blood. 1995 Nov 1;86(9):3287-94. Unique Identifier : AIDSLINE
       MED/96027492
 AB    Ten adult patients with human immunodeficiency virus (HIV)-associated
       malignancies (five with lymphoma and five with Kaposi's Sarcoma) were
       treated with a daily subcutaneous injection of interleukin-2 (IL-2) for
       90 consecutive days in a phase I dose-escalation study. Seven patients
       had absolute CD4 counts below 200/mm3 at the time malignancy was
       diagnosed. Each lymphoma patient had obtained a complete or partial
       remission with standard chemotherapy before initiating IL-2. The daily
       dose of IL-2 did not change during the 90-day course of therapy.
       Seventeen courses of IL-2 therapy were completed at doses ranging from
       0.4 x 10(6) U/m2/d to 1.2 x 10(6) U/m2/d without significant (grade III)
       toxicity. Two of two patients experienced grade III toxicity within 21
       days of initiating IL-2 at a dose of 1.4 x 10(6) U/m2/d, but both
       patients subsequently completed 90 days of therapy at the maximum
       tolerated dose (MTD) of 1.2 x 10(6) U/m2/d. Although there were no
       significant increases or decreases in T-cell subsets at any dose level,
       there was an increase in absolute natural killer (NK) cell number at the
       three highest doses of IL-2 (mean percent increase 247; 95% confidence
       interval, 124 to 369) that was statistically significant (Wilcoxon
       one-sample signed rank test, P = .015). One patient developed an
       anti-IL-2 antibody titer that correlated with minimal NK cell expansion
       in vitro and in vivo. An increase in eosinophils was noted during 9 of
       17 courses of IL-2 therapy without correlation to IL-2 dose, prior
       course of IL-2, or NK cell expansion. At the MTD, there was no
       consistent increase in the plasma HIV RNA level over time. Three of 10
       patients had progressive disease while on study. During 50 months of
       IL-2 therapy, no patient was treated for an opportunistic infection. We
       conclude that daily low dose subcutaneous IL-2 can be self-administered
       safely with good compliance for prolonged periods of time to patients
       with HIV-associated malignancies, including those with profound immune
       deficiency. The majority of patients show selective expansion of innate
       immune effectors, ie, NK cells and/or eosinophils, in the absence of
       significant clinical toxicity or increased viral burden. These results
       suggest that low-dose IL-2 therapy should be studied further in phase II
       clinical trials for evidence of activity against malignancy and
       opportunistic infection in this patient population.
 DE    Adult  Biological Response Modifiers/ADMINISTRATION & DOSAGE/ADVERSE
       EFFECTS/*THERAPEUTIC USE  Drug Administration Schedule
       Eosinophils/IMMUNOLOGY  Human  HIV Infections/*COMPLICATIONS
       *Immunotherapy  Injections, Subcutaneous  Interleukin-2/ADMINISTRATION &
       DOSAGE/ADVERSE EFFECTS/  *THERAPEUTIC USE  Killer Cells,
       Natural/IMMUNOLOGY  Lymphoma, AIDS-Related/IMMUNOLOGY/*THERAPY  Male
       Middle Age  Recombinant Proteins/ADMINISTRATION & DOSAGE/ADVERSE
       EFFECTS/  THERAPEUTIC USE  Sarcoma,
       Kaposi's/ETIOLOGY/IMMUNOLOGY/*THERAPY  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Treatment Outcome  CLINICAL TRIAL  CLINICAL TRIAL,
       PHASE I  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

