Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy.
OBJECTIVE
Glutamine has stimulatory effects on lymphocytes and mucosa cells in vitro and, when given with parenteral nutrition, has been shown to improve the clinical course of patients after bone marrow transplantation and in the critically ill. This study investigated the clinical and immunologic effects of parenteral glycyl-glutamine supplementation in patients with acute leukemia receiving intensive conventional chemotherapy without bone marrow transplantation.


METHODS
A randomized, double-blind, controlled study compared a standard glutamine-free parenteral nutrition with a glycyl-glutamine-supplemented parenteral nutrition (Glamin, Baxter, Erlangen, Germany) containing 20 g of glutamine in adult patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. Clinical end points included the duration of neutropenia and the incidence and duration of neutropenic fever. To analyze the effects of glutamine on immunocompetent cells, CD4+ and CD8+ T cells and HLA-DR expression on monocytes were assessed by flow cytometry throughout the treatment course.


RESULTS
Fifty-four adult patients entered the study and were randomized. In 45 of 127 chemotherapy cycles, parenteral nutrition was given, and 40 cycles (20 with and 20 without glutamine) were evaluated for comparison. The median durations of neutropenia were 18 d (range, 9-29 d) in the glutamine group and 22.5 d (range, 13-48 d) in the control group (P = 0.052), whereas the median durations of neutropenic fever were 5.5 d (range, 0-13 d) and 5 d (range, 0-31 d), respectively (P = 0.74). Using Kaplan-Meier analysis and controlling for the type of chemotherapy, we found a significantly faster neutrophil recovery in patients receiving glutamine than in the control group (P = 0.040) in patients receiving a high-dose cytarabine regimen. There was no significant difference in the recovery of CD4+ or CD8+ lymphocytes or monocyte activation between groups.


CONCLUSIONS
In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. However, no impact of glutamine on neutropenic fever or other criteria of immunologic recovery was detected.
Scheid
Christof
C
First Department of Medicine, Cologne, Germany. c.scheid@uni-koeln.de
Hermann
Karin
K
Kremer
Gisela
G
Holsing
Anja
A
Heck
Georg
G
Fuchs
Michael
M
Waldschmidt
Dirk
D
Herrmann
Hans-Joachim
HJ
Söhngen
Dietmar
D
Diehl
Volker
V
Schwenk
Achim
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004151:Dipeptides / Q000008:administration & dosage* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D010289:Parenteral Nutrition, Total; D011446:Prospective Studies
D000970:Antineoplastic Agents; D004151:Dipeptides; C039788:glycylglutamine