Pentostatin in T-non-Hodgkin's lymphomas: efficacy and effect on CD26+ T lymphocytes.
Pentostatin is an adenosine deaminase (ADA) inhibitor with antineoplastic activity. CD26 is a surface glycoprotein with a key role in T cell function as the ADA binding protein. We conducted a phase II study to evaluate pentostatin efficacy in relapsed T-non-Hodgkin's lymphoma (T-NHL) and to correlate response with tumor CD26 expression. We also examined the lymphopenic effect of pentostatin on CD26+ T lymphocytes. Eighteen patients were registered for the study. Pentostatin was administered as intravenous bolus daily over 3 days at an initial dose of 5 mg/m(2)/day, repeated every 4 weeks. CD26 surface expression on tumor cells and T lymphocytes was determined by flow cytometry. Out of 14 patients evaluable for response, there was 1 (7%) complete response (CR) and 6 (43%) partial responses (PR). Median progression-free survival for responders was 6 months (range: 2-15 months); median number of courses was 4 (range: 1-6). Responders included 1 of 2 CD26+ and 5 of 9 CD26- cases. Pentostatin also specifically depleted CD26+ rather than CD26- T lymphocytes, potentially associated with immunosuppression. We therefore conclude that while pentostatin is a safe and active agent for T-NHL regardless of CD26 expression, it may selectively deplete CD26+ T lymphocytes, with potentially significant clinical implications.
Dang
Nam H
NH
MD Anderson Cancer Center, Houston, TX 77030, USA. nhdang@mail.mdanderson.org
Hagemeister
Fredrick B
FB
Duvic
Madeleine
M
Romaguera
Jorge E
JE
Younes
Anas
A
Jones
Dan
D
Samuels
Barry
B
Fayad
Luis E
LE
Pro
Barbara
B
Samaniego
Felipe
F
Sarris
Andreas
A
Goy
Andre
A
McLaughlin
Peter
P
Tong
Ann T
AT
Walker
Pamela L
PL
Tiongson
Lili Paz
LP
Smith
Terry L
TL
Huh
Yang O
YO
Morimoto
Chikao
C
Rodriguez
Maria A
MA
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000009:adverse effects / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D015649:Pentostatin; D018819:Dipeptidyl Peptidase 4