title: Pentostatin in T-non-Hodgkin's lymphomas: efficacy and effect on CD26+ T lymphocytes.
abstract: 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.
authors.affiliation: MD Anderson Cancer Center, Houston, TX 77030, USA. nhdang@mail.mdanderson.org
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Fredrick B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Barry
authors.initials: B
authors.lastname: Samuels
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fayad
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.forename: Andreas
authors.initials: A
authors.lastname: Sarris
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Ann T
authors.initials: AT
authors.lastname: Tong
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Walker
authors.forename: Lili Paz
authors.initials: LP
authors.lastname: Tiongson
authors.forename: Terry L
authors.initials: TL
authors.lastname: Smith
authors.forename: Yang O
authors.initials: YO
authors.lastname: Huh
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rodriguez
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D015649:Pentostatin; D018819:Dipeptidyl Peptidase 4