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Titolo:
Plasma FLT3-L levels predict bone marrow recovery from myelosuppressive therapy
Autore:
Blumenthal, RD; Lew, W; Juweid, M; Alisauskas, R; Ying, ZL; Goldenberg, DM;
Indirizzi:
Garden State Canc Ctr, Belleville, NJ 07109 USA Garden State Canc Ctr Belleville NJ USA 07109 r, Belleville, NJ 07109 USA Rutgers State Univ, Dept Stat, Piscataway, NJ USA Rutgers State Univ Piscataway NJ USA Univ, Dept Stat, Piscataway, NJ USA
Titolo Testata:
CANCER
fascicolo: 2, volume: 88, anno: 2000,
pagine: 333 - 343
SICI:
0008-543X(20000115)88:2<333:PFLPBM>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
FACTOR G-CSF; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; CHEMOTHERAPY-INDUCED MYELOSUPPRESSION; HEMATOPOIETIC STEM-CELLS; MONOCLONAL-ANTIBODY; GROWTH-FACTORS; X-IRRADIATION; COLON-CANCER; SERUM LEVELS; IN-VIVO;
Keywords:
myelosuppression; cytokine; bone marrow; chemotherapy; clinical thrombocytopenia; FLT3-L;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Blumenthal, RD Garden State Canc Ctr, 520 Belleville Ave, Belleville, NJ 07109 USA Garden State Canc Ctr 520 Belleville Ave Belleville NJ USA 07109
Citazione:
R.D. Blumenthal et al., "Plasma FLT3-L levels predict bone marrow recovery from myelosuppressive therapy", CANCER, 88(2), 2000, pp. 333-343

Abstract

BACKGROUND. During the recovery period after anticancer myelosuppressive therapy, hematopoietic progenitor cells become mitotically active in order to replenish the bone marrow compartment and remain hyperproliferative even after normalization of peripheral white blood cells and platelets. At this stage, the progenitors are more radiosensitive and chemosensitive. Dosing patients with additional totoxic therapy during this phase will likely result in more severe toxicity. For example, the authors have noted that the redbone marrow (RM) dose resulting from radioantibody therapy does not correlate with observed bone marrow toxicity. Several patients given similar RM doses had Grade 3 or 4 toxicity, whereas others had Grade 0-2 toxicity even though their white blood cell (WBC) and (PLT) counts were normal at the time of dosing. The goal of these studies was to establish a noninvasive predictive marker of bone marrow activity that could determine stem cell and progenitor cell recovery from previous myelosuppressive therapy. METHODS. A retrospective study was conducted to quantitate plasma levels of 5 cytokines regulating hematopoiesis, namely, 2 stimulatory fms-like tyrosine kinase (FI,TS-L) and stem cell factor (SCF) and 3 inhibitory growth factors tumor necrosis factor-alpha (TNF alpha), tumor growth factor-beta, and macrophage inflammatory protein (MIP-1 alpha), by immunoassay in 43 patients enrolled in clinical trials at Garden State Cancer Center in Belleville, New Jersey. All patients had had previous chemotherapy with a duration of1-24 months. The serum cytokine values were with the magnitude of leukopenia or thrombocytopenia following a single dose radioantibody as the cytotoxic therapy. RESULTS. Plasma FLT3-L levels predicted excess platelet toxicity in 13 of 16 patients (mean = 225 +/- 106 pg/mL) and resulted in a false-positive in only 3 of 27 other patients (mean = 80 +/- 41 pg/mL). Plasma FLT3-L > 135 pg/mL resulted in 81% sensitivity and 89% and 86% specificity and accuracy, respectively, for pre dieting excess toxicity caused by additional cytotoxic therapy. The positive likelihood ratio was 7.5 (95% confidence interval, 2.5-22.5) and the negative likelihood ratio was 0.19 (95% confidence interval, 0.05-0.67). CONCLUSIONS. Elevated plasma FLT3-L in patients who previously received chemotherapy is a predictive measure of the stage of recovery of the bone compartment. FLT3-L seems to identify the likelihood that the patient will experience Grade greater than or equal to 3 thrombocytopenia if additional cytotoxic therapy is administered. Knowledge of bone marrow activity should permit therapy that is aggressive by establishing the earliest possible time for dosing with any agent for which myelosuppression is the dose-limiting toxicity. (C) 2000 American Cancer Society.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 23:02:28