An Intensive Chemotherapy of Adult T-Cell Leukemia/Lymphoma: CHOP Followed by Etoposide, Vindesine, Ranimustine, and Mitoxantrone with Granulocyte Colony-Stimulating Factor Support

Abstract

An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were < 1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to > 1.0 x 10(9)/L were <5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.

Effect of treatment of Strongyloides infection on HTLV‐1 expression in a patient with adult T‐cell leukemia

“…It occurs in four different subtypes, smoldering, chronic, leukemic, or lymphomatous disease [8]. The leukemic and lymphomatous subtypes account for 60-90% of cases; these are characterized by an aggressive course, with frequent skin, bone, central nervous system, and other visceral involvement, hypercalcemia, and limited responses to chemotherapy [9][10][11][12]. In contrast, chronic ATLL is characterized by lymphocytosis and minimal adenopathy or skin involvement, as manifested by our patient.…”

Longitudinal inhibition of PI3K/Akt/mTOR signaling by LY294002 and rapamycin induces growth arrest of adult T-cell leukemia cells

“…LY294002 and RAD001 inhibited the proliferation of freshly isolated leukemia cells (case #1) in a dose-dependent manner with IC50 of approximately 3 µM and 10 nM, respectively, as measured by 3 [H]-thymidine uptake (Fig 2I). Combination of both enhanced the inhibition of growth.…”

“…A similar enhanced growth inhibition by the combination of LY294002 and rapamycin also occurred with MT-4 and HUT102 cells (Fig E,F). We also performed 3 [H]-thymidine uptake studies to examine whether LY294002 enhanced the ability of rapamycin to inhibit the proliferation of HTLV-1-infected cells (Fig 2G,H). LY294002 (10 µM) or rapamycin (20 nM) alone inhibited the proliferation of HUT102 cells by approximately 40 % and 50 %, respectively (Fig 2H).…”

“…Despite the development of intensive combination chemotherapy regimens supported by granulocyte colony-stimulating factor, median survival time of individuals with ATL is less than 13 months [3,4].…”

Human T cell lymphotropic virus-associated leukemia/lymphoma

“…A variety of combination chemotherapy regimens have been used for leukemic or lymphomatous ATLL, but median survival remains at approximately 1 year, with a 5-year survival rate of less than 5% [29][30][31][32][33][34][35]. Promising results with the combination of interferon-α and zidovudine have been reported from some but not all groups of investigators [36][37][38][39][40][41][42].…”