CLINICAL-EXPERIENCE WITH FLUDARABINE AND ITS IMMUNOSUPPRESSIVE EFFECTS IN PRETREATED CHRONIC LYMPHOCYTIC LEUKEMIAS AND LOW-GRADE LYMPHOMAS

被引：53

作者：

FENCHEL, K ^{[1
]}

BERGMANN, L ^{[1
]}

WIJERMANS, P ^{[1
]}

ENGERT, A ^{[1
]}

PRALLE, H ^{[1
]}

MITROU, PS ^{[1
]}

DIEHL, V ^{[1
]}

HOELZER, D ^{[1
]}

机构：

[1] UNIV FRANKFURT,MED CLIN 3,FRANKFURT,GERMANY

来源：

LEUKEMIA & LYMPHOMA | 1995年 / 18卷 / 5-6期

关键词：

FLUDARABINE; CHRONIC LYMPHOCYTIC LEUKEMIA; NHL; IMMUNOCYTIC LYMPHOMA; IMMUNOSUPPRESSION; INFECTIOUS RATE;

D O I：

10.3109/10428199509059649

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Fludarabine monophosphate (FAMP) is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) and low-grade non-Hodgkin lymphomas (NHLs). Here, the clinical experience and side effects with FAMP are reported in 77 patients with pretreated CLL (59 B-CLL, 2 T-CLL) and low-grade NHLs (9 immunocytic lymphomas including 5 Waldenstrom's macroglobulinaemia, 2 centrocytic (cc) and 5 centroblastic-centrocytic (cb-cc) NHLs). 70/77 patients are evaluable for reponse. All except 8 patients were pretreated with one to four different regimens and had progressive disease. FAMP was administered at a dosage of 25 mg/m(2) daily for 5 days as 30 minute infusion every fifth week. Partial (PR) or complete remission (CR) was achieved in 38/56 (68%) and 3/56 (5%) of evaluable patients with CLL, respectively. In 7/8 (1 x CR, 6 x PR) evaluable patients with immunocytic lymphoma and in 3/6 (3 x PR) patients with cc or cb-cc lymphoma remissions were obtained. The probability of progression-free survival was 66% and the event-free survival was 25% and 22% at 12 and 18 months. The median progression-free survival until relapse or death, however, was only 7 months (2-20+). Major toxic effects included infections in 22 patients (grade 3 and 4 WHO), granulocytopenia (mainly grade 3) and nausea in 8 patients (mainly grade 1). 19/22 patients were in PR at the time of occurrence of infectious complications. Meanwhile, 14 patients died due to septicaemia, pneumonia or other infections. Nine patients developed severe septicaemia, 4 patients had pneumocystis carinii or aspergillus pneumonias. The high infection rate may not only be due to hypogammaglobulinaemia and granulocytopenia induced by FAMP but also to a remarkable decrease of CD4+ cells from a median of 2479 to 241 CD4+ cells/mu l after 6 cycles of FAMP. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. It is concluded that FAMP is effective even in patients with advanced CLL and low-grade NHLs refractory to multiple chemotherapy regimens. However, FAMP has a marked suppressive effect on granulocytes and T-lymphocytes, predominantly CD4+ lymphocytes.

引用

页码：485 / 492

页数：8

共 45 条

[1] Lennert K., Malignant lymphomas., pp. 106-152, (1978)
[2] Rabinowe S.N., Soiffer R.J., Gribben J.G., Daley H., Freedman A.S., Daley J., Pesek K., Neuberg D., Pinkus G., Leavitt P.R., Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia, Blood, 82, pp. 1366-1376, (1903)
[3] Keating M.J., Kantarjian H., Talpaz M., Redman J., Koller C., Barlogie B., Velasquez W., Plinkett W., Freireich E.J., McCredie K.B., Fludarabine: a new agent with major activity against chronic lymphocytic leukemia, Blood, 74, pp. 19-24, (1989)
[4] Cheson B.D., New antimetabolites in the treatment of human malignancies, Sem. Oncol., 19, pp. 695-706, (1989)
[5] Keating M.J., O'Brien S., Kantarjian H., Robertson L.B., Koller C., Beran M., Estey E., Nucleoside analogues in treatment of chronic lymphocytic leukemia, Leuk. Lymph., 10, pp. 139-145, (1993)
[6] Khouri I.F., Keating M.J., Vriesendorp H.M., Reading C.L., Przepiorka D., Huh Y.O., Anderson B.S., van Besien K.W., Mehra R.C., Giralt S.A., Ippoliti C., Marshall M., Thomas M.W., O'Brien S., Robertson L.E., Deisseroth A.B., Champlin R.E., Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results, J. Clin. Oncol., 4, pp. 748-758, (1994)
[7] Knospe W.H., Loeb V., Huguley C.M., Bi-weeklychlo-rambucil treatment of chronic lymphocytic leukemia, Cancer, 31, pp. 502-508, (1974)
[8] Raphael B., Andersen J.W., Silber R., Oken M., Moore D., Bennel J., Bonner H., Hahn R., Knospe W.H., Mazza J., Glick J., Comparison of chlorambucile and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: Long-term follow-up of an Eastern Cooperative Oncology Group randomized trial, J. Clin. Oncol., 9, pp. 770-777, (1991)
[9] French Cooperative Group on Chronic lymphocytic leukemia., Effectiveness of “CHOP” regimen in advanced chronic lymphocytic leukemia, Lancet, 1, pp. 1346-1349, (1986)
[10] Montserrat E., Alcala A., Parody R., Domingo A., Garcia-Conde J., Bueno J., Ferran C., Sanz M.A., Giralt M., Ruhio D., Anton I., Estape J., Rozman C., Treatment of chronic lymphocytic leukemia in advanced stages, Cancer, 56, pp. 2369-2375, (1985)

← 1 2 3 4 5 →