       Document 0462
 DOCN  M9640462
 TI    Clinical experience with fludarabine and its immunosuppressive effects
       in pretreated chronic lymphocytic leukemias and low-grade lymphomas.
 DT    9604
 AU    Fenchel K; Bergmann L; Wijermans P; Engert A; Pralle H; Mitrou PS; Diehl
       V; Hoelzer D; Medical Clinic III, J. W. Goethe University,
       Frankfurt/M.,; Federal Republic of Germany.
 SO    Leuk Lymphoma. 1995 Aug;18(5-6):485-92. Unique Identifier : AIDSLINE
       MED/96116890
 AB    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 response. 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/m2 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/microliters 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.
 DE    Adult  Aged  Antimetabolites, Antineoplastic/*THERAPEUTIC USE  CD4
       Lymphocyte Count  Female  Human  Immunosuppression  Leukemia,
       Lymphocytic, Chronic/*DRUG THERAPY  Leukocyte Count  Lymphoma,
       Non-Hodgkin's/*DRUG THERAPY  Male  Middle Age  Platelet Count  Survival
       Analysis  Vidarabine/*ANALOGS & DERIVATIVES/THERAPEUTIC USE  CLINICAL
       TRIAL  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

