Skip to main content
SpringerLink
Log in

Fludarabine

An Update of its Pharmacology and Use in the Treatment of Haematological Malignancies

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Synopsis

Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies.

Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin’s lymphoma.

A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation.

The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses.

Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.

Pharmacodynamic Properties

Postulated mechanisms for the antitumour activity of fludarabine include termination of DNA and RNA synthesis by incorporation of the active metabolite F-ara-A (9-β-D-arabino-furanosyl-2-fluoroadenine) triphosphate (F-ara-ATP) into elongating nucleic acid chains, inhibition of DNA and RNA polymerases, DNA primase, DNA ligase and ribonucleotide reductase and potentiation of deoxycytidine kinase activity. Both in vitro and in vivo studies have highlighted apoptosis as an additional important mode of fludarabine-induced cell death. However, the relative importance of inhibition of DNA and RNA synthesis in the induction of the apoptotic process by fludarabine has not been fully elucidated.

In vitro, fludarabine demonstrated concentration-and time-dependent cytotoxicity against human leukaemia cell lines. Fludarabine has been shown to potentiate the activity of a number of antitumour agents in vitro including cytarabine, cisplatin, mitoxantrone and gallium nitrate. Fludarabine has in vivo antitumour activity against a wide range of murine tumour models and has been shown to induce radiosensitisation in the Meth-a fibrosarcoma, SA-NH sarcoma and MCA-K and MCA-4 murine mammary carcinoma models. The mechanism of fludarabine-induced radiosensitisation appears to involve the elimination of cells in S-phase by apoptosis and synchronisation of the remaining cells to a more radiosensitive cell cycle phase. Fludarabine also reduced the number of lymphocytes able to proliferate and trigger rejection in mice after total body irradiation, suggesting a possible future immunosuppressant role for fludarabine in bone marrow transplantation conditioning.

Pharmacokinetic Properties

Within 5 minutes of intravenous administration, the prodrug fludarabine undergoes complete dephosphorylation to F-ara-A. The plasma pharmacokinetics of F-ara-A appear to be linear with no accumulation following repeated daily administration. In adults, volume of distribution at steady state and plasma clearance were up to ≈10-fold greater than the corresponding values in children, and wide interstudy differences in the area under the plasma concentration-time curve were reported at each fludarabine dosage level studied.

A predominantly biphasic decline in plasma F-ara-A concentrations has been reported with distribution and terminal elimination half-lives of 0.9 to 1.7 hours and 6.9 to 33.5 hours, respectively. However, a triphasic decline in plasma F-ara-A concentrations which included an initial distribution phase of 5 to 9 minutes has also been reported.

Peak intracellular levels of the active metabolite of fludarabine, F-ara-ATP, have been reported within 3 to 4 hours after termination of fludarabine infusion.

Renal mechanisms play an important role in the elimination of fludarabine with a reported correlation between increased serum creatinine and blood urea nitrogen levels and decreased F-ara-A elimination. In addition, fludarabine-associated neutropenia appears to be more severe in patients with a creatinine clearance <50 ml/min (<3 L/h).

Therapeutic Efficacy

In the treatment of advanced chronic lymphocytic leukaemia (CLL), response to fludarabine monotherapy has been shown to be strongly correlated to stage of disease, extent of previous chemotherapeutic treatment and response to prior chemotherapy.

Following treatment with single-agent fludarabine (20 to 30 mg/m2 /day for 5 days repeated every 3 to 5 weeks) in noncomparative studies, objective response rates of 12 to 94% have been reported in previously treated patients and up to 78% in chemotherapy-naive patients. Notably, the recent results of a large multicentre comparative study have shown fludarabine (25 mg/m2/day for 5 days repeated every 4 weeks) to be significantly more effective than chlorambucil (40 mg/m2/day on day 1 every 4 weeks) in the management of previously untreated patients with CLL in terms of objective response rate (70 vs 43%), response duration (33 vs 17 months) and progression-free survival (27 vs 17 months).

Comparative studies have also shown fludarabine (25 mg/m2/day for 5 days) to be at least as effective as standard therapy with CAP or CHOP in terms of response rate in patients with previously treated or untreated advanced CLL. A significant increase in remission duration and a tendency towards longer overall survival with fludarabine compared with CAP was also reported in chemotherapy-naive patients. Promising results have been reported following the use of fludarabine in combination with other chemotherapeutic agents such as doxorubicin, cyclophosphamide, epirubicin and mitoxantrone in the treatment of chemotherapy-naive and previously treated patients with CLL.

Complete remission rates of 36 to 64% in acute myelogenous leukaemia and/or myelodysplastic syndrome and 30 to 80% in acute lymphocytic leukaemia have been reported with sequential fludarabine and cytarabine therapy (with or without granulocyte colony-stimulating factor). Likewise, complete response rates of 4 to 37% were achieved with fludarabine monotherapy (18 to 30 mg/m2/day for 5 days repeated every 3 to 5 weeks) and up to 89% with fludarabine-based combination chemotherapy in patients with low grade NHL.

Fludarabine has also shown activity in the treatment of the cutaneous T cell lymphomas, mycosis fungoides and Sézary syndrome, lymphoplasmacytoid lymphoma including Waldenström’s macroglobulinaemia, CLL of T cell origin and prolymphocytic leukaemia. However, further evaluation in larger patient populations is necessary.

Recently the use of fludarabine-based combination chemotherapy has demonstrated promising utility as a nonmyeloablative conditioning regimen in allogeneic bone marrow or peripheral blood stem cell transplantation for patients with haematological malignancies.

Tolerability

In a study comparing fludarabine with CAP in patients with advanced-stage CLL, the most frequent adverse events (WHO grade III/IV) reported with fludarabine were granulocytopenia (19% of cycles), thrombocytopenia (14%) and anaemia (7%). Fludarabine produced less nausea/vomiting and alopecia than the standard CAP regimen but was associated with an increased incidence of autoimmune phenomena (including autoimmune haemolytic anaemia and thrombocytopenia). Compared with CAP, fludarabine did not increase the incidence of infectious events (which has been associated with a depletion of CD4+ cells); the results of other studies suggest that an increase in infectious episodes with fludarabine therapy is predominantly attributable to the concomitant administration of corticosteroids.

Severe neurotoxicity following fludarabine therapy is clearly dose-related and is minimal with the use of standard dosages of the drug. Isolated cases of tumour lysis syndrome, interstitial pneumonitis and haemolytic uraemic syndrome following treatment with fludarabine have also been reported.

Dosage and Administration

For the treatment of CLL, the recommended dose of fludarabine is 25 mg/m2, administered as a 30-minute intravenous infusion or as an intravenous bolus injection daily for 5 days and repeated at 28-day intervals. Dosages of 20 to 30 mg/m2/day for up to 5 consecutive days repeated every 3 to 5 weeks in combination with cytarabine in the treatment of acute leukaemia and as single-agent or combination therapy in NHL have also been used successfully.

Fludarabine dosage reductions based on creatinine clearance values is recommended in patients with known or suspected renal impairment; the drug is contraindicated in those with a creatinine clearance <30 ml/min (1.8 L/h).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ross SR, McTavish D, Faulds D. Fludarabine: a review of its pharmacological properties and therapeutic potential in malignancy. Drugs 1993 May; 45: 737–59

    Article  PubMed  CAS  Google Scholar 

  2. Plunkett W, Begleiter A, Liliemark O, et al. Why do drugs work in CLL? Leuk Lymphoma 1996; 22 Suppl. 2: 1–11

    Article  PubMed  Google Scholar 

  3. Gandhi V, Huang P, Plunkett W. Fludarabine inhibits DNA replication: a rationale for its use in the treatment of acute leukemias. Leuk Lymphoma 1994; 14 Suppl. 2: 3–9

    Article  PubMed  Google Scholar 

  4. Catapano CV, Chandler KB, Fernandes DJ. Inhibition of primer RN A formation in CCRF-CEM leukemia cells by fludarabine triphosphate. Cancer Res 1991 Apr; 51: 1829–35

    PubMed  CAS  Google Scholar 

  5. Catapano CV, Qiu J, Perrino FW, et al. Primer RNA chain termination induced by fludarabine phosphate. Proc Am Assoc Cancer Res 1992 Mar; 33: 542

    Google Scholar 

  6. Huang P, Chubb S, Plunkett W. Termination of DNA synthesis by 9-β-D-arabinofuranosyl-2-fluoroadenine. J Biol Chem 1990 Sep 25; 265(27): 16617–25

    PubMed  CAS  Google Scholar 

  7. Huang P, Plunkett W. Action of 9-β-D-arabinofuranosyl-2-fluoroadenine on RNA metabolism. Mol Pharmacol 1991 Apr; 39(4): 449–55

    PubMed  CAS  Google Scholar 

  8. Tseng W-C, Derse D, Cheng Y-C, et al. In vitro biological activity of 9-β-D-arabinofuranosyl-2-fluoroadenine and the biochemical actions of its triphosphate on DNA polymerases ribonucleotide reductase from HeLa cells. Mol Pharmacol 1982 Mar; 21(2): 474–7

    PubMed  CAS  Google Scholar 

  9. Yang S-W, Huang P, Plunkett W, et al. Dual mode of inhibition of purified DNA ligase I from human cells by 9-β-D-arabinofuranosyl-2-fluoroadenine triphosphate. J Biol Chem 1992 Feb 5; 267(4): 2345–9

    PubMed  CAS  Google Scholar 

  10. Gandhi V, Plunkett W. Modulation of arabinosylnucleoside metabolism by arabinosylnucleotides in human leukemia cells. Cancer Res 1988 Jan 15; 48: 329–34

    PubMed  CAS  Google Scholar 

  11. Robertson LE, Chubb S, Meyn RE, et al. Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2′-deoxyadenosine and 9-β-D-arabinosyl-2-fluoroadenine. Blood 1993 Jan 1; 81: 143–50

    PubMed  CAS  Google Scholar 

  12. Zinzani PL, Tosi P, Visani G, et al. Apoptosis induction with three nucleoside analogs on freshly isolated B-chronic lymphocytic leukemia cells. Am J Hematol 1994 Dec; 47: 301–6

    Article  PubMed  CAS  Google Scholar 

  13. Zinzani PL, Buzzi M, Farabegoli P, et al. Induction of in vitro apoptosis by fludarabine in freshly isolated B-chronic lymphocytic leukemia cells. Leuk Lymphoma 1994 Mar; 13: 95–7

    Article  PubMed  CAS  Google Scholar 

  14. Zinzani PL, Buzzi M, Farabegoli P, et al. Apoptosis induction with fludarabine on freshly isolated chronic myeloid leukemia cells. Haematologica 1994 Mar–Apr; 79: 127–31

    PubMed  CAS  Google Scholar 

  15. Meyn RE, Stephens LC, Hunter NR, et al. Apoptosis in murine tumors treated with chemotherapy agents. Anticancer Drugs 1995 Jun; 6: 443–50

    Article  PubMed  CAS  Google Scholar 

  16. Segat D, Scheid C, Schulz A, et al. Induction of apoptosis with 9-β-D-arabinosyl-2-fIuoroadenine, daunorubicine, 2-chlorodeoxyadenosine, 1-β-D-arabinofluranosyl-cytosine on freshly isolated leukemia cells in relation to clinical response to chemotherapy [abstract]. Onkologie 1995 Oct; 18 Suppl. 2: 139

    Article  Google Scholar 

  17. Huang P, Plunkett W. Fludarabine-and gemcitabine-induced apoptosis: incorporation of analogs into DNA is a critical event. Cancer Chemother Pharmacol 1995 Jul; 36: 181–8

    Article  PubMed  CAS  Google Scholar 

  18. Sandoval A, Consoli U, Plunkett W. Fludarabine-mediated inhibition of nucleotide excision repair induces apoptosis in quiescent human lymphocytes. Clin Cancer Res 1996; 2: 1731–41

    PubMed  CAS  Google Scholar 

  19. Van Den Neste E, Huang P, Plunkett W. Apoptosis induced in CLL cells by fludarabine and transcriptional inhibitors [abstract no. 932]. American Hematology Society Meeting; 1996 Dec 6–10; Orlando.

  20. Kitada S, Andersen J, Hines J, et al. Expression of BCL-2 family genes and in vitro sensitivity to fludarabine and 2-chlorodeoxy-adenosine in B-CLL: an ECOG Study [abstract]. Blood 1995 Nov 15; 86 Suppl. 1: 607

    Google Scholar 

  21. Döhner H, Fischer K, Bentz M, et al. p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood 1995 Mar 15; 85: 1580–9

    PubMed  Google Scholar 

  22. Wattel E, Preudhomme C, Hecquet B, et al. p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood 1994 Nov 1; 84: 3148–57

    PubMed  CAS  Google Scholar 

  23. Silber R, Degar B, Costin D, et al. Chemosensitivity of lymphocytes from patients with B-cell chronic lymphocytic leukemia to chlorambucil, fludarabine, and camptothecin analogs. Blood 1994 Nov 15; 84: 3440–6

    PubMed  CAS  Google Scholar 

  24. Robertson LE, Denny AW, Huh YO, et al. Natural killer cell activity in chronic lymphocytic leukemia patients treated with fludarabine. Cancer Chemother Pharmacol 1996 Mar; 37: 445–50

    Article  PubMed  CAS  Google Scholar 

  25. Avramis VI. Pharmacodynamics and proposed mechanism of therapeutic action and host toxicity of 9-β-D-arabinofuranosyl-2-fluoroadenine monophosphate (F-araAMP) in P388 murine leukemia-bearing mice. Cancer Invest 1989; 7(2): 129–37

    Article  PubMed  CAS  Google Scholar 

  26. Barrueco JR, Jacobsen DM, Chang C-H, et al. Proposed mechanism of therapeutic selectivity for 9-β-D-arabinofuranosyl-2-fluoroadenine against murine leukemia based upon lower capacities for transport and phosphorylation in proliferative intestinal epithelium compared to tumor cells. Cancer Res 1987 Feb 1; 47: 700–6

    PubMed  CAS  Google Scholar 

  27. Dow LW, Bell DE, Poulakos L, et al. Differences in metabolism and cytotoxicity between 9-β-D arabinofuranosyladenine and 9-β-D-arabinofuranosyl-2-fluoroadenine in human leukemic lymphoblasts. Cancer Res 1980 May; 40: 1406–10

    Google Scholar 

  28. Spriggs D, Robbins G, Mitchell T, et al. Incorporation of 9-β-D-arabinofuranosyl-2-fluroadenine into HL-60 cellular RNA and DNA. Biochem Pharmacol 1986; 35(2): 247–52

    Article  PubMed  CAS  Google Scholar 

  29. Hilgenfeld E, Knauf WU, Thiel E. In vitro and in vivo cytotoxicity of fludarabine and 2-chlorodeoxyadenosine in patients with B-cell chronic lymphocytic leukemia (B-CLL) [abstract]. Onkologie 1995 Oct; 18 Suppl. 2: 82

    Google Scholar 

  30. Begleiter A, Verburg L, Ashique A, et al. Comparison of anti-tumor activities of 2-chlorodeoxyadenosine and 9-β-arabinosyl-2-fluoroadenine in chronic lymphocytic leukemia and marrow cells in vitro. Leukemia 1995 Nov; 9: 1875–81

    PubMed  CAS  Google Scholar 

  31. Fernandes DJ, Wang L-M, Catapano CV. Inhibition of gene amplification and drug resistance by fludarabine phosphate [abstract]. 86th Annu Meet Am Assoc Cancer Res 1995 Mar; 36: 540

    Google Scholar 

  32. Gandhi V, Nowak B, Keating M, et al. Modulation of arabinosylcytosine metabolism by arabinosyl-2-fluoradenine in lymphocytes from patients with chronic lymphocytic leukeimia: implications for combination therapy. Blood 1989; 74(6): 2070–5

    PubMed  CAS  Google Scholar 

  33. Seymour JF, Huang P, Plunkett W, et al. Influence of fludarabine on pharmacokinetics and pharmacodynamics of cytarabine: implications for a continuous infusion schedule. Clin Cancer Res 1996 Apr; 2: 653–8

    PubMed  CAS  Google Scholar 

  34. Santini V, D’Ippolito G, Bernabei PA, et al. Effects of fludarabine and gemcitabine on human acute myeloid leukemia cell line HL 60: direct comparison of cytotoxicity and cellular Ara-C uptake enhancement. Leuk Res 1996 Jan; 20: 37–45

    Article  PubMed  CAS  Google Scholar 

  35. Rayappa C, McCulloch EA. A cell culture model for the treatment of acute myeloblastic leukemia with fludarabine and cytosine arabinoside. Leukemia 1993 Jul; 7: 992–9

    PubMed  CAS  Google Scholar 

  36. Tosi P, Visani G, Ottaviani E, et al. Fludarabine plus ARA-C+G-CSF: cytotoxic effect and induction of apoptosis on fresh acute myeloid leukemia cells. Leukemia 1994 Dec; 8: 2076–82

    PubMed  CAS  Google Scholar 

  37. Lichtenthaler U, Jahns-Streubel G, Hiddemann W. Effect of combined treatment with GM-CSF, fludarabine and ARA-C on ARA-C mediated cytotoxicity in AML [abstract]. Onkologie 1995 Oct; 18 Suppl. 2: 139

    Article  Google Scholar 

  38. Avramis VI, Kwock R, Reaman G. Synergistic antileukemic activity of fludarabine + ara-C + paclitaxel (Taxol) combination regimen against human leukemia cell lines [abstract]. 86th Annu Meet Am Assoc Cancer Res 1995 Mar; 36: 296

    Google Scholar 

  39. Knauf WU, Kreuser ED, Pottgieβer E, et al. In vitro and in vivo effectiveness of fludarabine in B-cell chronic lymphocytic leukemia (B-CLL) [abstract no. 203]. Ann Hematol 1992; 65(5): A80

    Google Scholar 

  40. Di Raimondo F, Romeo MA, Palumbo GA, et al. In vitro citotoxicity of fludarabine + mitoxantrone or vinorelbine on B-CLL cells [abstract no. 099]. Haematologica 1996 March–April; 81: 42

    Google Scholar 

  41. Lundberg JH, Chitambar CR. Interaction of gallium nitrate with fludarabine and iron chelators: effects on the proliferation of human leukemic HL60 cells. Cancer Res 1990 Oct 15; 50: 6466–70

    PubMed  CAS  Google Scholar 

  42. Yang L-Y, Li L, Keating MJ, et al. Arabinosyl-2-fluoroadenine augments cisplatin cytoxicity and inhibits cisplatin-DNA cross-link repair. Mol Pharmacol 1995; 47: 1072–9

    PubMed  CAS  Google Scholar 

  43. Zaffaroni N, Orlandi L, Gornati D, et al. Fludarabine as a modulator of cisplatin activity in human tumour primary cultures and established cell lines. Eur J Cancer 1996; 32A: 1766–73

    Article  PubMed  CAS  Google Scholar 

  44. Di Raimondo F, Palumbo GA, Romeo MA, et al. In vitro sensitivity of B-CLL cells to fludarabine and interferons. Leuk Lymphoma 1995 May; 17: 449–53

    Article  PubMed  Google Scholar 

  45. Morabito F, Callea I, Rodino A, et al. Modulation of purine analogs- and chlorambucil-induced cytotoxicity by alpha-in-terferon and interleukin-2 in chronic lymphocytic leukemia. Leukemia 1995 Sep; 9: 1450–5

    PubMed  CAS  Google Scholar 

  46. Avramis VI, Champagne J, Sato J, et al. Pharmacology of fludarabine phosphate after a phase I/II trial by a loading bolus and continuous infusion in pediatric patients. Cancer Res 1990 Nov 15; 50: 7226–31

    PubMed  CAS  Google Scholar 

  47. Brockman RW, Schabel FM, Montgomery JA. Preliminary communications. Biologic activity of 9-β-D-arabinofuranosyl-2-fluroadenine, a metabolically stable analog of 9-β-D-arabinofuranosyladenine. Biochem Pharmacol 1977; 26: 2193–6

    Article  PubMed  CAS  Google Scholar 

  48. Brockman RW, Cheng Y-C, Schabel Jr FM, et al. Metabolism and chemotherapeutic activity of 9-β-D-arabinofuranosyl-2-fluoroadenine against murine leukemia L1210 and evidence for its phosphorylation by deoxycytidine kinase. Cancer Res 1980 Oct; 40: 3610–5

    PubMed  CAS  Google Scholar 

  49. Chun HG, Leyland-Jones B, Cheson BD. Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. J Clin Oncol 1991 Jan; 9(1): 175–88

    PubMed  CAS  Google Scholar 

  50. McGinn CJ, Shewach DS, Lawrence TS. Radiosensitizing nucleosides. J Natl Cancer Inst 1996 Sep 4; 88(17): 1193–203

    Article  PubMed  CAS  Google Scholar 

  51. Kim JH, Alfieri AA, Kim SH, et al. The potentiation of radiation response on murine tumor by fludarabine phosphate. Cancer Lett 1986; 31: 69–76

    Article  PubMed  CAS  Google Scholar 

  52. Grégoire V, Hunter N, Milas L, et al. Potentiation of radiation-induced regrowth delay in murine tumors by fludarabine. Cancer Res 1994 Jan 15; 54: 468–74

    PubMed  Google Scholar 

  53. Grégoire V, Hunter N, Brock WA, et al. Fludarabine improves the therapeutic ratio of radiotherapy in mouse tumors after single-dose irradiation. Int J Radiat Oncol Biol Phys 1994 Sep 30; 30: 363–71

    Article  PubMed  Google Scholar 

  54. Grégoire V, Hunter NR, Brock WA, et al. Improvement in the therapeutic ratio of radiotherapy for a murine sarcoma by indomethacin plus fludarabine. Radiat Res 1996; 146: 548–53

    Article  PubMed  Google Scholar 

  55. Grégoire V, Ruifrok AC, Price RE, et al. Effect of intra-peritoneal fludarabine on rat spinal cord tolerance to fractionated irradiation. Radiother Oncol 1995 Jul; 36: 50–5

    Article  PubMed  Google Scholar 

  56. Grégoire V, Van Nguyen T, Stephens LC, et al. The role of fludarabine-induced apoptosis and cell cycle synchronization in enhanced murine tumor radiation response in vivo. Cancer Res 1994 Dec 1; 54: 6201–9

    PubMed  Google Scholar 

  57. Terenzi A, Anstei C, Chionne F, et al. Preliminary results on fludarabin as an immunosuppressor in bone marrow transplantation conditioning [abstract]. Bone Marrow Transplant 1996 Mar; 17 Suppl. 1: S11

    Google Scholar 

  58. Goodman ER, Fierdor PS, Fein S, et al. Fludarabine phosphate: a DNA synthesis inhibitor with potent immunosuppressive activity and minimal clinical toxicity. Am Surg 1996 Jun; 62: 435–42

    PubMed  CAS  Google Scholar 

  59. Plunkett W, Gandhi V, Huang P, et al. Fludarabine: pharmacokinetics, mechanisms of action, and rationales for combination therapies. Semin Oncol 1993 Oct; 20 Suppl. 7: 2–12

    PubMed  CAS  Google Scholar 

  60. Danhauser L, Plunkett W, Liliemark J, et al. Comparison between the plasma and intracellular pharmacology of 1 -β-D-arabinofuranosylcytosine and 9-β-D-arabinofuranosyl-2-fluoroadenine 5′-monophosphate in patients with relapsed leukemia. Leukemia 1987 Sep; 1(9): 638–43

    PubMed  CAS  Google Scholar 

  61. Hersh MR, Kuhn JG, Phillips JL, et al. Pharmacokinetic study of fludarabine phosphate (NSC 312887). Cancer Chemother Pharmacol 1986; 17: 277–80

    Article  PubMed  CAS  Google Scholar 

  62. Malspeis L, Grever MR, Staubus AE, et al. Pharmacokinetics of 2-F-ara-A (9-β-D-arabinofuranosyl-2-fIuoroadenine) in cancer patients during the phase I clinical investigation of fludarabine phosphate. Semin Oncol 1990 Oct; 17(5) Suppl. 8: 18–32

    PubMed  CAS  Google Scholar 

  63. Danhauser L, Plunkett W, Keating M, et al. 9-β-Arabinofuranosyl-2-fluroadenine 5′-monophosphate pharmacokinetics in plasma and tumor cells of patients with relapsed leukemia and lymphoma. Cancer Chemother Pharmacol 1986; 18: 145–52

    Article  PubMed  CAS  Google Scholar 

  64. Kemena A, Fernandez M, Bauman J, et al. A sensitive fluorescence assay for quantitation of fludarabine and metabolites in biological fluids. Clin Chim Acta 1991 Aug 30; 200: 95–106

    Article  PubMed  CAS  Google Scholar 

  65. Gandhi V, Kemena A, Keating MJ. Cellular pharmacology of fludarabine triphosphate in chronic lymphocytic leukemia cells during fludarabine therapy. Leuk Lymphoma 1993 May; 10: 49–56

    Article  PubMed  CAS  Google Scholar 

  66. Kemena A, Keating M, Plunkett W. Oral bioavailability of plasma fludarabine and fludarabine triphosphate (F-ara-ATP) in peripheral CLL cells. Onkologie 1991; 14(52): 83

    Google Scholar 

  67. Catovsky D, Murphy RLW. Key issues in the treatment of chronic lymphocytic leukaemia (CLL). Eur J Cancer A 1995; 13A(13-14): 2146–56

    Article  Google Scholar 

  68. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from multivariate survival analysis. Cancer 1981; 48: 198–206

    Article  PubMed  CAS  Google Scholar 

  69. Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood 1975; 46: 219–34

    PubMed  CAS  Google Scholar 

  70. Molica S, De Rossi G, Luciani M, et al. Prognostic features and therapeutical approaches in B-cell chronic lymphocytic leukemia: an update. Haematologica 1995 Mar–Apr; 80: 176–93

    PubMed  CAS  Google Scholar 

  71. O’Brien S, del Giglio A, Keating M. Advances in the biology and treatment of B-cell chronic lymphocytic leukemia. Blood 1995 Jan 15; 85: 307–18

    PubMed  Google Scholar 

  72. Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored working group guidelines for chronic lymphocytic leukaemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–7

    PubMed  CAS  Google Scholar 

  73. Morrison VA. Chronic leukemias. CA Cancer J Clin 1994 Nov–Dec; 44: 353–77

    Article  PubMed  CAS  Google Scholar 

  74. Montserrat E, Rozman C. Chronic lymphocytic leukemia: present status. Ann Oncol 1995 Mar; 6: 219–35

    PubMed  CAS  Google Scholar 

  75. The French Cooperative Group on Chronic Lymphocytic Leukaemia. Prognostic and therapeutic advances in CLL management: the experience of the French Cooperative Group. Semin Hematol 1987; 24: 275–90

    Google Scholar 

  76. Brugiatelli M, Jaksic B, Planinc-Peraica A, et al. Treatment of chronic lymphocytic leukemia in early and stable phase of the disease: long-term results of a randomized trial. Eur J Haematol 1995 Sep; 55: 158–63

    Article  PubMed  CAS  Google Scholar 

  77. French Cooperative Group on Chronic Lymphocytic Leukemia. Effects of chlorambucil and therapeutic decision in initial forms of chronic lymphocytic leukemia (stage A): results of a randomized clinical trial on 612 patients. Blood 1990; 75: 1414–21

    Google Scholar 

  78. Cheson BD, Bennett JM, Rai KR, et al. Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored working group. Am J Hematol 1988 Nov; 29: 152–63

    Article  PubMed  CAS  Google Scholar 

  79. Richardson DS, Johnson SA, Hopkins JA, et al. Absence of minimal residual disease detectable by FACS, Southern blot or PCR in patients with chronic lymphocytic leukaemia treated with fludarabine. Acta Oncol 1994; 33(6): 627–30

    Article  PubMed  CAS  Google Scholar 

  80. Maloum K, Magnac C, Sutton L, et al. Minimal residual disease assessment in chronic lymphocytic leukemia [abstract no. 297]. Blood 1996; 88 Suppl. 1: 772

    Google Scholar 

  81. Esteve J, Villamor N, Colomer D, et al. Fludarabine-induced molecular remissions in patients with previously treated chronic lymphoproliferative disorders [abstract no. 3021. Blood 1996; 88 Suppl. 1 (Pt 1): 78a

    Google Scholar 

  82. Angelopoulou MA, Poziopoulos C, Boussiotis VA, et al. Fludarabine monophosphate in refractory B-chronic lymphocytic leukemia: maintenance may be significant to sustain response. Leuk Lymphoma 1996; 21(3–4): 321–4

    PubMed  CAS  Google Scholar 

  83. De Rossi G, Mauro FR, Caruso R, et al. Fludarabine and prednisone in pretreated and refractory B-chronic lymphocytic leukemia (B-CLL) in advanced stages. Haematologica 1993 May–Jun;78: 167–71

    PubMed  Google Scholar 

  84. Fenchel K, Bergmann L, Wijermans P, et al. Clinical experience with fludarabine and its immunosuppressive effects in pretreated chronic lymphocytic leukemias and low-grade lymphomas. Leuk Lymphoma 1995 Aug; 18: 485–92

    Article  PubMed  CAS  Google Scholar 

  85. Gillis S, Dann EJ, Cass Y, et al. Activity of fludarabine in refractory chronic lymphocytic leukemia and low grade non-Hodgkin’s lymphoma- the Jerusalem experience. Leuk Lymphoma 1994 Sep; 15: 173–5

    Article  PubMed  CAS  Google Scholar 

  86. Gjedde SB, Hansen MM. Salvage therapy with fludarabine in patients with progressive B-chronic lymphocytic leukemia. Leuk Lymphoma 1996; 21(3–4): 317–20

    PubMed  CAS  Google Scholar 

  87. Grever MR, Kopecky KJ, Coltamn CA, et al. Fludarabine monophosphate: a potentially useful agent in chronic lymphocytic leukemia. Nouv Rev Fr Hematol 1988; 30: 457–9

    PubMed  CAS  Google Scholar 

  88. Hensel M, Fischer K, Haas R, et al. Fludarabine phosphate in the treatment of advanced stage chronic lymphocytic leukemia [abstract no. 190]. Ann Hematol 1993; 67 Suppl: A49

    Article  Google Scholar 

  89. Herrero M, Cabrera JR, Briz M, et al. Treatment of refractory chronic lymphocytic leukaemia with fludarabine [in Spanish]. Sangre 1995 Apr; 40: 115–9

    PubMed  CAS  Google Scholar 

  90. Hiddemann W, Rottmann R, Wörmann B, et al. Treatment of advanced chronic lymphocytic leukemia by fludarabine: results of a clinical phase-II study. Ann Hematol 1991 Jul; 63: 1–4

    Article  PubMed  CAS  Google Scholar 

  91. Hocepied AMLJ, Falkson CI, Falkson G. A phase II trial of fludarabine in patients with previously treated chronic lymphocytic leukaemia. S Afr Med J 1996 May; 86: 549–440

    PubMed  CAS  Google Scholar 

  92. Johnson SA, Hiddeman W, Coiffier B, et al. Fludarabine in the treatment of chronic lymphocytic leukaemia [abstract]. Ann Oncol 1994; 5 Suppl. 5: 141

    Google Scholar 

  93. Kemena A, O’Brien S, Kantarjian H, et al. Phase II clinical trial of fludarabine in chronic lymphocytic leukemia on a weekly low-dose schedule. Leuk Lymphoma 1993 Jun; 10: 187–93

    Article  PubMed  CAS  Google Scholar 

  94. Montillo M, Tedeschi A, Delfini C, et al. Effectiveness of fludarabine in advanced B-cell chronic lymphocytic leukemia. Tumori 1995 Nov–Dec; 81: 419–23

    PubMed  CAS  Google Scholar 

  95. Montserrat E, Lopez-Lorenzo JL, Manso F, et al. Fludarabine in resistant or relapsing B-cell chronic lymphocytic leukemia: the Spanish Group experience. Leuk Lymphoma 1996 May; 21: 467–72

    Article  PubMed  CAS  Google Scholar 

  96. O’Brien S, Kantarjian H, Beran M, et al. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood 1993 Sep 15; 82: 1695–700

    PubMed  Google Scholar 

  97. O’Brien MER, Matutes E, Cunningham D, et al. Fludarabine in lymphoproliferative disorders: the Royal Marsden Hospital experience. Leuk Lymphoma 1994; 14 Suppl. 2: 17–23

    Article  PubMed  Google Scholar 

  98. Puccio CA, Mitterlman A, Lichtman SM, et al. A loading dose/continuous infusion schedule of fludarabine phosphate in chronic lymphocytic leukemia. J Clin Oncol 1991 Sep; 9(9): 1562–9

    PubMed  CAS  Google Scholar 

  99. Robertson LE, O’Brien S, Kantarjian H, et al. A 3-day schedule of fludarabine in previously treated chronic lymphocytic leukemia. Leukemia 1995 Sep; 9: 1444–9

    PubMed  CAS  Google Scholar 

  100. Sorensen JM, Vena DA, Fallavollita A, et al. Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the Group C protocol mechanism of the National Cancer Institute: five-year follow-up report. J Clin Oncol 1997 Feb; 15: 458–65

    PubMed  CAS  Google Scholar 

  101. Whelan JS, Davis CL, Rule S, et al. Fludarabine phosphate for the treatment of low grade lymphoid malignancy. Br J Cancer 1991; 64: 120–3

    Article  PubMed  CAS  Google Scholar 

  102. Wijermans PW, Gerrits WBJ, Haak HL. Severe immunodeficiency in patients treated with fludarabine monophosphate. Eur J Haematol 1993 May; 50: 292–6

    Article  PubMed  CAS  Google Scholar 

  103. Zinzani PL, Lauria F, Rondelli D, et al. Fludarabine in patients with advanced and/or resistant B-chronic lymphocytic leukemia. Eur J Haematol 1993 Aug; 51: 93–7

    Article  PubMed  CAS  Google Scholar 

  104. Keating M, Lerner S, O’Brien S, et al. Long term follow-up of patients with chronic lymphocytic leukemia receiving fludarabine regimens as initial therapy [abstract]. Proc Am Soc Clin Oncol 1995 Mar; 14: 337

    Google Scholar 

  105. Keating MJ, O’Brien S, Kantarjian H, et al. Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent. Blood 1993 Jun 1; 81: 2878–84

    PubMed  CAS  Google Scholar 

  106. Keating MJ, Kantarjian H, Talpaz M, et al. Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood 1989 Jul; 74(1): 19–25

    PubMed  CAS  Google Scholar 

  107. The French Cooperative Group on CLL, Johnson S, Smith AG, et al. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. Lancet 1996; 347: 1432–8

    PubMed  CAS  Google Scholar 

  108. Leporrier M, Chevret S, French Cooperative Group on CLL. Randomized comparison of fludarabine, CAP and CHOP in 493 previously untreated stage B and C chronic lymphocytic leukemia (CLL) [abstract]. Can J Infect Dis 1995 Jul; 6 Suppl. C: 258C

    Google Scholar 

  109. Rai KR, Peterson B, Elias L, et al. A randomized comparison of fludarabine and chorambucil for patients with previously untreated chronic lymphocytic leukemia. A CALGB, SWOG, CTG/NCI-C and ECOG inter-group study [abstract no. 552]. Blood 1996; 88 Suppl. 1 (Pt 1): 141a

    Google Scholar 

  110. Jaksic B, Delmer A, Brugiatelli M, et al. Fludarabine vs high dose continuous chlorambucil: interim analysis of a randomised phase II study in untreated B-cell chronic lymphocytic leukemia (B-CLL) [abstract no. 2342. Blood 1996; 88 Suppl. 1 (Pt 1): 588a

    Google Scholar 

  111. Robertson LE, O’Brien S, Kantarjian H, et al. Fludarabine plus doxorubicin in previously treated chronic lymphocytic leukemia. Leukemia 1995 Jun; 9: 943–5

    PubMed  CAS  Google Scholar 

  112. Rummel M, Lengfelder E, Renner C, et al. Fludarabine and epirubicin in the treatment of CLL as first line therapy or first relapse-results of a phase II study [abstract no. 2343]. Blood 1996; 88 Suppl. 1 (Pt l): 589a

    Google Scholar 

  113. O’Brien S, Kantarjian H, Beran M, et al. Fludarabine (FAMP) and mitoxantrone therapy in chronic lymphocytic leukemia (CLL) [abstract no. 2341]. Blood 1996; 88 Suppl. 1 (Pt 1): 588a

    Google Scholar 

  114. Rai KR, Peterson B, Kolitz J, et al. Fludarabine induces a high complete remission rate in previously untreated patients with active chronic lymphocytic leukemia (CLL). A randomized inter-group study [abstract]. Blood 1995 Nov 15; 86 Suppl. 1: 607a

    Google Scholar 

  115. Weiss M, Spiess T, Berman E, et al. Concomitant administration of chlorambucil limits dose intensity of fludarabine in previously treated patients with chronic lymphocytic leukemia. Leukemia 1994 Aug; 8: 1290–3

    PubMed  CAS  Google Scholar 

  116. Elias L, Stock-Novack D, Head DR, et al. A phase I trial of combination fludarabine monophosphate and chlorambucil in chronic lymphocytic leukemia: a Southwest Oncology Group study. Leukemia 1993 Mar; 7: 361–5

    PubMed  CAS  Google Scholar 

  117. Gandhi V, Robertson LE, Keating MJ, et al. Combination of fludarabine and arabinosylcytosine for treatment of chronic lymphocytic leukemia: clinical efficacy and modulation of arabinosylcytosine pharmacology. Cancer Chemother Pharmacol 1994 Apr; 34: 30–6

    Article  PubMed  CAS  Google Scholar 

  118. Giles FJ, O’Brien S, Kantarjian HM, et al. Sequential cis-platinum, fludarabine, and arabinosyl cytosine (PFA) in patients with prior fludarabine therapy for chronic lymphocytic leukemia (CLL): a phase II study [abstract no. 3605]. Blood 1996; 88 Suppl. 1 (Pt 1): 219b

    Google Scholar 

  119. Giles FJ, O’Brien S, Kantarjian HM, et al. Sequential cis-platinum, fludarabine, and arabinosyl cytosine (PFA) or cyclophosphamide, fludarabine and arabinosyl cytosine (CFA) in patients with Richter’s syndrome (RS): a pilot study [abstract no. 360]. Blood 1996; 88 Suppl. 1 (Pt 1): 93a

    Google Scholar 

  120. Kantarjian HM, Childs C, O’Brien S, et al. Efficacy of fludarabine, a new adenine nucleoside analogue, in patients with prolymphocytic leukemia and the prolymphocytoid variant of chronic lymphocytic leukemia. Am J Med 1991; 90: 223–8

    PubMed  CAS  Google Scholar 

  121. Marlton P, McCarthy C, Taylor K. Fludarabine-induced cycogenetic remission in prolymphocytic leukemia [letter]. Am J Hematol 1992; 40: 71–2

    Article  PubMed  CAS  Google Scholar 

  122. Smith OP, Mehta AB. Fludarabine monophosphate for prolymphocytic leukaemia [letter]. Lancet 1990 Sep 29; 336: 820

    Article  PubMed  CAS  Google Scholar 

  123. Sporn JR. Sustained response of refractory prolymphocytic leukemia to fludarabine. Acta Haematol 1991; 85(4): 209–11

    Article  PubMed  CAS  Google Scholar 

  124. Doorduijn JK, Michiels JJ. Effectiveness of fludarabine in end-stage prolymphocytic leukemia. Leukemia 1994 Aug; 8: 1439

    PubMed  CAS  Google Scholar 

  125. Zinzani PL, Tabanelli M, Bendandi M, et al. Prolonged bone marrow aplasia of refractory prolymphocytoid variant of B-cell chronic lymphocytic leukemia related to fludarabine treatment. Eur J Haematol 1994 Jul; 53: 56–8

    Article  PubMed  CAS  Google Scholar 

  126. Witzig TE, Weitz JJ, Lundberg JH, et al. Treatment of refractory T-cell chronic lymphocytic leukemia with purine nucleoside analogues. Leuk Lymphoma 1994 Jun; 14: 137–9

    Article  PubMed  CAS  Google Scholar 

  127. Keating MJ, Estey E, Kantarjian H. Acute Leukemia. Cancer: principles and practice of oncology. 4th ed. Philadelphia: JB Lipincott Co, 1993

    Google Scholar 

  128. Keating MJ, Estey E, O’Brien S, et al. Clinical experience with fludarabine in leukaemia. Drugs 1994; 47 Suppl. 6: 39–49

    Article  PubMed  Google Scholar 

  129. Warrell Jr RP, Berman E. Phase I and II study of fludarabine phosphate in leukemia: therapeutic efficacy with delayed central nervous system toxicity. J Clin Oncol 1986 Jan; 4(1): 74–9

    PubMed  Google Scholar 

  130. Gandhi V, Estey E, Keating MJ, et al. Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol 1993 Jan; 11: 116–24

    PubMed  CAS  Google Scholar 

  131. Gandhi V, Keating MJ, Estey E, et al. Minimum dose of fludarabine (FL) to modulate metabolism of arabinosylcytosine (ara-C) in leukemia blasts during therapy [abstract]. Aust NZ J Med 1996 Apr; 26: 330

    Google Scholar 

  132. Clavio M, Carrara P, Miglino M, et al. High efficacy of fludarabine-containing therapy (FLAG-FLANG) in poor risk acute myeloid leukemia. Haematologica 1996; 81: 513–20

    PubMed  CAS  Google Scholar 

  133. Estey E, Plunkett W, Gandhi V, et al. Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia. Leuk Lymphoma 1993 Mar; 9: 343–50

    Article  PubMed  CAS  Google Scholar 

  134. Estey EH, Kantarjian HM, O’Brien S, et al. High remission rate, short remission duration in patients with refractory anemia with excess blasts (RAEB) in transformation (RAEB-t) given acute myelogenous leukemia (AML)-type chemotherapy in combination with granulocyte-CSF (G-CSF). Cytokine Mol Ther 1995 Mar; 1: 21–8

    CAS  Google Scholar 

  135. Fleischhack G, Graf N, Hasan C, et al. IDA-FLAG (idarubicin, fludarabine, high-dose cytarabine, granulocyte colony-stimulating factor)-an effective regimen in relapsed acute myelogenous leukemia in childhood [in German]. Klin Padiatr 1996; 208: 229–35

    Article  PubMed  CAS  Google Scholar 

  136. Parker JE, Cullis JO, Mijovic A, et al. Idarubicin, fludarabine, cytarabine and G-CSF (FLAG-IDA) for the treatment of high risk myeloid malignancies [abstract no. 1803]. Blood 1996; 88 Suppl. 1 (Pt l): 454a

    Google Scholar 

  137. Steinmetz HT, Staib P, Glasmacher A, et al. Phase II study of idarubicine, fludarabine, ARA-C, and G-CSF (IDA-Flag) for treatment of refractory, relapsed or secondary acute myeloid leukemia [abstract no. 821]. Br J Haematol 1996; 93 Suppl. 2: 219

    Google Scholar 

  138. Taylor K, Seely G, Jones A, et al. Fludarabine/Ara-C in poor risk acute myeloid leukaemia/myelodysplastic syndrome (MDS) [abstract]. Aust NZ J Med 1995 Feb; 25: 104

    Google Scholar 

  139. Visani G, Tosi P, Zinzani PL, et al. FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of ‘poor risk’ acute myeloid leukemias. Leukemia 1994 Nov; 8: 1842–6

    PubMed  CAS  Google Scholar 

  140. Wiersma S, Abonour R, Williams EC, et al. Fludarabine/cytosine arabinoside for poor prognosis adult AML [abstract]. Proc Am Soc Clin Oncol 1994 Mar; 13: 310

    Google Scholar 

  141. Montillo M, Tedeschi A, Discepoli G, et al. Fludarabine and cytosyne arabinoside + G-CSF in the treatment of relapsed acute lymphoblastic leukemia: preliminary results [abstract]. Blood 1994 Nov 15; 84 Suppl. 1: 622a

    Google Scholar 

  142. Suki S, Kantarjian H, Gandhi V, et al. Fludarabine and cytosine arabinoside in the treatment of refractory or relapsed acute lymphocytic leukemia. Cancer 1993 Oct 1; 72: 2155–60

    Article  PubMed  CAS  Google Scholar 

  143. Visani G, Tosi P, Zinzani PL, et al. FLAG (Fludarabine, Cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression: in vitro and in vivo effects. Eur J Haematol 1996 May; 56: 308–12

    Article  PubMed  CAS  Google Scholar 

  144. Sato JK, Wiersma S, Krailo M, et al. Phase I clinical and pharmacodynamic study of continuous infusion (CI) fludarabine followed by continuous infusion (CI) cytosine arabinoside (ara-C) in relapsed leukemia [abstract no. 1266]. Proc Am Assoc Cancer Res 1992; 33: 211

    Google Scholar 

  145. Gandhi V, Estey E, Du M, et al. Modulation of the cellular metabolism of cytarabine and fludarabine by granulocyte-colony-stimulating factor during therapy of acute myelogenous leukemia. Clin Cancer Res 1995 Feb; 1: 169–78

    PubMed  CAS  Google Scholar 

  146. Estey E, Thall P, Andreeff M, et al. Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor. J Clin Oncol 1994 Apr; 12: 671–8

    PubMed  CAS  Google Scholar 

  147. Glasmacher A, Steinmetz HT, Kleinschmidt R, et al. Treatment of chronic myeloid leukaemia blast crisis with fludarabine, cytarabine, filgrastim (G-CSF) and idarubicin (FLAG-IDA) [abstract no. 489]. Onkologie 1995 Oct; 18 Suppl. 2: 144

    Google Scholar 

  148. Martinelli G, Testoni N, Zuffa E, et al. FLANG (fludarabine + cytosine arabinoside + novantrone + G-CSF) induces partial remission in lymphoid blast transformation of Ph+ chronic myelogenous leukaemia. Leuk Lymphoma 1996 Jun; 22: 173–6

    Article  PubMed  CAS  Google Scholar 

  149. Visani G, Tosi P, Zinzani PL, et al. FLAG (fludarabine + cytosine arabinoside + G-CSF) induces complete remission in acute-phase chronic myeloid leukaemia: a case report. Br J Haematol 1994 Feb; 86: 394–6

    Article  PubMed  CAS  Google Scholar 

  150. Hiddemann W, Pott-Hoeck C. Fludarabine in the management of malignant lymphomas. Drugs 1994; 47 Suppl. 6: 50–6

    Article  PubMed  Google Scholar 

  151. Engert A. Current and future strategies for advanced low-grade non-Hodgkin’s lymphoma. Res Clin Forum 1996; 18(3): 21–7

    Google Scholar 

  152. Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Engl J Med 1984; 311: 1471–5

    Article  PubMed  CAS  Google Scholar 

  153. Leonard RCF, Winfield DA, Hancock BW. The palliative treatment of haematological cancers. J Cancer Care 1995 Jan; 4: 23–30

    Google Scholar 

  154. Falkson CI. Fludarabine: a phase II trial in patients with previously treated low-grade lymphoma. Am J Clin Oncol 1996 Jun; 19: 268–70

    Article  PubMed  CAS  Google Scholar 

  155. Hiddemann W, Unterhalt M, Pott C, et al. Fludarabine single-agent therapy for relapsed low-grade non-Hodgkin’s lymphomas: a phase II study of the German Low-Grade Non-Hodgkin’s Lymphoma Study Group. Semin Oncol 1993 Oct; 20 Suppl. 7: 28–31

    PubMed  CAS  Google Scholar 

  156. Hochster HS, Kim K, Green MD, et al. Activity of fludarabine in previously treated non-Hodgkin’s low-grade lymphoma: results of an Eastern Cooperative Oncology Group Study. J Clin Oncol 1992 Jan; 10(1): 28–32

    PubMed  CAS  Google Scholar 

  157. Leiby JM, Snider KM, Kraut EH, et al. Phase II trial of 9-β-D-arabinofuranosyl-2-fluoroadenine 5′-monophosphate in non-Hodgkin’s lymphoma: prospective comparison of response with deoxycytidine kinase activity. Cancer Res 1987 May 15; 47: 2719–22

    PubMed  CAS  Google Scholar 

  158. Moskowitz C, Offit K, Straus D, et al. Fludarabine in stage IV low grade non Hodgkin’s lymphoma (LGL): the Memorial hospital experience [abstract]. Proc Am Soc Clin Oncol 1994 Mar; 13: 379

    Google Scholar 

  159. Pigaditou A, Rohatiner AZS, Whelan JS, et al. Fludarabine in low-grade lymphoma. Semin Oncol 1993 Oct; 20 Suppl. 7: 24–7

    PubMed  CAS  Google Scholar 

  160. Pott C, Unterhalt M, Sandford D, et al. Fludarabine in combination with mitoxantrone and dexamethasone in relapsed and refractory low-grade non-Hodgkin’s lymphoma [abstract]. Onkologie 1994 Oct; 17 Suppl. 2: 114

    Article  Google Scholar 

  161. Redman JR, Cabanillas F, Velasquez WS, et al. Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma. J Clin Oncol 1992 May; 10(5): 790–4

    PubMed  CAS  Google Scholar 

  162. Solal-Céligny P, Brice P, Brousse N, et al. Phase II trial of fludarabine monophosphate as first-line treatment in patients with advanced follicular lymphoma: a multicenter study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 1996 Feb; 14: 514–9

    PubMed  Google Scholar 

  163. Whelan JS, Ganjoo R, Johnson PWM, et al. Treatment of low grade non-Hodgkin’s lymphomas with fludarabine. Leuk Lymphoma 1993; 10 Suppl.: 35–7

    Article  PubMed  Google Scholar 

  164. Zinzani PL, Lauria F, Rondelli D, et al. Fludarabine: an active agent in the treatment of previously-treated and untreated low-grade non-Hodgkin’s lymphoma. Ann Oncol 1993 Aug; 4: 575–8

    PubMed  CAS  Google Scholar 

  165. Chun HG, Ahmed T, Mittelman A, et al. Phase I trial of fludarabine monophosphate plus alpha-interferon in refractory low-grade non-Hodgkin’s lymphoma [abstract]. Blood 1995 Nov 15; 86 Suppl. 1: 810

    Google Scholar 

  166. Hochster H, Oken M, Bennett J, et al. Efficacy of cyclophosphamide (CYC) and fludarabine (FAMP) as first line therapy of low-grade non-Hodgkin’s lymphoma (NHL) — ECOG 1491 [abstract]. Blood 1994 Nov 15; 84 Suppl. 1: 383

    Google Scholar 

  167. McLaughlin P, Hagemeister FB, Romaguera JE, et al. Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol 1996 Apr; 14: 1262–8

    PubMed  CAS  Google Scholar 

  168. Tedeschi A, Montillo M, Capelli D, et al. Phase I study of the combination of fludarabine, idarubicin and dexamethasone in low-grade lymphoma [abstract no. 3505]. Blood 1996; 88 Suppl. 1 (Pt 2): 195b

    Google Scholar 

  169. Zinzani PL, Bendandi M, Tura S. FMP regimen (fludarabine, mitoxantrone, prednisone) as therapy in recurrent low-grade non-Hodgkin’s lymphoma. Eur J Haematol 1995 Oct; 55: 262–6

    Article  PubMed  CAS  Google Scholar 

  170. Zinzani PL, Bendandi M, Gherlinzoni F, et al. FLU-ID (fludarabine and idarubicin) regimen as salvage therapy in pretreated low-grade non-Hodgkin’s lymphoma. Haematologica 1996 Mar–Apr; 81: 168–71

    PubMed  CAS  Google Scholar 

  171. Jain V, Ogden J, Cooper B, et al. Achievement of molecular complete remissions in patients with bulky follicular lymphomas using alternating cycles of fludarabine, mitoxantrone, dexamethasone (FND) with chop chemotherapy [abstract no. 1798]. Blood 1996; 88 Suppl. 1 (Pt 1): 452a

    Google Scholar 

  172. Child JA, Johnson SAN, Smith GM, et al. Fludarabine-enhanced, dexamethasone, cytosine and cisplatinum for recurrent/refractory aggressive non-Hodgkin’s lymphoma (NHL)-the FluDAP regimen [abstract no. 2267]. Blood 1996; 88 Suppl. 1 (Pt l): 570a

    Google Scholar 

  173. McLaughlin P, Cabanillas F, Younes A, et al. Stage IV low grade lymphoma (LGL): randomized trial of two innovative regimens with monitoring of BCL-2 by PCR [abstract no. l09]. Ann Oncol 1996; 7 Suppl. 3: 34

    Google Scholar 

  174. Seymour JF, Grigg A, Szer J, et al. Fludarabine, cisplatin and Ara-C in patients with anthracycline-refractory intermediate-grade (IG) and high grade (HG) non-Hodgkin’s lymphoma: the International Oncology Study Group (IOSG) NHL2 Study [abstract no. 506]. Int J Hematol 1996; 64 Suppl. 1: S131

    Google Scholar 

  175. Bunn Jr PA, Hoffmann SJ, Golitz LE, et al. Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sezary syndrome). Ann Intern Med 1994; 121(8): 592–602

    PubMed  Google Scholar 

  176. Von Hoff DD, Dahlberg S, Hartstock RJ, et al. Activity of fludarabine monophosphate in patients with advanced mycosis fungoides: a Southwest Oncology Group Study. J Natl Cancer Inst 1990 Aug 15; 82(16): 1353–5

    Article  Google Scholar 

  177. Foss FM, Ihde DC, Linnoila IR, et al. Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 1994 Oct; 12: 2051–9

    PubMed  CAS  Google Scholar 

  178. Nikko AP, Rutherford CJ, Pandya AG. Successful treatment of Sézary syndrome with lymphomatous transformation to large cell lymphoma with fludarabine phosphate. Arch Dermatol 1996 Aug; 132: 978–9

    Article  PubMed  CAS  Google Scholar 

  179. O’Brien S, Kantarjian H, Keating MJ. Purine analogs in chronic lymphocytic leukemia and Waldenström’s macroglobulinemia. Ann Oncol 1996; 7 Suppl. 6: S27–33

    Article  PubMed  Google Scholar 

  180. Fenchel K, Wijermans P, Mitrou PS, et al. Fludarabine is an effective agent in immunocytic lymphoma. Onkologie 1994 Oct; 17: 508–13

    Article  Google Scholar 

  181. Zinzani PL, Gherlinzoni F, Bendandi M, et al. Fludarabine treatment in resistant Waldenstrom’s macroglobulinemia. Eur J Haematol 1995 Feb; 54: 120–3

    Article  PubMed  CAS  Google Scholar 

  182. Dimopoulos MA, O’Brien S, Kantarjian H, et al. Fludarabine therapy in Waldenström’s macroglobulinemia. Am J Med 1993 Jul; 95: 49–52

    Article  PubMed  CAS  Google Scholar 

  183. Kantarjian HM, Alexanian R, Koller CA, et al. Fludarabine therapy in macroglobulinemic lymphoma. Blood 1990 May; 75(10): 1929–31

    Google Scholar 

  184. Clavio M, Carrara P, Spriano M, et al. Fludarabine therapy in immunocytoma and other low-grade non-Hodgkins lymphomas. J Exp Clin Cancer Res 1994 Sep; 13: 257–63

    Google Scholar 

  185. Grubb H, Rule S, Johnson S. Treatment of Waldenstrom’s macroglobulinaemia with fludarabine: results in 7 patients with long term follow up [abstract]. Br J Haematol 1996 Apr; 93 Suppl. 1: 72

    Google Scholar 

  186. Groupe Coopératif Macroglobulinémie, Binet JL. Activity of fludarabine (FAMP) in heavily previously treated Waldenstrom’s macroglobulinemia (WM): a report of 74 cases [abstract no. 1914]. Blood 1996; 88 Suppl. 1 (Pt 1): 481a

    Google Scholar 

  187. Tiong Ong S, Koeppen H, Larson RA. Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia with fludarabine. Blood 1996 Sep 15; 88(6): 2354–65

    Google Scholar 

  188. Agrawal S, Abboudi Z, Matutes E, et al. First report of fludarabine in gamma-heavy chain disease. Br J Haematol 1994 Nov; 88: 653–5

    Article  PubMed  CAS  Google Scholar 

  189. Enzenauer RJ, Judson PH. Type II mixed cryoglobulinemia treated with fludarabine. J Rheumatol 1996 Apr; 23: 794–5

    PubMed  CAS  Google Scholar 

  190. Zaja F. Fludarabine in the treatment of essential mixed cryoglobulinaemia [letter]. Eur J Haematol 1996; 57: 259–60

    PubMed  CAS  Google Scholar 

  191. Paolini R, Ramazzina E, Zennaro R, et al. Remission of leukaemic meningitis after fludarabine. Lancet 1995 Oct 7; 346: 972

    Article  PubMed  CAS  Google Scholar 

  192. Björkholm M, Ösby E. Fludarabine and plasma cell leukemia. [letter]. Eur J Haematol 1995 May; 54: 334–5

    Article  PubMed  Google Scholar 

  193. Kraut EH, Crowley JJ, Grever MR, et al. Phase II study of fludarabine phosphate in multiple myeloma. A Southwest Oncology Group Study. Invest New Drugs 1990; 8: 199–200

    Article  PubMed  CAS  Google Scholar 

  194. Lichtman SM, Mittelman A, Budman DR, et al. Phase II trial of fludarabine phosphate in multiple myeloma using a loading dose and continuous infusion schedule. Leuk Lymphoma 1991; 6: 61–3

    Article  Google Scholar 

  195. Kantarjian HM, Schachner J, Keating MJ. Fludarabine therapy in hairy cell leukemia. Cancer 1991; 67(5): 1291–3

    Article  PubMed  CAS  Google Scholar 

  196. Kraut EH, Chun HG. Fludarabine phosphate in refractory hairy cell leukemia. Am J Hematol 1991; 37: 59–60

    Article  PubMed  CAS  Google Scholar 

  197. Giralt S, Estey E, van Besien K, et al. Induction of graft-versusleukemia without myeloablative therapy using allogeneic PBSC after purine analog containing regimens [abstract no. 2444]. Blood 1996; 88 Suppl. 1 (Pt 1): 614a

    Google Scholar 

  198. Slavin S, Nagler A, Naparstek E, et al. Immunotherapy of leukaemia in conjunction with non-myeloablative conditioning: engraftment of blood stem cells and eradication of host leukaemia with non-myeloablative conditioning based on fludarabine and anti-thymocyte globulin (ATG) [abstract no. 2443]. Blood 1996; 88 Suppl. 1 (Pt 1): 614a

    Google Scholar 

  199. Khouri I, Keating MJ, Przepiorka D, et al. Engraftment and induction of GVL with fludarabine (FAMP)-based non-ablative preparative regimen in patients with chronic lymphocytic leukemia (CLL) and lymphoma [abstract no. 1194]. Blood 1996; 88 Suppl. 1 (Pt 1): 301a

    Google Scholar 

  200. Terenzi A, Aversa F, Perruccio K, et al. Efficacy of fludarabine as immunosuppressor for bone marrow transplantation conditioning [abstract no. 2373]. Blood 1996; 88 Suppl. 1 (Pt 1): 596a

    Google Scholar 

  201. Meloni G, Mauro F, Guglielmi C, et al. Peripheral blood stem cell transplantation in CLL patients in remission after fludarabine therapy. A feasibility study [abstract]. Bone Marrow Transplant 1996 Mar; 17 Suppl. 1: S105

    Google Scholar 

  202. Bastion Y, Felman P, Dumontet C, et al. Intensive radio-chemotherapy with peripheral blood stem cell transplantation in young patients with chronic lymphocytic leukemia. Bone Marrow Transplant 1992 Nov; 10: 467–8

    PubMed  CAS  Google Scholar 

  203. Rabinowe SN, Soiffer RJ, Gribben JG, et al. Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia. Blood 1993 Aug 15; 82: 1366–76

    PubMed  CAS  Google Scholar 

  204. Khouri I, Keating MJ, Przepiorka D, et al. Stem cell transplantation (SCT) for chronic lymphocytic leukaemia (CLL): graftversus-leukemia (GVL) without acute graft-versus-host-disease (GVHD) [abstract no. 1814]. Blood 1995; 86 Suppl. 1: 457a

    Google Scholar 

  205. Michallet M, Archimbaud E, Juliusson G, et al. Autologous transplants in chronic lymphocytic leukemia: report of 18 cases [abstract no. 69]. Bone Marrow Transplant 1995; 15 Suppl. 2: S11

    Google Scholar 

  206. Kantarjian HM, Talpaz M, Hester J, et al. Collection of peripheral-blood diploid cells from chronic myelogenous leukemia patients early in the recovery phase from myelosuppression induced by intensive-dose chemotherapy. J Clin Oncol 1995 Mar; 13: 553–9

    PubMed  CAS  Google Scholar 

  207. Pott-Hoeck C, Hiddemann W. Purine analogs in the treatment of low-grade lymphomas and chronic lymphocytic leukemias. Ann Oncol 1995 May; 6: 421–33

    PubMed  CAS  Google Scholar 

  208. Leporrier M, Reman O, Troussard X. Pure red-cell aplasia with fludarabine for chronic lymphocytic leukaemia. Lancet 1993 Aug 28; 342: 555

    Article  PubMed  CAS  Google Scholar 

  209. Aboulafia DM, Demirer T. Fatal bone marrow necrosis following fludarabine administration in a patient with indolent lymphoma. Leuk Lymphoma 1995 Sep; 19: 181–4

    Article  PubMed  CAS  Google Scholar 

  210. Leenders A, Sonneveld P, de Marie S. Cryptococcal meningitis following fludarabine treatment for chronic lymphocytic leukemia. Eur J Clin Microbiol Infect Dis 1995 Sep; 14: 826–8

    Article  PubMed  CAS  Google Scholar 

  211. Muron T, Sebban C, Assouline D, et al. Infectious complications are frequent after treatment with fludarabine for CLL [abstract]. Br J Haematol 1994; 87 Suppl. 1: 173

    Google Scholar 

  212. Byrd JC, Hargis JB, Kester KE, et al. Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis. Am J Hematol 1995 Jun; 49: 135–42

    Article  PubMed  CAS  Google Scholar 

  213. Girmenia C, Mauro FR, Rahimi S. Late listeriosis after fludarabine plus prednisone treatment. Br J Haematol 1994 Jun; 87: 407–8

    Article  PubMed  CAS  Google Scholar 

  214. Cleveland KO, Gelfand MS. Listerial brain abscess in a patient with chronic lymphocytic leukemia treated with fludarabine. Clin Infect Dis 1993 Oct; 17: 816–7

    Article  PubMed  CAS  Google Scholar 

  215. Reis Borges R, Zylerait D, Broquie G, et al. Pneumocystosis, herpetic keratitis, cryptococcal meningitis in an HIV negative patient with lymphocytic leukemia and treated with fludarabin [in French]. Rev Med Interne 1992 Dec; 13(7) Suppl.: S463

    Article  Google Scholar 

  216. Sanders C, Perez EA, Lawrence HJ. Opportunistic infections in patients with chronic lymphocytic leukemia following treatment with fludarabine [letter]. Am J Hematol 1992; 39: 314–5

    Article  PubMed  CAS  Google Scholar 

  217. Anaissie E, Kontoyiannis DP, Kantarjian H, et al. Listeriosis in patients with chronic lymphocytic leukemia who were treated with fludarabine and prednisone. Ann Intern Med 1992; 117: 466–9

    PubMed  CAS  Google Scholar 

  218. Busuttil DP, Chasty RC, Copplestone JA, et al. Infections complicating treatment of lymphoid malignancies with fludarabine [abstract]. Br J Haematol 1996 Apr; 93 Suppl. 1: 69

    Article  Google Scholar 

  219. O’Brien S, Kantarjian H, Beran M, et al. The use of granulocyte colony stimulating factor (G-CSF) with fludarabine reduces the incidences of myelosuppression and pneumonia in high risk patients with chronic lymphocytic leukaemia [abstract no. 2340]. Blood 1996; 88 Suppl. 1 (Pt 1): 588a

    Google Scholar 

  220. Cheson BD, Vena DA, Foss FM, et al. Neurotoxicity of purine analogs: a review. J Clin Oncol 1994 Oct; 12: 2216–28

    PubMed  CAS  Google Scholar 

  221. Morgan AE. Chemotherapy-induced neurotoxicity. Cancer Control 1995 May–Jun; 2: 235–42

    PubMed  Google Scholar 

  222. Chun HG, Leyland-Jones BR, Caryk SM, et al. Central nervous system toxicity of fludarabine phosphate. Cancer Treat Rep 1986 Oct; 70(10): 1225–8

    PubMed  CAS  Google Scholar 

  223. Cohen RB, Abdallah JM, Gray JR, et al. Reversible neurologic toxicity in patients treated with standard-dose fludarabine phosphate for mycosis fungoides and chronic lymphocytic leukemia. Ann Intern Med 1992; 118(2): 114–6

    Google Scholar 

  224. Johnson PWM, Fearnley J, Domizio P, et al. Neurological illness following treatment with fludarabine. Br J Cancer 1994 Nov; 70: 966–8

    Article  PubMed  CAS  Google Scholar 

  225. Zabernigg A, Maier H, Thaler J, et al. Late-onset fatal neurological toxicity of fludarabine [letter]. Lancet 1994 Dec 24–31; 344: 1780

    Article  PubMed  CAS  Google Scholar 

  226. Kornblau SM, Cortes-Franco J, Estey E. Neurotoxicity associated with fludarabine and cytosine arabinoside chemotherapy for acute leukemia and myelodysplasia. Leukemia 1993 Mar; 7: 378–83

    PubMed  CAS  Google Scholar 

  227. O’Brien RK, Sparling TG. Gentamicin and fludarabine ototoxicity. Ann Pharmacother 1995 Feb; 29: 200–1

    PubMed  Google Scholar 

  228. Di Raimondo F, Giustolisi R, Cacciola E, et al. Autoimmune hemolytic anemia in chronic lymphocytic leukemia patients treated with fludarabine [see comments]. Leuk Lymphoma 1993 Sep; 11: 63–8

    Article  PubMed  Google Scholar 

  229. Tosti S, Caruso R, D’Adamo F, et al. Severe autoimmune hemolytic anemia in a patient with chronic lymphocytic leukemia responsive to fludarabine-based treatment. Ann Hematol 1992 Nov; 65: 238–9

    Article  PubMed  CAS  Google Scholar 

  230. Bastion Y, Coiffier C, Dumontet D, et al. Severe autoimmune hemolytic anemia in two patients treated with fludarabine for chronic lymphocytic leukemia. Ann Oncol 1992; 3: 171–3

    PubMed  CAS  Google Scholar 

  231. Myint H, Copplestone JA, Orchard J, et al. Fludarabine-related autoimmune haemolytic anaemia in patients with chronic lymphocytic leukaemia. Br J Haematol 1995 Oct; 91: 341–4

    Article  PubMed  CAS  Google Scholar 

  232. Byrd JC, Weiss RB, Kweeder SL, et al. Fludarabine therapy for lymphoid malignancies is associated with hemolytic anemia [abstract]. Proc Am Soc Clin Oncol 1994 Mar; 13: 304

    Google Scholar 

  233. Maclean R, Meiklejohn D, Soutar R. Fludarabine-related autoimmune haemolytic anaemia in patients with chronic lymphocytic leukaemia. Br J Haematol 1996 Mar; 92: 768–9

    PubMed  CAS  Google Scholar 

  234. Heuring A, Käbisch A, Hadam MR, et al. Effective anti-leukemic treatment with fludarabine regimens does not control autoimmune cytopenias in chronic lymphocytic leukemia patients [abstract]. Onkologie 1995 Oct; 18 Suppl. 2: 83

    Google Scholar 

  235. Flinn IW, Grever MR. Chronic lymphocytic leukemia. Cancer Treat Rev 1996 Jan; 22: 1–13

    Article  PubMed  CAS  Google Scholar 

  236. Montillo M, Tedeschi A, Leoni P. Recurrence of autoimmune thrombocytopenia after treatment with fludarabine in a patient with chronic lymphocytic leukemia. Leuk Lymphoma 1994 Sep; 15: 187–8

    Article  PubMed  CAS  Google Scholar 

  237. Bazarbachi A, Bachelez H, Dehen L, et al. Lethal paraneoplastic pemphigus following treatment of chronic lymphocytic leukaemia with fludarabine. Ann Oncol 1995 Sep; 6: 730–1

    PubMed  CAS  Google Scholar 

  238. Jaccard A, Oksenhandler E, Clauvel J-P. Cytopenia and fludarabine [letter]. Lancet 1993 Oct 23; 342: 1049–50

    Article  PubMed  CAS  Google Scholar 

  239. Montalban C, Liaño F, Aguilera A. Tumour lysis syndrome after treatment of chronic lymphocytic leukaemia with fludarabine. Postgrad Med J 1994 Sep; 70: 651–2

    Article  PubMed  CAS  Google Scholar 

  240. Mulligan SP, Dean MG. Fludarabine causing tumour lysis syndrome in chronic lymphocytic leukaemia. Aust NZ J Med 1994 Aug; 24: 406–7

    Article  CAS  Google Scholar 

  241. Montillo M, Tedeschi A, Leoni P. Acute renal failure as a consequence of urine stop flow in a patient with chronic lymphocytic leukemia after treatment with fludarabine. Am J Hematol 1995 Sep; 50: 73–4

    Article  PubMed  CAS  Google Scholar 

  242. Nakhoul F, Green J, Abassi ZA. Tumor lysis syndrome induced by fludarabine monophosphate: a case report. Eur J Haematol 1996 Apr; 56: 254–5

    Article  PubMed  CAS  Google Scholar 

  243. Crowley JJ, Knight L, Charan N. Lysis pneumonopathy associated with the use of fludarabine phosphate. West J Med 1994 Dec; 161: 597–9

    PubMed  CAS  Google Scholar 

  244. List AF, Kummet TD, Adams JD, et al. Tumor lysis syndrome complicating treatment of chronic lymphocytic leukemia with fludarabine phosphate. Am J Med 1990 Sep; 89: 388–90

    Article  PubMed  CAS  Google Scholar 

  245. Lärfars G, Udén-Blohmé A-M, Samuelsson J. Fludarabine as well as 2-chlorodeoxyadenosine, can induce eosinophilia during treatment of lymphoid malignancies. Br J Haematol 1996; 94: 709–12

    Article  PubMed  Google Scholar 

  246. Macheta MP, Parapia LA, Gouldesbrough DR. Renal failure in a patient with chronic lymphocytic leukaemia treated with fludarabine. J Clin Pathol 1995 Feb; 48: 181–2

    Article  PubMed  CAS  Google Scholar 

  247. Tisler A, Pierratos A, Lipton JH. Crescentic glomerulonephritis associated with p-ANCA positivity in fludarabine-treated chronic lymphocytic leukaemia [case report]. Nephrol Dial Transplant 1996; 11: 2306–8

    Article  PubMed  CAS  Google Scholar 

  248. Maung ZT, Wood AC, Jackson GH, et al. Transfusion-associated graft-versus-host disease in fludarabine-treated B-chronic lymphocytic leukaemia. Br J Haematol 1994 Nov; 88: 649–52

    Article  PubMed  CAS  Google Scholar 

  249. Briz M, Vilches C, Fernández MN. Transfusion-associated graft-versus-host disease (TA-GVHD) in fludarabine-treated patients: is it time to irradiate blood components? [letter: reply]. Br J Haematol 1996 Jun; 93: 740–1

    Google Scholar 

  250. Briz M, Cabrera R, Sanjuán I, et al. Diagnosis of transfusion-associated graft-versus-host disease by polymerase chain reaction in fludarabine-treated B-chronic lymphocytic leukaemia. Br J Haematol 1995 Oct; 91: 409–11

    Article  PubMed  CAS  Google Scholar 

  251. Briones J, Pereira A, Alcorta I. Transfusion-associated graft-versus-host disease (TA-GVHD) in fludarabine-treated patients: is it time to irradiate blood components? [letter]. Br J Haematol 1996 Jun; 93: 739–40

    PubMed  CAS  Google Scholar 

  252. Williamson LM, Wimperis JZ, Wood ME, et al. Fludarabine treatment and transfusion-associated graft-versus-host disease. Lancet 1996 Aug 17; 348: 472–3

    Article  PubMed  CAS  Google Scholar 

  253. Hawley D, Ness M, Balakrishnan K, et al. Graft versus host disease following fludarabine treatment and blood transfusion [abstract no. 117]. Hum Immunol 1996; 49 Suppl. 1: 101

    Google Scholar 

  254. Williamson LM, British Committee for Standards in Haematology Blood Transfusion Task Force. Guidelines on gamma irradiation of blood components for the prevention of transfusion-associated graft-versus-host disease. Transfus Med 1996; 6: 261–71

    Article  Google Scholar 

  255. Cervantes F, Salgado C, Montserrat E, et al. Fludarabine for prolymphocytic leukaemia and risk of interstitial pneumonitis [letter]. Lancet 1990 Nov 3; 336: 1130

    Article  PubMed  CAS  Google Scholar 

  256. Hurst PG, Habib MP, Garewal H, et al. Pulmonary toxicity associated with fludarabine monophosphate. Invest New Drugs 1987; 5: 207–10

    Article  PubMed  CAS  Google Scholar 

  257. Kane CG, McMichael AJ, Patrick H, et al. Pulmonary toxicity and acute respiratory failure associated with fludarabine monophosphate. Respir Med 1992; 86: 261–3

    Article  PubMed  CAS  Google Scholar 

  258. Cohn J, Fraifeld M, Desai A, et al. Hemolytic uremic syndrome and severe pulmonary toxicity associated with fludarabine treatment for non-Hodgkin’s lymphoma. Proc Am Soc Clin Oncol 1994 Mar; 13: 387

    Google Scholar 

  259. Martelli M, De Sanctis V, Avvisati G, et al. Current guidelines for the management of aggressive non-Hodgkin’s lymphoma. Drugs 1997 Jun; 53(6): 957–972

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Julie C. Adkins, David H. Peters & Anthony Markham

Authors
  1. Julie C. Adkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David H. Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anthony Markham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julie C. Adkins.

Additional information

Various sections of the manuscript reviewed by: M.K. Angelopoulou, First Department of Internal Medicine, National and Kapodistrian University of Athens School of Medicine, Laikon General Hospital, Athens, Greece; A.B. Astrow, Department of Medicine, Saint Vincent’s Hospital and Medical Center, New York, New York, USA; V. Avramis, Department of Medicine, Saint Vincent’s Hospital and Medical Center, New York, New York, USA; D. Catovsky, Academic Haematology and Cytogenetics, The Royal Marsden Hospital NHS Trust, London, England; B. Cheson, National Cancer Institute, Clinical Investigations Branch, Bethesda, Maryland, USA; S. Gillis, Department of Hematology, Hadassah Medical Center, Jerusalem, Israel; G. Juliusson, Department of Hematology, University Hospital, Linköping, Sweden; S.A. Johnson, Department of Haematology, Taunton and Somerset Hospital, Taunton, Somerset, England; M. Leporrier, Service d’Hématologie Clinique, Centre Hospitalier Universitaire, Caen, France; F.M. Muggia, Kaplan Cancer Center, New York University Medical Center, New York, New York, USA; J.F. Seymour, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adkins, J.C., Peters, D.H. & Markham, A. Fludarabine. Drugs 53, 1005–1037 (1997). https://doi.org/10.2165/00003495-199753060-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199753060-00007

Keywords

Search

Navigation