Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: A report from the non-Hodgkin's lymphoma co-operative study group

Gino Santini, Teodoro Chisesi, Sandro Nati, Adolfo Porcellini, Valerio Zoli, Vittorio Rizzoli, Simona Zupo, Gennaro Marino, Alessandra Rubagotti, Alessandro Polacco, Mauro Spriano, Renato Vimercati, Angela Marina Congiu, Jean Louis Ravetti, Savina Aversa, Marco Candela, Caterina Patti

Research output: Contribution to journalArticle

Abstract

The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL). Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36-70), received FLU/CY/MITO regimen (FLU 25 mg/m2 days 1-3, CY 300 mg/m2 days 1-3, Mito 10 mg/m2 day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87%: 46 patients achieved complete response (CR) (77%), 6 a partial response (10%) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2% and 45% respectively. Thirty-five patients (58%) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76%) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.

Original languageEnglish
Pages (from-to)1141-1147
Number of pages7
JournalLeukemia and Lymphoma
Volume45
Issue number6
DOIs
Publication statusPublished - Jun 2004

Fingerprint

Mitoxantrone
Follicular Lymphoma
Non-Hodgkin's Lymphoma
Cyclophosphamide
Agranulocytosis
Antibiotic Prophylaxis
Granulocyte Colony-Stimulating Factor
fludarabine
Bone Marrow
Polymerase Chain Reaction
Survival
Residual Neoplasm
Therapeutics
Intercellular Signaling Peptides and Proteins

Keywords

  • Cyclophosphamide
  • Fludarabine
  • Follicular non-Hodgkin's lymphoma
  • Mitoxantrone

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma : A report from the non-Hodgkin's lymphoma co-operative study group. / Santini, Gino; Chisesi, Teodoro; Nati, Sandro; Porcellini, Adolfo; Zoli, Valerio; Rizzoli, Vittorio; Zupo, Simona; Marino, Gennaro; Rubagotti, Alessandra; Polacco, Alessandro; Spriano, Mauro; Vimercati, Renato; Congiu, Angela Marina; Ravetti, Jean Louis; Aversa, Savina; Candela, Marco; Patti, Caterina.

In: Leukemia and Lymphoma, Vol. 45, No. 6, 06.2004, p. 1141-1147.

Research output: Contribution to journalArticle

Santini, G, Chisesi, T, Nati, S, Porcellini, A, Zoli, V, Rizzoli, V, Zupo, S, Marino, G, Rubagotti, A, Polacco, A, Spriano, M, Vimercati, R, Congiu, AM, Ravetti, JL, Aversa, S, Candela, M & Patti, C 2004, 'Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: A report from the non-Hodgkin's lymphoma co-operative study group', Leukemia and Lymphoma, vol. 45, no. 6, pp. 1141-1147. https://doi.org/10.1080/10428190310001623874
Santini, Gino ; Chisesi, Teodoro ; Nati, Sandro ; Porcellini, Adolfo ; Zoli, Valerio ; Rizzoli, Vittorio ; Zupo, Simona ; Marino, Gennaro ; Rubagotti, Alessandra ; Polacco, Alessandro ; Spriano, Mauro ; Vimercati, Renato ; Congiu, Angela Marina ; Ravetti, Jean Louis ; Aversa, Savina ; Candela, Marco ; Patti, Caterina. / Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma : A report from the non-Hodgkin's lymphoma co-operative study group. In: Leukemia and Lymphoma. 2004 ; Vol. 45, No. 6. pp. 1141-1147.
@article{1e5e2bd56ba948ee870cc1990d37b65f,
title = "Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: A report from the non-Hodgkin's lymphoma co-operative study group",
abstract = "The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL). Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36-70), received FLU/CY/MITO regimen (FLU 25 mg/m2 days 1-3, CY 300 mg/m2 days 1-3, Mito 10 mg/m2 day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87{\%}: 46 patients achieved complete response (CR) (77{\%}), 6 a partial response (10{\%}) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2{\%} and 45{\%} respectively. Thirty-five patients (58{\%}) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76{\%}) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.",
keywords = "Cyclophosphamide, Fludarabine, Follicular non-Hodgkin's lymphoma, Mitoxantrone",
author = "Gino Santini and Teodoro Chisesi and Sandro Nati and Adolfo Porcellini and Valerio Zoli and Vittorio Rizzoli and Simona Zupo and Gennaro Marino and Alessandra Rubagotti and Alessandro Polacco and Mauro Spriano and Renato Vimercati and Congiu, {Angela Marina} and Ravetti, {Jean Louis} and Savina Aversa and Marco Candela and Caterina Patti",
year = "2004",
month = "6",
doi = "10.1080/10428190310001623874",
language = "English",
volume = "45",
pages = "1141--1147",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Taylor and Francis Ltd.",
number = "6",

}

TY - JOUR

T1 - Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma

T2 - A report from the non-Hodgkin's lymphoma co-operative study group

AU - Santini, Gino

AU - Chisesi, Teodoro

AU - Nati, Sandro

AU - Porcellini, Adolfo

AU - Zoli, Valerio

AU - Rizzoli, Vittorio

AU - Zupo, Simona

AU - Marino, Gennaro

AU - Rubagotti, Alessandra

AU - Polacco, Alessandro

AU - Spriano, Mauro

AU - Vimercati, Renato

AU - Congiu, Angela Marina

AU - Ravetti, Jean Louis

AU - Aversa, Savina

AU - Candela, Marco

AU - Patti, Caterina

PY - 2004/6

Y1 - 2004/6

N2 - The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL). Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36-70), received FLU/CY/MITO regimen (FLU 25 mg/m2 days 1-3, CY 300 mg/m2 days 1-3, Mito 10 mg/m2 day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87%: 46 patients achieved complete response (CR) (77%), 6 a partial response (10%) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2% and 45% respectively. Thirty-five patients (58%) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76%) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.

AB - The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL). Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36-70), received FLU/CY/MITO regimen (FLU 25 mg/m2 days 1-3, CY 300 mg/m2 days 1-3, Mito 10 mg/m2 day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87%: 46 patients achieved complete response (CR) (77%), 6 a partial response (10%) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2% and 45% respectively. Thirty-five patients (58%) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76%) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.

KW - Cyclophosphamide

KW - Fludarabine

KW - Follicular non-Hodgkin's lymphoma

KW - Mitoxantrone

UR - http://www.scopus.com/inward/record.url?scp=2342516718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342516718&partnerID=8YFLogxK

U2 - 10.1080/10428190310001623874

DO - 10.1080/10428190310001623874

M3 - Article

C2 - 15359993

AN - SCOPUS:2342516718

VL - 45

SP - 1141

EP - 1147

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN - 1042-8194

IS - 6

ER -