Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival

K. Van Besien, A. Rodriguez, S. Tomany, A. Younes, M. Donato, A. Sarris, S. Giralt, R. Mehra, B. Andersson, J. Gajewski, R. Champlin, F. Cabanillas

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The purpose of the study was to evaluate in patients with recurrent intermediate-grade NHL, the tolerance to and efficacy of an intensive salvage regimen consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF support, followed by autologous stem cell transplantation and to identify prognostic factors for survival in patients with recurrent aggressive lymphoma. Patients with recurrent intermediate-grade NHL under the age of 60 years were eligible. Induction consisted of ifosfamide 10 g/m2 and etoposide 900 mg/m2 with G-CSF 5 μg/kg twice a day. Upon recovery, patients underwent stem cell apheresis. Patients achieving complete remission (CR) underwent autologous stem cell transplantation using BEAM conditioning. Those with partial remission (PR) received treatment with ifosfamide 10 g/m2, mitoxantrone 20 mg/m2 and G-CSF 5 μg/kg. Those with CR received BEAM, those with PR received cyclophosphamide 4.5 g/m2, etoposide 1200 mg/m2 and cisplatin 135 mg/m2 with stem cell rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment cycles. The results were compared with those obtained in a prior study that used MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL were enrolled between March 1994 and September 1996. Median age was 50 years (24-61). Eleven patients had transformed lymphoma and seven had a T cell phenotype. Response rate to the high-dose ifosfamide regimen was 77% ± 12% after two cycles and the complete response rate was 41% ± 14%. Myelosuppression was profound but short. Median nadir ANC was 0 and the median duration of ANC 9/l was 6 days (range 3-12). No severe infections occurred; 55% of the patients required blood transfusion and 42% required platelet transfusions. Myelosuppression and transfusion requirements were similar after the first and second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell transplantation and one transplant-related death occurred. With a median follow-up of 52 months, progression-free survival at 2 years is 38% ± 14% and survival is 52% ± 15%. Data from these 44 patients were pooled with data on 53 patients who had received salvage treatment with MINE-ESHAP, for a multivariate analysis of prognostic factors. In multivariate analysis, serum LDH was strongly associated with survival. The use of a more intensive salvage regimen, did not result in a significant increase in long-term outcome, despite a high response rate. In conclusion, duration of treatment, response rates, treatment-related mortality and survival compare favorably with previous salvage regimens, but recurrence remains a major problem. Long-term survival in recurrent large cell lymphoma is influenced more by disease characteristics than by the type of salvage regimen used.

Original languageEnglish (US)
Pages (from-to)397-404
Number of pages8
JournalBone Marrow Transplantation
Volume27
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

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Ifosfamide
Intercellular Signaling Peptides and Proteins
Drug Therapy
Survival
Stem Cell Transplantation
Granulocyte Colony-Stimulating Factor
Etoposide
Lymphoma
Mitoxantrone
Stem Cells
Multivariate Analysis
Salvage Therapy
Platelet Transfusion
Blood Component Removal
Antibiotic Prophylaxis
Therapeutics
Blood Transfusion
Cyclophosphamide
Cisplatin
Disease-Free Survival

Keywords

  • Lymphoma
  • Prognostic factors
  • Transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival. / Van Besien, K.; Rodriguez, A.; Tomany, S.; Younes, A.; Donato, M.; Sarris, A.; Giralt, S.; Mehra, R.; Andersson, B.; Gajewski, J.; Champlin, R.; Cabanillas, F.

In: Bone Marrow Transplantation, Vol. 27, No. 4, 2001, p. 397-404.

Research output: Contribution to journalArticle

Van Besien, K, Rodriguez, A, Tomany, S, Younes, A, Donato, M, Sarris, A, Giralt, S, Mehra, R, Andersson, B, Gajewski, J, Champlin, R & Cabanillas, F 2001, 'Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival', Bone Marrow Transplantation, vol. 27, no. 4, pp. 397-404. https://doi.org/10.1038/sj.bmt.1702793
Van Besien, K. ; Rodriguez, A. ; Tomany, S. ; Younes, A. ; Donato, M. ; Sarris, A. ; Giralt, S. ; Mehra, R. ; Andersson, B. ; Gajewski, J. ; Champlin, R. ; Cabanillas, F. / Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival. In: Bone Marrow Transplantation. 2001 ; Vol. 27, No. 4. pp. 397-404.
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abstract = "The purpose of the study was to evaluate in patients with recurrent intermediate-grade NHL, the tolerance to and efficacy of an intensive salvage regimen consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF support, followed by autologous stem cell transplantation and to identify prognostic factors for survival in patients with recurrent aggressive lymphoma. Patients with recurrent intermediate-grade NHL under the age of 60 years were eligible. Induction consisted of ifosfamide 10 g/m2 and etoposide 900 mg/m2 with G-CSF 5 μg/kg twice a day. Upon recovery, patients underwent stem cell apheresis. Patients achieving complete remission (CR) underwent autologous stem cell transplantation using BEAM conditioning. Those with partial remission (PR) received treatment with ifosfamide 10 g/m2, mitoxantrone 20 mg/m2 and G-CSF 5 μg/kg. Those with CR received BEAM, those with PR received cyclophosphamide 4.5 g/m2, etoposide 1200 mg/m2 and cisplatin 135 mg/m2 with stem cell rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment cycles. The results were compared with those obtained in a prior study that used MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL were enrolled between March 1994 and September 1996. Median age was 50 years (24-61). Eleven patients had transformed lymphoma and seven had a T cell phenotype. Response rate to the high-dose ifosfamide regimen was 77{\%} ± 12{\%} after two cycles and the complete response rate was 41{\%} ± 14{\%}. Myelosuppression was profound but short. Median nadir ANC was 0 and the median duration of ANC 9/l was 6 days (range 3-12). No severe infections occurred; 55{\%} of the patients required blood transfusion and 42{\%} required platelet transfusions. Myelosuppression and transfusion requirements were similar after the first and second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell transplantation and one transplant-related death occurred. With a median follow-up of 52 months, progression-free survival at 2 years is 38{\%} ± 14{\%} and survival is 52{\%} ± 15{\%}. Data from these 44 patients were pooled with data on 53 patients who had received salvage treatment with MINE-ESHAP, for a multivariate analysis of prognostic factors. In multivariate analysis, serum LDH was strongly associated with survival. The use of a more intensive salvage regimen, did not result in a significant increase in long-term outcome, despite a high response rate. In conclusion, duration of treatment, response rates, treatment-related mortality and survival compare favorably with previous salvage regimens, but recurrence remains a major problem. Long-term survival in recurrent large cell lymphoma is influenced more by disease characteristics than by the type of salvage regimen used.",
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T1 - Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival

AU - Van Besien, K.

AU - Rodriguez, A.

AU - Tomany, S.

AU - Younes, A.

AU - Donato, M.

AU - Sarris, A.

AU - Giralt, S.

AU - Mehra, R.

AU - Andersson, B.

AU - Gajewski, J.

AU - Champlin, R.

AU - Cabanillas, F.

PY - 2001

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N2 - The purpose of the study was to evaluate in patients with recurrent intermediate-grade NHL, the tolerance to and efficacy of an intensive salvage regimen consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF support, followed by autologous stem cell transplantation and to identify prognostic factors for survival in patients with recurrent aggressive lymphoma. Patients with recurrent intermediate-grade NHL under the age of 60 years were eligible. Induction consisted of ifosfamide 10 g/m2 and etoposide 900 mg/m2 with G-CSF 5 μg/kg twice a day. Upon recovery, patients underwent stem cell apheresis. Patients achieving complete remission (CR) underwent autologous stem cell transplantation using BEAM conditioning. Those with partial remission (PR) received treatment with ifosfamide 10 g/m2, mitoxantrone 20 mg/m2 and G-CSF 5 μg/kg. Those with CR received BEAM, those with PR received cyclophosphamide 4.5 g/m2, etoposide 1200 mg/m2 and cisplatin 135 mg/m2 with stem cell rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment cycles. The results were compared with those obtained in a prior study that used MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL were enrolled between March 1994 and September 1996. Median age was 50 years (24-61). Eleven patients had transformed lymphoma and seven had a T cell phenotype. Response rate to the high-dose ifosfamide regimen was 77% ± 12% after two cycles and the complete response rate was 41% ± 14%. Myelosuppression was profound but short. Median nadir ANC was 0 and the median duration of ANC 9/l was 6 days (range 3-12). No severe infections occurred; 55% of the patients required blood transfusion and 42% required platelet transfusions. Myelosuppression and transfusion requirements were similar after the first and second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell transplantation and one transplant-related death occurred. With a median follow-up of 52 months, progression-free survival at 2 years is 38% ± 14% and survival is 52% ± 15%. Data from these 44 patients were pooled with data on 53 patients who had received salvage treatment with MINE-ESHAP, for a multivariate analysis of prognostic factors. In multivariate analysis, serum LDH was strongly associated with survival. The use of a more intensive salvage regimen, did not result in a significant increase in long-term outcome, despite a high response rate. In conclusion, duration of treatment, response rates, treatment-related mortality and survival compare favorably with previous salvage regimens, but recurrence remains a major problem. Long-term survival in recurrent large cell lymphoma is influenced more by disease characteristics than by the type of salvage regimen used.

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KW - Lymphoma

KW - Prognostic factors

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