Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma

M. L. McMaster, J. P. Greer, S. N. Wolff, D. H. Johnson, F. A. Greco, R. S. Stein, J. B. Cousar, J. M. Flexner, J. D. Hainsworth

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Abstract

A novel chemotherapeutic approach was designed for the treatment of intermediate and high-grade histology non-Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long-term survival rate of less than 25% in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high-grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71%; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55%; multiple extranodal sites of disease, 52%; elevated lactic dehydrogenase (> 300 IU/l), 43%; and bulky (> 10 cm) tumor masses, 30%. Thirty-three of 56 patients (59%) were in Shipp's Category 3. During the 6-year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2-month course of therapy as follows: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m2 IV on days 1, 2, and 3 and 100 mg/m2 on days 29, 30, 31; doxorubicin 45 mg/m2 IV on days 29, 30; vincristine 1.4 mg/m2 IV on days 8, 22, 36, and 50; bleomycin 10 units/m2 on days 8, 22, 36, and 50; methotrexate 200 mg/m2 IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m2 IV every 6 hours for six doses; and prednisone 60 mg/m2 orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77% (95% confidence interval, 64% to 86%). There were ten relapses, only one of which occurred after 18 months of follow-up. Overall event-free survival (EFS) was 52% (95% confidence interval, 36% to 68%), with a median follow-up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61%. Myelosuppression occurred in all patients, with severe leukopenia (< 1000/μl) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9%; 95% confidence interval, 4% to 19%). This intensive approach improved the response and survival of very poor risk non-Hodgkin's lymphoma patients.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalCancer
Volume68
Issue number2
DOIs
StatePublished - 1991

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Non-Hodgkin's Lymphoma
Drug Therapy
Therapeutics
Confidence Intervals
Disease-Free Survival
Lymphoma
Histology
Leucovorin
Poisons
Bleomycin
Leukopenia
Vincristine
Etoposide
Prednisone
Methotrexate
Doxorubicin
Cyclophosphamide
Inpatients
Oxidoreductases
Milk

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma. / McMaster, M. L.; Greer, J. P.; Wolff, S. N.; Johnson, D. H.; Greco, F. A.; Stein, R. S.; Cousar, J. B.; Flexner, J. M.; Hainsworth, J. D.

In: Cancer, Vol. 68, No. 2, 1991, p. 233-241.

Research output: Contribution to journalArticle

McMaster, M. L. ; Greer, J. P. ; Wolff, S. N. ; Johnson, D. H. ; Greco, F. A. ; Stein, R. S. ; Cousar, J. B. ; Flexner, J. M. ; Hainsworth, J. D. / Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma. In: Cancer. 1991 ; Vol. 68, No. 2. pp. 233-241.
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abstract = "A novel chemotherapeutic approach was designed for the treatment of intermediate and high-grade histology non-Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long-term survival rate of less than 25{\%} in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high-grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71{\%}; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55{\%}; multiple extranodal sites of disease, 52{\%}; elevated lactic dehydrogenase (> 300 IU/l), 43{\%}; and bulky (> 10 cm) tumor masses, 30{\%}. Thirty-three of 56 patients (59{\%}) were in Shipp's Category 3. During the 6-year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2-month course of therapy as follows: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m2 IV on days 1, 2, and 3 and 100 mg/m2 on days 29, 30, 31; doxorubicin 45 mg/m2 IV on days 29, 30; vincristine 1.4 mg/m2 IV on days 8, 22, 36, and 50; bleomycin 10 units/m2 on days 8, 22, 36, and 50; methotrexate 200 mg/m2 IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m2 IV every 6 hours for six doses; and prednisone 60 mg/m2 orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77{\%} (95{\%} confidence interval, 64{\%} to 86{\%}). There were ten relapses, only one of which occurred after 18 months of follow-up. Overall event-free survival (EFS) was 52{\%} (95{\%} confidence interval, 36{\%} to 68{\%}), with a median follow-up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61{\%}. Myelosuppression occurred in all patients, with severe leukopenia (< 1000/μl) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9{\%}; 95{\%} confidence interval, 4{\%} to 19{\%}). This intensive approach improved the response and survival of very poor risk non-Hodgkin's lymphoma patients.",
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T1 - Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma

AU - McMaster, M. L.

AU - Greer, J. P.

AU - Wolff, S. N.

AU - Johnson, D. H.

AU - Greco, F. A.

AU - Stein, R. S.

AU - Cousar, J. B.

AU - Flexner, J. M.

AU - Hainsworth, J. D.

PY - 1991

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N2 - A novel chemotherapeutic approach was designed for the treatment of intermediate and high-grade histology non-Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long-term survival rate of less than 25% in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high-grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71%; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55%; multiple extranodal sites of disease, 52%; elevated lactic dehydrogenase (> 300 IU/l), 43%; and bulky (> 10 cm) tumor masses, 30%. Thirty-three of 56 patients (59%) were in Shipp's Category 3. During the 6-year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2-month course of therapy as follows: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m2 IV on days 1, 2, and 3 and 100 mg/m2 on days 29, 30, 31; doxorubicin 45 mg/m2 IV on days 29, 30; vincristine 1.4 mg/m2 IV on days 8, 22, 36, and 50; bleomycin 10 units/m2 on days 8, 22, 36, and 50; methotrexate 200 mg/m2 IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m2 IV every 6 hours for six doses; and prednisone 60 mg/m2 orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77% (95% confidence interval, 64% to 86%). There were ten relapses, only one of which occurred after 18 months of follow-up. Overall event-free survival (EFS) was 52% (95% confidence interval, 36% to 68%), with a median follow-up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61%. Myelosuppression occurred in all patients, with severe leukopenia (< 1000/μl) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9%; 95% confidence interval, 4% to 19%). This intensive approach improved the response and survival of very poor risk non-Hodgkin's lymphoma patients.

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