Interferon Alfa-2b Combined with Cytarabine versus Interferon Alone in Chronic Myelogenous Leukemia

Guilhot, François; Chastang, Claude; Michallet, Mauricette; Guerci, Agnès; Harousseau, Jean‐Luc; Maloisel, Frédéric; Bouabdallah, Réda; Guyotat, Denis; Cheron, Nathalie; Nicolini, Franck E.; Abgrall, Jean-François; Tanzer, J; Navarro, Maurice; Bron, Dominique; Morice, Patrick; Ifrah, Norbert; Rochant, H; Vilque, Jean-Pierre; Delain, Martine; Bauters, F; Guilhot, Joëlle

doi:10.1056/nejm199707243370402

Cited by 507 publications

(295 citation statements)

References 23 publications

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“…The same comparisons were then made for patients in the advanced phases of CML. The median follow-up was similar for both groups by Fisher exact test ( [13][14][15][16][17][18][19][20][21][22][23][24][25], for patients with and without deletions, respectively, P ϭ .14, Figure 3). However, when time to disease progression following imatinib therapy was analyzed, there was a significant difference between patients in advanced phase according to deletion status (median time to progression, 8 months [95% CI, 3-13] versus 16 months [95% CI, [13][14][15][16][17][18][19], for patients with and without deletions, respectively, P ϭ .02, Figure 3).…”

Section: Survival and Time To Disease Progression Following Initiatiomentioning

confidence: 99%

“…Although interferon-␣ prolongs survival and some patients achieve long-lasting remissions, conventional drug therapy is rarely if ever curative, although it offers good symptomatic control. [18][19][20] By contrast, allogeneic stem cell transplantation is capable of eradicating the malignant clone and thus has curative potential, but it is associated with considerable treatment-associated mortality. 21 None of the standard medical treatments appear to improve the outcome of patients with deletions of the derivative chromosome 9.…”

Section: Introductionmentioning

confidence: 99%

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Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions

Huntly

Guilhot²,

Reid³

et al. 2003

Blood

112

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Deletions of the derivative chromosome 9 occur in a subset of patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) and are associated with a poor prognosis on standard drug therapy. However, it is currently unknown if the presence of deletions influences the response to imatinib, an Abl-specific tyrosine kinase inhibitor, that has recently shown excellent hematologic and cytogenetic responses in patients with CML. We, therefore, compared hematologic and cytogenetic responses with imatinib in 397 patients with CML, and survival and progression in 354 of these patients, according to deletion status and disease phase. We found no difference in survival between patients with and without deletions, contrasting with previous reports in cohorts with a lower proportion of patients treated with imatinib. However, the time to disease progression on imatinib treatment was significantly shorter for patients with deletions, both in chronic phase (P ‫؍‬ .02) and advanced phases (P ‫؍‬ .02). Moreover, both in chronic phase and more advanced phases of CML, hematologic and cytogenetic responses were uniformly lower in patients with deletions, with significant differences seen for hematologic response (P ‫؍‬ .04), for major cytogenetic response (P ‫؍‬ .008) in chronic phase, and for hematologic response in advanced phases (P ‫؍‬ .

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Section: Survival and Time To Disease Progression Following Initiatiomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions

Huntly

Guilhot²,

Reid³

et al. 2003

Blood

112

View full text Add to dashboard Cite

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“…With IFN-␣-based therapy, the major cytogenetic response rate was 38% (cytogenetic complete response [CR] rate, 26%), and the rate increased with the addition of cytarabine, [1][2][3][4] with a median survival of 7 years. 1,2 It has been demonstrated that the achievement of minimal tumor burden, such as a cytogenetic CR, is associated independently with the prolongation of survival.…”

mentioning

confidence: 99%

“…1,2 It has been demonstrated that the achievement of minimal tumor burden, such as a cytogenetic CR, is associated independently with the prolongation of survival. [3][4][5][6][7][8] Thus, new modalities to improve cytogenetic response and, ultimately, survival remain an important research strategy.…”

mentioning

confidence: 99%

Simultaneous homoharringtonine and interferon‐α in the treatment of patients with chronic‐phase chronic myelogenous leukemia

O’Brien

Talpaz

Cortes

et al. 2002

Cancer

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BACKGROUNDHomoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon‐α (IFN‐α), and cytarabine (ara‐C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN‐α therapy in patients with chronic‐phase CML who were not exposed previously to either agent.METHODSForty‐seven patients were treated: 37 patients with early chronic‐phase CML (2 patients with clonal evolution) and 10 patients with late chronic‐phase CML. Their median age was 62 years (range, 23–73 years). HHT was given at a dose of 2.5 mg/m2 by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN‐α was given daily at a target dose of 5 × 106 units/m2 subcutaneously. Response, survival, and treatment toxicity were analyzed.RESULTSOverall, the complete hematologic response (CHR) rate was 85%; the cytogenetic response rate was 66%, with major cytogenetic responses (Ph positive in < 35% of metaphases) in 49% of patients and complete cytogenetic responses in 21% of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84%, 69%, and 52%, respectively, in patients with early chronic‐phase CML. Among the 10 patients with late chronic‐phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80%, 50%, and 40%, respectively. Response rates in patients age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6–24 courses, the median daily IFN‐α dose was 1 MU/m2, and the median number of days on HHT per month was 2 days. With a median follow‐up of 26 months, the estimated 2‐year survival rate was 90% (95% confidence interval, 79–100%).CONCLUSIONSThe simultaneous combination of HHT and IFN‐α is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal‐transduction inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN‐α chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored. Cancer 2002;94:2024–32. © 2002 American Cancer Society.DOI 10.1002/cncr.10436

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“…To this end we developed a 24 h Ara-C protection assay. Ara-C was selected because of its relative cytotoxic specificity for S phase cells, 33 its confirmed efficacy in the treatment of CML, 34 and as an in vitro purging reagent. 35 Furthermore, in vitro studies 36 and preliminary clinical experience 37 suggest a preferential cytotoxic Ara-C effect on CFC GM from CML patients in chronic phase of the disease as compared to haemopoietic progenitors from normal subjects.…”

Section: Discussionmentioning

confidence: 99%

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1999

Leukemia

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The clonogenic cells of chronic myeloid leukaemia (CML), unlike normal haemopoietic colony forming cells (CFC), are resistant to the growth inhibitory effects of the chemokine, macrophage inflammatory protein-1␣ (MIP-1␣). Here, we tested the hypothesis that MIP-1␣ protects normal, but not CML, CFC from the cytotoxic effects of the cell-cycle active drug cytosine arabinoside (Ara-C). Using a 24-h Ara-C protection assay we showed that MIP-1␣ confers protection to normal CFC but also sensitises CML CFC to Ara

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Interferon Alfa-2b Combined with Cytarabine versus Interferon Alone in Chronic Myelogenous Leukemia

Abstract: The combination of interferon and cytarabine, as compared with interferon alone, increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia.

Cited by 507 publications

References 23 publications

Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions

Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions

Simultaneous homoharringtonine and interferon‐α in the treatment of patients with chronic‐phase chronic myelogenous leukemia

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