Clinical Course and Therapy of Chronic Myelogenous Leukemia With Interferon-Alpha and Chemotherapy

Kantarjian, Hagop M.; Giles, Francis J.; O’Brien, Susan; Talpaz, Moshe

doi:10.1016/s0889-8588(05)70496-2

Cited by 60 publications

(45 citation statements)

References 177 publications

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“…However, this agent causes serious adverse effects, including myelosuppression as well as pulmonary, hepatic, and cardiac fibrosis [4,39,40]. Hydroxyurea (HU), a ribonucleotide reductase inhibitor, has demonstrated a more rapid onset of action and better side-effect profile than BUS [39].…”

Section: Chemotherapymentioning

confidence: 99%

Optimizing Treatment of Chronic Myeloid Leukemia: A Rational Approach

Stone

2004

The Oncologist

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Imatinib mesylate, a novel, molecularly targeted agent for the treatment of chronic myeloid leukemia (CML), has expanded the management options for this disease and provided a paradigm for the treatment of other cancers. Imatinib is a potent, specific inhibitor of BCR-ABL, the constitutively active protein tyrosine kinase critical to the pathogenesis of CML. A randomized, phase III comparison of imatinib with interferon-alfa plus cytarabine as initial treatment for newly diagnosed chronic-phase CML, which demonstrated significantly higher rates of disease response with less toxicity, better quality of life, and a significantly longer progression-free survival time, provided the most persuasive data supporting a major role for imatinib. Currently, allogeneic stem cell transplantation is the only treatment modality with long-term data demonstrating curative potential in CML. An option for less than half of CML patients and associated with substantial morbidity and mortality, transplantation may still be appropriate initial therapy for certain patients. Busulfan and hydroxyurea have no demonstrable effect on disease natural history. The interferon-plus-cytarabine combination can induce durable cytogenetic remissions and was previously the CML pharmacotherapy standard of care, but it is often poorly tolerated. Imatinib is now indicated as firstline therapy for CML in all phases.

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Section: Chemotherapymentioning

confidence: 99%

Optimizing Treatment of Chronic Myeloid Leukemia: A Rational Approach

Stone

2004

The Oncologist

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“…20,21 A CHR was defined as normalization of peripheral counts and differential (WBC count Ͻ 10 ϫ 10 9 /L, platelet count Յ 450 ϫ 10 9 /L) and the disappearance of all signs and symptoms of the disease, including palpable splenomegaly. Patients who achieved a CHR were categorized further by their cytogenetic response: cytogenetic CR (no Ph positive metaphases), cytogenetic partial response (PR; 1-34% Ph positive metaphases), and minor cytogenetic response (35-90% Ph positive metaphases).…”

Section: Response Criteriamentioning

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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“…13,36 Other studies showed that achieving a cytogenetic response within 12-24 months was associated with a statistically significant survival benefit. 37 In particular, major cytogenetic responders fare better than patients with no or only a minor cytogenetic response ( Figure 5). 36 Complete cytogenetic responders may fare even better, with 72% of patients alive at 10 years ( Figure 6).…”

Section: Treatment Of Chronic Phase CMLmentioning

confidence: 99%

“…Furthermore, severe side effects may result in discontinuation of treatment in up to 25% of patients. 37 Therefore, there is a need for an alternative to IFN-a in order to offer the potential of a cure, to further prolong survival, and to manage patients who are suffering from IFN-a-induced adverse events or whose disease is progressing.…”

Section: Spotlightmentioning

confidence: 99%

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Perspectives on the treatment of chronic phase and advanced phase CML and Philadelphia chromosome positive ALL

2003

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Chronic myeloid leukaemia (CML) is a malignant disease of the bone marrow characterised by the presence of the Philadelphia (Ph) chromosome. About 20% of acute lymphoblastic leukaemia (ALL) patients also show this genetic abnormality. A new drug, imatinib (Glivec s , Novartis Pharma AG, Basel, Switzerland, and formerly STI571) is having a profound effect on the treatment and management of all stages of CML and Philadelphia chromosome positive (Ph+) ALL. New treatment algorithms are being developed. Should imatinib replace or be combined with existing therapies? To address this question, we review the pros and cons of therapy with interferon-a (IFN-a), allogeneic transplantation, autologous transplantation, imatinib, and in the case of Ph+ ALL, chemotherapy and experimental approaches. Conservative and aggressive treatments will be discussed and new molecular methods of monitoring cytogenetic response and their significance will also be reviewed.

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Clinical Course and Therapy of Chronic Myelogenous Leukemia With Interferon-Alpha and Chemotherapy

Cited by 60 publications

References 177 publications

Optimizing Treatment of Chronic Myeloid Leukemia: A Rational Approach

Optimizing Treatment of Chronic Myeloid Leukemia: A Rational Approach

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

Perspectives on the treatment of chronic phase and advanced phase CML and Philadelphia chromosome positive ALL

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