Hematologic remission and cytogenetic improvement after treatment of stable‐phase chronic myelogenous leukemia with continuous infusion of low‐dose cytarabine

Michael J. Robertson, Ramana Tantravahi, James D. Griffin, George P. Canellos, Stephen A. Cannistra

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Prolonged exposure to low concentrations of cytarabine preferentially inhibits in vitro growth of neoplastic myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared to that of normal myeloid progenitors. Continuous infusions of cytarabine in doses of 15–30 mg/m2/day were therefore administered for extended periods to patients with CML in stable phase to determine if this treatment could achieve selective cytoreduction of Philadelphia chromosome (Ph)‐positive cells. Five patients demonstrating >90% Ph‐positive metaphases before treatment received a total of 43 cycles of cytarabine infusional therapy. Cytarabine was administered on an outpatient basis using a portable, battery‐operated syringe pump until the total leukocyte count reached 2500/μl or the platelet count reached 75,000/μl. A new cycle was begun when the total leukocyte count exceeded 4,000/μl and the platelet count exceeded 100,000/μl. The median duration of cytarabine administration per cycle was 29 days (range 15–72 days). Leukocytosis was readily controlled by low‐dose cytarabine therapy in all patients. All five patients experienced complete hematologic responses during cytarabine therapy. The fraction of Phpositive metaphases in the marrow of the five patients was reduced to 0, 10%, 43%, 72%, and 84%, respectively, during therapy. The median time to achieve optimal cytogenetic response was 4.8 months (range 2.8–8.6 months). One patient demonstrated a complete cytogenetic response after three cycles of cytarabine. Another patient demonstrated persistent cytogenetic improvement during 20 cycles of cytarabine, with a median 38% Ph‐positive marrow metaphases (range 10–53%) over 32 months. Cytarabine therapy was generally well‐tolerated, but was discontinued in one patient because of persistent asymptomatic elevations in hepatic enzymes, which resolved within 2 months after discontinuing therapy. There were no episodes of fever during neutropenia, and platelet transfusions were not required. However, symptomatic anemia requiring transfusion of red cells occurred during most cycles of treatment. In summary, treatment of CML with low‐dose cytarabine can induce prolonged cytogenetic improvement in some patients with acceptable toxicity. Further evaluation is needed to ascertain the effects of this treatment on duration of stable phase and overall survival.

Original languageEnglish (US)
Pages (from-to)95-102
Number of pages8
JournalAmerican Journal of Hematology
Volume43
Issue number2
DOIs
StatePublished - Jun 1993

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Leukemia, Myeloid, Chronic Phase
Cytarabine
Cytogenetics
Metaphase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Therapeutics
Platelet Count
Leukocyte Count
Bone Marrow
Philadelphia Chromosome
Platelet Transfusion
Leukocytosis
Syringes
Neutropenia
Anemia
Fever
Outpatients

Keywords

  • CML
  • Philadelphia chromosome
  • cytogenetic remission

ASJC Scopus subject areas

  • Hematology

Cite this

Hematologic remission and cytogenetic improvement after treatment of stable‐phase chronic myelogenous leukemia with continuous infusion of low‐dose cytarabine. / Robertson, Michael J.; Tantravahi, Ramana; Griffin, James D.; Canellos, George P.; Cannistra, Stephen A.

In: American Journal of Hematology, Vol. 43, No. 2, 06.1993, p. 95-102.

Research output: Contribution to journalArticle

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abstract = "Prolonged exposure to low concentrations of cytarabine preferentially inhibits in vitro growth of neoplastic myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared to that of normal myeloid progenitors. Continuous infusions of cytarabine in doses of 15–30 mg/m2/day were therefore administered for extended periods to patients with CML in stable phase to determine if this treatment could achieve selective cytoreduction of Philadelphia chromosome (Ph)‐positive cells. Five patients demonstrating >90{\%} Ph‐positive metaphases before treatment received a total of 43 cycles of cytarabine infusional therapy. Cytarabine was administered on an outpatient basis using a portable, battery‐operated syringe pump until the total leukocyte count reached 2500/μl or the platelet count reached 75,000/μl. A new cycle was begun when the total leukocyte count exceeded 4,000/μl and the platelet count exceeded 100,000/μl. The median duration of cytarabine administration per cycle was 29 days (range 15–72 days). Leukocytosis was readily controlled by low‐dose cytarabine therapy in all patients. All five patients experienced complete hematologic responses during cytarabine therapy. The fraction of Phpositive metaphases in the marrow of the five patients was reduced to 0, 10{\%}, 43{\%}, 72{\%}, and 84{\%}, respectively, during therapy. The median time to achieve optimal cytogenetic response was 4.8 months (range 2.8–8.6 months). One patient demonstrated a complete cytogenetic response after three cycles of cytarabine. Another patient demonstrated persistent cytogenetic improvement during 20 cycles of cytarabine, with a median 38{\%} Ph‐positive marrow metaphases (range 10–53{\%}) over 32 months. Cytarabine therapy was generally well‐tolerated, but was discontinued in one patient because of persistent asymptomatic elevations in hepatic enzymes, which resolved within 2 months after discontinuing therapy. There were no episodes of fever during neutropenia, and platelet transfusions were not required. However, symptomatic anemia requiring transfusion of red cells occurred during most cycles of treatment. In summary, treatment of CML with low‐dose cytarabine can induce prolonged cytogenetic improvement in some patients with acceptable toxicity. Further evaluation is needed to ascertain the effects of this treatment on duration of stable phase and overall survival.",
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AU - Canellos, George P.

AU - Cannistra, Stephen A.

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AB - Prolonged exposure to low concentrations of cytarabine preferentially inhibits in vitro growth of neoplastic myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared to that of normal myeloid progenitors. Continuous infusions of cytarabine in doses of 15–30 mg/m2/day were therefore administered for extended periods to patients with CML in stable phase to determine if this treatment could achieve selective cytoreduction of Philadelphia chromosome (Ph)‐positive cells. Five patients demonstrating >90% Ph‐positive metaphases before treatment received a total of 43 cycles of cytarabine infusional therapy. Cytarabine was administered on an outpatient basis using a portable, battery‐operated syringe pump until the total leukocyte count reached 2500/μl or the platelet count reached 75,000/μl. A new cycle was begun when the total leukocyte count exceeded 4,000/μl and the platelet count exceeded 100,000/μl. The median duration of cytarabine administration per cycle was 29 days (range 15–72 days). Leukocytosis was readily controlled by low‐dose cytarabine therapy in all patients. All five patients experienced complete hematologic responses during cytarabine therapy. The fraction of Phpositive metaphases in the marrow of the five patients was reduced to 0, 10%, 43%, 72%, and 84%, respectively, during therapy. The median time to achieve optimal cytogenetic response was 4.8 months (range 2.8–8.6 months). One patient demonstrated a complete cytogenetic response after three cycles of cytarabine. Another patient demonstrated persistent cytogenetic improvement during 20 cycles of cytarabine, with a median 38% Ph‐positive marrow metaphases (range 10–53%) over 32 months. Cytarabine therapy was generally well‐tolerated, but was discontinued in one patient because of persistent asymptomatic elevations in hepatic enzymes, which resolved within 2 months after discontinuing therapy. There were no episodes of fever during neutropenia, and platelet transfusions were not required. However, symptomatic anemia requiring transfusion of red cells occurred during most cycles of treatment. In summary, treatment of CML with low‐dose cytarabine can induce prolonged cytogenetic improvement in some patients with acceptable toxicity. Further evaluation is needed to ascertain the effects of this treatment on duration of stable phase and overall survival.

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