A pilot study of carboplatin and mitoxantrone in blast crisis of chronic myeloid leukemia

Janice P. Dutcher, Evelyn L. Morris, Bruce Gaynor, Elisabeth M. Paietta, Peter H. Wiernik

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The efficacy and toxicity of carboplatin plus mitoxantrone in blast crisis of chronic myeloid leukemia (CMLBC) were evaluated. Between 1990 and 1996, 20 patients (11 males and nine females, median age of 49 years [range 30-75 years]) were treated with carboplatin, 250 mg/m2/day × 5 days as an infusion and mitoxantrone, 10 mg/m2/day × 3 days, IV bolus. Median time from diagnosis of CML to BC was 4.25 years (range 0-11 years). CMLBC was myeloid in 13 patients, lymphoid in six, and megakaryocytic in one. All patients were Philadelphia (Ph) chromosome positive; four had a single Ph chromosome, five had double Ph chromosome, three had abnormalities of chromosome 17, and eight had complex cytogenetic abnormalities. Prior treatment for chronic phase included hydroxyurea (12 patients), interferon-α (11 patients), cytarabine or all-trans retinoic acid, three patients each and other agents (four patients). Eight patients (five myeloid and three lymphoid) had an objective response (median duration, 3 months). Five had complete responses (CR) of 2, 3, 3, 6, and 6+ months duration, and three had partial responses (PR) for 1, 2, and 4 months. Seven patients died too early to evaluate (TETE): three died pancytopenic in <30 days from initiation of chemotherapy, two patients had pancytopenia for >30 days but had only blasts in their day 30 bone marrow, and two patients were pancytopenic >30 days but demonstrated trilineage marrow regeneration. Three of eight responders survived ≥1 year. Toxicity was primarily hematologic. The objective response rate was 61% (8/13) among those who did not die TETE and 40% among all treated patients. Carboplatin plus mitoxantrone are highly active in CMLBC, with marrow aplasia as the dose-limiting toxicity, and these agents deserve further study in CMLBC, perhaps in combination with tyrosine kinase inhibitors.

Original languageEnglish (US)
Pages (from-to)728-735
Number of pages8
JournalMedical Oncology
Volume27
Issue number3
DOIs
StatePublished - Sep 2010
Externally publishedYes

Fingerprint

Blast Crisis
Mitoxantrone
Carboplatin
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Bone Marrow
Chromosomes, Human, Pair 17
Hydroxyurea
Cytarabine
Proxy
Tretinoin
Chromosome Aberrations
Protein-Tyrosine Kinases
Interferons
Regeneration

Keywords

  • Blast crisis
  • Carboplatin
  • Chronic myeloid leukemia-blast crisis
  • CML
  • Mitoxantrone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Hematology

Cite this

A pilot study of carboplatin and mitoxantrone in blast crisis of chronic myeloid leukemia. / Dutcher, Janice P.; Morris, Evelyn L.; Gaynor, Bruce; Paietta, Elisabeth M.; Wiernik, Peter H.

In: Medical Oncology, Vol. 27, No. 3, 09.2010, p. 728-735.

Research output: Contribution to journalArticle

Dutcher, Janice P. ; Morris, Evelyn L. ; Gaynor, Bruce ; Paietta, Elisabeth M. ; Wiernik, Peter H. / A pilot study of carboplatin and mitoxantrone in blast crisis of chronic myeloid leukemia. In: Medical Oncology. 2010 ; Vol. 27, No. 3. pp. 728-735.
@article{69d5c7629ec1485a8010b733f35f7418,
title = "A pilot study of carboplatin and mitoxantrone in blast crisis of chronic myeloid leukemia",
abstract = "The efficacy and toxicity of carboplatin plus mitoxantrone in blast crisis of chronic myeloid leukemia (CMLBC) were evaluated. Between 1990 and 1996, 20 patients (11 males and nine females, median age of 49 years [range 30-75 years]) were treated with carboplatin, 250 mg/m2/day × 5 days as an infusion and mitoxantrone, 10 mg/m2/day × 3 days, IV bolus. Median time from diagnosis of CML to BC was 4.25 years (range 0-11 years). CMLBC was myeloid in 13 patients, lymphoid in six, and megakaryocytic in one. All patients were Philadelphia (Ph) chromosome positive; four had a single Ph chromosome, five had double Ph chromosome, three had abnormalities of chromosome 17, and eight had complex cytogenetic abnormalities. Prior treatment for chronic phase included hydroxyurea (12 patients), interferon-α (11 patients), cytarabine or all-trans retinoic acid, three patients each and other agents (four patients). Eight patients (five myeloid and three lymphoid) had an objective response (median duration, 3 months). Five had complete responses (CR) of 2, 3, 3, 6, and 6+ months duration, and three had partial responses (PR) for 1, 2, and 4 months. Seven patients died too early to evaluate (TETE): three died pancytopenic in <30 days from initiation of chemotherapy, two patients had pancytopenia for >30 days but had only blasts in their day 30 bone marrow, and two patients were pancytopenic >30 days but demonstrated trilineage marrow regeneration. Three of eight responders survived ≥1 year. Toxicity was primarily hematologic. The objective response rate was 61{\%} (8/13) among those who did not die TETE and 40{\%} among all treated patients. Carboplatin plus mitoxantrone are highly active in CMLBC, with marrow aplasia as the dose-limiting toxicity, and these agents deserve further study in CMLBC, perhaps in combination with tyrosine kinase inhibitors.",
keywords = "Blast crisis, Carboplatin, Chronic myeloid leukemia-blast crisis, CML, Mitoxantrone",
author = "Dutcher, {Janice P.} and Morris, {Evelyn L.} and Bruce Gaynor and Paietta, {Elisabeth M.} and Wiernik, {Peter H.}",
year = "2010",
month = "9",
doi = "10.1007/s12032-009-9276-y",
language = "English (US)",
volume = "27",
pages = "728--735",
journal = "Medical Oncology and Tumor Pharmacotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "3",

}

TY - JOUR

T1 - A pilot study of carboplatin and mitoxantrone in blast crisis of chronic myeloid leukemia

AU - Dutcher, Janice P.

AU - Morris, Evelyn L.

AU - Gaynor, Bruce

AU - Paietta, Elisabeth M.

AU - Wiernik, Peter H.

PY - 2010/9

Y1 - 2010/9

N2 - The efficacy and toxicity of carboplatin plus mitoxantrone in blast crisis of chronic myeloid leukemia (CMLBC) were evaluated. Between 1990 and 1996, 20 patients (11 males and nine females, median age of 49 years [range 30-75 years]) were treated with carboplatin, 250 mg/m2/day × 5 days as an infusion and mitoxantrone, 10 mg/m2/day × 3 days, IV bolus. Median time from diagnosis of CML to BC was 4.25 years (range 0-11 years). CMLBC was myeloid in 13 patients, lymphoid in six, and megakaryocytic in one. All patients were Philadelphia (Ph) chromosome positive; four had a single Ph chromosome, five had double Ph chromosome, three had abnormalities of chromosome 17, and eight had complex cytogenetic abnormalities. Prior treatment for chronic phase included hydroxyurea (12 patients), interferon-α (11 patients), cytarabine or all-trans retinoic acid, three patients each and other agents (four patients). Eight patients (five myeloid and three lymphoid) had an objective response (median duration, 3 months). Five had complete responses (CR) of 2, 3, 3, 6, and 6+ months duration, and three had partial responses (PR) for 1, 2, and 4 months. Seven patients died too early to evaluate (TETE): three died pancytopenic in <30 days from initiation of chemotherapy, two patients had pancytopenia for >30 days but had only blasts in their day 30 bone marrow, and two patients were pancytopenic >30 days but demonstrated trilineage marrow regeneration. Three of eight responders survived ≥1 year. Toxicity was primarily hematologic. The objective response rate was 61% (8/13) among those who did not die TETE and 40% among all treated patients. Carboplatin plus mitoxantrone are highly active in CMLBC, with marrow aplasia as the dose-limiting toxicity, and these agents deserve further study in CMLBC, perhaps in combination with tyrosine kinase inhibitors.

AB - The efficacy and toxicity of carboplatin plus mitoxantrone in blast crisis of chronic myeloid leukemia (CMLBC) were evaluated. Between 1990 and 1996, 20 patients (11 males and nine females, median age of 49 years [range 30-75 years]) were treated with carboplatin, 250 mg/m2/day × 5 days as an infusion and mitoxantrone, 10 mg/m2/day × 3 days, IV bolus. Median time from diagnosis of CML to BC was 4.25 years (range 0-11 years). CMLBC was myeloid in 13 patients, lymphoid in six, and megakaryocytic in one. All patients were Philadelphia (Ph) chromosome positive; four had a single Ph chromosome, five had double Ph chromosome, three had abnormalities of chromosome 17, and eight had complex cytogenetic abnormalities. Prior treatment for chronic phase included hydroxyurea (12 patients), interferon-α (11 patients), cytarabine or all-trans retinoic acid, three patients each and other agents (four patients). Eight patients (five myeloid and three lymphoid) had an objective response (median duration, 3 months). Five had complete responses (CR) of 2, 3, 3, 6, and 6+ months duration, and three had partial responses (PR) for 1, 2, and 4 months. Seven patients died too early to evaluate (TETE): three died pancytopenic in <30 days from initiation of chemotherapy, two patients had pancytopenia for >30 days but had only blasts in their day 30 bone marrow, and two patients were pancytopenic >30 days but demonstrated trilineage marrow regeneration. Three of eight responders survived ≥1 year. Toxicity was primarily hematologic. The objective response rate was 61% (8/13) among those who did not die TETE and 40% among all treated patients. Carboplatin plus mitoxantrone are highly active in CMLBC, with marrow aplasia as the dose-limiting toxicity, and these agents deserve further study in CMLBC, perhaps in combination with tyrosine kinase inhibitors.

KW - Blast crisis

KW - Carboplatin

KW - Chronic myeloid leukemia-blast crisis

KW - CML

KW - Mitoxantrone

UR - http://www.scopus.com/inward/record.url?scp=77956900894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956900894&partnerID=8YFLogxK

U2 - 10.1007/s12032-009-9276-y

DO - 10.1007/s12032-009-9276-y

M3 - Article

VL - 27

SP - 728

EP - 735

JO - Medical Oncology and Tumor Pharmacotherapy

JF - Medical Oncology and Tumor Pharmacotherapy

SN - 0340-7004

IS - 3

ER -