The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells.
BACKGROUND
Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells.


METHODS
The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-phase CML who were treated with imatinib mesylate after failure of interferon-alpha according to whether they attained a major cytogenetic response (MCR) (n = 324 patients), an MCR with CCA/Ph-negative status (n = 30 patients), or no MCR (n = 161 patients).


RESULTS
CCA/Ph-negative status most frequently involved chromosomes Y, 8, and 7. No significant differences in pretherapeutic risk factors were detected between patients who attained an MCR with and without CCA/Ph-negative cells, except that exposure to alkylating agents was more frequent in patients with CCA/Ph-negative cells, and overall and progression-free survival were identical. With a median follow-up of 51 months, only 2 patients developed myelodysplastic syndromes (MDS).


CONCLUSIONS
The overall prognosis for patients who had CML with CCA/Ph-negative status was good and was driven by the CML response to imatinib mesylate. Isolated CCA/Ph-negative cells in the absence of morphologic evidence of MDS do not justify a change in therapy.
Deininger
Michael W N
MW
Division of Hematology and Medical Oncology, Oregon Health & Science University Cancer Institute, Portland, Oregon 97239, USA. deininge@ohsu.edu
Cortes
Jorge
J
Paquette
Ron
R
Park
Byung
B
Hochhaus
Andreas
A
Baccarani
Michele
M
Stone
Richard
R
Fischer
Thomas
T
Kantarjian
Hagop
H
Niederwieser
Dietger
D
Gambacorti-Passerini
Carlo
C
So
Charlene
C
Gathmann
Insa
I
Goldman
John M
JM
Smith
Douglas
D
Druker
Brian J
BJ
Guilhot
François
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D002908:Chronic Disease; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced; D017211:Treatment Failure; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate