Chronic myeloid leukemia following therapy with imatinib mesylate (Gleevec). Bone marrow histopathology and correlation with genetic status.
We evaluated bone marrow pathologic features and cytogenetic and molecular genetic status of 13 patients with interferon-resistant, chronic-phase chronic myeloid leukemia (CML), treated with imatinib mesylate (Gleevec). All had morphologic evidence of CML in the blood and bone marrow and were positive for bcr-abl by reverse transcriptase-polymerase chain reaction, fluorescence in situ hybridization (FISH), or both. Follow-up marrow biopsies, interphase FISH for bcr-abl, and conventional cytogenetics were performed at 3-month intervals (up to 24 months) after therapy initiation. All patients exhibited a reduction in bone marrow cellularity with decreases in myeloid/erythroid ratios at 3 to 6 months after therapy. The percentage of bcr-abl-positive cells by FISH decreased in all patients (pretherapy median, 73%; 3 months median, 47%). Cytogenetic and FISH data defined 2 groups after 6 months of follow-up: 5 patients became negative for bcr-abl by FISH; 8 remained positive, 4 of whom developed signs of clonal cytogenetic evolution. Patients who became negative for bcr-abl had no morphologic evidence of CML at 15 to 24 months of follow-up, whereas patients who remained positive redeveloped morphologic features of CML as cellularity increased. Some bcr-abl-positive patients showed signs of progression, including 2 patients who developed myeloid blast phase. Although all patients demonstrated an initial decrease in bone marrow cellularity after imatinib mesylate therapy, continued follow-up showed that histopathologic findings correlated with genetic response.
Frater
John L
JL
Department of Pathology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Tallman
Martin S
MS
Variakojis
Daina
D
Druker
Brian J
BJ
Resta
Debra
D
Riley
Mary Beth
MB
Hrisinko
Mary Ann
MA
Peterson
LoAnn C
LC
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D020732:Cytogenetic Analysis; D004351:Drug Resistance; D005355:Fibrosis; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006644:Histiocytes / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007372:Interferons; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D007958:Leukocyte Count; D008533:Megakaryocytes / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012155:Reticulin / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012155:Reticulin; D000068877:Imatinib Mesylate; D007372:Interferons; D016044:Fusion Proteins, bcr-abl