Extended follow-up of patients treated with imatinib mesylate (gleevec) for chronic myelogenous leukemia relapse after allogeneic transplantation: durable cytogenetic remission and conversion to complete donor chimerism without graft-versus-host disease.
OBJECTIVE
Over the last several years, donor lymphocyte infusions have become the standard approach for patients with chronic myelogenous leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT). Recent reports indicate that imatinib mesylate (Gleevec) can induce remissions in these patients as well. Less is known about the extent and durability of these responses.


METHODS
We studied 15 patients treated with imatinib for recurrent CML after SCT, 10 patients with stable phase CML (SP-CML), 1 with accelerated phase (AP-CML), and 4 with blast phase (BP-CML). The dose of imatinib was 600 mg (n = 10) or 400 mg (n = 5) daily. Patients were followed for hematological, cytogenetic, and molecular response. A susbset of responders was followed for changes in donor-derived hematopoietic chimerism.


RESULTS
Of the 10 patients with SP-CML, all achieved a hematological response. Within 3 months, five of these patients had achieved a complete cytogenetic response (CCR). By six months, 9 of 10 patients had achieved CCR. The BCR-ABL transcript could not be detected by reverse transcription-PCR in 7 of these 9 patients. Patients who achieved CCR showed evidence of conversion to complete donor chimerism. No patient developed graft-versus-host disease. With a median follow up of 25 months, all patients are alive and 9 of 10 patients remain in CCR. Only one of the 5 patients with AP/BP-CML achieved a complete cytogenetic response.


CONCLUSIONS
We find that imatinib is well tolerated in patients with SP-CML who relapse after SCT. Responses were rapid, durable, and associated with conversion to full donor chimerism without graft-versus-host disease. Imantinib was far less effective in patients who relapsed with AP/BP-CML. Imatinib should be evaluated as either an alternative or as an adjunct to donor lymphocyte infusions for patients with SP-CML who relapse after SCT.
Dana-Farber Cancer Institute, Department of Adult Oncology, Boston, Massachusetts 02115, USA.
Daniel J
DJ
DeAngelo
Ephraim P
EP
Hochberg
Edwin P
EP
Alyea
Janina
J
Longtine
Stephanie
S
Lee
Ilene
I
Galinsky
Ben
B
Parekkedon
Jerome
J
Ritz
Joseph H
JH
Antin
Richard M
RM
Stone
Robert J
RJ
Soiffer
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D003582:Cytogenetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods; D013997:Time Factors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl