Continuous Complete Molecular Remission after Withdrawal of Imatinib Mesylate in Relapsed CML after Allogeneic Stem Cell Transplantation.
Authors: Siciliano Raffaele D. , Schmid Michael , Stussi Georg , Halter Joerg , Fehr Joerg , Schanz Urs 
Published: April 2020

Abstract
Imatinib mesylate (Gleevec®) has changed the treatment of chronic myelogenous leukemia (CML), but allogeneic stem cell transplantation (SCT) is still considered the only curative therapy. Moreover, several reports indicate that imatinib mesylate may also induce complete remission in relapsed CML following SCT, but it is not known, whether imatinib mesylate can be stopped after achieving complete remission. We report a patient who is in a complete molecular remission 4 months after withdrawal of imatinib mesylate therapy.
A 41-year old man was diagnosed with Philadelphia chromosome (Ph)-positive CML in first chronic phase without additional cytogenetic abnormalities. Hydroxyurea therapy was started and he received allogeneic SCT from an HLA-identical and sex-matched sibling donor within one year after the initial diagnosis. The conditioning regimen consisted of cyclophosphamide and total body irradiation (12Gy). A combination with cyclosporin A (CsA) and methotrexate was administered as a graft versus host disease (GvHD) prophylaxis. Nevertheless chronic extensive GvHD of the oral mucosa developed 3 months after SCT and resolved without further therapy. CsA was tapered after 3 and stopped after 6 months. The patient achieved complete cytogenetic remission (CCR) 9 months following SCT, but BCR-ABL remained positive by reverse transcriptase polymerase chain reaction (RT-PCR). Four years after SCT he experienced cytogenetic and morphologic relapse. Donor lymphocyte infusions were not administered, because the donor was not available, and Interferon therapy was started with an escalated dose of 9 Mio units per day.
With this treatment, a second CCR and also an acceptable molecular control (BCR-ABL measurements with RT-PCR between 0.3–2.5%) was achieved. The therapy was changed to imatinib mesylate (300–400mg per day) 6 years after SCT, because of persistent molecular detection of BCR-ABL. With this treatment, complete hematologic and molecular remission were attained 5 months later and 18 months after the beginning of imatinib mesylate treatment bone marrow examination revealed no abnormalities by morphological, cytogenetic or molecular analysis. Imatinib mesylate was stopped thereafter and RT-PCR to detected residual BCR-ABL transcripts was performed monthly. Four months after stopping imatinib mesylate, the patient remains in a complete molecular remission without clinical signs of GvHD.
Imatinib mesylate can induce sustained complete hematologic and molecular remission in patients with relapsed CML after allogeneic SCT. The combination of the imatinib mesylate and tumor reduction by graft versus leukemia may have synergistic effects in-vivo, and therefore facilitate the withdrawal of imatinib mesylate. Thus, the presented case shows the successful withdrawal of imatinib mesylate in a patient with relapse CML 6 years after allogeneic SCT. He continues to be in a complete molecular remission 4 months after withdrawal. However controlled studies are needed to establish the role of imatinib mesylate in the posttransplant setting.