Is Imatinib Maintenance Required for Patients with Relapse Chronic Myeloid Leukemia Post-Transplantation Obtaining CMR? A Pilot Retrospective Investigation

Jin, Hua; Xiong, Yufeng; Sun, Jing; Huang, Fen; Zhou, Hongsheng; Zhang, Fan; Xu, Dan; Wei, Yongqiang; Dai, Min; Feng, Ru; Liu, Qifa

doi:10.1371/journal.pone.0065981

Cited by 4 publications

(4 citation statements)

References 48 publications

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“…On the other hand, GVHD seems to be highly correlated to response rates [ 21 , 22 ]. TKIs are now accepted as the preferred alternative for treating CML relapse after allo-SCT [ 23 – 25 ]. TKIs can induce complete cytogenetic responses (CCRs) and deep molecular response (MR), even in patients failing DLI, and the treatment is without risk of GVHD [ 26 – 28 ].…”

Section: Discussionmentioning

confidence: 99%

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Chronic Myeloid Leukemia Relapsing 25 Years after Allogenic Stem Cell Transplantation

Reikvam

Skavland

Gullaksen

et al. 2018

Case Reports in Hematology

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Chronic myeloid leukemia (CML) is a myeloproliferative disorder in which neoplastic cells exhibit the Philadelphia chromosome and the related oncoprotein BCR-ABL1. Allogeneic stem cell transplantation (allo-SCT) was considered the first-line treatment for CML, before the introduction of tyrosine kinase inhibitors (TKIs). However, patients are at risk for relapse years after transplantation. We present a patient who relapsed 25 years after allo-SCT for chronic phase CML. Polymerase chain reaction (PCR) detected gradually evaluated levels of BCR-ABL1 transcripts, eventually leading to the diagnosis of relapsed disease. Additional mutational analyses did not reveal mutations in the BCR-ABL1 gene, or other cooperating mutations. The patient was successfully treated with imatinib 400 mg daily, leading to new molecular remission. The case presentation emphasizes the need for long-term follow-up of such patients and the potential benefit of initiating TKI treatment with early signs of relapse.

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Section: Discussionmentioning

confidence: 99%

“…TKIs have the potential for changing the kinetics of the disease and should probably be recommended for CML patients allo-grafted [ 33 , 34 ], also in the advanced phase of the disease [ 33 , 34 ]. Maintenance therapy may not be required for patients that achieve full donor chimerism and deep MR [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic Myeloid Leukemia Relapsing 25 Years after Allogenic Stem Cell Transplantation

Reikvam

Skavland

Gullaksen

et al. 2018

Case Reports in Hematology

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“…In an early study by Weisser et al [26], DLI was superior to treatment with imatinib in terms of leukemia-free survival, suggesting that TKI alone might not provide definite cure for relapsed CML after alloSCT. In contrast, a more recent report demonstrated that imatinib treatment resulted in higher overall and diseasefree survival compared with those after DLI [27]. Moreover, concomitant use of imatinib was not associated with an increased risk of secondary GVHD [17], and in a small series, imatinib was shown to synergize with DLI to achieve rapid CMR of CML relapsing after alloSCT [28].…”

Section: Discussionmentioning

confidence: 92%

Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

Radujkovic

Guglielmi

Bergantini

et al. 2015

Biology of Blood and Marrow Transplantation

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Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.

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“…In recent years, TKIs have been used as pretransplant and maintenance therapy following allogeneic HSCT in CML, especially in advanced phase disease. Historically, in TKI naïve patients, imatinib resulted in higher rates of overall and disease-free survival than DLI in CML relapse after HSCT [ 76 ]. TKIs were also found to be better tolerated than DLI and produced durable remission in most patients with CML who have relapsed disease, especially chronic-phase relapses, after HSCT [ 77 ].…”

Section: Leveraging the Immune System To Enhance Tfr In Cml: Nonspecific Immune Approachesmentioning

confidence: 99%

Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape

2021

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The quest for treatment-free remission (TFR) and deep molecular response (DMR) in chronic myeloid leukemia (CML) has been profoundly impacted by tyrosine kinase inhibitors (TKIs). Immunologic surveillance of residual leukemic cells is hypothesized to be one of the critical factors in successful TFR, with self-renewing leukemic stem cells implicated in relapse. Immunological characterization in CML may help to develop novel immunotherapies that specifically target residual leukemic cells upon TKI discontinuation to improve TFR rates. This review focuses on immune dysfunction in newly diagnosed CML patients, and the role that TKIs and other therapies have in restoring immune surveillance. Immune dysfunction and immunosurveillance in CML points towards several emerging areas in the key goals of DMR and TFR, including: (1) Aspects of innate immune system, in particular natural killer cells and the newly emerging target plasmacytoid dendritic cells. (2) The adaptive immune system, with promise shown in regard to leukemia-associated antigen vaccine-induced CD8 cytotoxic T-cells (CTL) responses, increased CTL expansion, and immune checkpoint inhibitors. (3) Immune suppressive myeloid-derived suppressor cells and T regulatory cells that are reduced in DMR and TFR. (4) Immunomodulator mesenchymal stromal cells that critically contribute to leukomogenesis through immunosuppressive properties and TKI- resistance. Therapeutic strategies that leverage existing immunological approaches include donor lymphocyte infusions, that continue to be used, often in combination with TKIs, in patients relapsing following allogeneic stem cell transplant. Furthermore, previous standards-of-care, including interferon-α, hold promise in attaining TFR in the post-TKI era. A deeper understanding of the immunological landscape in CML is therefore vital for both the development of novel and the repurposing of older therapies to improve TFR outcomes.

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Is Imatinib Maintenance Required for Patients with Relapse Chronic Myeloid Leukemia Post-Transplantation Obtaining CMR? A Pilot Retrospective Investigation

Cited by 4 publications

References 48 publications

Chronic Myeloid Leukemia Relapsing 25 Years after Allogenic Stem Cell Transplantation

Chronic Myeloid Leukemia Relapsing 25 Years after Allogenic Stem Cell Transplantation

Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape

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