scholarly journals Efficacy of Allogeneic Hematopoietic Cell Transplantation in Patients with Chronic Phase CML Resistant or Intolerant to Tyrosine Kinase Inhibitors

2021 ◽  
Author(s):  
Farah Yassine ◽  
Tea Reljic ◽  
Muhamad Alhaj Moustafa ◽  
Madiha Iqbal ◽  
Hemant S. Murthy ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Kinase Inhibitors ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Phase ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation

scholarly journals Tyrosine kinase inhibitors and immune checkpoint blockade in allogeneic hematopoietic cell transplantation

Blood ◽  
2018 ◽  
Vol 131 (10) ◽  
pp. 1073-1080 ◽  
Author(s):  
Robert J. Soiffer ◽  
Matthew S. Davids ◽  
Yi-Bin Chen
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Immune Checkpoint ◽  
Kinase Inhibitors ◽  
Hematopoietic Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Therapeutic Window

Abstract Advances in the prevention of graft-versus-host disease (GVHD) and opportunistic infection have improved survival after allogeneic hematopoietic cell transplantation (allo-HCT) in the past decade. However, few inroads have been made into the treatment or prevention of relapse of the underlying malignancy for which allo-HCT is being performed. The introduction of US Food and Drug Administration–approved agents with significant activity in a variety of hematologic malignancies provides an opportunity to evaluate these interventions in the allo-HCT setting. Some of the most promising new agents include tyrosine kinase inhibitors (TKIs) directed at bcr-abl, kinase inhibitors targeting fms-like tyrosine kinase 3, and immune checkpoint inhibitors blocking both CTLA4 and PD-1. Data have emerged indicating potential efficacy of these agents in preventing or treating relapse, though definitive evidence remains elusive. However, potential toxicity can be considerable, highlighting the need for further clinical trials to define the therapeutic window. This review explores the immunologic and clinical consequence of treatment with both TKIs and checkpoint inhibitors in the peri- and post–allo-HCT setting.

Three decades of transplantation for chronic myeloid leukemia: what have we learned?

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 755-763 ◽  
Author(s):  
Jiří Pavlů ◽  
Richard M. Szydlo ◽  
John M. Goldman ◽  
Jane F. Apperley
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Hematopoietic Stem

Abstract Last year marked 30 years of hematopoietic stem cell transplantation as a curative treatment of chronic myeloid leukemia (CML). Initially studies used stem cells from identical twins but techniques rapidly developed to use cells first from HLA-identical siblings and later unrelated donors. During the 1990s CML became the most frequent indication for allogeneic transplantation worldwide. This, together with the relative biologic homogeneity of CML in chronic phase, its responsiveness to graft-versus-leukemia effect and the ability to monitor low level residual disease placed CML at the forefront of research into different strategies of stem cell transplantation. The introduction of BCR-ABL1 tyrosine kinase inhibitors during the last decade resulted in long-term disease control in the majority of patients with CML. In those who fail to respond and/or develop intolerance to these agents, transplantation remains an effective therapeutic solution. The combination of tyrosine kinase inhibitors with transplantation is an exciting new strategy and it provides inspiration for similar approaches in other malignancies.

Response to Tyrosine Kinase Inhibitors Therapy and Donor Lymphocyte Infusion In Patients with Chronic Myelogenous Leukemia Relapsing After Allogenic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4482-4482
Author(s):  
Malgorzata Sobczyk-Kruszelnicka ◽  
Tomasz Czerw ◽  
Anna Waclawik ◽  
Ryszard Wichary ◽  
Wlodzimierz Mendrek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Donor Chimerism

Abstract Abstract 4482 Tyrosine kinase inhibitors (TKIs) and donor limfocyte infusion (DLI) are nowadays possible treatment options to treat relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (alloHSCT). This report aim was to analyze management and outome of CML relapse after alloHSCT based on single centre experience. We retrospectively reviewed 8 patients treated with TKIs and/or DLI for CML relapse after alloHSCT. Study group chracteristic before transplantation: 8 patients (4 women, 4 men); median age 31 years (25-53); disease duration before alloHSCT 10 months (4-33); prior transplantation treatment: imatinib (n=8), nilotinib (n=1); CML phase: chronic phase 1 (n=7), chronic phase 2 (n=1); remission status: hematological (n=8), cytogenetic (n=4), molecular (n=3); donor type (identical sibling – 4, matched unrelated –3, 1 HLA-antigen mismatched unrelated – 1); stem cell source (bone marrow – 7, peripheral blood – 1); conditioning regimen (treosulfan and fludarabine – 7; busulfan and cyclophosphamide – 1); EBMT transplant risk score 2.5 (1-5). All transplantations were performed in intensive care, sterile air units. Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine A and short course of standard dose methotrexate. The median number of transplanted cells: nucleated cells 3.3 × 10^8 (2.1-8.9); CD34(+) cells 3.6 × 10^6 (0.8-12.9); CD3(+) cells 19.3 × 10^6 (17.6-237)/kg recipient body weight. All patients engrafted and achieved full donor chimerism before day 100 after transplantation. Hematopoietic recovery was as follows: leukocytes to 1,0 G/l – median 21 days (12-39); granulocytes to 0,5 G/l - 21 (12-42); platelets to 50 G/l –23 (18-38). Only 3 patients had signs of acute GvHD – grade I (1pt – skin 2 degree; 2pts – skin 1 degree). 8 patients relapsed at median time 5 months after HSCT (4-24). Type of relapse: hematologic –0, cytogenetic-4, molecular – 8. At the time of relapse four patients were still treated with immunosuppressive agents. The median donor chimerism at the relapse was 90% (40-100%) and in 5 cases was lower than 95%. All patients who relapsed started treatment with TKIs (imatinib-7; nilotinib-1). The madian treatment time is 10 months (2-50). Four of them are still treated with TKIs. Seven patients recieved also DLI – median 1.5 times (1-6). 7 of 8 patients patients achieved molecular remission and 1 patient a complete cytogenetic response. All patients who achieved remission showed evidence of conversion to complete donor chimerism. DLI have become the treatment of choise for CML patients who relapsed after allogenic HSCT. An alternative to DLI are now TKIs: imatinib or second line TKIs. Is the DLI still the “gold standard”? Or better chose only TKIs to achieve remission without the risk of GvHD? Or chose the combination with lower doses of DLI to maximise responses while minimising the risk of GvHD? We are still looking for optimal and most effective treatment option for these patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Direct Comparison of Long-Term Outcome of Allogeneic Transplantation for Myelofibrosis in Chronic and Leukemic Stage in a Single Institute

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5382-5382
Author(s):  
Shinsuke Takagi ◽  
Takashi Mitsuki ◽  
Mitsuhiro Yuasa ◽  
Kosei Kageyama ◽  
Daisuke Kaji ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Phase ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Toranomon Hospital

INTRODUCTION: Allogeneic hematopoietic cell transplantation provides an opportunity for a cure of myeloproliferative neoplasms (MPNs). Although several studies showed its efficacy even for leukemic transformation (LT) from MPNs, no direct evidence exists which compared the long-term outcome of patients in chronic phase (CP) and LT in a same cohort. METHODS: We retrospectively studied allogeneic hematopoietic cell transplantation for MPNs between 1999 and 2017 in Toranomon Hospital. LT was defined according to the WHO classification in 2016. Risk stratification was according to the dynamic international prognostic scoring system (DIPSS). The spleen index was defined as the measurement of spleen on CT scan. The day of neutrophil and platelet engraftment was defined as the first 3 consecutive days on which the patient's absolute neutrophil and platelet count was >0.5 x 109/L and >20 x 109/L without platelet transfusion, respectively. The study was approved by the ethics committee of Toranomon Hospital (research number #1796), and conducted in accordance with the Declaration of Helsinki. RESULTS: A total of 36 patients were extracted. At transplantation, the disease status of MPN was CP in 16 patients (44%) and LT in 20 (56%). Median spleen index was significantly lower in LT than CP (104 cm2 vs. 150 cm2, p < 0.01), and more CP patients received splenic irradiation before transplantation (p = 0.04). At the start of conditioning regimen, a half of the patients in LT was not in remission even after chemotherapy. Most patients in CP used bone marrow or peripheral blood stem cells, whereas umbilical cord blood (U-CB) was preferred for patients in LT (p < 0.001). Among these 2 cohorts, the cumulative incidence of neutrophil and platelet engraftment was comparable at day 60 and at 1 year after transplantation, respectively (neutrophil engraftment: 87.5% in CP vs. 80.0% in LT, p = 0.11; platelet engraftment: 68.8% in CP vs. 65.0% in LT, p = 0.70). Overall survival (OS) was significantly superior for patients in CP to ones in LT (p = 0.02) (Figure). OS rate at 5 and 10 years after transplantation for patients in CP and LT were 56.2% (95% confidence interval [CI], 1.0 - 35.4) vs. 11.2% (95% CI, 29.5 - 76.2), and 45.0% (95% CI, 17.8 - 69.1) vs. 0%, respectively. Median survival was 7.5 and 0.9 years for patients in CP and LT, respectively. Median follow up of survivors in CP and LT was 1652 days (range, 980 - 5395) and 906 days (range, 522 - 1014), respectively. At 10 years after transplantation, the cumulative incidence of relapse was significantly higher for patients in LT than ones in CP (6.2% in CP vs. 38.0% in LT, p = 0.04). In LT patients, disease recurrence occurred within 3 years after transplantation and 7 out of 17 patients (41%) died of relapse after transplantation. CONCLUSION: To achieve a long-term relapse-free survival, it is crucial for MPN patients to undergo transplantation in chronic phase, not after the development of LT. Delayed decision to transplant may be critical for patients who are at high risk for LT. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia

2018 ◽  
Vol 2 (21) ◽  
pp. 2922-2936 ◽  
Author(s):  
Saurabh Chhabra ◽  
Kwang Woo Ahn ◽  
Zhen-Huan Hu ◽  
Sandeep Jain ◽  
Amer Assal ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Phase ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Research Database ◽  
Significant Difference ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.

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