Response to Tyrosine Kinase Inhibitors Therapy and Donor Lymphocyte Infusion In Patients with Chronic Myelogenous Leukemia Relapsing After Allogenic Hematopoietic Stem Cell Transplantation.
Authors: Sobczyk-Kruszelnicka Malgorzata , Czerw Tomasz , Waclawik Anna , Wichary Ryszard , Mendrek Wlodzimierz , Kyrcz-Krzemien Slawomira 
Published: October 2019

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.