ISSN 1866-8836
Клеточная терапия и трансплантация

CM-03. Changes in treatment strategy for patients with advanced phase CML in the era of tyrosine kinase inhibitors

Elena V. Morozova, Yulia Y. Vlasova, Maria V. Barabanshikova, Evgenij A. Bakin, Ksenia S. Jurovskaya, Tatyana L. Gindina, Ildar M. Barkhatov, Sergey N. Bondarenko, Ivan S. Moiseev, Ludmila S. Zubarovskaya, Alexander D. Kulagin

RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia

Contact: Dr. Elena V. Morozova, e-mail:

doi 10.18620/ctt-1866-8836-2020-9-3-1-152



Although there is evident progress in treatment of advanced phase CML patients due to use of second- and third-generation tyrosine kinase inhibitors (TKIs), the overall prognosis is still unfavorable as most responses obtained are not durable enough. In our study we compared the results in cohorts matched by age and disease status based on whether the patient received conservative treatment or allo-HSCT in order to determine whether the latter strategy is able to improve the treatment outcomes.

Patients and methods

Eighty-two patients with AP/BC-CML with (allo-HSCT+TKIs,) or without (TKI n=80) history of allo-HSCT were included in this retrospective study. All patients received allo-HSCT with a reduced-intensity conditioning regimen with fludarabine 180 mg/m2 and busulfan 8-14 mg/kg or melphalan 140 mg/m2. Forty-two patients received TKIs for post-transplant relapse prophylaxis. In the majority of cases dasatinib was used (n=36). In the remaining 80 patients allo-HSCT was not performed due to refusal for personal reasons, delay in referral to transplant center or transplant-associated risks in patients with low ECOG score values.

The patients in TKI group were treated with chemotherapy+TKIs (60) or TKIs only (20). Eighty-one percent received second or third line TKIs. There were no significant differences in age, sex, comorbidity status, disease phase, and additional chromosomal aberrations incidence between allo-HSCT+TKI and TKI groups (Table 1). Overall survival (OS) was defined as the time from the start of treatment (allo-HSCT/TKI, chemotherapy) to death, event-free survival (EFS) – as the time between commencement of treatment and loss of response or post-transplant relapse, death. Response was defined according to European Leukemia Net and National Comprehensive Cancer Network recommendations. All patients signed an informed consent for processing of personal data; the trial was approved by Pavlov University local ethical committee.

Table 1. Patient characteristics



The median follow-up was 44 months (1-344). The engraftment was documented in 71 (86%) patients. The cumulative incidence of non-relapse mortality at day 100 and 1 year after allo-HSCT were 10% and 18%, respectively. Grade 2-4 acute graft-versus-host disease (GVHD) was documented in 21 (29%), grade 3-4 acute GVHD – 14 (20%), chronic GVHD – 18 (27%) including mild, moderate and severe form in 6 (9%), 8 (12%) and 4 (6%) patients, respectively. Two-year cumulative incidence of relapse was 39%. Twenty-four patients received donor lymphocyte infusions and TKIs after relapse, in 4 cases chemotherapy was added. In four cases only TKIs were administered to treat relapse. Nine patients achieved sustained complete molecular response (CMR), in 19 cases disease progression was documented. The data on response was available for 71 patients in TKI group. Among patients with BC 36 (59%) patients did not respond to therapy, while complete hematological response (CHR), complete cytogenetic response (CCR) and CMR were achieved in 22 (34%), 1 (2%) and 2 (3%) cases, respectively. Nine patients (90%) without BC history achieved response to therapy (CHR 5, CCR 2, CMR 2), while 1 patient failed to respond. Sixty-nine patients died; all deaths were CML-related. Four-year OS was 58% in allo-HSCT+TKIs versus 33% in TKI group (p=0.032) (Figure 1A). There was no significant difference in 4-year EFS between groups: 35% vs 17% (p=0.5), accordingly. BC at the moment of allo-HSCT significantly worsened 4-year OS: 23% vs 63% (p=0.007). The 4-year OS in patients transplanted in BC (n=10) was comparable to one in TKI group: 23% vs 33% (p=0.3) (figure 1B).


Figure 1. А. Four-year OS for allo-HSCT+TKIs and TKIs groups. B. Four-year OS for patients with history of AP/BC receiving allo-HSCT+TKIs, TKIs, and allo-HSCT in BC


While significant part of patients with advanced phase CML respond to conservative therapy, the responses are short-term. Our data suggest that timely referral of responders to transplant center can improve the outcome of allo-HSCT and prognosis in these group of patients.


Chronic myelogenous leukemia, BCR/ABL, advanced phase, allogeneic hematopoietic stem cell transplantation, tyrosine kinase inhibitors.

Volume 9, Number 3

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doi 10.18620/ctt-1866-8836-2020-9-3-1-152

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