Pre and post-transplantation factors associated with primary graft failure and severe poor graft function after allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia
Allogeneic stem cell transplantation (allo-HSCT) is used worldwide for long-term management and cure of hematological malignancies, still remaining a valuable option for treatment of chronic myeloid leukemia (CML) in all fit patients who are unable to achieve a durable complete cytogenetic response after treatment with tyrosine kinase inhibitors (TKIs), and in advanced-phase disease. Along with relapse risk, the unfavorable HSCT results may be associated with primary graft failure (PrGF), or poor graft function (PoGF). Hence, the aim of our study was to assess frequency and outcome of PrGF and severe poor graft function (sPGF) after allo-HSCT in CML patients. Patients and methods We performed a retrospective analysis of 121 consecutive patients with CML who received allo-HSCT in the RM Gorbacheva Research Institute at the Pavlov University over 25 years. HSCT was indicated in cases of advanced-phase disease, or TKI resistance/intolerance of CML patients. BCR/ABL transcript levels and additional chromosomal abnormalities were used as laboratory markers of advanced disease. 80 patients (66%) were transplanted in chronic phase (CP); 41 patients (34%) were in acceleration phase (AP), or blast crisis (BC) at the time of HSCT. Matched unrelated donors were used in 65% of the cases; matched related donors, in 28%, and haploidentical donors, in 7% of cases. Results Engraftment was documented in 106 (88%) patients. Post-transplant relapses were registered in 31 patients within 15-333 days after HSCT. PrGF was documented in 8 cases (7%). Two patients developed secondary graft failure within two months after initial engraftment, with lethal infectious complications. Severe poor graft function (PoGF) was diagnosed in 11 cases (9%) at cumulative incidence of 10% within 1 year post-transplant. Among various pre-transplant characteristics, age factor, and, especially, presence of additional chromosomal abnormalities (ACA) were associated with cumulative incidence of PrGF and sPGF after HSCT. I.e., PrGF was 14% in the group with detectable ACA versus 3% in the group without ACA, (p=0.02), whereas incidence of sPGF in patients with ACA was 2% versus 12% in those without ACA (p=0.09). The incidence of post-transplant relapses did not differ in the patients with PrGF and sPGF. Conclusions Primary graft failure (PrGF) contributes to the non-relapse mortality during the first year after allo-HSCT in CML patients. Emergence of post-transplant relapses was not associated with PrGF and sPGF in CML. Further assessment of risk factors for the graft failure or poor graft function is required in order to improve the results of HSCT technologies.