Retrospective Analysis of Treatment Outcomes of Allogeneic Stem Cell Transplantation for Chronic Myeloid Leukemia After TKI Failure

Allogeneic stem cell transplantation (SCT) remains the only currently available treatment that can render patients durably molecularly negative, but the associated procedural-related morbidity and mortality remain a major deterrent.

Currently the followings are accepted as reasonable indication for allogeneic SCT for CML: failure to 2nd generation tyrosine kinase inhibitor (2GTKI) after imatinib failure, 2GTKI frontline failure, or any patients meeting the criteria of failure such as development of additional cytogenetic abnormality (ACA), clonal evolution in ph neg clone, development of mutation and loss of CCyR as well as any advanced disease stage including accelerated or blastic phase. However, insufficient numbers of patients have been transplanted in recent years and after TKI therapy, thus necessitating update of this data.

The EBMT risk score has been used for a decade for the decision making of transplantation in the pre-imatinib era. However, it has never been re-evaluated in a larger cohort of CML patients treated with TKIs prior to SCT then received alloSCT, thus requiring to be reanalysed for its prognostic implication on long-term survival.

As mentioned above, any update was not reported on the transplant outcomes in the patients failed TKI therapy, thus necessitating update of this data. Also, the EBMT risk score2 is still of value, but insufficient numbers of patients have been transplanted in recent years and after TKI therapy to allow a robust reanalysis.

This is retrospective study. The medical records will be reviewed retrospectively. The treatment outcomes such as complete cytogenetic response (CCyR), major molecular response (MMR), molecular response at 4.5 log reduction (MR4.5), treatment failure (TF), progression free survival (PFS) and overall survival (OS) will be estimated using Kaplan-Meier method. The CCR will be defined as 0% of Ph+ metaphase cells in the marrow or less than 1% by international scale using BCR-ABL1 transcript polymerase chain reaction (PCR) test. The MMR is defined as lower than or equal to a 0.1%IS of BCR-ABL1 fusion gene transcripts, and MR4.5 is defined as 0.0032%IS BCR-ABL1 transcript level, equivalent to a 4.5 log reduction of BCR-ABL1 transcript level. Time to treatment failure (TTF) is defined as the interval between allogeneic SCT and the occurrence of events that indicated that CML has relapsed including primary hematologic resistance, cytogenetic resistance, loss of CCyR, development of ABL tyrosine kinase domain mutation, clonal evolution and progression to accelerated phase (AP) or blastic crisis (BC). Death is considered as censored for TTF. Time to PFS is defined as the interval between transplantation and confirmation of progression to AP or BC or death from any cause, while OS was calculated from transplantation until the date of death from any cause or of latest follow-up.