HCT not precluded by prior second-generation TKI therapy in chronic, advanced phase CML

By Shreeya Nanda, Senior medwireNews Reporter

Allogeneic haematopoietic stem cell transplantation (HCT) can be considered for chronic- and accelerated-phase chronic myeloid leukaemia (CML) patients with prior exposure to second-generation tyrosine kinase inhibitors (TKIs), say Polish researchers.

Patients in blast phase, however, have an increased risk of severe complications and relapse after HCT, they write in the Annals of Hematology, adding that the “optimal approach” in these patients is to reduce the leukaemic burden before HCT.

HCT engraftment was successful in all but one of the 28 CML patients treated with second-line dasatinib, nilotinib or both sequentially prior to undergoing HCT. Eighteen patients attained a deep molecular response and five a major molecular response, at a median of 1.8 months and 1.1 months after HCT, respectively. And four patients achieved a minor molecular response.

After a median follow-up of 19 months, 1- and 3-year overall survival (OS) rates were identical at 71.4%, as all nine deaths occurred in the first year after HCT.

One of 14 patients in the first chronic phase and two of eight in the second chronic or accelerated phase died post-transplantation, giving Kaplan–Meier estimates for OS of 92.9% and 85.7%, respectively. By contrast, all six patients who received transplantation in blast phase died shortly after transplantation, either due to relapse or complications.

In all, 29.6% of the study cohort experienced post-HCT relapse, with relapse rates of 21.4%, 12.5% and 50.0% for patients in the first chronic, second chronic or accelerated, and blast phases, respectively.

Veno-occlusive disease (VOD) occurred in 25.0% of the overall cohort, in 13.6% of patients in the first chronic, second chronic or accelerated phase, and in 66.7% of those in blast phase. Two blast-phase patients died as a result of VOD, one of whom also experienced multiorgan failure. The remaining five patients – of whom two were in blast phase – had mild or moderate VOD, which resolved after treatment, the investigators report.

Acute graft versus host disease (GvHD) was observed in 25.9% of 27 patients, of whom 14.9% had grade III or IV disease. The incidence rate by CML phase was 7.1% for patients in the first chronic phase, 37.5% for those in the second chronic or accelerated phase and 50.0% for blast-phase patients.

And chronic GvHD developed in 42.9% of 21 patients with more than 100 days of follow-up.

Non-relapse mortality rates, which included deaths attributable to VOD and GvHD-related complications, were 7.1%, 12.5% and 50.0%, for patients in the first chronic, second chronic or accelerated, and blast phases, respectively.

The team led by Agnieszka Piekarska (Medical University of Gdansk) emphasises that HCT is a “safe and reasonable approach” for second-generation TKI-treated patients with chronic- or accelerated-phase CML.

“Nonetheless, further studies are warranted to assess the individual influence of nilotinib and dasatinib on the transplant-related toxicity and the outcome of HCT”, say the authors.

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