Salvage alloSCT remains option for progressing CML patients

By Lynda Williams, Senior medwireNews Reporter

Research demonstrates the continuing role of allogeneic stem cell transplantation (alloSCT) as a salvage option for patients with chronic myeloid leukaemia (CML) who progress to accelerated phase or blast crisis after tyrosine kinase inhibitor (TKI) failure.

The review shows the declining use of alloSCT in CML patients in Australia and New Zealand following the introduction of imatinib in 2001, from 71 cases in 2000 to 201 cases in 2000-2004 and 80 patients in 2005-2010, as recorded in the Australasian Bone Marrow Transplant Recipient Registry.

The latest cohort were aged a median of 40 years, 60% were male and the majority (73%) were in their first, second or third chronic phase, while 26% had advanced phase disease. In all, 91% of these patients had been given imatinib, dasatinib or nilotinib before transplantation and 88% had experienced TKI resistance or intolerance.

Overall survival (OS) 5 years after alloSCT did not differ significantly for patients who underwent transplantation between 2005 and 2010 and those treated between 2000 and 2004, at 60.9% versus 58.1%, which the researchers describe as "very encouraging" considering the later population included higher proportions of older, advanced patients and those with unrelated donors.

And 5-year leukaemia-free survival was achieved by 45.7% of patients treated between 2005 and 2010, write Paul Kruger, from Fiona Stanley Hospital in Perth, Western Australia, and co-workers in a letter to Bone Marrow Transplantation.

For this later cohort, 48% developed grade II-IV acute graft versus host disease (GVHD) in the 100 days after alloSCT and 61% had developed any grade of acute GVHD after 2 years. CML relapse occurred in 7.7% within 6 months of transplantation and 14.1% after a year. Non-relapse-related rates of death at 100 days and 1 year post-transplantation were 13.8% and 22.6%, respectively.

Of note, various alloSCT risk factor combinations affected the OS of patients who underwent transplantation between 2001 and 2004. But for the later cohort, the only significant difference in OS was detected between patients aged up to 40 years who received an HLA-identical sibling alloSCT and older patients with an unrelated donor transplant, at 72.5% versus 37.6%.

"This suggests that in the TKI era, patients aged >40 with unrelated donors may have lower survival post alloSCT, although other risk factors may have less influence on survival", the authors write.

"Whether this is attributable to TKI therapy before alloSCT or other factors is uncertain and ultimately further experience is needed", they continue, noting that "[n]o negative outcomes have been documented if CML patients received TKI before alloSCT."

Kruger et al acknowledge ongoing efforts to reduce transplantation-related mortality and morbidity, such as reduced intensity conditioning, improvements in HLA matching and better supportive care, and suggest this may allow a wider range of patients to be considered for salvage alloSCT.

"Patients destined to fail TKI therapy at a relatively early stage as discovered by molecular monitoring and mutation analysis, and those presenting in advanced disease seem optimal for alloSCT", they observe.

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