CML and allogeneic transplantation - who and when?

2016 ASH Meeting on Hematologic Malignancies; Chicago, Illinois, USA: 16–17 September

medwireNews: The role of allogeneic stem cell transplantation in patients with chronic myeloid leukaemia (CML) was discussed at the American Society of Hematology Meeting on Hematologic Malignancies in Chicago, Illinois, USA.

Bart Scott, from the Fred Hutchinson Cancer Research Center in Seattle, Washington, USA, opened the education session by reviewing the stages of CML, noting that accelerated phase (AP) can be defined on the basis of haematological or cytogenetic findings.

He also highlighted the distinction in treating patients who present with AP CML and those who are diagnosed initially with chronic phase (CP) CML and later progress to AP disease.

TKI use may avoid need for allogeneic transplantation in CP CML

Scott noted the “sharp decline” in use of allogeneic transplantation for CML since the approval of the tyrosine kinase inhibitor (TKI) imatinib in 2001, as demonstrated in transplant numbers at the Fred Hutchinson Cancer Research Center and monitoring by the European Bone Marrow Transplant Registry. It is not the standard approach to use allogeneic transplantation for patients in CP CML or patients with resistance to front-line TKI therapy, he said.

Data were presented showing response and survival after second-line TKIs in patients resistant to imatinib. In particular, second-line dasatinib^{1, 2} achieved a major cytogenetic response (MCyR) in 63% of patients at 2 years and a complete cytogenetic response (CCyR) in 50%. Progression-free survival was 80% at 2 years in this population.

Discussing “these pretty impressive results”, Scott said the data also included some patients intolerant to imatinib, thus forming “the argument to not perform allogeneic transplantation as second-line”.

However, he continued that it is particularly important to monitor cytogenetic and molecular responses in patients using second-line TKIs, as absence of cytogenetic response is an argument for considering allogeneic transplantation and early detection may benefit patients.

Use of allogeneic transplantation for newly diagnosed AP CML

Allogeneic transplantation is not usually considered for patients with a new CML diagnosis in the AP, Scott said.

He emphasized that a significant proportion of patients with a haematological and/or cytogenetic AP diagnosis will achieve a sustained haematological response, MCyR and CCyR to front-line TKI therapy.

CML survival after allogeneic transplantation

Survival after allogeneic transplantation is poorest for patients in blast crisis followed by those in AP, and best in patients with CP CML, data from the Fred Hutchinson Cancer Research Center showed. But Scott highlighted the 20% mortality rate in CP CML patients in the year after transplantation, leading to the recommendation for TKI therapy instead.

CML treatment summary

Scott summarised that CP CML should be treated with first-line and second-line TKIs, with allogeneic transplantation as a possible third-line option. Patients who are diagnosed with CML in the AP should be treated with first-line TKIs but those who have progressed to AP from CP should be considered for transplantation after TKIs.

For patients with blast phase CML, the approach should be an acute lymphocytic leukaemia or acute myeloid leukaemia chemotherapy regimen plus TKIs, with allogeneic transplantation at first available opportunity.

Audience question

Scott asked the audience to consider which of four patient case studies should be offered allogeneic transplantation.

The majority (68%) voted to offer the procedure to the 56-year-old woman who was newly diagnosed with blast crisis CML, including 30% myeloid blasts.

Seven percent of the audience opted to offer transplantation to a 48-year-old female with AP CML meeting both haematological and cytogenetic criteria for diagnosis, and a further 7% chose to offer transplantation to a 51-year-old patient with CP CML who did not respond to imatinib.

Just 1% of the audience considered offering allogeneic transplantation to a 32-year-old man with CP CML and concerns regarding the side effects of TKIs.

By Lynda Williams, Senior medwireNews Reporter

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