Transplantation conditioning choices impact on CML outcomes revealed

By Lynda Williams, Senior medwireNews Reporter

For chronic myeloid leukaemia (CML) patients in their first chronic phase, the optimal pretransplantation conditioning regimen may be cyclophosphamide (Cy) combined with intravenous (iv) busulfan, research suggests.

Haematological, cytogenetic or molecular relapse occurred in the 5 years after transplantation in just 7% of patients given Cy with iv busulfan, relative to 17% of patients given Cy with total body irradiation (TBI) or Cy with oral busulfan, report Edward Copelan, from Levine Cancer Institute in Charlotte, North Carolina, USA, and co-workers.

As published in Biology of Blood and Marrow Transplantation, medical records were examined for 438 CML patients who received human leukocyte antigen (HLA)-matched sibling grafts and 235 CML patients with unrelated donor grafts between 2000 and 2006.

These included 222 patients whose preconditioning regimen was Cy alongside TBI, 354 patients who received Cy plus oral busulfan and 97 patients who were given Cy plus iv busulfan.

The majority of patients given oral busulfan (83%) or iv busulfan (67%) were given an HLA-identical sibling transplantation. TBI-treated patients were more likely to have received an unrelated donor graft (64%).

Multivariate analysis confirmed that iv busulfan was significantly associated with a reduced risk of relapse compared with TBI (relative risk [RR]=0.36) or oral busulfan (RR=0.39), but the choice of treatment did not influence the likelihood of nonrelapse mortality or overall survival.

However, there was a significant relationship between the likelihood of grade 3 or more severe acute graft versus host disease (GVHD), chronic GVHD and leukaemia-free survival, treatment choice and the type of donor transplantation received.

For patients with a HLA-identical sibling donor, the rates of acute and chronic GVHD did not significantly differ between the treatment groups, explain Copelan et al.

By contrast, patients with an unrelated donor had significantly higher rates of acute grade 3 or above GVHD if they received oral busulfan or iv busulfan than if they had TBI (RR=1.76 and 2.62, respectively). Chronic GVHD was also higher among unrelated donor recipients given oral busulfan, but not iv busulfan, compared with TBI (RR=2.73)

Leukaemia-free survival was significantly better for HLA-identical sibling recipients who received oral or iv busulfan versus TBI (RR=0.64 and 0.53, respectively), but this was not true for unrelated donor recipients.

Finally, tyrosine kinase inhibitor treatment before transplantation was associated with significantly better leukaemia-free survival, but did not impact on other outcomes.

“Absent results of a randomized trial, the association of i.v. [busulfan] with lower relapses rates in first chronic phase CML patients, and better [leukaemia-free survival] compared with TBI among recipients of HLA-identical sibling grafts, favors its use in that setting”, they conclude.

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