P. Lewalle MD, PhD

Practical management of chronic myeloid leukaemia in Belgium

Summary

Imatinib has drastically changed the outcome of patients with chronic myeloid leukaemia, with the majority of them showing a normal life span. Recently, the development of second and third generation tyrosine kinase inhibitors and the possibility of treatment discontinuation made the management of these patients more challenging. In this review, practical management guidelines of chronic myeloid leukaemia are presented adapted to the Belgian situation in 2014. In first line chronic phase patients, imatinib, nilotinib and dasatinib can be prescribed. While second generation tyrosine kinase inhibitors give faster and deeper responses, their impact on long-term survival remain to be determined. The choice of the tyrosine kinase inhibitor depends on chronic myeloid leukaemia risk score, priority for a deep response to allow a treatment-free remission protocol, age, presence of comorbid conditions, side effect profile, drug interactions, compliance concerns and price. Monitoring the response has to be done according the 2013 European LeukemiaNet criteria, and is based on the bone-marrow cytogenetic response during the first months and on the blood molecular response. Molecular follow-up is sufficient in patients with a complete cytogenetic response. For patients who fail frontline therapy, nilotinib, dasatinib, bosutinib and ponatinib are an option depending on the type of intolerance or resistance. T315I patients are only sensitive to ponatinib, which has to be carefully handled due to cardiovascular toxicity. Advanced phase diseases are more difficult to handle, with treatments including allogeneic stem cell transplantation, which is also an option for patients failing at least two tyrosine kinase inhibitors. The possibility of treatment-free remission and pregnancy are also discussed.

(BELG J HEMATOL 2015;6(1): 16–32)

P1.03 Thymoquinone induces DNA damage, apoptosis and inhibits proliferation in germinal center subtype of diffuse large B-cell lymphoma

P1.09 Follicular dendritic cell sarcoma in the retropharyngeal region: diagnostic and therapeutic challenges

P4.18 A long (GT)n repeat genetic variant in the promoter region of heme oxygenase-1 is associated with severe graft-versus-host disease

O.3 Comparison of 2 nonmyeloablative regimens for allogeneic HCT: a phase II randomized study from the HCT committee of the BHS

P1.11 Acute myeloblastic leukemia infiltrating-T lymphocyte characterization, from bone marrow and peripheral blood

A phase I/II single centre study of haploidentical transplantation combined with G-GSF, or GM-CSF, and escalating DLI in high-risk patients with no matched donors

Summary

In 1999, we decided to start a phase I/II study of haploidentical transplantation for high-risk patients. The aim of the work was to implement a strategy to accelerate and strengthen the immune reconstitution by using nonspecific manipulation post-transplant and by developing specific strategies directed against viral antigens. The goal was to increase the graft-versus-leukemia effect without inducing or aggravating the deleterious graft-versus-host disease. The conditioning regimen, adapted to our group of patients, remained the same throughout. Importantly, the first recruited patients were in refractory disease, over time we were referred less advanced patients (complete remission 2 or more). There were 45 patients, all at high-risk, among which 27 were in refractory relapse. We questioned the importance of post-transplant growth factors policy and the influence of donor lymphocyte infusion. Because of the conditioning, transplant-related mortality was low at 3 months, but thereafter changed unfavourably when using granulocyte macrophage-colony stimulating factors in an increased incidence of acute graft-versus-host disease. As a whole the long-term survival of the patients was poor (18%) but improved a lot when transplanted patients were in complete remission (leukaemia-free survival of 39% at five years). Regarding the use of growth factors and donor lymphocyte infusion, granulocyte macrophage-colony stimulating factors with donor lymphocyte infusion induced a very high transplant-related mortality due to a high rate of severe graft-versus-host disease, while the combination of granulocyte colony-stimulating factors and a moderate dose of donor lymphocyte infusion was much safer but didn’t overcome the high relapse rate in refractory patients. The combination of granulocyte colony-stimulating factors and donor lymphocyte infusion might nonetheless be sufficient to decrease the infection rate in patients transplanted in complete remission. The use of granulocyte macrophage-colony stimulating factors leads to an unacceptable lethal graft-versus-host disease rate. The 39% at five years leukaemia-free survival in patients in complete remission compares favourably with what can be achieved with matched unrelated donors in complete remission 2 or more.

(BELG J HEMATOL 2013;4(4): 151–160)