Heart and Blood Diseases

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Hypertension

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Leukemia

Leukemia, Myeloid

Hypertension, Pulmonary

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

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Hematologic Diseases

Myeloproliferative Disorders

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Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

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Nilotinib

Dasatinib

echo, exercise echo, and if indicated, right heart catheter

routine echocardiography and special measurements of the right heart are performed at rest and during exercise

Echo, exercise echo, and if indicated, right heart catheter

Horst Olschewski, MD

Chronic myelogenous leukemia (CML) is a chronic myeloproliferative disorder characterized by a translocation between chromosome 9 and 22, leading to a pathogenic tyrosine kinase signal transduction protein. CML can be treated with tyrosine kinase inhibitors (TKIs), which inhibit BCR/ABL kinase, such as imatinib. In about 20% of CML patients who are treated by imatinib, a complete cytogenetic response cannot be achieved. The other two novel TKIs (dasatinib and nilotinib), achieve higher rates of complete cytogenetic response and they are proposed as second-line therapy for imatinib-resistant patients or for those who do not tolerate imatinib. Dasatinib inhibits BCR/ABL kinase in about \>300 times in vitro in more than imatinib and also inhibits several other kinases, including the Src family. Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries. Imatinib and nilotinib do not inhibit the Src.

Incident cases of precapillary PH have been reported in patients who have CML treated with the dasatinib. Improvements were usually observed after withdrawal of dasatinib.

This study is designed to identify incident cases of dasatinib-associated PH and describe pulmonary vascular changes induced by dasatinib. As comparison population will be patients who receive another second-line TKI (nilotinib).

Doppler echocardiography at rest will be performed in each patient. Patients without exercise capacity limitation an exercise test (Doppler echocardiography with spiroergometry) will be performed. Patients who show elevated SPAP at rest or during exercise (in this study SPAP ≥ 40 mmHg) or with reduced exercise capacity (peak VO2 \< 75%) a right heart catheterization (RHC) will be suggested. Additionally for the evaluation of exercise capacity a 6 MWD will be performed. This work- up of patients allows clinical and hemodynamic evaluation.

Samples with DNA will be retained for later examinations at the Biobank, in case that the patient agrees (extra patient information). The blood samples are taken only during routine tests.

Pulmonary Vasculopathy Under Second-line Therapy of Chronic Myeloid Leukemia

Pulmonary Vascular Changes in Patients With Chronic Myeloid Leukemia With Second-line Therapy Dasatinib vs. Nilotinib

In patients who undergo stressechocardiography: systolic pulmonary arterial pressure (SPAP) at 50W will be measured and the comparison between patients under dasatinib and nilotinib therapy will be performed.

Mean PAP at rest, mPAP at 50W, peak VO2, 6 minute walk distance (6MWD), N terminal pro brain natriuretic peptide (NT-proBNP) at "dasatinib" vs."nilotinib" patients.

Changes of SPAP at 50 W, pulmonary vascular resistance (PVR) at rest, changes of mPAP at rest and at 50W, peak VO2, 6 MWD, NT-pro BNP- in patients with dasatinib and nilotinib between the baseline and 6 months after.

Changes of SPAP at 50 W, pulmonary vascular resistance (PVR) at rest, changes of mPAP at rest and at 50W, peak VO2, 6 MWD, NT-pro BNP- in patients with dasatinib and nilotinib between the baseline and 6 months after.

In patients who undergo a RHC: pulmonary vascular resistance (PVR) at rest will be measured and the comparison of patients with dasatinib and nilotinib therapy will be performed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pulmonary Vasculopathy Under Second-line Therapy of Chronic Myeloid Leukemia	NCT01805843	Chronic Myeloid...	Echo, exercise ...	18 Years - 95 Years	Medical University of Graz
Pulmonary Vasculopathy Under Second-line Therapy of Chronic Myeloid Leukemia	NCT01805843	Chronic Myeloid...	Echo, exercise ...	18 Years - 95 Years	Medical University of Graz

Spots Global Cancer Trial Database for echo, exercise echo, and if indicated, right heart catheter