Contributions
Abstract: PB1513
Type: Publication Only
Session title: Chronic myeloid leukemia - Clinical
Background
Dasatinib, a tyrosine kinase inhibitor (TKI), is known to induce pulmonary hypertension (PH) in patients with chronic myelogenous leukemia (CML). Although PH is usually reversed on discontinuation of dasatinib, this is based mainly on case reports and small case series. It remains unclear whether other TKIs, such as imatinib or nilotinib, are also linked to PH. In addition, there have been few reports on PH in newly diagnosed CML patients.
Aims
In this study, we analyzed the prevalence of PH and its clinical implications in both newly diagnosed and TKI-treated CML patients.
Methods
The medical records of newly diagnosed CML patients who underwent transthoracic echocardiographic examination (TTE) at diagnosis, and of TKI-treated patients who underwent TTE at least once during treatment at Chungnam National University Hospital from January 2003 to June 2020, were analyzed retrospectively. The TTE results were reviewed by two cardiologists and a diagnosis of PH was made when the PH probability was “high” according to the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines.
Results
Of 189 CML patients diagnosed and/or treated during the study period, 57 (30.2%) and 112 (59.3%) underwent TTE at the time of CML diagnosis and during TKI treatment, respectively, and were therefore enrolled in the study. The majority of patients underwent TTE more recently; 40 (70.2%) of the 57 newly diagnosed patients and 92 (82.1%) of the 112 TKI-treated patients underwent TTE between January 2017 and June 2020, respectively. The majority of patients underwent TTE to screen for PH; only 7 (12.3%) of the 57 newly diagnosed patients and 11 (9.8%) of the 112 TKI-treated patients underwent TTE due to cardiopulmonary symptoms. Among the 57 newly diagnosed patients, 4 (7.0%) had PH. PH resolved in three (75.0%) of those four patients after TKI treatment (imatinib in two patients and nilotinib in one patient). PH continued for 8 years in a male patient (aged 61 years at CML diagnosis) despite changes in the TKI (from imatinib to nilotinib, and then to dasatinib); he had no specific PH-related symptoms. In TKI-treated patients, the median TKI treatment time was 40.4 months (range: 0.1–167.2 months). PH was found in 12 (10.7%) of the 112 TKI-treated patients, most frequently in the dasatinib-treated patients [i.e., in 3 (7.5%) of 40 in the imatinib-treated group, 1 (3.1%) of 32 in the nilotinib-treated group, and 8 (21.6%) of 37 in the dasatinib-treated group]. In multivariate logistic regression analyses, age > 60 years (OR, 12.3; 95% CI, 1.1–142.1, p = 0.044), dasatinib treatment (OR, 8.2; 95% CI, 1.3–50.6, p = 0.026), and positive cardiopulmonary symptoms/signs at the time of undergoing TTE (OR, 36.1; 95% CI, 5.3–247.3, p = 0.001) were statistically significant risk factors for developing PH. PH resolved in five (62.5%) of the eight dasatinib-treated patients after discontinuation of the agent. However, PH persisted in three patients, i.e., in one since CML diagnosis and in two despite discontinuing dasatinib; one of those patients had exertional dyspnea. All three imatinib-treated patients recovered from PH: one after the TKI was changed and two despite continuing imatinib. One nilotinib-treated patient also recovered from PH after the TKI was changed.
Conclusion
PH is common in CML patients treated with dasatinib; however, it is also observed in patients treated with imatinib or nilotinib, and even in newly diagnosed patients. Careful screening for PH both at the time of diagnosis and during any TKI treatment is warranted in patients with CML.
Keyword(s): Chronic myeloid leukemia, Pulmonary hypertension, Tyrosine kinase inhibitor
Abstract: PB1513
Type: Publication Only
Session title: Chronic myeloid leukemia - Clinical
Background
Dasatinib, a tyrosine kinase inhibitor (TKI), is known to induce pulmonary hypertension (PH) in patients with chronic myelogenous leukemia (CML). Although PH is usually reversed on discontinuation of dasatinib, this is based mainly on case reports and small case series. It remains unclear whether other TKIs, such as imatinib or nilotinib, are also linked to PH. In addition, there have been few reports on PH in newly diagnosed CML patients.
Aims
In this study, we analyzed the prevalence of PH and its clinical implications in both newly diagnosed and TKI-treated CML patients.
Methods
The medical records of newly diagnosed CML patients who underwent transthoracic echocardiographic examination (TTE) at diagnosis, and of TKI-treated patients who underwent TTE at least once during treatment at Chungnam National University Hospital from January 2003 to June 2020, were analyzed retrospectively. The TTE results were reviewed by two cardiologists and a diagnosis of PH was made when the PH probability was “high” according to the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines.
Results
Of 189 CML patients diagnosed and/or treated during the study period, 57 (30.2%) and 112 (59.3%) underwent TTE at the time of CML diagnosis and during TKI treatment, respectively, and were therefore enrolled in the study. The majority of patients underwent TTE more recently; 40 (70.2%) of the 57 newly diagnosed patients and 92 (82.1%) of the 112 TKI-treated patients underwent TTE between January 2017 and June 2020, respectively. The majority of patients underwent TTE to screen for PH; only 7 (12.3%) of the 57 newly diagnosed patients and 11 (9.8%) of the 112 TKI-treated patients underwent TTE due to cardiopulmonary symptoms. Among the 57 newly diagnosed patients, 4 (7.0%) had PH. PH resolved in three (75.0%) of those four patients after TKI treatment (imatinib in two patients and nilotinib in one patient). PH continued for 8 years in a male patient (aged 61 years at CML diagnosis) despite changes in the TKI (from imatinib to nilotinib, and then to dasatinib); he had no specific PH-related symptoms. In TKI-treated patients, the median TKI treatment time was 40.4 months (range: 0.1–167.2 months). PH was found in 12 (10.7%) of the 112 TKI-treated patients, most frequently in the dasatinib-treated patients [i.e., in 3 (7.5%) of 40 in the imatinib-treated group, 1 (3.1%) of 32 in the nilotinib-treated group, and 8 (21.6%) of 37 in the dasatinib-treated group]. In multivariate logistic regression analyses, age > 60 years (OR, 12.3; 95% CI, 1.1–142.1, p = 0.044), dasatinib treatment (OR, 8.2; 95% CI, 1.3–50.6, p = 0.026), and positive cardiopulmonary symptoms/signs at the time of undergoing TTE (OR, 36.1; 95% CI, 5.3–247.3, p = 0.001) were statistically significant risk factors for developing PH. PH resolved in five (62.5%) of the eight dasatinib-treated patients after discontinuation of the agent. However, PH persisted in three patients, i.e., in one since CML diagnosis and in two despite discontinuing dasatinib; one of those patients had exertional dyspnea. All three imatinib-treated patients recovered from PH: one after the TKI was changed and two despite continuing imatinib. One nilotinib-treated patient also recovered from PH after the TKI was changed.
Conclusion
PH is common in CML patients treated with dasatinib; however, it is also observed in patients treated with imatinib or nilotinib, and even in newly diagnosed patients. Careful screening for PH both at the time of diagnosis and during any TKI treatment is warranted in patients with CML.
Keyword(s): Chronic myeloid leukemia, Pulmonary hypertension, Tyrosine kinase inhibitor