Patients with long-standing autoimmune diseases like systemic lupus erythematosus (SLE) are at a higher risk of developing hematological malignancies. However, chronic myeloid leukemia (CML) has rarely been reported in patients with SLE. Advancements in medical diagnostics and treatment have led to the life expectancy of SLE and CML patients moving closer to that of the general population, and it is not uncommon to encounter more than one malignancy in a cancer survivor. Although squamous cell carcinoma (SCC) of the skin has been reported in CML patients, mucosal SCC of the head and neck has rarely only been reported in CML survivors. The objective of this case report is to share our experience in treating a patient with dual metachronous primary malignancies, CML, and tongue carcinoma, along with long-standing SLE, managed by a multidisciplinary team.

UNASSIGNED: Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often experience cutaneous adverse events, such as rashes and pruritus. In this study, we aimed to compare the risks of cutaneous adverse events between imatinib- and second-generation TKI-treated patients with CML.
UNASSIGNED: Paired reviewers independently obtained studies from PubMed, Embase, and Cochrane Library published until 15 March 2022. The following terms were searched: (Leukemia, Myelogenous, Chronic and BCR-ABL Positive), chronic myeloid leukemia, tyrosine kinase inhibitor, TKI, imatinib, dasatinib, nilotinib, bosutinib, and radotinib. Two independent reviewers screened the results and selected articles on cutaneous adverse events. RevMan 5.4 and the Cochrane Collaboration tool were used to perform the meta-analysis and risk of bias assessment.
UNASSIGNED: Eleven trials involving 4502 patients were analyzed in this study. Patients treated with second-generation TKIs were significantly more likely to experience cutaneous adverse events than those treated with imatinib with a relative risk (RR) of 1.62 (95% confidence interval [CI], [1.25-2.09]). Except dasatinib (RR [95% CI], 1.39 [0.75-2.56]), the risk of adverse events was more with second-generation TKIs than with imatinib as follows: nilotinib (2.11 [1.53-2.90]), bosutinib (1.41 [1.07-1.86]), and radotinib (1.87 [1.33-2.63]). Rash was the most common cutaneous adverse event that was observed in 21.6% of cases across all grades, followed by pruritus (5.7%) and alopecia (4.3%). In conclusion, our findings suggest that cutaneous adverse events occur more frequently with second-generation TKIs than with imatinib. Therefore, effective management of the cutaneous outcome is necessary to achieve high patient adherence to medication and successful treatment with TKIs.

Cancer therapy-related pulmonary hypertension is a rare yet potentially fatal cardiotoxicity. However, it is a reversible cause of pulmonary hypertension if detected in its early stages. Cancer therapy-related pulmonary hypertension has been encountered in patients using tyrosine kinase inhibitors, particularly dasatinib. However, it is also well known that many agents used in cancer treatment such as alkylating agents, proteasome inhibitors, thoracic radiation exposure, and immune checkpoint inhibitors are particularly associated with pulmonary hypertension evolution. In case that history, symptoms, and clinical findings suggest a potential cancer therapy-related pulmonary hypertension, echocardiography is considered as the initial tool to detect pulmonary hypertension. If the possibility of pulmonary hypertension is high based on echocardiographic data, cancer treatment, as the initial step, should be discontinued due to its potential risks and other causes for pulmonary hypertension should be investigated thoroughly. Right heart catheterization should be the next step to establish the final diagnosis, and medical management, where appropriate, should be started without delay in these patients according to their pulmonary hypertension subgroup. There exists limited information regarding the diagnostic and management strategies of cancer therapy-related pulmonary hypertension in the current guidelines. In this review article, we aim to present current literature data on the mechanisms and management of cancer therapy-related pulmonary hypertension along with its follow-up algorithm in the setting of cardio-oncology practice.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype with a poor prognosis under conventional chemotherapy. Ph-like ALL has a similar gene expression profile to Philadelphia chromosome-positive (Ph+) ALL, but is highly heterogeneous in terms of genomic alterations. Approximately 10-20% of patients with Ph-like ALL harbor ABL class (e.g. ABL1, ABL2, PDGFRB, and CSF1R) rearrangements. Additional genes that form fusion genes with ABL class genes are still being researched. These aberrations result from rearrangements including chromosome translocations or deletions and may be targets of tyrosine kinase inhibitors (TKIs). However, due to the heterogeneity and rarity of each fusion gene in clinical practice, there is limited data on the efficacy of tyrosine kinase inhibitors. Here, we report three cases of Ph-like B-ALL with ABL1 rearrangements treated with the dasatinib backbone for the CNTRL::ABL1, LSM14A::ABL1, and FOXP1::ABL1 fusion genes. All three patients achieved rapid and profound remission with no significant adverse events. Our findings suggest that dasatinib is a potent TKI for the treatment of ABL1-rearranged Ph-like ALL and can be used as a first-line treatment option for such patients.

The treatment of chronic myeloid leukemia (CML) was revolutionized with the advent of the first-generation tyrosine kinase inhibitors (TKIs), but drug resistance developed during treatment, leading to the development of the second-generation (dasatinib, nilotinib, and bosutinib) and third-generation (ponatinib) TKI. Compared with previous treatment regimens, specific TKI can significantly improve the response rate, overall survival rate and prognosis of CML. Only a few patients with BCR-ABL mutation are insensitive to the second-generation TKIs, so it is suggested to select the second-generation TKIs for patients with specific mutations. For patients with other mutations and without mutations, the second-generation TKI should be selected according to the patient\'s medical history, while the third-generation TKIs should be selected for mutations that are insensitive to the second-generation TKIs, such as T315I mutation that is sensitive to ponatinib. Due to different BCR-ABL mutations in patients with different sensitivity to the second and third-generation TKIs, this paper will review the latest research progress of the efficacy of the second and third-generation TKIs in CML patients with BCR-ABL mutations.
UNASSIGNED: 慢性髓性白血病BCR-ABL 突变与二、三代TKI的疗效研究进展.
UNASSIGNED: 随着第一代酪氨酸激酶抑制剂（TKI）的问世，慢性髓性白血病的治疗发生了革命性变化，但在治疗过程中出现了耐药性，由此研发了第二代（达沙替尼、尼洛替尼和博苏替尼）和第三代（普纳替尼）TKI。相比之前的治疗方案，选择特定的TKI能显著提高慢性髓性白血病的缓解率、总生存率，改善预后，仅少数BCR-ABL 突变患者对二代TKI不敏感，建议针对有特定突变的患者选择二代TKI，对于其他突变和没有突变的患者，应根据患者的病史选择二代TKI，对二代TKI不敏感的突变可选择三代TKI，如T315I突变对第三代TKI普纳替尼敏感。由于不同BCR-ABL 突变的患者对二、三代TKI的敏感性不同，本文将对二、三代TKI在BCR-ABL 突变的慢性髓性白血病患者中疗效的最新研究进展作一综述。.

UNASSIGNED: Dasatinib is an effective 2nd generation tyrosine kinase inhibitor for the treatment of newly diagnosed or intolerant to imatinib chronic myeloid leukemia (CML), and in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). The most common adverse effects of dasatinib include gastrointestinal upset, pancytopenia, skin rash, diarrhea and fluid retention. Pleural effusion (PE), which occurs in almost 15-35% of patients, is the most frequent manifestation of fluid retention. However, Dasatinib-induced chylothorax is extremely rare. There are solely 13 cases of dasatinib-related chylothorax in adults in the literature, while only one pediatric patient has been reported. The preferred treatment options are usually with systemic steroids, diuretics, and dasatinib discontinuation. We report the second pediatric case and propose the hypothesis of its mechanism and summarize the relevant cases to facilitate the understanding of the pathophysiology, clinical manifestation, management and prognosis of dasatinib-induced chylothorax.
UNASSIGNED: An 11-year-old boy diagnosed with breakpoint cluster region-Abelson (BCR-ABL) fusion was treated with dasatinib. After 38 months, the patient was admitted for dyspnea characterized by decreased breath sounds on both lungs during physical examination. Computed tomography (CT) showed bilateral PE with local insufficiency of both lungs. Drug-induced chylothorax was presumed based on clinical manifestations, excluding other possible causes. Dasatinib was withdrawn, diuretics as well as steroids were given for supportive therapy and octreotide was administered to decrease fat absorption in the intestine. However, the chylous fluid did not decrease significantly. The patient was then being fasted. Unexpectedly, after fasted for two days, the chylous fluid became clear and the drainage volume was decreased. The patient was advised to use nilotinib. We followed up the patient for 8 months, and there was no recurrence of chylothorax.
UNASSIGNED: Our patient had a shorter treatment course for chylothorax than those in the literature. In addition to dasatinib withdrawal, fasting treatment was also utmost critical. We summarize the literature of known existing cases to improve the understanding of the side effects and management of dasatinib in the treatment of CML.

暂无摘要。

Dasatinib, a tyrosine kinase inhibitor, is usually prescribed for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, some patients may develop an intolerance to this drug over the years. Among various toxicities related to dasatinib, dasatinib-associated interstitial pneumonitis is not reported frequently in the literature yet. Moreover, published studies have reported only few cases of dasatinib-associated pneumonitis, almost exclusively in chronic myeloid leukemia. In this study, we describe three cases of dasatinib-associated interstitial pneumonitis in patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia (a 56-year-old man, a 34-year-old man, and a 46-year-old woman) at our institution. In all three patients, the time from the initiation of dasatinib therapy to the onset of interstitial pneumonitis varied greatly. Among them, one patient underwent a surgical lung biopsy, which revealed chronic granulomatous inflammation without any causative pathogen. In all patients, dasatinib was discontinued after the diagnosis of interstitial pneumonitis, and two patients were treated with systemic steroids. Although infrequent, dasatinib-induced pneumonitis should be considered a possible diagnosis in dasatinib-treated patients with fever and respiratory symptoms. In addition, hematologists and pulmonologists should be aware of this rare but critical toxicity.

The management of chronic myeloid leukemia is associated with an extensive economic burden, and as novel interventions are being tested in this disease, understanding the comparative effectiveness is of interest. Findings and conclusions of this important issue continue to evolve with improvements in clinical research and economic understanding. This systematic literature review aims to conduct a comprehensive assessment of economic evaluations in chronic phase chronic myeloid leukemia.
Embase®, MEDLINE®, and the National Health Service Economic Evaluation Database were searched on 4 July, 2022 to identify economic evaluations of chronic myeloid leukemia. Health technology assessment websites and key conference proceedings were also searched. Economic evaluations comparing treatment options in adult patients with chronic phase chronic myeloid leukemia were included. The quality of the studies were assessed using Drummond\'s checklists.
The search retrieved 47 studies and 16 health technology assessments that fulfilled the eligibility criteria. Most were cost-utility analyses (23 studies and 11 health technology assessments) and were from the USA (n = 15) and China (n = 7). Twenty-seven studies and six health technology assessments included only patients with chronic phase chronic myeloid leukemia. Most models had a Markov structure, a 1 year to lifetime time horizon, and a 1-month cycle length. Commonly assessed treatments were various tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) and other interventions such as interferon-α, hydroxyurea, and allogeneic stem cell transplant.
In patients with newly diagnosed chronic myeloid leukemia, imatinib regimens were cost effective, mostly owing to the availability of generics. Nilotinib and dasatinib were generally cost effective as second-line agents for patients who were resistant or intolerant to imatinib. Though progress has been made to better characterize the cost effectiveness of first-line and second-line chronic myeloid leukemia therapies, the paucity of published cost-effectiveness studies of third-line treatments increases the uncertainty associated with economic evaluations of later lines of therapy.

Dasatinib, a second-generation tyrosine kinase inhibitor (TKI), used as treatment for chronic myeloid leukemia, BCR::ABL1-positive (CML), is complicated by pleural or pericardial effusions in about one-third of patients. Besides, in exceptional instances, effusion-based neoplastic B-cell lymphoproliferations have been described. Here, we report an HHV8-negative, EBV-positive large B-cell lymphoma presenting as a pericardial effusion in a patient with CML treated with dasatinib for 23 months, without associated tumor mass or lymphadenopathies. Large tumor cells showed a B-cell phenotype (CD20+, CD79+), with evidence of EBV infection (EBER-ISH+), but HHV8 (LANA-1) negative. Monoclonal IG gene rearrangements were identified. BCL2, BCL6, and MYC genes were not rearranged. Despite the aggressive cytomorphology the patient was in complete remission after 4 cycles of R-CHOP after 8 months follow-up. Four other cases of large B-cell effusion-based lymphomas developed in the setting of dasatinib therapy for CML have been reported in the literature. The four cases were HHV8-negative and one case was EBV-positive. Three of the four patients experienced a benign clinical course, which is in contrast to HHV8-positive primary effusion lymphoma (PEL). The mechanisms of development of these effusion-based B-cell lymphoproliferations in patients receiving TKI are not completely elucidated. Acute or relapsing effusions during TKI treatment in the setting of CML should be cytologically examined to exclude clonal B-cell lymphoproliferations.