Germline genetic variants in Turkish familial multiple myeloma/monoclonal gammopathy of undetermined significance cases.

Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM-affected families, comprising 77 individuals, were included. Targeted next-generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease-causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease-causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.

A Comparative Analysis of Skin Cancer Detection Applications Using Histogram-Based Local Descriptors.

Among the most serious types of cancer is skin cancer. Despite the risk of death, when caught early, the rate of survival is greater than 95%. This inspires researchers to explore methods that allow for the early detection of skin cancer that could save millions of lives. The ability to detect the early signs of skin cancer has become more urgent in light of the rising number of illnesses, the high death rate, and costly healthcare treatments. Given the gravity of these issues, experts have created a number of existing approaches for detecting skin cancer. Identifying skin cancer and whether it is benign or malignant involves detecting features of the lesions such as size, form, symmetry, color, etc. The aim of this study is to determine the most successful skin cancer detection methods by comparing the outcomes and effectiveness of the various applications that categorize benign and malignant forms of skin cancer. Descriptors such as the Local Binary Pattern (LBP), the Local Directional Number Pattern (LDN), the Pyramid of Histogram of Oriented Gradients (PHOG), the Local Directional Pattern (LDiP), and Monogenic Binary Coding (MBC) are used to extract the necessary features. Support vector machines (SVM) and XGBoost are used in the classification process. In addition, this study uses colored histogram-based features to classify the various characteristics obtained from the color images. In the experimental results, the applications implemented with the proposed color histogram-based features were observed to be more successful. Under the proposed method (the colored LDN feature obtained using the YCbCr color space with the XGBoost classifier), a 90% accuracy rate was achieved on Dataset 1, which was obtained from the Kaggle website. For the HAM10000 data set, an accuracy rate of 96.50% was achieved under a similar proposed method (the colored MBC feature obtained using the HSV color space with the XGBoost classifier).

Cytogenetic profile of adult AML patients in Turkey: a single center study with comprehensive comparison with literature.

Background: Cytogenetic findings are important prognostic factors in acute myeloid leukemia. Large systematic data about chromosomal characteristics of Turkish AML patients have not been reported to date. Objectives: The karyotypic profiles of 157 adult AML patients were evaluated retrospectively and compared with other reports from different populations. Methods: Cytogenetics analyses were performed on bone marrow samples using G-banding. Patients were categorized according to their cytogenetic results into four groups with the addition of a normal karyotyped group to the favorable, intermediate and adverse groups of European Leukemia Network. Results: Cytogenetic analyses were carried out successfully in 138 patients (88%). Abnormal karyotypes were found in 79 (57.2%) patients of which 13 (9.4%) were in favorable, 37 (26.8%) in intermediate and 29 (21%) in adverse groups. t(8;21) (5%) was the most common favorable abnormality while monosomal karyotypes (15.9%) in adverse group. Conclusion: This single center study is the most comprehensive study about the cytogenetic profile of acute myeloid leukemia in Turkey with comparison of other population-based studies. While there were similarities and differences with different publications, our results did not show a marked tendency to the findings of any specific geographic region.

Efficacy and Safety of Imatinib Treatment in Elderly Patients With Chronic Myeloid Leukemia: Real-Life Data and a Single-Center Experience.

BACKGROUND: In the era of tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) patients generally live close to a normal lifespan, and the number of elderly patients with CML with comorbidities is increasing. PATIENTS AND METHODS: We retrospectively compared the efficacy and safety of frontline imatinib between elderly patients (≥60 years old) and younger patients (<60 years old) with CML. RESULTS: The study included 33 elderly and 125 younger patients. Elderly patients had significantly higher Charlson comorbidity index (CCI) scores. Efficacy and toxicity were comparable among the older patients with CCI scores of 0 and ≥1. There were significantly more hematologic adverse events (AEs) in elderly patients (P = .005). Although not significant, nonhematologic AEs were also more common in older cases (P = .056). Elderly patients had significantly higher rates of imatinib dose reduction (P < .001). Cumulative response rates were similar in both groups. Event-free survival was comparable, and overall survival (OS)-when non-CML-related deaths were censored-was also similar. In the multivariate analysis, age at diagnosis and CCI were associated with OS, and patients ≥ 60 years of age had a 5.998-times higher risk of death compared with the patients < 60 years of age (P = .011). Similarly, patients with CCI scores ≥ 2 had a 3.758-times higher risk of death compared with patients with a CCI score of 0 (P = .033). CONCLUSIONS: Upfront imatinib was generally well tolerated among elderly Turkish patients with CML with non-inferior responses and long-term outcomes when compared with younger patients. Comorbidities can be problematic in elderly patients, and today the survival of patients with CML is determined mostly by comorbidities.

The prognostic value of serum levels of a proliferation-inducing ligand (APRIL) in treatment-naïve patients with chronic lymphocytic leukemia

Background/aim: A proliferation-inducing ligand (APRIL) has been investigated as a prognostic marker in chronic lymphocytic leukemia (CLL) patients. However, there is no cut-off level for serum APRIL (sAPRIL) levels that predict time to treatment in CLL patients. Materials and methods: Between May and December 2012, 94 consecutive CLL patients and 25 healthy controls were assessed. sAPRIL levels were measured by ELISA. Demographic data and prognostic markers were obtained from the patients' files. Treatment-naïve patients were followed up for 6.5 years for any treatment need. Results: Patients were divided into 3 groups: Treatment-naïve (n = 47), chemotherapy receiving (n = 25), and those who had received chemotherapy previously (n = 22). There was no difference in median sAPRIL levels of patients who were receiving chemotherapy at the sampling time and the healthy controls, which indicates that sAPRIL levels might be influenced by treatment. For treatment-naïve patients, the best cut-off in predicting time to treatment was found at the sAPRIL level of 2.04 ng/mL, with 78% sensitivity and 63% specificity. Time to treatment was significantly earlier in the APRIL high group (n = 27) than in the APRIL low group (n = 20) (P = 0.010, log-rank test). Conclusion: sAPRIL, a simple, promising blood test which can be measured by ELISA, will likely obtain a place in the wide range of prognostic markers in CLL. Prospective large-scale studies are required to validate and confirm the feasibility of the proposed cut-off level of 2.04 ng/mL as a predictor of time to treatment in treatment-naïve CLL patients.

Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma.

BACKGROUND: In countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. PATIENTS AND METHODS: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. RESULTS: The median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). The overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. The median duration of response was 4.9 months. The median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. The median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. The depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade ≥ 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation. CONCLUSION: The present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM.

The Outcomes of Chronic Myeloid Leukemia Patients With Molecular Warning Responses During Imatinib Treatment According to the European LeukemiaNet 2013 Recommendations.

BACKGROUND: In the European LeukemiaNet (ELN) 2013 recommendations, chronic myeloid leukemia (CML) patients with warning response (WR) were suggested to be monitored closely continuing with the same tyrosine kinase inhibitor (TKI). Differently, the guidelines of the National Comprehensive Cancer Network considers switching to another TKI as an option. PATIENTS AND METHODS: We retrospectively evaluated 73 CML patients receiving first-line imatinib, who were followed and managed in accordance with ELN recommendations. We compared patients with molecular WR with patients with optimal response (OR) and failure regarding short- and long-term outcomes. RESULTS: The cumulative major molecular response (MMR) rates in patients with OR were significantly higher at any time point than those achieved by the WR group. Patients with WR at 3 months had significantly inferior failure-free survival (FFS) than optimal responders, but overall survival (OS) was similar. For 6 and 12 months, the WR and OR groups had similar FFS and OS. Twenty of 23 patients with WR at 12 months achieved MMR during imatinib treatment. CONCLUSION: It takes longer to get to ELN time points with imatinib than second-generation TKIs (2GTKIs). Treatment might fail in a small proportion of the patients with WR during imatinib treatment, but close and careful monitoring and timely switching to 2GTKIs might translate into favorable outcomes. Avoiding early switch to 2GTKIs would prevent patients from experiencing potential toxicities. There is still a need for prospective comparative studies (ie, continuing imatinib treatment vs. switching to 2GTKIs) in patients with WR, to justify the validity of this response category and to explore the benefit of treatment change in these patients.

Third-line treatment with second-generation tyrosine kinase inhibitors (dasatinib or nilotinib) in patients with chronic myeloid leukemia after two prior TKIs: real-life data on a single center experience along with the review of the literature.

OBJECTIVES: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib → nilotinib or imatinib → dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. METHODS: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated. RESULTS: Out of 209 patients, third-line dasatinib/nilotinib was administered in 21. During the follow-up, 16 out of 21 patients gained and/or maintained an optimal response, and 4 patients died due to progression. Seventeen patients were alive at the time of the analysis, of which 13 were still on TKI, whereas 4 patients quit treatment. DISCUSSION: In patients failing two lines of TKI, dasatinib or nilotinib can be beneficial and safely administered as a third-line treatment especially in nations with restricted resources.

Retrospective Evaluation of Hairy Cell Leukemia Patients Treated with Three Different First-Line Treatment Modalities in the Last Two Decades: A Single-Center Experience.

OBJECTIVE: In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL) cases. MATERIALS AND METHODS: Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA) was administered in 31 cases, 19 patients received interferon-alpha (INF-α), splenectomy was performed in 16 cases, and rituximab was used in one. RESULTS: Although the highest overall response rate (ORR) was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS) rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem. CONCLUSION: Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.

Outcomes of Chronic Myeloid Leukemia Patients With Early Molecular Response at 3 and 6 Months: A Comparative Analysis of Generic Imatinib and Glivec.

BACKGROUND: The molecular response at 3 months of the original imatinib (OI) in patients with chronic myeloid leukemia has prognostic significance; however, this has never been tested for generic imatinib (GI). PATIENTS AND METHODS: We evaluated the BCR-ABL1 [international reporting scale (IS)] transcript levels at 3 and 6 months to determine whether an early molecular response (EMR) had a prognostic effect on the outcome among chronic myeloid leukemia patients receiving GI. Ninety patients were divided into 2 groups, according to the imatinib they received, as OI (group A) and GI (group B). RESULTS: Two groups were equally balanced for age, gender, Sokal risk score, and optimal response. The 2 groups did not differ in achieving an EMR at 3 months, and patients with EMR at 3 months had significantly superior complete cytogenetic response and major molecular response rates compared with patients who did not achieve an EMR in both groups. The percentage of an optimal response [BCR-ABL1 (IS), < 1%] and a warning response [BCR-ABL1 (IS), 1%-10%] at 6 months was 93% and 95% for groups A and B, respectively (P = .553). Patients with an optimal response (OR) at both 3 and 6 months had significantly superior event-free survival rates compared with patients without an OR in groups A and B. CONCLUSION: The results of the present study have demonstrated most probably for the first time that an OR at 3 and 6 months in patients receiving either first-line GI and OI is clearly associated with greater response and event-free survival rates. Prospective randomized trials with larger numbers of patients and longer follow-up periods are needed to address the effect of EMR in patients receiving GI.

Clinical Outcomes Related to the Use of Bendamustine Therapy for Multiple Myeloma Patients Relapsed/Refractory to Immunomodulatory Drugs and Proteasome Inhibitors.

OBJECTIVE: Multiple myeloma patients who are relapsed or refractory to both proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have been reported to have poor outcomes. Bendamustine has been reported to have an antitumor effect in newly diagnosed as well as relapsed/refractory multiple myeloma (RRMM). The aim of this retrospective study was to evaluate the efficacy of bendamustine therapy in heavily pretreated MM patients who were refractory to PIs and IMiDs. MATERIALS AND METHODS: Nineteen RRMM patients treated either with bendamustine and steroids (n=13) or a combination of bendamustine with novel drugs (n=6) were included. The median number of previous treatment lines was 5 (minimum-maximum: 3-8) and median time from diagnosis was 6 years (minimum-maximum: 1-16). All of the patients were resistant to at least one of the IMiDs and one of the PIs. Bendamustine was given at doses ranging from 90 mg/m2 to 120 mg/m2 on days 1 and 2 of 28-day cycles. RESULTS: A median of 2 (minimum-maximum: 1-8) treatment cycles was administered per patient. The toxicity of bendamustine was mild and mostly of hematological origin. No complete remission was achieved. There was partial remission and stable disease in 21% and 11% of the patients, respectively. Sixty-eight percent of patients had progressive disease. The median progression-free survival and overall survival was 2 and 4 months, respectively. CONCLUSION: Bendamustine therapy was well tolerated but showed limited anti-myeloma activity in heavily pretreated patients who were refractory to IMiDs and PIs.

The role of 68Ga-DOTA-TATE PET/CT scanning in the evaluation of patients with multiple myeloma: preliminary results.

OBJECTIVE: In this observational pilot study, we aimed to evaluate the role of gallium-68-labelled DOTA-TATE (Ga-TATE) PET/computed tomography (CT) scanning in patients with multiple myeloma (MM), considering previous promising results obtained from conventional somatostatin receptor scintigraphy with In pentetreotide. MATERIALS AND METHODS: Twenty-one patients with a diagnosis of MM were prospectively included in this study: eight patients were referred for initial staging and 13 patients for restaging purpose. Both fluorine-18 fluorodeoxyglucose (F-FDG) and TATE PET/CT scanning were performed in all patients. RESULTS: All patients had one or more PET-positive lesion on either F-FDG or TATE scans. Six patients had an additional diffusely increased bone marrow activity on F-FDG scans, five of whom also had a concordant bone marrow appearance on TATE scans. Each PET set (either F-FDG or TATE) was positive in 19 patients. There was a discordant result in four (19%) patients between F-FDG and TATE scans. F-FDG scans showed 112 lesions (86 TATE-positive; 26 TATE-negative) in 19 patients, whereas TATE scans showed 108 lesions (86 F-FDG-positive; 22 F-FDG-negative) in 19 patients. No significant difference was found between the two modalities in terms of lesion numbers detected (P=0.67). However, the presence of diffuse bone marrow uptake of TATE seems to be a predicting factor for the overall survival (P=0.033, hazard ratio: 15.2 and 95% confidence interval: 1.2-185.5). CONCLUSION: TATE PET/CT seems to be an alternative imaging modality and may play a complementary role in MM management, at least by providing a different pathobiological insight into the disease.

Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia.

AIMS: Before the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy. METHODS: The study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated. RESULTS: Severe MF (grade II-III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0-I) and severe (grade II-III) groups (p=0.278). CONCLUSIONS: According to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.

Early Changes of Mannose-Binding Lectin, H-Ficolin, and Procalcitonin in Patients with Febrile Neutropenia: A Prospective Observational Study.

OBJECTIVE: The significance of mannose-binding lectin (MBL) and H-ficolin deficiency in febrile neutropenic (FN) patients and the correlation of these markers along with consecutive C-reactive protein (CRP) and procalcitonin (PCT) levels during the infectious process are investigated. MATERIALS AND METHODS: Patients with any hematological malignancies who were defined to have "microbiologically confirmed infection", "clinically documented infection", or "fever of unknown origin" were included in this single-center prospective observational study. Serum levels of CRP, PCT, MBL, and H-ficolin were determined on 3 separate occasions: at baseline (between hospital admission and chemotherapy), at the onset of fever, and at the 72nd hour of fever. RESULTS: Forty-six patients (54% male, mean age 41.7 years) with 61 separate episodes of FN were evaluated. Eleven patients (23.9%) had "microbiologically confirmed infection", 17 (37%) had "clinically documented infection", and 18 (39.1%) had "fever of unknown origin". Fourteen (30.4%) patients had low (<500 ng/mL) initial MBL levels and 7 (15.21%) had low (<12,000 ng/mL) H-ficolin levels. Baseline MBL and H-ficolin levels did not significantly change on the first and third days of fever (p=0.076). Gram-negative bacteremia more frequently occurred in those with low initial MBL levels (p=0.006). PCT levels were significantly higher in those with microbiologically documented infections. Mean and median PCT levels were significantly higher in cases with bacteremia. There was no significant difference between hemoculture-positive and-negative patients in terms of CRP levels. CONCLUSION: Monitoring serum H-ficolin levels was shown to be of no benefit in terms of predicting severe infection. Low baseline MBL levels were correlated with high risk of gram-negative bacteremia; however, no significant correlation was shown in the follow-up. Close monitoring of PCT levels is warranted to provide more accurate and specific data while monitoring cases of bacteremia.

Secondary Infections in Febrile Neutropenia in Hematological Malignancies: More Than Another Febrile Neutropenic Episode.

INTRODUCTION: Febrile neutropenic episodes (FNEs) are among major causes of mortality in patients with hematological malignancies. Secondary infections develop either during the empirical antibiotic therapy or one week after cessation of therapy for a FNE. The aim of the study was to investigate the risk factors associated with secondary infections in febrile neutropenic patients. METHODS: We retrospectively analyzed 750 FNEs in 473 patients between January 2000 and December 2006. RESULTS: Secondary infections were diagnosed in 152 (20%) of 750 FNEs. The median time to develop secondary infection was 10 days (range 2-34 days). The duration of neutropenia over 10 days significantly increased the risk of secondary infections (p<0.001). The proportion of patients with microbiologically documented infections was found to be higher in primary infections (271/750, 36%) compared to secondary infections (43/152, 28%) (p=0.038). Age, sex, underlying disease, antibacterial, antifungal or antiviral prophylaxis, blood transfusion or bone marrow transplantation, central venous catheter or severity of neutropenia did not differ significantly between primary and secondary infections (p>0.05) While fever of unknown origin (FUO) (p=0.005) and catheter-related bacteremia (p<0.001) were less frequently observed in secondary infections, the frequency of microbiologically (p=0.003) and clinically (p<0.001) documented infections, fungal pneumonias (p<0.001), infections related with gram positive bacteria (p=0.04) and fungi (p<0.001) and 30-day mortality rate (p<0.001) were significantly higher in secondary infections (p<0.001). DISCUSSION AND CONCLUSION: Secondary infections should be regarded as life-threatening complications of febrile neutropenia. Secondary infections represent a more severe and mortal complication and cannot be regarded just as another febrile neutropenic episode.

Bone-Specific Alkaline Phosphatase Levels among Patients with Multiple Myeloma Receiving Various Therapy Options.

OBJECTIVE: This study aimed to investigate the impact of the different therapy regimens used in multiple myeloma (MM) on bone-specific alkaline phosphatase (BALP) levels. MATERIALS AND METHODS: One hundred and thirteen patients with MM were included in the study. Patients were grouped according to the regimens they received, as follows: group 1, melphalan and prednisolone (MP); group 2, vincristine, adriablastin, and dexamethasone (VAD); group 3, thalidomide plus dexamethasone; and group 4, bortezomib plus dexamethasone. BALP levels were measured before treatment and at the third and sixth months of treatment. A fifth group consisted of patients in the post-treatment remission period at study entry (no-treatment group). RESULTS: The BALP levels at the third and sixth months of the treatment were significantly higher than the pre-treatment levels in the bortezomib and the no-treatment groups, whereas no significant difference was observed in the MP, VAD, and thalidomide groups. CONCLUSION: Considering that BALP is a surrogate marker of bone formation, our study suggests that bortezomib more efficiently leads to the improvement of bone disease in myeloma than other treatment options.

Chronic myeloid leukemia patients who develop grade I/II pleural effusion under second-line dasatinib have better responses and outcomes than patients without pleural effusion.

Dasatinib is a potent second generation TKI, and it is widely used in patients with CML, both in the up-front setting and failure after imatinib. Lymphocytosis in cases receiving dasatinib therapy has been shown to be associated with pleural effusion (PE) and better outcome. Although patients who gather lymphocytosis during dasatinib have superior responses, there is only little data about the correlation between PE, response rates, and survival. In order to answer this question, the aim of our study was to determine the frequency of PE and lymphocytosis among our CML patients receiving second-line dasatinib, and to compare the responses and outcomes between patients with or without PE. There were 18 patients (44%) who developed PE, in a total of 41 patients, with a median time of 15 months. Lymphocytosis was observed in nine patients (9/41, 22%) with a median duration of 6.5 months of dasatinib treatment. There were fourteen patients with at least one comorbidity that may play a role in the generation of PE. The cumulative MMR and CCyR rates were greater in PE+ patients (p<0.05). The PFS was significantly higher in PE+ group than PE- patients (p=0.013), also the OS was higher among PE+ patients than PE- group (p=0.042). In patients with a grade I/II PE, and durable responses under dasatinib, performing the management strategies for the recovery of effusion, together with continuing dasatinib can be a reasonable choice mainly in countries where third generation TKIs are not available. But alternative treatment strategies such as nilotinib or third generation TKIs can be chosen in patients with grade III/IV PE especially if the quality of life is severely affected.