Effect of Tyrosine Kinase Inhibitor Therapy on Estimated Glomerular Filtration Rate in Patients with Chronic Myeloid Leukemia.

INTRODUCTION: The advent of tyrosine kinase inhibitors (TKIs) was revolutionary in the management of chronic myeloid leukemia (CML). Although TKIs were generally considered to be safe, they can be associated with renal injury. We evaluated the effect of TKIs on renal functions in a cohort of patients with long-term follow-up. MATERIAL AND METHODS: We retrospectively examined patients with chronic phase CML treated with TKIs. We analyzed the estimated glomerular filtration rate (eGFR) of patients from the initiation of TKI to the last follow-up. eGFR values of CML patients were compared to those of patients with stage 1 or 2 chronic kidney disease (CKD). RESULTS: A total of 195 patients with CML and 138 patients with CKD were examined. eGFR decline was 1.556 ml/min/1.73m2/year for patients with CML (P = .221). Patients receiving second-generation TKIs (2GTKI) were estimated to have 0.583 ml/min/1.73m2 higher eGFR value than that of the imatinib group, but it was not significant (P = .871). eGFR of patients who had used bosutinib had a downward trend. Duration of TKI therapy, age, and hypertension were found to be significant factors in eGFR decline for CML patients. Lower baseline GFR was associated with an increased risk of CKD development. CONCLUSION: Imatinib could result in a decline in eGFR which was clinically similar to early-stage CKD patients. We did not observe significant kidney function deterioration in patients receiving 2GTKIs including dasatinib and nilotinib. We recommend close renal function monitoring in patients receiving imatinib, especially for elderly patients with lower baseline eGFR and hypertension.

Does discontinuing bleomycin due to toxicity increase the risk of lymphoma progression? Real-life data from a homogeneous population of advanced stage Hodgkin lymphoma.

Hodgkin Lymphoma (HL) is often curable with ABVD therapy and improving outcomes is a main goal of ongoing research. Bleomycin-associated pneumonitis (BAPT) is a potentially life-threatening complication that necessitates bleomycin discontinuation. We conducted this study on a homogenous cohort of advanced stage HL treated only with ABVD for frontline therapy to assess if bleomycin discontinuation increases the risk of lymphoma progression. After the exclusion of patients who received radiotherapy or other drugs, 106 and 28 patients in the six-cycle ABVD and BAPT groups respectively had similar survival curves for progression and death with a 49-month median follow-up. PFS rates were also very similar at two and four years from diagnosis with 2-year PFS rates of 83.9% and 82.1% (RR = 1.1 95%CI = 0.45-2.2). Outcome comparisons were also similar between the two groups when stratified according to early response assessment with PET/CT. Patients who discontinued bleomycin due to toxicity did not experience an increased risk of progression compared to patients who completed six ABVD cycles.

A cross-sectional study on restless legs syndrome (RLS) in polycythemia vera (PV): is iron deficiency the only culprit?

INTRODUCTION: In polycythemia vera (PV) patients undergoing phlebotomy, iron deficiency (ID) may develop. ID has been linked to restless legs syndrome (RLS), and in one study, 29.6% of PV patients had RLS. We aimed to evaluate the frequency of RLS in PV and to evaluate factors that might play a role in RLS development among PV and essential thrombocythemia (ET) patients. METHODS: We consecutively included PV cases as the patient group, and ET and ID patients and healthy subjects (HSs) were included as controls. Those with conditions that could lead to RLS were excluded. All subjects were questioned according to the diagnostic criteria of the International Restless Legs Syndrome Study Group. RESULTS: Twenty-seven PV, 23 ET, and 22 ID patients and 23 HSs were included. RLS was detected in 25.9%, 34.8%, and 45.5% of PV, ET, and ID patients, respectively. None of the HSs had RLS. In univariate analysis, interferon-α and anagrelide use, magnesium levels, and the Leeds assessment of neuropathic symptoms and signs (LANSS) scores had a significant impact on RLS in PV and ET patients (p = 0.014, p = 0.032, p = 0.036, and p = 0.003, respectively). CONCLUSION: RLS was more common among PV and ET patients than HSs, which was irrespective to the iron status. RLS was more frequent in ET patients than that observed in PV cases, indicating that ID may not be the only causative factor for RLS development in PV. Further prospective studies are needed to determine the prevalence and risk factors of RLS developing in PV and ET.

Short-Term Clinical Outcomes of Packed Red Blood Cell Transfusions with Isolated Enzyme-Phase Crossmatch Incompatibility: A Single-Center Cross-Sectional Study

Acute hemolytic transfusion reactions (AHTRs) are feared complications of packed red blood cell (PRBC) transfusions. This study aimed to investigate the clinical consequences of isolated enzyme-phase crossmatch-incompatible PRBC transfusions by clinically observing all events during the study period at a single institution with the primary goal of detecting AHTRs. Ninety-four transfusions of interest were administered during the study period. Laboratory investigations were adequate in 73 episodes, where no AHTR developed and a mean hemoglobin concentration rise of 1.1 g/dL was documented. Three transfusions were terminated prematurely; however, further investigations ruled out AHTR. The remaining 21 transfusions were also completed uneventfully without noteworthy clinical deterioration. This study's results provide clinical validation to omit pretransfusion screening with enzyme-phase crossmatch and document the safety and short-term efficacy of isolated enzyme-phase incompatible transfusions. The findings may encourage future clinical research to better understand the long-term efficacy of such transfusions, which may be valuable for transfusion-dependent patients.

Diagnosis and Management of Classical Hodgkin Lymphoma During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has brought life to a standstill globally. Intermittent quarantines were applied to control the pandemic and reduce contamination. During the pandemic, patients with hematological malignancies were among the most vulnerable population. Our aim was to compare in terms of demographic data, disease-related factors, symptom-to-diagnosis interval, diagnosis-to-treatment interval , and interim and end-of-treatment response in classical Hodgkin lymphoma patients diagnosed during the pandemic and in the pre-pandemic periods. A total of 90 patients were included, of which 65 and 25 were diagnosed in the 2 years before the pandemic and the 12-month period during the pandemic, respectively. Demographic features were comparable in both groups. Although the percentage of patients with advanced-stage disease was higher during the pandemic (64% vs 53.8%), this difference did not reach statistical significance (P = 0.384). The median symptom-to-diagnosis interval was significantly longer during the pandemic than was observed within the pre-pandemic era (16 weeks vs 8 weeks, P = 0.042). The median diagnosis-to-treatment intervals was similar in both groups (13 days vs 15 days, P = 0.253). In the pre-pandemic and pandemic periods, 85.2% and 72.7% of the patients had complete response at end-of-treatment evaluation, respectively (P = 0.208). We found that symptom-to-diagnosis interval was significantly prolonged during the pandemic. Higher percentage of patients with advanced-stage disease during the pandemic might also be due to this delay, nevertheless, this difference did not reach to a significant difference regarding treatment response in both groups.

A clinicopathological experience in acute myeloid leukemia: Effects of clinical data and status of FLT3, CEBPA and NPM1 on prognosis.

Background: The purpose of the study was to analyze the expression of nucleophosmin (NPM1), CCAT/enhancer-binding protein alpha (CEBPA), and FMS-like tyrosine kinase 3 (FLT3) with immunohistochemistry and evaluate the relationship with clinicopathologic data with special emphasis on prognosis in bone marrow biopsy specimens diagnosed with acute myeloid leukemia (AML). Materials and Methods: Bone marrow biopsies of 104 patients who were diagnosed with AML were re-evaluated for diagnosis and subclassification. Immunohistochemically, anti-NPM1, anti-CEBPA, and anti-FLT3 antibodies were applied to slides prepared from formalin-fixed paraffin-embedded tissues. Sixty-three of these patients had their follow-up in our institutional hematology clinic and these patients' clinical, biochemical, and radiological data were obtained and analyzed from patient files. These data were analyzed with survival times statistically. Results: Except for age, no significant effect of clinical data on prognosis was detected. Immunohistochemical results were also statistically compared with clinical data. No correlation was found between overall survival and disease-free survival with the expression of anti-CEBPA or anti-NPM1 antibodies. However, immunohistochemical reactivity for anti-FLT3 antibody was found to be a poor prognostic factor and statistically significant. Also, when the expression of FLT3 was analyzed with that of NPM1 or CEBPA, a correlation (dependent on the expression of FLT3) was found with disease-free survival. Conclusions: FLT3 is an independent prognostic factor for AML. CEBPA and NPM1 should be considered as good prognostic factors only in the absence of FLT3 abnormalities.

Treatment Responses, Toxicity, and Survival in Patients with Classical Hodgkin Lymphoma Aged ≥50 Years: A Single-Center Experience Over Two Decades.

Introduction: The aim of this study was to evaluate treatment responses, toxicity, and survival among cHL patients aged ≥50 years. Methods: We retrospectively identified all newly diagnosed cHL patients and only included cases who were ≥50 years old at the time of diagnosis and with data available between 1999 and 2020. Results: There were 101 patients, of which 52 were between 50 and 59 years of age, and 49 patients were ≥60 years old. Sixty-two patients were male, and the most common histopathological subtype was mixed cellularity cHL (58.4%). ECOG PS, CCI, CIRS, and ACE-27 scores were significantly higher in patients aged ≥60 years than those of 50-59 age group. While all patients aged 50-59 years received ABVD as first-line therapy, 79% (n=39) of cases aged ≥60 years had ABVD. In patients receiving ABVD, 95% and 92.7% of the cases aged 50-59 and ≥60 years had CR, respectively (p=0.999). Age groups were comparable in terms of hematological and non-hematological toxicities (p=0.369, p=0.127, respectively). Although not statistically significant, median survival was longer in patients receiving a transplant than in those without transplantation (108 months vs 52 months, p=0.069). In multivariate analysis, the risk of progression was higher in patients with lymphocyte ≤600/mm3 and in those who were unresponsive to first-line therapy (p=0.002 and p<0.001, respectively). Patients with B symptoms, age ≥60 years, and CIRS >3 had higher risk of mortality (p=0.001, p=0.012, p=0.038, respectively). By using these 3 parameters, we defined a new risk score, which divided our patient cohort into two as low- and high-risk groups. Low-risk patients had significantly higher survival rates than the high-risk group (83.9% vs 40.5%, p<0.001). Discussion: This new prognostic score should be further tested and validated in other patient populations. Although our study has some limitations including the limited number of patients and its retrospective nature, there are not so many studies in elderly cHL patients and elderly and/or frail patients are generally excluded in most of the clinical trials. Thus, this real-life single-center experience would contribute to the literature.

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.

[Clinical Characteristics of Mild-Moderate COVID-19 Patients and Risk Factors for the Development of Pneumonia]. / Hafif-Orta Klinik Seyirli COVID-19 Hastalarinin Genel Özellikleri ve Pnömoni Gelisimi için Risk Faktörler.

Limited data exists to date on the predictors for the development of pneumonia in patients with mild and moderate coronavirus (COVID-19). In this study, it was aimed to evaluate the demographic characteristics and clinical findings of mild and moderate COVID-19 and to determine the risk factors for the development of COVID-19 pneumonia in patients admitted to the pandemic outpatient clinic of a university hospital. A total of 414 patients with laboratory confirmed COVID-19 were included. Of these, 220 (53.1%) were male, the mean age was 38.3 ± 12.7. Median duration of hospital admission from the onset of symptoms was three days (0-11). Of the confirmed COVID-19 cases, 154 (37.2%) had a history of family contact and the most common symptoms were weakness (68.4%), myalgia (61.8%), headache (56.5%), loss of smell (45.2%), loss of taste (43.2%) and anorexia (42.8%). Among females, weakness (p= 0.016), headache (p= 0.008), sore throat (p= 0.032), nausea (p= 0.003), anorexia (p= 0.045), loss of taste (p= 0.005) and loss of smell (p<0.001) were more common. Loss of taste (47.6% vs. 25%, p<0.001) and loss of smell (50% vs. 26.3%, p<0.001) were more common in patients with under the age of 50 and cough (43.4% vs. 29.3%, p= 0.003) was more common in patients with above the age of 40. Among 46 (11.1%) patients with asymptomatic COVID-19, there was no significant difference (p= 0.500) between the genders. Pneumonia was detected in 150 (43.8%) of 339 patients who underwent thorax computed tomography. In the univariate analysis; advanced age (p<0.001, odds ratio (OR)= 1.44), obesity (p<0.001 OR= 2.5), not being actively smoking (p<0.001, OR= 6.19), fever at first admission (p= 0.002, OR= 2.02), cough (p<0.001, OR= 3.26), shortness of breath (p<0.001, OR= 23.37), weakness (p= 0.042, OR= 1.63), anorexia (p= 0.009, OR= 1.79) and elevation of D-dimer (p= 0.014, OR= 1.92) were associated with the development of pneumonia. In multivariate analysis, obesity (p= 0.005, OR= 2.69), not being actively smoking (p<0.001, OR= 5.43), cough at first admission p= 0.017, OR= 2.16) and shortness of breath (p= 0.008, OR= 16.22) was determined as an independent risk factor for the development of pneumonia. CRP (p<0.001), D-dimer (p<0.001), ferritin (p<0.001) values among 108 (26.1%) patients with a body-mass index(BMI) >30 were high, and 60.9% of the patients had pneumonia (p<0.001) . CRP (p<0.001), D-dimer (p= 0.010) values were low, lymphocyte count (p= 0.001) was high among 106 (25.6%) active smokers, and 15.6% of the patients had pneumonia (p<0.001). Of the patients reported with persistent symptoms, 25.9% had loss of smell, 25% had weakness, and 23.1% had loss of taste on the seventh day; 21.1% had loss of smell, 21.1% had myalgia, and 19.7% had loss of taste on the 14th day. During their follow-up, the COVID-19 polymerase chain reaction (PCR) test was studied in 286 patients for control purposes. The median time of being negative for COVID-19 PCR test was eight days (3-56). In conclusion, symptoms may last longer than 14 days in 20- 30% of patients presenting with mild-moderate clinical findings. In addition, obesity should be considered as an important risk factor for COVID-19 pneumonia.

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.

Copy-number variations in adult patients with chronic immune thrombocytopenia.

OBJECTIVES: Immune thrombocytopenia (ITP) is an autoimmune disease with heterogeneous background. FCGR2C mutations were defined in one third of the patients but genetic players have not been fully elucidated yet. Although childhood ITP present as benign, ITP in adulthood is chronic disease with treatment challenges. This study aimed to focus on adult ITP patients using a whole genome genotyping that is valuable approach to identify the responsible genomic regions for the disease. METHODS: Herein 24 adult primary-refractory for ITP patients were evaluated using HumanCytoSNP12BeadChip,Illumina. Forty-six age and sex matched healthy individuals, and ptients awith nonhematological conditions were analyzed as controls. Identified CNV regions were verified by qRTPCR. T-cell receptor beta and delta (TCRB/TCRG) clonality were assessed by heteroduplex analysis in mosaic cases. RESULTS: Several CNV losses and gains were defined (losses:2q,7q,17q,19p, and gains: 1q,2p,3q,4q,7q,10q,12p,13q,14q,15q,17p,20q,21p,22q,Xp). Mosaic changes of different sizes (0.2-17.77Mb) were identified in five patients and three of them showed clonality. CNV regions that were unique to ITP patients were identified for the first time and among these genes, those related to immune regulation, and cellular trafficking were noteworthy. Conclusion: Identified CNV regions harbor several candidate genes, the functions of which might shed light on the pathogenesis of chronic ITP.

Hepatitis B reactivation in hematopoietic stem cell transplanted patients: 20 years of experience of a single center from a middle endemic country.

Hematopoietic stem cell transplantation (HSCT) is a risk factor for viral hepatitis reactivations because it affects lymphocyte number and functions. Latent hepatitis B virus (HBV) may stay in dormant form in hepatocytes and may be reactivated in prolonged immunosuppression. This study analyzes the incidence of reactivation of HBV infections in HSCT patients in a middle endemic country like Turkey. Five hundred and sixty-one HSCT patients from 1994 to 2015 were retrospectively evaluated. Sixty-six patients had a serologic feature of HBV infection. Fifteen patients were hepatitis B surface antigen (HBsAg)-positive patients (3 allogeneic and 12 autologous) while 51 of them were anti-hepatitis B core IgG (anti-HBc IgG)-positive patients (22 allogeneic and 29 autologous). Although under lamivudine prophylaxis, reactivation was seen in three of 12 (25%) chronic HBV (HBsAg positive) patients who received autologous HSCT and in two of the three HBsAg-positive patients who received allogeneic HSCT. Rate of reactivation in the whole HBsAg-positive group was 33%. Reactivation occurred on median 270th day (range: 60-730). Reverse seroconversion incidence was 10% on 133th day for HBsAg negative, but anti-HBc IgG-positive patients, which increased to 17% on 360th and to 23% on 1500th day. Cumulative incidence increased to 41% on 2280th day for isolated anti-HBc IgG-positive patients. Hepatitis B surface antibodies (anti-HBs) were found to be protective as reactivation did not exceed 11% on 5050th day when anti-HBs was positive. When anti-HBc IgG-positive cases were analyzed according to their transplantation types, allogeneic HSCT was found to have higher cumulative incidence (45% on 3258th day) for HBV reactivation than autologous HSCT (7% on 5050th day). Besides, HBV reactivation in anti-HBc IgG-positive patients who received allogeneic transplantation was related to mortality. Findings of this study suggest that HBV prophylaxis extending over 1 year should be prescribed for HBsAg-positive patients independent of the transplantation type. Prophylaxis should also be given to anti-HBc IgG-positive patients if an allogeneic HSCT is to be performed.

The impact of transfusion burden and comorbidities on the prognosis of patients with myelodysplastic syndromes.

PURPOSE: Early comorbidity detection has been reported to be associated with treatment-related outcomes in several diseases. Two main goals of the present study were to investigate both the impact of comorbidities and transfusion frequencies on the survival and quality of life of patients with myelodysplastic syndromes (MDS). METHODS: One hundred and four MDS patients with a median International Prognostic Scoring System (IPSS) score of 0.5 (range: 0-3) were included in the study. Almost half of the patients had more than one comorbidity. RESULTS: Median short form health surveys (SF)-36 mental and physical scores were 42.1 (range: 20.6-66.1) and 38.7 (range: 18-59.7), respectively. Mean scores of the Eastern Cooperative Oncology Group (ECOG) performance scales at diagnosis and during recruitment were 1.0 (1.4 ± 1.0) and 2.0 (1.8 ± 1.1), respectively. The mean Charlson Comorbidity Index (CCI) score was 1.0 (1.4 ± 1.5). In the model that was constructed using variables with a p value < 0.100 in the univariate analysis, factors that predicted death were refractory anemia with excess blasts (RAEB) and ECOG scores at recruitment. When ECOG was removed from the model, RAEB and CCI at diagnosis moved to the forefront as mortality predictors. CONCLUSION: This study demonstrated that both CCI and ECOG performance status had an impact on survival in MDS patients who had low IPSS scores. ECOG stood out as a better and more practical predictor of survival than CCI, especially after considering its (ECOG) ease of use.

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.

Deep sequencing of BCR-ABL1 kinase domain mutations in chronic myeloid leukemia patients with resistance to tyrosine kinase inhibitors.

Tyrosine kinase inhibitor (TKI) therapy is the current treatment of choice for patients with chronic phase chronic myeloid leukemia (CML) leading to rapid and durable hematological as well as molecular responses. However, emergence of resistance to TKIs has been the major obstacle to treatment success on long term. In this regard kinase domain mutations are the most common mechanism of therapy failure. In this study, we analyzed peripheral blood samples from 17 CML patients who had developed resistance to various TKIs by using next-generation sequencing parallel to Sanger sequencing. BCR-ABL1 kinase domain mutations have been found in 59% of the cohort. Our results demonstrate that next-generation sequencing results in a higher mutational detection rate than reported with conventional sequencing methodology. Furthermore, it showed the clonal diversity more accurately.

Vincristine as an Adjunct to Therapeutic Plasma Exchange for Thrombotic Thrombocytopenic Purpura: A Single-Institution Experience

Background: Thrombotic thrombocytopenic purpura is a potentially life-threatening condition. Although the introduction of therapeutic plasma exchange has reduced mortality rates from over 90% to 10%-20%, approximately 40% of patients relapse, and outcomes may be fatal in refractory patients. There is clearly a need for additional therapeutic approaches. Aims: To describe the outcomes of relapsed/refractory thrombotic thrombocytopenic purpura patients treated with vincristine as an adjunct to therapeutic plasma exchange. Study Design: Cross-sectional study. Methods: The medical records of all relapsed/refractory patients with thrombotic thrombocytopenic purpura treated with vincristine adjunct to therapeutic plasma exchange between October 2000 and December 2016 were retrospectively reviewed. Diagnosis of thrombotic thrombocytopenic purpura was based on clinical history, physical examination, and laboratory examinations. Patient demographics, laboratory findings, initial date and duration of therapeutic plasma exchange, dosage and time of administration of vincristine, and outcomes were recorded. Results: The study included 15 patients [median age: 37 years (range: 26-65); 7 women and 8 men] with either relapsed or refractory thrombotic thrombocytopenic purpura who were treated with vincristine as an adjunct to therapeutic plasma exchange for a total of 22 episodes. Eighty-seven percent of patients achieved remissions in 20 of 22 episodes, with a median duration of remission of 29.5 months (range: 3-105). After a median follow-up of 55 months, 11 patients were alive. Vincristine was well tolerated with no safety concerns. Conclusion: Vincristine offers a reasonable option for the treatment of patients with relapsed/refractory thrombotic thrombocytopenic purpura. Further studies evaluating vincristine in the front-line setting and in the relapsed/refractory setting are needed to validate the role of vincristine in thrombotic thrombocytopenic purpura 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.