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.

Biosimilar Rituximab (Redditux) Added to CHOP Chemotherapy for De Novo Diffuse Large B-Cell Lymphoma Patients: Real-Life Single-Center Experience

Objective: Redditux® (RED), as a biosimilar rituximab, was approved in Turkey for all indications of the original Mabthera® (MAB) in March 2018. The aim of our study was to evaluate the efficacy and safety of RED in de novo diffuse large B-cell lymphoma. Materials and Methods: Fifty-one patients received RED combined with the CHOP regimen. The median follow-up was 31 months. The historical control group included 219 patients treated with the MAB-CHOP regimen and the median follow-up time was 38 months. We compared the response rates and survival outcomes of these RED-CHOP and MAB-CHOP cohorts. Results: In the RED cohort, the overall response rate (ORR) at the end of the treatment protocol was 86%, with 37 (72.5%) cases of complete response (CR) and 7 (13.5%) cases of partial response (PR). In the historical MAB cohort, the ORR was 84%, with CR and PR rates of 82% and 2%, respectively. The 24-month progression-free survival (PFS) rates were 73.76% (95% confidence interval [CI]: 0.59-0.84) and 85.2% (95% CI: 0.79-0.90) for the RED and MAB cohorts, respectively (p=0.0106). The 24-month overall survival rates were 78.4% (95% CI: 0.64-0.87) and 81.4% (95% CI: 0.75-0.86) for the RED and MAB cohorts, respectively (p=0.7461). For patients with high revised International Prognostic Index scores, 24-month PFS was 45.5% (95% CI: 0.17-0.71) and 63% (95% CI: 0.37-0.80) for the RED and MAB cohorts, respectively (p=0.0711). In the RED cohort, central nervous system (CNS) relapse was significantly increased compared to the MAB cohort (10% vs. 1.83%, p=0.004). Among the RED cohort, bone involvement at the time of diagnosis was a risk factor for CNS relapse (p=0.028). Thirteen patients died in follow-up. There were no serious adverse events causing the cessation of the drugs. Conclusion: RED has an ORR similar to that of MAB. However, PFS rates were worse in the RED cohort. Additionally, CNS relapse ratio was a major concern for our RED cohort. Large prospective controlled studies and real-life data with longer follow-up are needed to document the non-inferiority of RED compared to MAB.

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.

Investigation of 13q14.3 deletion by cytogenetic analysis and FISH technique and miRNA-15a and miRNA-16-1 by real time PCR in chronic lymphocytic leukemia.

Background: The most frequent cytogenetic aberration is 13q14.3 deletion in Chronic Lymphocytic Leukemia (CLL). HsamiR-15a/hsa-miR-16-1 are tumor suppressor miRNAs encoded from 13q14.3 region. Objectives: The aim of this study was to investigate the 13q14.3 deletion using molecular and cytogenetic techniques and association with miRNA-15a/miRNA-16-1. Materials And Methods: We used peripheral blood samples of 30 CLL patients who were either induced and or non-induced with DSP30+IL-2 to determine 13q14.3 deletion by karyotyping and iFISH. Expression levels of hsa-miR-15a/miR-16-1 were measured using qRT PCR and compared with deletions. Results: 13q14.3 deletion was detected in 8.6% of cases by karyotyping and in 65% by iFISH. Mosaic forms (monoallelic+biallelic) were observed in 50% of cases. Besides determining common chromosome abnormalities such as add(2)(q37), t(2;7) (p11.2;q22), del(6)(q13q21), del(6)(q25), add(9)(q21), del(11)(q23), t(11;14)(q13;q32), del(13)(q11q12), del(13)(q12q14), add(14) (q23), del(14)(q23), t(14;19)(q32;q13.1), del(15)(q23), del(17)(p12), t(18;22)(q21;q11.2), add(21)(p13) and t(17;21)(q11.2;122), we also determined t(1;13)(q32;q34), inv(2)(p25q21), del(13)(q22q32), t(14;19)(q24;q13), dup(17)(q21q23), der(21;21)(p13;p13) which have not been reported previously. Mitotic index data was found statistically significant and DSP30+IL-2 increased mitotic index by 2.5 folds. Association between decreased miR-16-1 expression and deletions was statistically significant. Conclusion: We suggest that cytogenetic and iFISH analyses are complementary and use of DSP30+IL-2 is effective .in CLL. Decreased expression of hsa-miR-16-1 is remarkable.

An Overview of Lenalidomide in Combination with Rituximab for the Treatment of Adult Patients with Follicular Lymphoma: The Evidence to Date.

Follicular lymphoma (FL) is an indolent (low-grade) malignancy of B cells and is among the most common hematological cancers affecting adults. Its clinical presentation, natural course, and severity are highly variable. Management of FL depends on the clinical setting; most patients require multiple lines of treatment. Chemoimmunotherapy is the standard of care for FL patients needing treatment; however, alternative treatments are limited for refractory patients or those unfit for chemoimmunotherapy. Multiple alternatives to chemoimmunotherapy for FL are being developed, with some showing significant promise. Lenalidomide combination with rituximab (LR) is among the most successful and extensively studied novel approaches. LR has been compared head-to-head in clinical trials with rituximab monotherapy and chemoimmunotherapy in the frontline and to lenalidomide or rituximab monotherapy in the relapsed or refractory setting for the treatment of FL. Initial reports of these nine trials have been published in the last decade, and their long-term data will be available in the coming years. LR offered superior efficacy to either lenalidomide or rituximab monotherapy alone. The RELEVANCE trial compared the efficacy of LR with chemoimmunotherapy among 1030 FL patients and demonstrated similar efficacy with a different side effect profile. Myelosuppression, rash, and fatigue were among the significant adverse events. Most patients treated with LR received thromboprophylaxis. This paper aims to summarize and comment on the published evidence regarding LR treatment for FL through a literature review. The clinical trials will be presented in detail, and methodological differences complicating their comparisons will be discussed.

Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations.

Assessment of measurable residual disease (often referred to as "minimal residual disease") has emerged as a highly sensitive indicator of disease burden during and at the end of treatment and has been correlated with time-to-event outcomes in chronic lymphocytic leukemia. Undetectable-measurable residual disease status at the end of treatment demonstrated independent prognostic significance in chronic lymphocytic leukemia, correlating with favorable progression-free and overall survival with chemoimmunotherapy. Given its utility in evaluating depth of response, determining measurable residual disease status is now a focus of outcomes in chronic lymphocytic leukemia clinical trials. Increased adoption of measurable residual disease assessment calls for standards for nomenclature and outcomes data reporting. In addition, many basic questions have not been systematically addressed. Here, we present the work of an international, multidisciplinary, 174-member panel convened to identify critical questions on key issues pertaining to measurable residual disease in chronic lymphocytic leukemia, review evaluable data, develop unified answers in conjunction with local expert input, and provide recommendations for future studies. Recommendations are presented regarding methodology for measurable residual disease determination, assay requirements and in which tissue to assess measurable residual disease, timing and frequency of assessment, use of measurable residual disease in clinical practice versus clinical trials, and the future usefulness of measurable residual disease assessment. Nomenclature is also proposed. Adoption of these recommendations will work toward standardizing data acquisition and interpretation in future studies with new treatments with the ultimate objective of improving outcomes and curing chronic lymphocytic leukemia.

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.

Age-Related Co-Expression of BCOR and BCORL1 mRNA in Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematological malignancy caused by a variety of genetic abnormalities and epigenetic dysregulation. The incidence of AML is strongly related to age, with the highest incidence rates being in older adults. The loss of function mutations in BCOR and BCORL1 genes have been identified in AML. BCL6 corepressor (BCOR) and BCL6 corepressor like 1 (BCORL1) are important epigenetic regu-lators as a member of Polycomb repressive complex 1 (PRC1.1), involved in histone modification processes. METHODS: We analyzed the BCOR and BCORL1 mRNA expression in 74 adult and 22 pediatric patients with AML by Real-Time quantitative PCR in this study. RESULTS: Our results indicated that both BCOR and BCORL1 mRNA expressions decrease with age (p = 0.009 and p = 0.008, respectively) and there is a positive correlation between BCOR and BCORL1 mRNA expression (p < 0.001). BCOR and BCORL1 mRNA expressions were not significantly different in both adult and pediatric patients with AML compared to control (p > 0.05). CONCLUSIONS: Our findings indicate that expression of BCOR and BCORL1 mRNA are down-regulated with age. The increase in AML incidence with age suggests that age-associated BCOR and BCORL1 down-regulation might potentially contribute to age-related epigenetic alterations and form a predisposing condition for the development of elderly AML.

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.

Patterns of Hydroxyurea Prescription and Use in Routine Clinical Management of Polycythemia Vera: A Multicenter Chart Review Study

Objective: This study aimed to evaluate real-life data on patterns of hydroxyurea prescription/use in polycythemia vera (PV). Materials and Methods: This retrospective chart review study included PV patients who had received hydroxyurea therapy for at least 2 months after PV diagnosis. Data were collected from 10 representative academic medical centers. Results: Of 657 patients, 50.9% were in the high-risk group (age ≥60 years and/or history of thromboembolic event). The median duration of hydroxyurea therapy was 43.40 months for all patients; 70.2% of the patients had ongoing hydroxyurea therapy at last follow-up. Hydroxyurea was discontinued in 22.4% of the patients; the most common reason was death (38.5%). The predicted time until hydroxyurea discontinuation was 187.8 months (standard error: ±21.7) for all patients. This duration was shorter in females (140.3±37.7 vs. 187.8±29.7) (p=0.08). This trend was also observed in surviving patients aged ≥50 years at hydroxyurea initiation (122.2±12.4 vs. 187.8±30.7, p=0.03). Among the patients who were still on hydroxyurea therapy, 40.3% had a hematocrit concentration of ≥45% at their last follow-up visit, and the rate of patients with at least one elevated blood cell count was 67.8%. Conclusion: Hydroxyurea prescription patterns and treatment aims are frequently not in accordance with the guideline recommendations. Its discontinuation rate is higher in females.

The Impact and Prognostic Significance of Chronic Lymphocytic Leukemia Upregulated 1 (CLLU1) Gene Expression in Patients with Chronic Lymphocytic Leukemia: A Single Center Experience.

OBJECTIVES: To determine CLLU1 gene levels and the relationship of that gene among other prognostic parameters in patients with chronic lymphocytic leukemia. METHODS: Bone-marrow infiltration pattern, ß2-microglobulin (ß 2-M), cluster of differentiation (CD)38, and ZAP-70 status were recorded. CLLU1 levels were assessed by real-time polymerase chain reaction (RT-PCR) and expressed as folds. The relationship between CLLU1 and other known prognostic parameters was evaluated. RESULTS: CLLU1 expression was positive in 81 patients and negative in 3 patients. The median (interquartile range [IQR]) CLLU1 level was 6.45 folds (3.75-16.57 folds) in patients with ß 2-M normal values and 16.22 folds (3.91-62.00 folds) in patients with increased ß 2-M (P = .15). Patients with a higher CD38 value than the median level had 3 times higher CLLU1 levels than the other group (P = .07). The median (IQR) CLLU1 level was 4.25 folds (2.75-13.71 folds) in patients with CLL who tested negative on ZAP-70, whereas it was 49.52 folds (15.06-446.36 folds) in those who tested positive via ZAP-70 (P = .005). CONCLUSIONS: CLLU1 is a specific parameter to CLL, and its level corresponds well with the ZAP-70 level.

Long-term results of brentuximab vedotin in relapsed and refractory Hodgkin lymphoma: multi-center real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4-84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05-0.22) and 26% (95% CI, 0.16-0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13-0.54) and 60% (95% CI, 0.33-0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.

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.