Clinical Impact of JAK2V617F Allele Burden in Philadelphia-Negative Myeloproliferative Neoplasms

Objective: The impact of JAK2V617F allele burden on clinical course in Philadelphia-negative (Ph-negative) myeloproliferative neoplasms (MPNs) is not clear. We analyzed the clinical impact of JAK2V617F allele burden in a relatively large series of patients with Ph-negative MPNs and long-term follow-up. Materials and Methods: A total of 228 patients with Ph-negative MPNs, including 118 with essential thrombocythemia (ET), 84 with primary myelofibrosis (PMF), and 26 with polycythemia vera (PV), were analyzed. The JAK2 MutaScreen assay was used to quantify JAK2V617F allele burden in genomic DNA. Results: In PV cases, high JAK2V617F allele burden was associated with a trend towards inferior overall survival. In ET, high JAK2V617F allele burden was associated with lower hemoglobin and hematocrit levels, higher lactate dehydrogenase (LDH) levels, larger spleen size, and increased bleeding and mortality rates. In PMF, high JAK2V617F allele burden was associated with higher leukocyte counts and larger spleen size. In the entire cohort, high allele burden was associated with higher leukocyte and lower platelet counts, higher LDH levels, larger spleen size, higher percentage of bleeding events, higher death rate, and inferior overall survival. Conclusion: Our results suggest that high JAK2V617F allele burdens are associated with more severe disease in PV and ET. In PMF, high JAK2V617F allele burdens were associated with more pronounced myeloproliferative phenotypes. In Ph-negative MPNs, high allele burdens were associated with more aggressive phenotypes. Our data with a long follow-up period support the possibility of JAK2V617F allele burden being used as a marker for predicting clinical phenotype in cases of Ph-negative MPNs.

Raman spectroscopy-based biomarker screening by studying the fingerprint and lipid characteristics of Polycythem..a Vera cases blood serum.

This study aimed to develop a novel approach for diagnosing Polycythemia Vera (PV), a stem cell-derived neoplasm of the myeloid lineage. The approach utilized Raman spectroscopy coupled with multivariate analysis to analyze blood serum samples collected from PV patients. The results showed that PV serum exhibited lower protein and lipid levels and structural changes in the functional groups that comprise proteins and lipids. The study also demonstrated differences in lipid biosynthesis and protein levels in PV serum. Using the Partial Least Square Discriminant Analysis (PLS-DA) model, Raman-based multivariate analysis achieved high accuracy rates of 96.49 and 93.04% in the training sets and 93.10% and 89.66% in the test sets for the 800-1800 cm-1 and 2700-3000 cm-1 ranges, respectively. The area under the curve (AUC) values of the test datasets were calculated as 0.92 and 0.89 in the 800-1800 cm-1 and 2700-3000 cm-1 spectral regions, respectively, demonstrating the effectiveness of the PLS-DA models for the diagnosis of PV. This study highlights the potential of Raman spectroscopy-based analysis in the early and accurate diagnosis of PV, enabling the application of effective treatment strategies.

The association of CMV infection with bacterial and fungal infections in hematopoietic stem cell transplant recipients: a retrospective single-center study.

This study aims to evaluate the probable association between CMV infection and bacterial or fungalinfections in 91 consecutive adult patients who underwent autologous or allogeneic HSCT within aperiod of two years.The medical records of the patients were retrospectively reviewed. Blood cultures were evaluatedby an automated blood culture system. A quantitative real-time polymerase chain reaction was performedto detect CMV DNA.CMV infection and CMV disease were detected in 42 (46%) and six (6.6%) patients, respectively. Ofthe 158 microorganisms isolated, 115 (73%) were Gram-positive bacteria. Bacteremia and fungemiadeveloped in 55 (60%) and eight (8%) patients, respectively. Concurrent CMV infection and bacteremiawere detected in 17 (18.7%) patients and concurrent CMV infection and fungal infection weredetected in five (5.5%) patients. Graft versus host disease (GVHD) developed in 15 (50%) allogeneicHSCT recipients and two (2.2%) autologous HSCT recipients. Twenty-one (23%) patients including13 (43%) allogeneic and eight (13%) autologous HSCT recipients died.The most common infection is bacteremia, and it develops concurrently with CMV infection in approximatelyone-fifth of HSCT recipients. Gram-positive bacteria are more common in bacteremia.Further studies on the follow-up and treatment of infections after HSCT will improve post-HSCTsurvival rates.

The Real-World Experience With Single Agent Ibrutinib in Relapsed/Refractory CLL.

INTRODUCTION/BACKGROUND: The emergence of novel agents targeting the B-cell receptor pathway and BCL-2 has significantly changed the therapeutic landscape of CLL. We evaluated the safety and efficacy of single-agent ibrutinib in relapsed/refractory CLL in real-world settings. PATIENTS/METHODS: A total of 200 relapsed/refractory CLL patients with a median age of 68 were included in this retrospective, multicenter, non-interventional study. Data of the study were captured from the patient charts of the participating centers. RESULTS: The median for lines of previous chemotherapy was 2 (1-6); 62 (31.8%) patients had del17p and/or p53 mutations (del17p+/p53mut). Of the study group, 146 (75%) patients achieved at least PR, while 16 (8.7%) patients discontinued ibrutinib due to TEA. The most common drug-related adverse events were neutropenia (n: 31; 17.4%) and thrombocytopenia (n: 40; 22.3%), which were ≥ grade 3 in 9 (5%) and 5 (3.9%) patients, respectively. Pneumonia (n: 42; 23.7%) was the most common nonhematologic TEA. Atrial fibrillation (n: 5; 2.8%) and bleeding (n: 11; 6.3%) were relatively rare during the study period. Within a median follow-up period of 17 (1-74) months, 42 (21%) patients died. The estimated median OS of the study cohort was 52 months. Only the response to ibrutinib (CR/PR vs. SD/PD) was significantly associated with OS. CONCLUSION: Our results indicate good safety and efficacy for single-agent ibrutinib in R/R CLL in daily practice.

Clinical Characteristics and Outcomes of COVID-19 in Turkish Patients with Hematological Malignancies

Objective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection. Results: Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use. Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.

Brentuximab vedotin and bendamustine: an effective salvage therapy for relapsed or refractory Hodgkin lymphoma patients.

The prognosis is poor for relapsed or refractory (R/R) classical Hodgkin Lymphoma (cHL) patients. The brentuximab vedotin (Bv) and bendamustine (B) combination has been used as a preferable salvage regimen in R/R cHL patient trials. We retrospectively evaluated response rates, toxicities, and the survival in R/R cHL patients treated with the BvB combination. In a multi-centre real-life study, 61 R/R HL patients received intravenous doses of 1.8 mg/kg Bv on the first day plus 90 mg/m2 B on the first and second days of a 21-day cycle as a second-line or beyond-salvage regimen. Patients' median age at BvB initiation was 33 (range: 18-76 years). BvB was given as median third-line treatment for a median of four cycles (range: 2-11). The overall and complete response rates were 82% and 68.9%, respectively. After BvB initiation, the median follow-up was 14 months, and one- and two-year overall survival rates were 85% and 72%, respectively. Grade 3/4 toxicities included neutropenia (24.6%), lymphopenia (40%), thrombocytopenia (13%), anaemia (13%), infusion reactions (8.2%), neuropathy (6.5%), and others. The BvB combination could be given as salvage regimen aiming a bridge to autologous stem cell transplant (ASCT), in patients relapse after ASCT or to transplant-ineligible patients with manageable toxicity profiles.

The impact of JAK2V617F mutation on Philadelphia-negative myeloproliferative neoplasms.

BACKGROUND: JAK2V617F mutation is expressed in almost all polycthemia vera (PV), 55% of essential thrombocythemia (ET), and 65% of primary myelofibrosis (PMF) patients. Studies investigating phenotypic effects of JAK2V617F mutation on Philadelphianegative myeloproliferative neoplasms (Ph-negative MPNs) have reported controversial results. This study aims to determine the impact of JAK2V617F mutation on clinical phenotype and outcome in Ph-negative MPNs. METHODS: Clinical correlates and long-term prognostic relevance of the JAK2V617F mutation were analyzed in 410 Phnegative MPNs-170 ET, 135 PV, 105 PMF- from two institutions and followed for a mean of 76.7 months (SD 62.1) (mean 87 months (SD 67.8), 70.4 months (SD 56.4), 68 months (SD 57.4), respectively for ET, PV, and PMF). Two hundred and twenty-eight patients were genotyped for JAK2V617F mutation using the JAK2 Ipsogen MutaScreen assay, which involves allele-specific polymerase chain reaction (PCR), and 182 patients were genotyped using melting curve analysis. RESULTS: In PV patients, JAK2V617F mutation was associated with higher rate in females, lower hemoglobin (Hgb) level, higher leukocyte and platelet count and higher prevalence of thrombosis (p = 0.008, p = 0.018, p = 0.001, p = 0.001, and p = 0.035, respectively). In ET patients, JAK2V617F mutation was associated with higher Hgb and hematocrit (Hct) levels and lower platelet count (p = 0.001, p = 0.001, and p = 0.001, respectively). JAK2V617F-negative ET patients showed a trend towards higher rate of leukemic transformation (p = 0.061). JAK2V617F mutation-positive PMF patients had higher leukocyte count, greater spleen size and showed a trend towards higher Hgb level (p = 0.019, p = 0.042, and p = 0.056, respectively). Among PMF patients with JAK2V617F mutation, the rate of female patients was lower (p = 0.001). Overall survival (OS) in Dynamic International Prognostic Scoring System (DIPSS) - plus high risk PMF patients was shorter compared to the other risk groups (p = 0.001). Leukemia-free survival (LFS) was shorter in DIPSS - plus high risk PMF patients than the other risk groups (p = 0.005). In the entire cohort of Ph-negative MPN patients, JAK2V617F mutation was associated with higher leukocyte count, higher Hgb and Hct levels and lower platelet count, higher frequency of phlebotomies, a trend towards older age, a trend towards greater spleen size, a trend towards a higher prevalence of risk factors for cardiovascular diseases and thrombosis (p = 0.001, p = 0.005, p = 0.001, p = 0.003, p = 0.004, p =0.052, p = 0.056, p = 0.052, and p = 0.059, respectively).

Pralatrexate experience in PTCL: A multicenter retrospective study from Turkey.

PURPOSE: Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine the general characteristics of the patients receiving pralatrexate therapy in Turkey, contributing to the literature on the effectiveness of pralatrexate therapy in peripheral T-cell lymphomas by determining the response levels of such patients to the therapy. The study also attempts to clinically examine the major side effects observed in patients during treatment with pralatrexate. METHODS: The study included patients with peripheral T-cell lymphoma followed up in the hematology units of several hospitals in Turkey. Overall, 20 patients aged 18 and over were included in the study. RESULTS: The median age at the time of diagnosis was 58.5 years. PTCL-NOS (Peripheral T-cell lymphoma, not otherwise specified) subtype was in 40% of patients, making the PTCL-NOS the most common subtype in the study. In general, most patients were diagnosed with disease at an advanced stage. Pralatrexate therapy was given to the patients at a median treatment line of 3.5. Pralatrexate dose reduction was required in only 3 patients (15%). Response to pralatrexate therapy with partial remission (PR) and above was observed in 11 (55%) of the patients. CONCLUSION: Pralatrexate seemed to be a promising novel treatment in relapsed refractory PTCL patients. However, patients receiving pralatrexate should be followed up carefully for skin reactions, mucosal side effects, thrombocytopenia and neutropenia.

IgG4 producing POEMS syndrome: A rarely recognized subtype.

Serum IgG4 is typically measured for Immunoglobulin G4-related Disease (IgG4-RD), a fibroinflammatory condition associated with polyclonal increase in serum IgG4. Yet, increased IgG4 may still be monoclonal, and little is known about IgG4 POEMS syndrome. We present a case of 40-year-old male with a mass lesion in the left sacral ala. The mass was composed of non-neoplastic fibrous tissue and dense infiltrate of mature plasmacytes with dense eosinophilic cytoplasm and eccentrically placed nuclei that express monoclonal Lambda free light chains and show diffuse positivity for IgG and IgG4. We discuss clinical manifestations and challenges encountered in the diagnosis and treatment of this rare coexistence.

Case Report: Severe COVID-19 Pneumonia in a Patient With Relapsed/Refractory Hodgkin's Lymphoma.

First identified in China in December 2019, coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. The presence of haematological malignancies are expected to increase the risk of adverse outcomes from this viral infection due to the immunosuppression brought about by the underlying cancer and the effects of therapy. We present a 55-year-old woman diagnosed with relapsed/refractory Hodgkin's lymphoma (HL) who had been heavily pretreated with multiagent chemotherapy, autologous hematopoietic stem cell transplantation (autoHCT), allogeneic hematopoietic stem cell transplantation (alloHCT) and was complicated with EBV associated posttransplant lymphoproliferative disease (PTLD) and chronic graft-versus-host-disease (GVHD). The patient was recently treated with brentuximab and donor lymphocyte infusion (DLI) for relapse after alloHCT. She suffered from severe COVID-19 pneumonia and eventually succumbed to acute respiratory distress syndrome (ARDS) and multiorgan failure. Of note, this is the first reported case of COVID-19 in a HL patient who was being treated with brentuximab for relapse after alloHCT.

The mortality rate of COVID-19 was high in cancer patients: a retrospective single-center study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has quickly turned into a global pandemic with close to 5 million cases and more than 320,000 deaths. Cancer patients constitute a group that is expected to be at risk and poor prognosis in COVID pandemic. We aimed to investigate how cancer patients are affected by COVID-19 infection, its clinical course and the factors affecting mortality. METHODS: In our single-center retrospective study, we included cancer patients with laboratory confirmed COVID-19 in our hospital. Demographic, clinical, treatment, and laboratory data were obtained from electronic medical records. Logistic regression methods were used to investigate risk factors associated with in-hospital death. RESULTS: In the hospital, 4489 patients were hospitalized with COVID infection and 77 were cancer patients. The mean age of cancer patients was 61.9 ± 10.9 and 44 of them were male (62%). While the mortality rate in non-cancer patients was 1.51% (n = 68), this rate was significantly higher in cancer patients, 23.9% (n = 17). The stage of the disease, receiving chemotherapy in the last 30 days also lymphopenia, elevated troponin I, D-dimer, CRP, and CT findings were associated with severe disease and mortality. Severe lung involvement (OR = 22.9, p = 0.01) and lymphopenia (OR = 0.99, p = 0.04) are the most important factors influencing survival in logistic regression. CONCLUSIONS: The disease is more severe in cancer patients and mortality is significantly higher than non-cancer patients. These data show that it may be beneficial to develop dynamic prevention, early diagnosis and treatment strategies for this vulnerable group of patients who are affected by the infection so much.

The impact of CYP2D6*4 and GSTP1 Ile105Val polymorphisms on the susceptibility to develop BCR-ABL1 negative myeloproliferative neoplasms.

Inter-individual variations in the genes encoding xenobiotic-metabolizing enzymes have been reported to alter susceptibility to various diseases involving hematological disorders. The purpose of this case-control study was to investigate the relationship between CYP2D6*4 and GSTP1 Ile105Val polymorphisms and the risk of developing BCR-ABL1 negative myeloproliferative neoplasms (MPN). PCR-RFLP was used for genotyping single nucleotide polymorphisms (SNP) in CYP2D6 and GSTP1 in 139 patients with MPN and 126 controls. There was a significantly increased risk for developing BCR-ABL1 negative MPN for the group bearing the CYP2D6*4 variant allele (X2: 4.487; OR 1.738; 95% CI 1.040-2.904; p = 0.034). The platelet count was higher in CYP2D6*4 allele carriers (p = 0.047). There was no association between the GSTP1 Ile105Val polymorphism and the risk of developing MPNs. MPN patients bearing the GSTP1 Ile105Val variant allele had a higher prevalence of bleeding complications (X2: 7.510; OR 4.635; 95% CI 1.466-14.650; p = 0.006). Our study provides new data that the CYP2D6*4 polymorphism may be associated with an increased risk to develop MPNs while the GSTP1 Ile105Val polymorphism does not show such an association. To our knowledge, the current study is the first to investigate the relationship between CYP2D6*4 and GSTP1 Ile105Val polymorphisms and the risk of developing MPNs in the Turkish population. Further studies with more patients and controls are needed to support our data.

Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia: Results from a Single Center, 1993-2011.

Background: For adult ALL patients, the indications and appropriate timing of allogeneic hematopoietic stem cell transplantation (AHSCT) continue to be debated. The primary aim of this single-institution study was to compare the results of our adult ALL patients that had been allografted with those reported in the current literature. Subjects and Methods: This study included 53 consecutive adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (AHSCT) with myeloablative (92%) and reduced-intensity (8%) conditioning between 1993 and 2011. Results: Mean patient age was 27 years (SD:8.62) and donor age was 33.7 years (SD:9.47). Fourteen patients were in first remission; 21 in ≥2nd remission, 15 in relapse and 3 had primary refractory leukemia. Thirty-four, 15 and 4 patients received busulfan plus cyclophosphamide, cyclophosphamide/total body irradiation and fludarabine-based regimens, respectively. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine plus methotrexate were used. Forty-six donors were related and 7 were unrelated. Thirty patients received granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood and 23 received bone marrow as stem cell source. Twenty-six patients relapsed at a mean duration of 11.3 months (SD:19.1). Forty-four patients succumbed to their disease after a mean follow-up of 13.6 months (SD:19.5). The cause of mortality was relapse (n=24; 54.5%) and transplant-related etiologies (n=20; 45.5%). The estimated five year probabilities of overall survival (OS) and progression-free survival (PFS) were 37% and 12%, respectively. Conclusion: By multivariate analyses, transplantation in first remission was the most important predictor of transplant success.

Rituximab Therapy in Adults with Refractory Symptomatic Immune Thrombocytopenia: Long-Term Follow-Up of 15 Cases.

OBJECTIVE: This paper prospectively evaluates the long-term follow-up [mean ± standard deviation (SD) duration: 89.7±19.4 months] data of 15 patients (13 females and 2 males) with refractory symptomatic immune thrombocytopenia (ITP) treated with rituximab. MATERIALS AND METHODS: Rituximab was administered at 375 mg/m2 weekly for a total of 4 doses. Complete response (CR) was defined as a platelet count of ≥100,000/mm3 and partial response (PR) as a platelet count of ≥30,000/mm3 but less than 100,000/mm3. Early response (ER) and late response (LR) were defined as response within 42 days and after 42 days of initiation of rituximab therapy, respectively. Sustained response (SR) was defined as response lasting for at least 6 months. RESULTS: Mean age (±SD) at the start of rituximab was 46.6±11.3 years. Mean platelet count (±SD) prior to rituximab treatment was 17,400±8878/mm3. The mean time (±SD) between rituximab therapy and response to rituximab in early responders and late responders was 1.8±1.3 weeks and 10±2.8 weeks, respectively. Mean durations (±SD) of ER and LR were 51±47.2 months and 6±4.2 months, respectively. Seven of the 15 patients (46.7%) showed an initial response to rituximab (5 ER and 2 LR). The rate of SR over 6 months was 26.7% (4/15). Among the responders to rituximab, 3 (3/7, 42.9%) maintained their response 1 year after rituximab treatment and 2 (2/7, 28.6%) had ongoing response 5 years after initiation of rituximab. Two of the 7 patients (28.6%) still maintained their response 98 months after initiation of rituximab. All 5 initial responders with subsequent relapse achieved response from subsequent treatment modalities (3 CR, 2 PR). CONCLUSION: Our data confirm, over a long period of observation, that rituximab is safe and effective in the management of patients with chronic refractory primary ITP.

Primary B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma of the Hard Palate and Parotid Gland: Report of One Case and Review of the Literature.

A 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. Incisional biopsy from the hard palate revealed an extranodal marginal zone B-cell lymphoma, also called mucosa-associated lymphoid tissue (MALT) lymphoma. Final diagnosis was MALT lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. To our knowledge, this report illustrates the first case of MALT lymphoma of the hard palate and parotid gland without an underlying autoimmune disease. Rituximab-based combination regimen (R-CHOP) provided complete remission with total regression of mass lesions at the hard palate and parotid gland. At 44-month follow-up, there is no disease relapse. We adressed the manifestations and management of MALT lymphoma patients with involvement of salivary gland and oral cavity.

MALT lymphoma of the left biceps muscle: a rare case with an interesting presentation.

BACKGROUND: Extranodal marginal zone lymphoma (MZL), also called mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 7-8 % of non-Hodgkin lymphomas (NHLs) and most commonly involves the stomach. However, muscle involvement is very rare. CASE DESCRIPTION: A 57-year-old woman was referred to our orthopaedics and traumatology clinic with a painful lump in the left arm. Physical examination revealed a red-colored mass on the left arm and an enlarged lymph node measuring almost 5 cm in the left axillary region and 3 cm in the right axillary region. Tru-cut biopsy of the mass in the left arm was consistent with MZL. The diagnosis was MALT lymphoma infiltrating the skeletal muscle (stage IIEA). R-CHOP was started. Two additional infusions of rituximab were administered after the sixth cycle of R-CHOP. Then, the patient received radiotherapy to the left arm at a dose of 30 Gy. After 1 year of follow-up, the patient had no evidence of disease. DISCUSSION AND EVALUATION: MALT lymphoma arises in a number of epithelial tissues. The clinical presentation of MALT lymphoma varies depending upon the tissue involved. To our knowledge, rare cases of MALT lymphoma of the skeletal muscle have been reported. Although the available literature suggests that primary skeletal muscle NHL with advanced stage is associated with poor prognosis, the case presented here suggests that rituximab based combination therapy followed by radiotherapy can be an effective treatment for primary skeletal MALT lymphoma. CONCLUSION: There is limited data regarding the prognosis and treatment of MALT lymphoma of the skeletal muscle. This case implies that rituximab based combination therapy followed by radiotherapy should be considered for the treatment of primary skeletal MALT lymphoma.

The Clinical Significance of IDH Mutations in Essential Thrombocythemia and Primary Myelofibrosis.

BACKGROUND: Limited data exist regarding impact of IDH mutations in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs). Prognostic significance of IDH mutations was asessed in 184 Ph-negative MPN patients - 107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF). METHODS: High-resolution melting (HRM) analysis was used to detect IDH1 and IDH2 mutations. RESULTS: PMF and ET patients showed no significant difference for prevalence of IDH mutations. Mutant IDH (IDH1 or IDH2) was documented in five of PMF (6.5%) and two of ET patients (1.9%). IDH mutations in ET patients included one IDH1 R132C and one IDH2 R140Q. Of the five IDH-mutated PMF patients, four (80%) displayed IDH1 (three IDH1 R132C and one IDH1 R132S) and one (20%) carried IDH2 (IDH2 R140Q) mutation. Sixty percent (three in five) of IDH-mutated PMF patients carried JAK2V617F with following allele burdens: 31-50%, 5-12.5% and 31-50%, respectively. Three of 77 PMF patients (3.9%) simultaneously harbored IDH and JAK2V617F mutations. IDH mutations in PMF showed a trend towards higher rate in females (100% and 52.8%, respectively). Bleeding complications were significantly higher in IDH-mutated PMF patients compared to IDH wild-type counterparts. Trend towards a lower prevalance of acetylsalicylic acid (ASA) use was present in IDH mutant PMF patients compared to wild-type counterparts (20% and 63.9%, respectively). Death rate was higher in IDH-mutated PMF patients compared to IDH wild-type PMF patients (60% and 15.3%). In univariate analysis, a significantly shorter leukemia-free survival (LFS) was observed in IDH-mutated PMF patients. CONCLUSIONS: We conclude that IDH mutations indicate a risk for leukemic transformation in PMF.