Authors:Ritu Gupta; Gurvinder Kaur; Lalit Kumar; Lata Rani; Nitin Mathur; Atul Sharma; Meetu Dahiya; Varun Shekhar; Sadaf Khan; Anjali Mookerjee; Om Dutt Sharma Pages: 2447 - 2454 Abstract: The recently introduced Revised International Staging System (R-ISS) for multiple myeloma (MM) integrates albumin, β2 microglobulin, lactate dehydrogenase (LDH) with high-risk cytogenetic aberrations (CA), i.e., t(4;14) and t(14;16) and del17p using fluorescent in situ hybridization (FISH). We evaluated utility of nucleic acid-based tests of multiplex ligation-based probe amplification (MLPA) and quantitative real-time polymerase chain reaction (qRT-PCR) to define the CA and the R-ISS categories as per this approach were evaluated for their ability to predict outcome in terms of response, progression-free (PFS), and overall survival (OS). In this study (n = 180), 17 (9.4%), 118 (65.6%), and 45 (25%) patients were assigned to R-ISS1, R-ISS2, and R-ISS3 categories with statistically significant differences in median PFS (p = 0.02) and OS (p < 0.001).On univariate analysis, serum creatinine, LDH, 17p deletion, chromosome 1q gain, and response after first induction therapy were associated with statistically significant differences (p < 0.05) in PFS and in addition, age> 65 years and use of triplet therapy with OS. On multivariate analysis, only serum creatinine, LDH, and response after first induction therapy retained significance for predicting PFS and in addition, use of triplet therapy retained significance for the OS. The proposed nucleic acid-based algorithm using qRT-PCR and MLPA for R-ISS is resource-effective in terms of small quantities of sample required; feasibility of batch processing and reduced overall cost for the total number of regions evaluated and retained the prognostic significance of R-ISS, making it suitable for clinical practice for molecular characterization of MM. PubDate: 2018-12-01 DOI: 10.1007/s00277-018-3457-8 Issue No:Vol. 97, No. 12 (2018)
Authors:Andreas Tiede; Andrew Worster Pages: 2531 - 2531 Abstract: The article Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia, written by Andreas Tiede and Andrew Worster, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 26 May 2018 without open access. PubDate: 2018-12-01 DOI: 10.1007/s00277-018-3504-5 Issue No:Vol. 97, No. 12 (2018)
Authors:Amin T. Turki; Wolfgang Lamm; Christoph Schmitt; Evren Bayraktar; Ferras Alashkar; Martin Metzenmacher; Philipp Wohlfarth; Dietrich W. Beelen; Tobias Liebregts Abstract: The author name Philipp Wohlfarth was incorrectly spelled as Philipp Wohlfahrth in the original version of this article. PubDate: 2018-12-14 DOI: 10.1007/s00277-018-3580-6
Authors:M. Rinelli; E. Bellacchio; F. Berardinelli; G. Pascolini; P. Grammatico; A. Sgura; A. P. Iori; L. Quattrocchi; A. Novelli; S. Majore; E. Agolini Abstract: The original version of this article contained a mistake in the affiliation of E. Bellacchio. Correct affiliation is presented here. PubDate: 2018-12-14 DOI: 10.1007/s00277-018-3581-5
Authors:Wolfgang Lamm; Barbara Kiesewetter; Hannah Puhr; Werner Dolak; Marius E. Mayerhöfer; Markus Raderer PubDate: 2018-12-13 DOI: 10.1007/s00277-018-3588-y
Authors:Chuen Wen Tan; Wan Hui Wong; Roserahayu Idros; Yiong Huak Chan; Hartirathpal Kaur; Alvin Ren Kwang Tng; Lai Heng Lee; Heng Joo Ng; Ai Leen Ang Abstract: Non-transfusion-dependent thalassaemia (NTDT) is associated with a hypercoagulable state with thrombotic risk highest after splenectomy. Various mechanisms have been proposed. Although an antiplatelet agent is commonly recommended as thromboprophylaxis in NTDT, the role of platelets contributing to this hypercoagulable state is not well-defined. This study aims to evaluate the role of platelets contributing to hypercoagulability in NTDT patients using thrombin generation (TG). Platelet-rich (PRP) and platelet-poor plasma (PPP) were collected from NTDT patients (n = 30) and normal controls (n = 20) for TG measurement and compared. Controls had higher endogenous thrombin potential (ETP) in PPP (1204.97 nM.min vs 911.62 nM.min, p < 0.001) and PRP (1424.23 nM.min vs 983.99 nM.min, p < 0.001) than patients. Patients’ mean normalized ETP ratio [{PRP ETP (patient)/PPP ETP (patient)}/{mean PPP ETP (controls)/mean PPP ETP (controls)}], demonstrated that the presence of platelet does not alter ETP (mean ratio 0.97, 95% CI 0.93–1.02, equivalence defined as 10%). Types of thalassaemia, splenectomy, and severity of liver iron overload did not significantly influence patients’ ETP in PPP and PRP by multivariate analysis. Platelets did not increase the TG potential of NTDT patients. Instead of being hypercoagulable, our NTDT patients were hypocoagulable by ETP measurement, although this could not be conclusively demonstrated to correlate with their iron overloading state giving rise to reduced synthesis of coagulation factors. The guideline recommendations for thromboprophylaxis with antiplatelet agents in similar NTDT patients should be re-examined. PubDate: 2018-12-13 DOI: 10.1007/s00277-018-3579-z
Authors:Monica Bianchi; Dominik Heim; Claudia Lengerke; Jörg Halter; Sabine Gerull; Martina Kleber; Dimitrios A. Tsakiris; Jakob Passweg; Alexandar Tzankov; Michael Medinger Abstract: Acute graft-versus-host disease (aGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Prophylaxis with cyclosporine A (CsA) is the backbone of GvHD prevention. In a retrospective analysis of patients treated with allo-HSCT, we correlated CsA levels on the day of transplantation (day 0) and on day + 10 with the incidence of acute and chronic GvHD. We assessed 660 patients with either AML n = 248, lymphoma/myeloma n = 127, MDS/MPN n = 124, ALL n = 79, CLL n = 36, CML n = 23, or bone marrow failure n = 22. In patients with clinically relevant aGvHD grade ≥ 2, mean CsA levels was lower on day 0 and day + 10 (142 ± 88 μg/L and 183 ± 64 μg/L, respectively) compared to patients without aGvHD (156 ± 81 μg/L and 207 ± 67 μg/L, respectively; day 0: p = 0.003; day + 10: p = 7.57 × 10−9). In patients with CsA level < 200 μg/L, the incidence of aGvHD was significantly more frequent compared to patients with CsA levels > 200 μg/L [(234/356 (66%) versus 91/248 (37%); p = 1.34 × 10−12]. In patients with cGvHD, there was no significant difference between CsA levels < 200 μg/L (128/330) compared to CsA levels > 200 μg/L (96/233; p = 0.312). The optimal CsA cutoff level for the prevention (i.e., roughly 50% incidence reduction) of aGvHD was > 201 μg/L at day 0 and > 195 μg/L at day + 10. In a competing risk analysis, time to aGvHD grade ≥ 2 (using death of other causes as competing risk) was associated with CsA levels > 200 μg/L on day 0 and on day 10, unrelated donors, myeloablative conditioning (MAC), and for the diagnosis lymphoma/myeloma. Our data support close monitoring with active adjustments of CsA dosing to maintain therapeutic CsA levels above 195 μg/L in the first 10 days of allo-HCST to reduce aGvHD. PubDate: 2018-12-12 DOI: 10.1007/s00277-018-3577-1
Authors:J. Radocha; R. Hájek; L. Brožová; L. Pour; I. Špička; J. Minařík; E. Gregora; A. Jungová; T. Jelínek; A. Heindorfer; M. Sýkora; V. Maisnar Abstract: The main goal was to find a simple prognostic to evaluate overall survival of patients older than 65 years of age with myeloma. Retrospective registry-based analysis from the Registry of Monoclonal Gammopathies was conducted. Patients over 65 years with symptomatic myeloma were included. The four major parameters with impact on survival were identified: male gender, age > 75, creatinine > 152 μmol/L, and ECOG performance status 2–4. The patients were scored as good (0 points), intermediate good (1 point), intermediate poor (2 points), poor (3–4 points). Patients (1410 MM) were included. Median OS (months) was 65.7 (95% CI 49.8–81.7) for good, 51.0 (44.1–57.8) for intermediate good, 32.2 (26.2–38.2) for intermediate poor, and 18.9 (15.1–22.7) for poor. The differences in OS were statistically significant (p < 0.0001). Good score was used as reference for hazard ratios, which for each other score were 1.43 (1.09–1.84) for intermediate good, 2.58 (2.00–3.33) for intermediate poor, and 3.88 (2.94–5.10) for poor. Time to progression showed medians (months) 20.5 (17.4–62.4) for good, 19.3 (17.0–21.7) for intermediate good, 19.6 (16.2–23.0) for intermediate poor, and 13.0 (10.8–15.2) for poor. The suggested scoring system provides readily available information about the prognosis of MM patients above 65 years. PubDate: 2018-12-11 DOI: 10.1007/s00277-018-3568-2
Authors:Zhenyang Gu; Lu Wang; Quanshun Wang; Honghua Li; Jian Bo; Shuhong Wang; Yu Zhao; Fei Li; Chunji Gao; Daihong Liu; Wenrong Huang Abstract: There was limited information about the efficacy of myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in non-complete remission (non-CR) patients with relapsed/refractory peripheral T cell lymphomas (PTCLs). We conducted a retrospective study of 21 consecutive non-CR patients with relapsed/refractory PTCLs who received myeloablative allo-PBSCT between January 2008 and June 2016. The median follow-up of survivors was 46.5 months (range, 14–105 months). The estimated 3-year relapse rate was 24% (95% CI, 9 to 43%). The 3-year non-relapsed mortality rate was 24% (95% CI, 9 to 44%). Overall, the estimated 3-year overall survival was 47% (95% CI, 25 to 66%). And the estimated 3-year progression-free survival was 46% (95% CI, 24 to 66%). Specifically, eight patients failed to achieve a CR at the first evaluation 3 months after allo-PBSCT and received withdraw of immunosuppression. Five patients also received donor lymphocytes infusions. Five (5/8, 62.5%) patients responded subsequently to these interventions (complete = 4, partial = 1). Overall, ten patients were alive at our last follow-ups, and durable CR were achieved in nine patients without further therapy. Five (50%) of these ten alive patients experienced chronic graft-versus-host disease (GVHD). Our favorable clinical outcomes suggested myeloablative allo-PBSCT was a valid therapeutic option for non-CR patients with relapsed/refractory PTCLs. The sustained CR after immunotherapeutic intervention and high prevalence of chronic GVHD in alive patients provided evidence of graft versus T cell lymphoma effects. PubDate: 2018-12-11 DOI: 10.1007/s00277-018-3559-3
Authors:Renato Zambello; Filippo Crimì; Albana Lico; Gregorio Barilà; Antonio Branca; Annamaria Guolo; Cristiano Varin; Roberto Vezzaro; Lucia Checuz; Vanna Scapin; Tamara Berno; Marco Pizzi; Alberto Ponzoni; Ercole De Biasi; Stefania Vio; Gianpietro Semenzato; Pietro Zucchetta; Carmelo Lacognata Abstract: We evaluated differences in density and 18F-FDG PET/MRI features of lytic bone lesions (LBLs) identified by whole-body low-dose CT (WB-LDCT) in patients affected by newly diagnosed multiple myeloma (MM). In 18 MM patients, 135 unequivocal LBLs identified by WB-LDCT were characterized for inner density (negative or positive Hounsfield unit (HU)), where negative density (HU < 0) characterizes normal yellow marrow whereas positive HU correlates with tissue-like infiltrative pattern. The same LBLs were analyzed by 18F-FDG PET/DWI-MRI, registering DWI signal with ADC and SUV max values. According to HU, 35 lesions had a negative density (− 56.94 ± 31.87 HU) while 100 lesions presented positive density (44.87 ± 23.89 HU). In seven patients, only positive HU LBLs were demonstrated whereas in eight patients, both positive and negative HU LBLs were detected. Intriguingly, in three patients (16%), only negative HU LBLs were shown. At 18F-FDG PET/DWI-MRI analysis, negative HU LBLs presented low ADC values (360.69 ± 154.38 × 10−6 mm2/s) and low SUV max values (1.69 ± 0.56), consistent with fatty marrow, whereas positive HU LBLs showed an infiltrative pattern, characterized by higher ADC (mean 868.46 ± 207.67 × 10−6 mm2/s) and SUV max (mean 5.04 ± 1.94) values. Surprisingly, histology of negative HU LBLs documented infiltration by neoplastic plasma cells scattered among adipocytes. In conclusion, two different patterns of LBLs were detected by WB-LDCT in MM patients. Both types of lesions were indicative for active disease, although only positive HU LBL were captured by 18F-FDG PET/DWI-MRI imaging, indicating that WB-LDCT adds specific information. PubDate: 2018-12-11 DOI: 10.1007/s00277-018-3555-7
Authors:Antoine Lafarge; R. Bertinchamp; C. Pichereau; S. Valade; A. Chermak; I. Theodose; E. Canet; V. Lemiale; B. Schlemmer; L. Galicier; E. Azoulay; E. Mariotte Abstract: Patients with autoimmune hemolytic anemia (AIHA) may require intensive care unit (ICU) admission. In order to describe the characteristics of AIHA patients in ICU and identify prognosis factors, clinical and biological data from 44 patients admitted in one ICU between 2002 and 2015 were retrospectively analyzed. The main reasons for ICU admission were profound anemia without any organ failure in 19 patients (either for safer transfusion or continuous monitoring only). Twenty-five (57%) patients had a past history of hemopathy. Twenty patients presented with a direct anti-globulin test (DAT) positive for immunoglobulin G (DAT-IgG) only (46%), 8 with a DAT positive for both IgG and complement (DAT-IgG+C) (36%), and 16 with a DAT positive for complement only (DAT-IgG+C) (18%). Corticosteroids and rituximab were administered to respectively 44 (100%) and 12 (25%) patients. Red blood cell transfusion was required in 28 (64%) patients. Ten (23%) patients received vasopressors. Renal replacement therapy was necessary in 14 (31.8%) patients. Thirteen (30%) patients died in the ICU. There was no difference between survivors and non-survivors regarding associated comorbidities like hemopathy (18/31 [58%] vs. 7/13 [54%], p = 0.80). In decedents, age was higher (72 years [57.8–76.3] vs. 50 years [34.3–64], p < 0.01) and organ dysfunctions were more severe at day 1 (SOFA 8 [7–11] vs. 5.5 [3–7], p < 0.01). Patients with a DAT-IgG displayed poorer outcome in comparison with patients with DAT-IgG+C/C (hospital mortality 69% vs. 36%, p = 0.04). Mortality rate of AIHA patients requiring ICU admission is consequential and appears to be impacted by age, organ failures, and DAT-IgG. PubDate: 2018-12-10 DOI: 10.1007/s00277-018-3553-9
Authors:Julia Asp; Vibe Skov; Beatriz Bellosillo; Thomas Kristensen; Eric Lippert; Frank Dicker; Jiri Schwarz; Marzena Wojtaszewska; Lars Palmqvist; Susanna Akiki; Anni Aggerholm; Morten Tolstrup Andersen; François Girodon; Lasse Kjær; Elisabeth Oppliger Leibundgut; Alessandro Pancrazzi; Marta Vorland; Hajnalka Andrikovics; Robert Kralovics; Bruno Cassinat; Margarida Coucelo; Aleksandar Eftimov; Karl Haslam; Rajko Kusec; Dorota Link-Lenczowska; Laurence Lodé; Karolina Matiakowska; Dina Naguib; Filippo Navaglia; Guy Wayne Novotny; Melanie J Percy; Andrey Sudarikov; Sylvie Hermouet; Niels Pallisgaard Abstract: External quality assurance (EQA) programs are vital to ensure high quality and standardized results in molecular diagnostics. It is important that EQA for quantitative analysis takes into account the variation in methodology. Results cannot be expected to be more accurate than limits of the technology used, and it is essential to recognize factors causing substantial outlier results. The present study aimed to identify parameters of specific importance for JAK2 V617F quantification by quantitative PCR, using different starting materials, assays, and technical platforms. Sixteen samples were issued to participating laboratories in two EQA rounds. In the first round, 19 laboratories from 11 European countries analyzing JAK2 V617F as part of their routine diagnostics returned results from in-house assays. In the second round, 25 laboratories from 17 countries participated. Despite variations in starting material, assay set-up and instrumentation the laboratories were generally well aligned in the EQA program. However, EQA based on a single technology appears to be a valuable tool to achieve standardization of the quantification of JAK2 V617F allelic burden. PubDate: 2018-12-08 DOI: 10.1007/s00277-018-3570-8
Authors:A. Collignon; C. Houillier; G. Ahle; O. Chinot; S. Choquet; A. Schmitt; P. Agape; C. Soussain; K. Hoang-Xuan; Emeline Tabouret Abstract: Recurrent primary central nervous system lymphomas (PCNSL) have a very poor prognosis. For young and fit patients, intensive chemotherapy followed by autologous stem cell transplantation could be proposed at relapse. In the other cases (unfit or elderly patients), therapeutic options are limited with no consensual regimen. The poly-chemotherapy by (R)-GEMOX is associated with anti-tumor activity in systemic lymphomas and a favorable toxicity profile. Our objective was to evaluate the activity and tolerance of (R)-GEMOX in PCNSL patients enrolled in the French nation-wide LOC cohort. We retrospectively analyzed all refractory or recurrent patients included in the LOC network who benefited from (R)-GEMOX (rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatine 100 mg/m2). Administration, tolerance, and efficacy data were analyzed. Thirteen patients, treated in five different institutions, benefited from the (R)-GEMOX regimen from February 2013 to August 2017. At the initiation of (R)-GEMOX, median age was 71.4 years old (range, 49.5–82.5) and median Karnofsky performance status (KPS) was 60 (range, 40–80). Seven patients were in second line of treatment whereas the six others were in third line or over. All patients had received methotrexate-based polychemotherapy as first-line treatment except one. Overall response rate was 38% with two complete responses and three partial responses. Median progression-free survival was 3.2 months (95%CI: 0.2–6.2), and median overall survival was 8.2 months (95%CI: 0.6–15.8). Toxicity was mainly hematological including grade ¾ neutropenia (38%), lymphopenia (23%), and thrombopenia (23%). Older age (p = 0.046) and low KPS (p = 0.054) tended to be associated with a worse prognosis. (R)-GEMOX is associated with substantial response rate and favorable toxicity profile in unfit patients with recurrent PCNSL. (R)-GEMOX could be considered to be an additional option in patients with recurrent/refractory PCNSL. PubDate: 2018-12-07 DOI: 10.1007/s00277-018-3564-6
Authors:Roberto Tamma; Luisa Limongelli; Eugenio Maiorano; Domenico Pastore; Eliano Cascardi; Angela Tempesta; Paola Carluccio; Mauro G. Mastropasqua; Saverio Capodiferro; Claudia Covelli; Monica Pentenero; Tiziana Annese; Gianfranco Favia; Giorgina Specchia; Domenico Ribatti Abstract: Hematopoietic stem cell transplantation (HSCT) recipients have been reported to have an increased risk of chronic graft versus host disease (cGVHD) and hematological and solid cancers. Oral manifestations are the first signs of cGVHD observed in the majority of patients, and oropharyngeal cancer is the most frequent secondary malignancy occurred after HSCT. In this study, we have evaluated the inflammatory infiltrate cell content and correlated with the vascular density in patients affected by primary oral squamous cell carcinoma (OSCC) from previous healthy controls and OSCC after cGVHD. Results have demonstrated that patients with OSCC after GVHD show a more consistent inflammatory infiltrate as compared with the OSCC ones. In detail, the inflammatory background composed of CD3-positive T cells, tryptase-positive mast cells, CD31-positive endothelial cells, and CD68-positive macrophages may be more pronounced in the setting of GVHD + OSCC than in the control group. By contrast, CD20-positive B cells and CD1a-positive dendritic cells were more abundant in the latter population. Finally, a positive correlation was found as between vascular density and inflammatory cell infiltration in both GVHD + OSCC and OSCC groups. Overall, these results confirm the role played by immune cells in enhancing tumor progression and angiogenesis and suggest a potential therapeutic strategy involving inhibition of recruitment of immune cells to the tumor microenvironment and blockade of pro-tumoral effects and pro-angiogenic functions. PubDate: 2018-12-05 DOI: 10.1007/s00277-018-3575-3
Authors:Massimo Breccia; Daniela Bartoletti; Massimiliano Bonifacio; Giuseppe A. Palumbo; Nicola Polverelli; Elisabetta Abruzzese; Micaela Bergamaschi; Alessia Tieghi; Mario Tiribelli; Alessandra Iurlo; Francesco Cavazzini; Nicola Sgherza; Gianni Binotto; Alessandro Isidori; Mariella D’Adda; Monica Crugnola; Costanza Bosi; Florian Heidel; Matteo Molica; Luigi Scaffidi; Daniele Cattaneo; Roberto Latagliata; Giuseppe Auteri; Roberto M. Lemoli; Renato Fanin; Domenico Russo; Franco Aversa; Antonio Cuneo; Gianpietro Semenzato; Lucia Catani; Michele Cavo; Nicola Vianelli; Robin Foà; Francesca Palandri Abstract: Comorbidities defined by the Charlson comorbidity index (CCI) and body mass index (BMI) are significantly associated with outcome in patients who receive continuous treatment with tyrosine kinase inhibitors. We evaluated the impact of CCI and BMI on responses, drug-related toxicities, and outcome in a cohort of 402 patients with myelofibrosis (MF) treated with ruxolitinib in 23 European Hematology Centers. Comorbidities were evaluable in all 402 patients. A higher (≥ 3) CCI did not correlate with a lower spleen reduction at any time (p = 0.68) or symptoms’ response (p = 0.11), but influenced the onset of anemia during the first 3 months of treatment and later (p = 0.02 and p = 0.03, respectively) in patients without anemia baseline. BMI was evaluable in 380 patients and did not correlate with differences in spleen and symptoms response (p = 0.57 and p = 0.49, respectively). A higher CCI and a lower BMI correlated also with a reduced overall survival (p < 0.001 and p = 0.02, respectively). The achievement of a spleen response at 6 months could counterbalance the negative impact of comorbidities, while patients who were underweight when starting ruxolitinib and did not achieve a spleen response at 6 months were projected to the worse outcome. In MF patients treated with ruxolitinib, BMI and comorbidities did not influence the achievement of spleen/symptom responses, but they contributed to the early identification of patients who deserve a strict monitoring during treatment. PubDate: 2018-12-04 DOI: 10.1007/s00277-018-3569-1
Authors:Xia Wu; Lu Zhang; Jun Feng; Yue-ying Mao; Xin-xin Cao; Dao-bin Zhou; Jian Li Abstract: Light chain-associated Fanconi syndrome (LCFS) is a disorder of renal proximal tubule due to immunoglobulin light chains. Cases of LCFS are rare and mostly sporadically reported, and treatment of this entity is still controversial. This single-center retrospective study included 22 patients diagnosed with LCFS in Peking Union Medical College Hospital. Monoclonal gammopathy of undetermined significance was diagnosed in 13 patients, and overt multiple myeloma in six patients, with two smoldering myeloma and one Waldenstrom macroglobulinemia. Light chain was mostly kappa type (90.9%). Baseline median estimated glomerular filtration rate was 66 (13–126) ml/min/1.73 m2, with one patient presented as end-stage renal disease. After a median follow-up of 37 months, three patients died. Twelve patients were treated with chemotherapy, including 7 with bortezomib-based regimens. Renal function was significantly improved in the group of patients who received chemotherapy (p = 0.026). Compared with other chemotherapy regimens, patients with bortezomib-based treatment had a better hematological response (p = 0.027) as well as a better proximal tubule outcome (p = 0.015). Chemotherapy likely outweighs supportive treatment in patients with LCFS. Bortezomib-based regimen seems to be a safe first-line therapy for management of those patients. PubDate: 2018-12-04 DOI: 10.1007/s00277-018-3572-6
Authors:Harinder Gill; Ho-Wan Ip; Rita Yim; Wing-Fai Tang; Herbert H. Pang; Paul Lee; Garret M. K. Leung; Jamilla Li; Karen Tang; Jason C. C. So; Rock Y. Y. Leung; Jun Li; Gianni Panagioutou; Clarence C. K. Lam; Yok-Lam Kwong Abstract: Current prognostication in myelofibrosis (MF) is based on clinicopathological features and mutations in a limited number of driver genes. The impact of other genetic mutations remains unclear. We evaluated for mutations in a myeloid panel of 54 genes using next-generation sequencing. Multivariate Cox regression analysis was used to determine prognostic factors for overall survival (OS) and leukaemia-free survival (LFS), based on mutations of these genes and relevant clinical and haematological features. One hundred and one patients (primary MF, N = 70; secondary MF, N = 31) with a median follow-up of 49 (1–256) months were studied. For the entire cohort, inferior OS was associated with male gender (P = 0.04), age > 65 years (P = 0.04), haemoglobin < 10 g/dL (P = 0.001), CUX1 mutation (P = 0.003) and TP53 mutation (P = 0.049); and inferior LFS was associated with male gender (P = 0.03), haemoglobin < 10 g/dL (P = 0.04) and SRSF2 mutations (P = 0.008). In primary MF, inferior OS was associated with male gender (P = 0.03), haemoglobin < 10 g/dL (P = 0.002), platelet count < 100 × 109/L (P = 0.02), TET2 mutation (P = 0.01) and CUX1 mutation (P = 0.01); and inferior LFS was associated with haemoglobin < 10 g/dL (P = 0.02), platelet count < 100 × 109/L (P = 0.02), TET2 mutations (P = 0.01) and CUX1 mutations (P = 0.04). These results showed that clinical and haematological features and genetic mutations should be considered in MF prognostication. PubDate: 2018-12-04 DOI: 10.1007/s00277-018-3563-7
Hybrid journal (It can contain Open Access articles)
[2352 journals]
