Annals of Hematology (Ann Hematol)

Publisher: Deutsche Gesellschaft für Hämatologie und Onkologie; Gesellschaft für Thrombose- und Hämostaseforschung; Österreichische Gesellschaft für Hämatologie und Onkologie, Springer Verlag

Journal description

Continuation of Blut and Folia Haematologica Organ of Deutsche Gesellschaft für Hämatologie und Onkologie Gesellschaft für Thrombose- und Hämostaseforschung Österreichische Gesellschaft für Hämatologie und Onkologie Annals of Hematology covers the whole spectrum of clinical and experimental hematology hemostaseology blood transfusion and related aspects of medical oncology including the diagnosis and treatment of leukemias lymphatic neoplasias and solid tumors as well as transplantation of hematopoietic stem cells. Information is also presented on general aspects of oncology molecular biology and immunology as pertinent to problems of human blood disease.  

Current impact factor: 2.40

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.396
2012 Impact Factor 2.866
2011 Impact Factor 2.615
2010 Impact Factor 2.688
2009 Impact Factor 2.919
2008 Impact Factor 2.454

Impact factor over time

Impact factor
Year

Additional details

5-year impact 2.64
Cited half-life 5.90
Immediacy index 0.62
Eigenfactor 0.01
Article influence 0.80
Website Annals of Hematology website
Other titles Annals of hematology (Online)
ISSN 1432-0584
OCLC 41903082
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

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  • Classification
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Publications in this journal

  • Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2353-8
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    ABSTRACT: The optimal intensity of conditioning for allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) remains undefined. Traditionally, myeloablative conditioning regimens improve disease control, but at the risk of greater nonrelapse mortality. Because fludarabine with myeloablative doses of intravenous busulfan using pharmacokinetic monitoring has excellent tolerability, we reasoned that this regimen would limit relapse without substantially elevating toxicity when compared to reduced intensity conditioning. We retrospectively analyzed 148 consecutive AML patients in remission receiving T cell replete HCT conditioned with fludarabine and intravenous busulfan at doses defined as reduced (6.4 mg/kg; FluBu2, n = 63) or myeloablative (12.8 mg/kg; FluBu4, n = 85). Early and late nonrelapse mortality (NRM) was similar among FluBu4 and FluBu2 recipients, respectively (day + 100: 4 vs 0 %; 5 years: 19 vs 22 %; p = 0.54). NRM did not differ between FluBu4 and FluBu2 in patients >50 years of age (24 vs 22 %, p = 0.75). Relapse was lower in recipients of FluBu4 (5 years: 30 vs 49 %; p = 0.04), especially in patients with poor risk cytogenetics (22 vs 59 %; p = 0.02) and those >50 years of age (28 vs 51 %; p = 0.02). Overall survival favored FluBu4 recipients at 5 years (53 vs 34 %, p = 0.02), a finding confirmed in multivariate analysis (HR: 0.57; 95 % CI: 0.34-0.95; p = 0.03). These data suggest that myeloablative FluBu4 may provide equivalent NRM, reduced relapse, and improved survival compared to FluBu2, emphasizing the importance of busulfan dose in conditioning for AML.
    Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2349-4
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    ABSTRACT: Whether paroxysmal nocturnal hemoglobinuria (PNH) clone in aplastic anemia (AA) is a prognostic factor to immunosuppressive therapy is a subject of debate. We evaluated hematological responses to immunosuppressive therapy (IST) in severe AA (SAA) patients with or without the presence of a PNH clone. In 97 SAA patients who received first-line IST between January and December 2011, 24 (24.7 %) had a PNH clone prior to treatment, with a median clone size of 7.82 % (range 1.19-45.46 %). The response rates to IST for patients with or without a PNH clone were 66.7 and 50.7 % (P < 0.172), 79.2 and 57.5 % (P < 0.057), and 79.2 and 67.1 % (P < 0.264) at 3, 6, and 12 months, respectively. Combined rate of complete and good partial responses differed between patients with or without a PNH clone: insignificantly at 3 months (41.7 vs. 21.9 %, P < 0.058), but significantly at 6 (66.7 vs. 31.5 %, P < 0.002) and 12 (75.0 vs. 46.6 %, P < 0.015) months. Multivariate analysis revealed that a pretreatment neutrophil count of >0.2 × 10(9)/L is indicative of a better response, while the presence of a PNH clone is predictive to a higher combined rate of complete and good partial responses. This study demonstrated that the presence of a PNH clone could predict a better hematological response instead of a higher response rate in patients with SAA.
    Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2348-5
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    ABSTRACT: This study outlines trends in quality of delivered non-Hodgkin's lymphoma (NHL) care in the Netherlands between 2007 and 2011 and to what extend this was influenced by the national Visible Care program, which aimed at increasing transparency by providing insight into the quality of healthcare. We analyzed data collected from medical records in two observational studies, combined into 20 validated quality indicators (QIs) of which 6 were included in the national program. A random sample of 771 patients, diagnosed with NHL in 26 Dutch hospitals, was examined. Multilevel regression analyses were used to assess differences in quality of NHL care and to provide insight into the effect of the national program. We reported improved adherence to only 3 out of 6 QIs involved in the national program and none of the other 14 validated QIs. Improvement was shown for performance of all recommended staging techniques (from 26 to 43 %), assessment of International Prognostic Index (from 21 to 43 %), and multidisciplinary discussion of patients (from 23 to 41 %). We found limited improvement in quality of NHL care between 2007 and 2011; improvement potential (<80 % adherence) was still present for 13 QIs. The national program seems to have a small positive effect, but has not influenced all 20 indicators which represent the most important, measurable parts in quality of NHL care. These results illustrate the need for tailored implementation and quality improvement initiatives.
    Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2340-0
  • Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2346-7
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    ABSTRACT: Dear Editor,The acceptable human leukocyte antigen (HLA) mismatching between a recipient and a cord blood unit is one of the most attractive advantages for patients who receive cord blood transplantation (CBT). Although the impact of the number [1-3], direction [4-7], or allele level [8, 9] of the HLA mismatch on the outcomes of CBT has been extensively analyzed, the effect of a specific HLA locus mismatch on the outcomes after CBT remains unclear. We retrospectively analyzed whether the type of mismatch at low resolution for HLA-A and HLA-B or high resolution for HLA-DRB1 affected the outcomes of single-unit myeloablative CBT in 107 adult patients with acute myeloid leukemia (AML) in our institute between August 1998 and July 2014. The institutional review board of our institute approved this study. Methods were described in Supplementary methods.The characteristics of the patients and CBTs are shown in Supplementary Table 1. The probability of overall survival (OS) was significantly ...
    Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2347-6
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    ABSTRACT: Iron chelation therapy can improve hematopoiesis in myelodysplastic syndromes. Only few studies showed hematologic improvement with deferoxamine, and the erythroid responses were correlated with good compliance to long-term treatment. Indeed, single-case reports and data from clinical trials testing the efficacy of deferasirox reported hematologic improvements with varying rates of response in different lineages. Overall, about 760 myelodysplastic syndrome (MDS) patients with iron overload receiving deferasirox were included in six different studies, and an increase in hemoglobin level was reported to range from 6 to 44.5 %, an increase in platelet count from 13 to 61 %, and in neutrophil count from 3 to 76 %. In all the published studies, hematologic improvements were not related to serum ferritin or to non-total binding iron changes; indeed, other pathways were indicated as possible pathogenetic mechanisms, such as decreased NF-kB activity, modulation of mTOR signalling, and reduced reactive oxygen species. The aims of this review are to provide all available information relating clinical and hematologic changes after chelation therapy and to discuss potential mechanisms involved in such responses.
    Annals of Hematology 03/2015; 94(5). DOI:10.1007/s00277-015-2341-z
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    ABSTRACT: Recent advances in genomic sequencing technologies now allow results from deep next-generation sequencing to be obtained within clinically meaningful timeframes, making this an attractive approach to better guide personalized treatment strategies. No multiple myeloma-specific gene panel has been established so far; we therefore designed a 47-gene-targeting gene panel, containing 39 genes known to be mutated in ≥3 % of multiple myeloma cases and eight genes in pathways therapeutically targeted in multiple myeloma (MM). We performed targeted sequencing on tumor/germline DNA of 25 MM patients in which we also had a sequential sample post treatment. Mutation analysis revealed KRAS as the most commonly mutated gene (36 % in each time point), followed by NRAS (20 and 16 %), TP53 (16 and 16 %), DIS3 (16 and 16 %), FAM46C (12 and 16 %), and SP140 (12 and 12 %). We successfully tracked clonal evolution and identified mutation acquisition and/or loss in FAM46C, FAT1, KRAS, NRAS, SPEN, PRDM1, NEB, and TP53 as well as two mutations in XBP1, a gene associated with bortezomib resistance. Thus, we present the first longitudinal analysis of a MM-specific targeted sequencing gene panel that can be used for individual tumor characterization and for tracking clonal evolution over time.
    Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2344-9
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    ABSTRACT: Epidemiologic studies indicate on an increased risk of cardiovascular disease and cancer in shift workers, although the underling mechanism is obscure. Heparanase directly enhances tissue factor (TF) activity leading to increased factor Xa production and subsequent activation of the coagulation system. In the present study, a comparison of coagulation markers among healthy shift working (SW) vs. healthy daytime working (DW) female nurses was performed. Thirty SW and 30 DW female nurses were enrolled. For each of the 60 participants, blood was drawn between 7:00 and 8:00 a.m. and at least 8 h after the last work shift. Plasma was studied for coagulation marker that included TF/heparanase procoagulant activity, TF activity, heparanase procoagulant activity, heparanase level, factor Xa level, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-antiplasmin, fibrinogen, global protein C, von Willebrand factor, and D-dimer by chromogenic assays and enzyme-linked immunosorbent assays (ELISAs). Sleep quality was assessed by self-report according to the Pittsburgh Sleep Quality Index. The heparanase procoagulant activity increased by 2-fold and the TF/heparanase procoagulant activity increased by 1.5-fold in SW nurses compared to DW nurses (P < 0.05). Factor Xa levels and PAI-1 levels were significantly higher among SW nurses compared to the DW group (22 vs. 18 ng/ml, P < 0.05, and 32 vs. 22 ng/ml, P < 0.005, respectively). No significant differences were found in the other tested coagulation markers between the study groups. Heparanase procoagulant activity, factor Xa level, and PAI-1 level were significantly higher in SW nurses compared to the DW group. These alterations of blood coagulation activation may potentially contribute to cardiovascular and cancer morbidity.
    Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2345-8
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    ABSTRACT: The use of cardiac and hepatic T2* MRI measurements to predict the amount of iron accumulation in these organs has been studied extensively and was suggested to be used reliably. However, it may not be practical to screen other organs with MRI related to economical issues and also the prolonged imaging durations. Herein, we aimed to test the use of fasting glucose, fasting, and postprandial insulin, homeostasis model assessment-insulin resistance (HOMA-IR) (calculated as insulin (μIU/ml) × glucose (mg/dl)/22.5), and homeostasis model assessment B score (HOMA-B) (calculated as insulin (μIU/ml) × 20/glucose (mg/dl) - 3.5) to estimate the tissue iron measured with MRI. A total of 37 patients with β-thalassemia major (BTM), age 20.8 ± 6.3 years (7.1-36.8), were enrolled. MRI measurements were done concomitantly to the biochemical tests for glucose metabolism. A positive correlation between HOMA-IR and hepatic iron loading and a negative correlation between pancreatic T2* and fasting blood glucose were found. A positive correlation was found between fasting insulin levels and pancreatic R2* measures. Additionally, a correlation was detected between cardiac and pancreatic iron accumulations. In centers where T2*/R2* MRI facilities are unavailable, fasting insulin, fasting glucose, and HOMA-IR measurements may be used to predict iron overload and may urge the physician for MRI assessment in case of a deterioration in these biochemical tests. Since hepatic iron loading correlated with insulin resistance development, the insulin resistance among patients with BTM may partially be explained with decreased hepatic insulin clearance from heavily iron-loaded liver.
    Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2342-y
  • Annals of Hematology 03/2015; DOI:10.1007/s00277-015-2343-x
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    ABSTRACT: High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (AHSCT) is a promising approach to treatment of multiple sclerosis (MS) patients. In this paper, we present the long-term outcomes of a prospective single-center study with the analysis of the safety and efficacy of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in 99 MS patients: mean age-35 years old; male/female-39/60; median Expanded Disability Status Scale (EDSS) = 3.5; 43 relapsing/remitting MS, 56 progressive MS. No transplant-related deaths were observed. The mobilization and transplantation procedures were well tolerated. At 6 months post-transplant, neurological improvement or stabilization was observed in all the patients except one. Cumulative incidence of disease progression was 16.7 % at 8 years after HDIT + AHSCT. Estimated event-free survival at median follow-up of 48.9 months was 80 %: 83.3 % in relapsing/remitting MS vs 75.5 % in progressive MS. Sixty-four patients who did not progress during the first 3 years post-transplant and were monitored for more than 3 years were included in long-term outcome analysis. At the median long-term follow-up of 62 months, 47 % of patients improved by at least 0.5 points on the EDSS scale as compared to baseline and exhibited improvement during the entire period of follow-up; 45 % of patients were stable. No active, new, or enlarging lesions on magnetic resonance imaging were registered in patients without disease progression. AHSCT was accompanied by a significant improvement in patient's quality of life. Due to the fact that patient selection was quite different to the other studies and that the information about disease activity prior in the disease course and its treatment was inhomogeneous, comparison with the results in the literature should be done with caution. Thus, the risk/benefit ratio of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in our population of MS patients is very favorable. The consistency of our long-term clinical and quality of life results, together with the persistence of improvement, is in favor of the efficacy and safety of this treatment approach in MS patients.
    Annals of Hematology 02/2015; DOI:10.1007/s00277-015-2337-8
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    ABSTRACT: The introduction of reduced-intensity conditioning (RIC) regimens has made possible allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML). However, the optimal timing of allo-HCT in these patients and its relative risks and benefits when compared with chemotherapies have not been determined. This retrospective study by the Fukuoka Blood and Marrow Transplant Group compared RIC allo-HSCT with non-transplant therapies, the choice based on donor availability, in AML patients in their first complete remission (CR1). The prognostic value of various patient characteristics and disease-specific variables were investigated in 299 patients aged ≥60 years with AML in CR1. Among the 107 patients aged 60-65 years, 54 of whom received allo-HCT and 53 of whom continued chemotherapies; allo-HCT, adverse-risk group, and hematopoietic cell transplantation-comorbidity index were significant predictors of survival outcomes. Among 192 patients aged ≥66 years deemed ineligible for allo-HCT, relapse and Karnofsky performance status after induction therapy were significant predictors of survival outcomes. Findings from this study may facilitate a new standard of care for older AML patients in CR1 who are considered candidates for allo-HCT.
    Annals of Hematology 02/2015; DOI:10.1007/s00277-015-2338-7
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    ABSTRACT: Antithrombin III (AT III) in cerebrospinal fluid (CSF) has been suggested to have high specificity and sensitivity in separating primary central nervous system (CNS) lymphoma from other neurological conditions. We measured with ELISA CSF and serum AT III and albumin levels in 12 lymphoma patients with CNS involvement, 30 lymphoma patients without CNS involvement, and 41 patients with non-neoplastic neurological diseases. AT III immunostaining was also carried out, in lymphoma patients. Both CSF AT III and albumin levels were higher in lymphoma patients with CNS involvement. AT III/albumin ratio in CSF was the most sensitive and specific measure for diagnosis. Lowest it was in patients with known CNS lymphoma. Serum AT III levels were lower both in CNS lymphoma and systemic lymphoma. CSF AT III levels were shown to be higher in lymphoma patients with CNS involvement, when AT III/albumin ratios were lower. This was probably a result of lowered serum AT III levels, indicating that high levels of AT III in CSF might reflect only leakage of the blood-brain barrier. Thus, AT III fails to be a specific marker for diagnosis of lymphoma CNS involvement.
    Annals of Hematology 02/2015; DOI:10.1007/s00277-015-2334-y
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    ABSTRACT: Invasive aspergillosis (IA) is a life-threatening complication in hematological cancer patients. Voriconazole (VCZ) is the established first-line treatment of IA. VCZ has a nonlinear pharmacokinetic profile and exhibits considerable variability of drug exposure. Therefore, therapeutic drug monitoring (TDM) of VCZ may help to improve treatment results in IA patients, but evidence-based data on the clinical use of TDM in patients treated with VCZ for IA are scarce. Evidence-based guidance is needed to support decisions on the use of TDM in routine VCZ therapy of IA. Our present analysis assessed published studies for evidence-based criteria for TDM of VCZ to improve efficacy and safety of IA therapy in cancer patients. Literature searches of MEDLINE and Cochrane database were performed. We identified 27 clinical studies reporting on the use of plasma level monitoring and/or TDM for VCZ. For each study, strength of recommendation and quality of evidence were categorized according to predefined criteria. A number of studies were published on plasma level monitoring (PLM) and TDM in VCZ therapy of IA. Across studies, VCZ levels >5-5.5 mg/L were found to be associated with toxicity, while reaching minimum levels of >1-2 mg/L appeared to improve efficacy. Timing, frequency, and intervention thresholds and dosage increments of VCZ for adjustment of plasma levels remain to be established. Currently, there is still no conclusive evidence for recommendations in routine clinical practice. More data from prospective randomized studies with TDM are desirable to provide a solid evidence basis for these approaches.
    Annals of Hematology 02/2015; 94(4). DOI:10.1007/s00277-015-2333-z
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    ABSTRACT: The basis for variability of hemoglobin (Hb) F in homozygous Hb E disease is not well understood. We have examined multiple mutations of the Krüppel-like factor 1 (KLF1) gene; an erythroid specific transcription factor and determined their associations with Hbs F and A2 expression in homozygous Hb E. Four KLF1 mutations including G176AfsX179, T334R, R238H, and -154 (C-T) were screened using specific PCR assays on 461 subjects with homozygous Hb E and 100 normal controls. None of these four mutations were observed in 100 normal controls. Among 461 subjects with homozygous Hb E, 306 had high (≥5 %) and 155 had low (<5 %) Hb F. DNA analysis identified the KLF1 mutations in 35 cases of the former group with high Hb F, including the G176AfsX179 mutation (17/306 = 5.6 %), T334R mutation (9/306 = 2.9 %), -154 (C-T) mutation (7/306 = 2.3 %), and R328H mutation (2/306 = 0.7 %). Only two subjects in the latter group with low Hb F carried the G176AfsX179 and -154 (C-T) mutations. Significant higher Hb A2 level was observed in those of homozygous Hb E with the G176AfsX179 mutation as compared to those without KLF1 mutations. These results indicate that KLF1 is among the genetic factors associated with increased Hbs F and A2, and in combination with other factors could explain the variabilities of these Hb expression in Hb E syndrome.
    Annals of Hematology 02/2015; DOI:10.1007/s00277-015-2335-x
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    ABSTRACT: Dear Editor,Somatic mutations in DNMT3A, TET2, and RHOA are frequently found in peripheral T cell lymphomas (PTCLs) and other hematological malignancies [1-4]. Among these mutations, RHOA mutations are confined to tumor cells, but TET2 and DNMT3A mutations are found in normal bone marrow and blood cells in multiple lineages in addition to tumor tissues/cells [1, 5]. This has led to an idea that the origin of the TET2 and DNMT3A mutations in some PTCLs may be hematopoietic stem cells (HSCs) or progenitors (HPCs). Here, we report an interesting case of a 74-year-old male patient suffering from PTCL.Tumor tissue was positive for TET2 and DNMT3A mutations (Supplementary Table 1) [1]. CD4+ PD1+ cells, considered to consist of a tumor cell-enriched fraction, were purified from peripheral blood (PB) and showed mutations in TET2 and DNMT3A at allele frequencies of 46.13 and 50.00 %, respectively, indicating that almost all circulating tumor cells had both mutations. The identical TET2 and DNMT ...
    Annals of Hematology 02/2015; DOI:10.1007/s00277-015-2332-0
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    ABSTRACT: Peripheral T cell lymphomas account for approximately 10 % of all the non-Hodgkin lymphomas and are characterized by an aggressive clinical course and poor treatment outcome. In contrast to the improvement in the treatment of B cell lymphomas, there is no established standard chemotherapy regimen for relapsed/refractory T cell lymphomas. Our institute introduced modified ESHAP (mESHAP) regimen to reduce renal toxicity of standard ESHAP therapy, in which cisplatin was switched to carboplatin. We retrospectively analyzed the efficacy of mESHAP against relapsed/refractory T cell lymphomas. Twenty-two patients with relapsed/refractory T cell lymphomas were treated with mESHAP regimen at the University of Tokyo Hospital between January 2001 and December 2012. The median age was 59 years (range, 36-77). The diagnosis comprised peripheral T cell lymphoma, not otherwise specified (n = 10), angioimmunoblastic T cell lymphoma (AITL; n = 9), mycosis fungoides (n = 1), and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (n = 2). The median follow-up period was 9.5 months (range, 2.5-62.3). Complete remission (CR) was achieved in four patients (18 %) and partial remission (PR) in three patients (14 %). The median overall survival (OS) and progression-free survival (PFS) were 11.0 and 2.5 months, respectively. Leukopenia was the most frequent side effect and renal impairment was rare. According to a multivariate analysis, better OS and PFS were recorded in patients without bone marrow invasion (OS, hazard ratio (HR) 0.13, p = 0.0079; PFS, HR 0.13, p = 0.0044) or those with AITL (OS, HR 0.21, p = 0.021; PFS, HR 0.15, p = 0.0043). Although overall outcomes of mESHAP for relapsed/refractory T cell lymphomas were not excellent, this regimen remains one of the possible candidates for those with AITL histology or without bone marrow invasion.
    Annals of Hematology 02/2015; DOI:10.1007/s00277-015-2309-z
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    ABSTRACT: The prognosis of advanced stage natural killer/T-cell lymphoma (NKTCL) remains relatively disappointing, and the optimal treatment strategy for this disease has yet to be discovered. Seventy-three patients with Ann Arbor stage III or IV NKTCL were retrospectively reviewed. The treatment efficacies of asparaginase-containing and asparaginase-absent chemotherapy regimens were compared, and the effects of postchemotherapeutic radiotherapy were explored. The overall response rate (ORR) of the asparaginase-containing regimens was marginally higher than that of the asparaginase-absent regimens (56.5 vs 32.6 %, P = 0.057). However, no significant difference was observed in 2-year overall survival (OS) (38.3 vs 22.7 %, P = 0.418) or 2-year progression-free survival (PFS) (25.4 vs 14.9 %, P = 0.134) between the asparaginase-containing and asparaginase-absent groups. Postchemotherapeutic radiotherapy was associated with a significantly prolonged survival (2-year OS 57.5 vs 14.5 %, P < 0.001; 2-year PFS 46.3 vs 8.4 %, P < 0.001) and was an independent predictor of both OS and PFS. Radiotherapy significantly improved the prognosis among the patients who exhibited complete or partial remission after initial chemotherapy (2-year OS 81.5 vs 40.2 %, P = 0.002; 2-year PFS 65.6 vs 23.4 %, P = 0.008) but failed to provide a significant survival advantage among those who experienced stable or progressive disease after initial chemotherapy. In conclusion, the use of asparaginase did not significantly improve survival for the treatment of patients with stage III/IV NKTCL. Postchemotherapeutic radiotherapy provided additional prognostic benefits to patients who responded well to the initial chemotherapy, which requires further validation in future prospective studies using larger sample sizes.
    Annals of Hematology 02/2015; DOI:10.1007/s00277-015-2336-9