[Show abstract][Hide abstract] ABSTRACT: Background
The influence of comorbidities in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has been modestly investigated. Different comorbidity scoring systems are available for cancer patients.
In order to evaluate the impact of comorbidities on the overall survival (OS) we have performed retrospective analyses of clinical records of the patients with DLBCL treated with R-CHOP, R-EPOCH and R-CVP protocol. The following comorbidity scores were used: Cumulative Illness Rating Scale (CIRS), Charlson Comorbidity Index (CCI), age adjusted CCI (aaCCI) and Hematopoietic-Cell-Transplantation Comorbidity Index (HCT-CI)
A total of 378 patients (195 female/183male) were included in the study. Median age was 58 years (range 18-80). Elderly population (70 years and older) represented 20.2% of analyzed group. According to the Ann Arbor classification, stage I, II, III and IV had 51patients (13.5%), 129 (34.1%), 72 (19%) and 129 (33.3%), respectively. Bulky disease was present in 88 patients (23.3%) and B symptoms in 248 patients (65.6%). Regarding Eastern Cooperative Group (ECOG) performance status (PS), 23.7% of patients had ECOG PS ≥ 2. The most frequent extranodal localization were bone marrow (27.2% of patients) and gastrointestinal tract (28.8% of patients). Revised International Prognostic Index (R-IPI) was represented as low score in 70 patients (18.5%), intermediate in 203 (53.7%) and high in 105 (27.8%). Approximately 55% of patients didn`t have any comorbidity. Regarding comorbidity indexes (CI), CIRS ≥ 17 had 4% of patients (minimal score was 14), CCI ≥ 3 had 3.2%, aaCCI ≥ 5 had 34.1%, and HCT-CI ≥ 2 had 31.2% of patients. The patients were treated with R-EPOCH protocol (13 patients, 34.4%), R-CVP (22 patients, 5.8%), and R-CHOP (343 patients, 90.7%).
Complete and partial remission were achieved in 334 (88.4%) of patients and 44 patients (12.6%) had primary resistant disease. The prognostic value of R-IPI was highly statistically significant (Log Rank χ2 53.569, p < 0.01). The patients with ECOG PS ≥ 2 had poorer outcome than the patients in good PS (Log Rank χ2 33.075, p < 0.01). In patients with CIRS ≥ 17 median OS was 30 months (95% CI 10.147-49.859) comparing to the patients with CIRS 14-16 whose median OS was not reached (Log Rank χ2 10.046, p < 0.01). The patients with CCI ≥ 3 had poorer outcome (median OS of 24 months, 95% CI 0.00-50.877) than the patients with CCI 0-2 (Log Rank χ2 12.659, p < 0.01). The patients with HCT-CI≥2 had significantly poorer outcome than the patients with low CI (Log Rank χ2 8.041, p < 0.01). OS in patients with HCT-CI≥2 after 1, 2 and 5 years was 69%, 63% and 49% respectively, and 89%, 81% and 72% for those with HCT-CI 0-1. The patients treated with R-CHOP and R-EPOCH protocol had statistically significant better OS than the patients treated with R-CVP protocol (Log Rank χ2 8.754, p < 0.01). Multivariant analysis (CIRS, CCI, aaCCI, HCT-CI, therapeutic approach, R-IPI) revealed that the most predictable factor for OS was R-IPI (p < 0.0001).
Comorbidities are an independent prognostic parameters for worse OS in patients with DLBCL treated with immunochemotherapy. Omission of the antracyclines due to the frailty, older age or high comorbidity score leads to significantly poorer outcome. Finally, in the rituximab era prognosis is appreciably influenced with the value of initial R-IPI.
Keyword(s): Comorbidities, Diffuse large B cell lymphoma, Prognostic factor, Rituximab
European Hematology Association, EHA-Congress Vienna 2015; 06/2015
[Show abstract][Hide abstract] ABSTRACT: Diffuse
large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable prognostic factor in DLBCL. However, the underlying mechanisms of BCL-6 expression in DLBCL relapse are not yet elucidated. Here, we present so far undescribed clinical phenomenon of switching BCL-6+ protein expression into BCL-6− expression in 19 of 41 relapsed DLBCL patients. The switch in relapsed DLBCL was associated with more aggressive clinical course of the disease. Bone marrow infiltration and high IPI risk were more often present in BCL-6− patients. Significantly increased biochemical parameters, such as LDH, beta-2 macroglobulin, CRP, and ferritin have been found, as well as significantly decreased serum Fe, TIBC, and hemoglobin. A Ki-67 proliferation marker was considerably high in relapsed DLBCL, but without significant differences between BCL-6+ and BCL-6− groups of patients. Thus, switching of the positive into negative BCL-6 expression during DLBCL relapse could be used as a prognostic factor and a valuable criterion for treatment decision.
Indian Journal of Hematology and Blood Transfusion 12/2014; 30(4):269-274. DOI:10.1007/s12288-014-0346-8 · 0.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We herein present the case of a 55-year-old woman with a previous history of malignancies - uterine adenocarcinoma, basal cell carcinoma (which occurred twice consecutively), recurrent respiratory infections due to common variable immunodeficiency (CVID), and systemic granulomatous disease diagnosed at a later age. The patient suffered from diffuse large B cell lymphoma (DLBCL), which was successfully treated with R-CHOP chemotherapy, and continued with immunoglobulin supplementation. The patient was free of lymphoma and infectious complications for over 20 months despite her persistent immunodeficiency, but eventually developed colorectal adenocarcinoma. To the best of our knowledge, this is the first reported case of CVID associated with multiple solid tumours and DLBCL.
Singapore medical journal 10/2014; 55(10):e162-4. DOI:10.11622/smedj.2014147 · 0.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Primary testicular lymphoma (PTL) is a rare and highly aggressive extranodal non-Hodgkin's lymphoma.
Patients and methods:
We evaluated the clinical and histopathological features and outcomes of 10 PTL patients treated in the period of 2003-2013 with multimodal therapy (rituximab, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), intrathecal prophylaxis, irradiation of the contralateral testis) following orchiectomy.
Complete remission was achieved in 8 patients after first-line therapy while 2 patients had disease progression. The median follow-up duration was 30 months (range 6-110 months). Relapse occurred in 3 patients. 1 patient relapsed in the contralateral testis, while the other 2 patients relapsed to the skin and the central nervous system (CNS), respectively. The time to relapse was 2, 8, and 9 months. Patients with disease progression and relapse received ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) as salvage treatment, except for 1 patient who was treated with palliative radiotherapy. After second-line therapy, only 1 patient had a short partial remission of 2 months. The median overall survival was 48 months, and the mean progression-free survival was 36 months (the median was not reached).
We evaluated 10 patients with PTL treated with rituximab plus CHOP, prophylactic intrathecal chemotherapy, and prophylactic irradiation of the contralateral testis, resulting in good outcome and low incidence of relapse in the contralateral testis; however, the benefit of intrathecal chemotherapy is not yet confirmed.
Oncology Research and Treatment 05/2014; 37(5):239-42. DOI:10.1159/000362399
[Show abstract][Hide abstract] ABSTRACT: Based on the results of clinical trials, there is no global consensus on the optimal first line therapy for patients with advanced Hodgkin lymphoma (HL) with both, ABVD and BEACOPP currently being used. However, the results of clinical trials are usually better than those in daily practice. We thus describe here our experience on 314 advanced classical HL patients treated with ABVD at the Clinical Center of Serbia and associated centers between 1997 and 2008. The median follow-up for all patients was 91 months; the estimated 5-year event free survival was 62% and the 5-year OS 76%. Multivariate Cox regression analysis revealed that patients with IPS≥3 and extranodal disease involving more than one site have a poorer outcome. The data presented here show on overall improvement in outcome as compared to more previous data and illustrate the problems of treating advanced stage HL outside the setting of a clinical trial.This article is protected by copyright. All rights reserved.
European Journal Of Haematology 05/2014; 93(5). DOI:10.1111/ejh.12364 · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The combination of absolute lymphocyte count (ALC) and absolute monocyte count (AMC) at diagnosis has prognostic relevance in patients with diffuse large B cell lymphoma (DLBCL).
The present study was designed to investigate the prognostic significance of ALC and AMC and to determine whether ALC/AMC ratio or ALC/AMC prognostic score is better predictor of outcome in DLBCL.
We retrospectively analyzed the prognostic significance of ALC and AMC, ALC/AMC ratio and ALC/AMC prognostic score at diagnosis in 222 DLBCL patients treated with R-CHOP.
ROC analysis showed that optimal cut-off values of AMC and ALC/AMC ratio with the best sensitivity and specificity were 0.59 × 109/L and 2.8, respectively. Cut-off of ALC was determined according to the literature data (1 × 109/L). Low ALC, high AMC, low ALC/AMC ratio and high ALC/AMC prognostic score were in significant association with lower rate of therapy response and survival. In contrast, these parameters were not in significant correlation with relapse rate. The patients with low ALC, “high” AMC, low ALC/AMC ratio and high ALC/AMC prognostic score at diagnosis had significantly shorter EFS and OS. In multivariate analysis all tested parameters (ALC, AMC, ALC/AMC prognostic score and ALC/AMC ratio) are independent risk factors along with “bulky” disease and IPI.
All tested parameters (ALC, AMC, ALC/AMC score and ALC/AMC ratio) may be useful prognostic factors in DLBCL patients. ALC/AMC score has a slight advantage as it allows the classification of patients into three prognostic groups. Further studies are needed to determine which of these parameters has the highest predictive value.
European Journal of Internal Medicine 03/2014; 25(3). DOI:10.1016/j.ejim.2014.01.019 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Orbital and ocular andexal Mucosa-Associated Lymphoid Tissue Lymphoma (MALT) or ocular adnexal MALT lymphoma (OAML) is the most common of all eye non-Hodgkin lymphomas. Autoimmune inflammatory disorders and chronic infections are important etiological factors and CD5 and CD43 (sialophorin) tumor markers are significant negative prognostic factors. Disease signs and symptoms can occur a long time before diagnosis. Varieties of treatment options are available. The aim of this retrospective analysis was to compare the efficiency of different treatment options and to investigate disease outcome. Twenty OAML patients, diagnosed in the Clinic of Hematology, Clinical Centre of Serbia, between 2003 and 2013, were enrolled. In most cases, OAML developed in the eighth decade with greater incidence in the male population. Median age was 67.5 years. The median period between the appearance of local signs and symptoms and diagnosis was 7 months. The dominant sign at presentation was swelling of involved tissue (40 %). The most common was orbital involvement (55 %). All patients had localized disease. Observed laboratory parameters on presentation showed low disease activity. Sialophorin prognostic significance was not registered. Our patients were initially treated differently but there was no significant difference in progression-free survival (PFS) due to initial treatment option (p = 0.2957). Median PFS was 22 months (3-89), and 5-year PFS was 60 %. Median overall survival (OS) was 43 months (1-105) and 5-year OS 95 %. Eight patients (40 %) relapsed and one patient died due to non-hematological complications. In our experience, most modern induction treatment options appear to result in the same, favorable outcome.
Medical Oncology 12/2013; 30(4):722. DOI:10.1007/s12032-013-0722-5 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Special entities like solitary bone plasmocytoma (SBP) or extramedullary plasmacytoma (EMP) can be found in a less than 5% of patients with plasma cell disorders. EMP of the tongue represents very rare localization of the head and neck plasmacytoma.
We report a case of 78-years-old woman who developed EMP of the tongue base detected by the magnetic resonance imaging (MRI) of the head and neck region. Immunohistochemical profile of the tumor tissue biopsy (CD38, IgG, kappa positivity) indicated diagnosis of EMP. The diagnosis was established with additional staging which confirmed the absence of other manifestation of the disease. The patient was treated with 40 Gy of radiotherapy in 20 doses resulting in the achievement of the complete remission of the disease. This case was discussed with the reference to the literature.
EMP of the tongue base is a very rare entity of plasma cell dyscrasias. Appropriate irradiation results in the achievement of a long-term remission and a potential cure of the disease.
[Show abstract][Hide abstract] ABSTRACT: Treatment of blood products by riboflavin and ultraviolet (UV) light prevents of white blood cell (WBC) replication and inactivates of pathogens. The aim of this study was to determine the effects of the inactivation by riboflavin and UV light upon plasma clinical performance, based on effect on the pretransfusion international normalized ratio (INR). A prospective, controlled randomized study included 60 patients who received transfusion of plasma on the Clinic for hematology of Clinical Centre in Nis. Experimental group (EG; 30 patients) was treated with Mirasol-inactivated fresh frozen plasma (FFP) and control group (CG; 30 patients) was transfused with noninactivated FFP. Besides pretransfusion vs. posttransfusion INR, the improvement in INR patient's plasma level per one FFP unit transfused was evaluated. Total of 68 units of FFP were transfused to patients of CG (2.24±0.83 units per patient). Patients of EG received 84 units of Mirasol-inactivated plasma (i.e. 2.80±1.19 units per patient). There was significant increase in number of FFP transfusions that normalized coagulation parameters in EG compared to CG (p=0.039). Also, there was a significant improvement of INR after every FFP unit application (p=0.046). We found a linear relationship between pretransfusion INR and improvement of INR (r=0.97; p<0.001). Plasma treated with riboflavin and UV light retains hemostatic competence and can be used efficiently in the therapy of congenital or acquired coagulopathies, but in larger quantity as compared to noninactivated FFP volume.
[Show abstract][Hide abstract] ABSTRACT: Angiogenesis in solid tumors is important for tumor growth, invasion, and metastasis. However, angiogenesis plays also an important role in hematological malignancies. We have analyzed the expression of vascular endothelial growth factor (VEGF) in the leukemic blast cells and microvessel density (MVD) in the bone marrow biopsy samples of the patients with acute lymphoblastic leukemia (ALL). Bone marrow MVD of the patients with ALL was significantly higher compared with normal controls and complete remission (P<0.001), but slightly lower than in patients with relapsed ALL (P>0.05). The bone marrow blast VEGF expression was significantly higher in newly diagnosed ALL patients, with predominant strong VEGF expression as compared with complete remission patients (who had negative or weak VEGF expression) (P<0.05), whereas initial values were slightly lower than in relapsed patients. There was a strong positive correlation between VEGF expression and MVD at presentation of ALL. Stronger expression of VEGF on blast cells indicates shorter overall survival in ALL. Furthermore, initial values of MVD had positive correlation with overall survival and leukemia-free survival (P=0.024 and P=0.017, respectively). Our data suggest that increased angiogenesis (confirmed by immunohistochemical expression of VEGF in leukemic blasts), and MVD may play an important role in the pathophysiology of ALL with prognostic implications. Thus, targeting VEGF pathway may bring the new approach for ALL treatment-using antiangiogenic drugs and tyrosine kinase inhibitors in combination with standard chemotherapy regimens.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 03/2012; 20(5):488-93. DOI:10.1097/PAI.0b013e3182414c3b · 2.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introducing tyrosine kinase inhibitors (TKIs) has essentially changed curative approach, to be precise, clearly improved treatment efficacy for chronic myeloid leukemia (CML). Thus, the place and usage of allogeneic stem cell transplant (SCT) in CML treatment--as a former "nearly monopolistic" therapeutic manner--is nowadays controversial. The objective of this retrospective study was to evaluate the results obtained in the treatment of CML patients, with a particular attempt to define parameters critical for clinical benefit and superior overall outcome following allogeneic SCT.
A total of 32 CML patients (27 in chronic phase and 5 with advanced disease), with female/male ratio 11/21, aged from 9 to 54 (32 in average) years, underwent allogeneic SCTs (1993 to 2009). The initial treatment for 25 patients was interferon alpha (IFN-alpha) with or without ARA-C, and additional 7 patients with no response to imatinib mesylat (IM). The time from diagnosis to SCT was approximately 12 (range 3-37) months. The patient were categorized according to the risk for the disease, transplant-related mortality (TRM) scoring system, and stem cell (SC) source. The basic conditioning regimen was a combination of busulphan and cyclophosphamide (BuCy-2). Graft-versus-host disease (GvHD) was typically prevented with cyclosporine-A (CsA) and methotrexate (MTX).
Engraftment was observed in 26 (84.4%) patients, with polymorphonuclear (PMNs) and platelet (Plt) recovery on the 15th (range 10-22) and 19th (range 11-29) posttranspalnt days, respectively. Acute GvHD (aGvHD) had 13/26 (50%), and chronic GvHD (cGvHD) 10/21 (47.1%) patients. The incidence of overall TRM was 46.8% (15/32), while early death was noticed in 4 (12.5%) patients. A cause of death in 9 (28.1%) patients was cGvHD, in 2 (6.25%) patients infection, and in 3 (9.35%) cases disease-relapse was occurred. Fourteen (43.7%) of the patients are still alive, 9 from the low-risk group for TRM, with long-term survival from 1 to 16 years. Patients who received SCs from peripheral blood (PB) vs bone marrow (BM) had significantly faster engraftment (p < 0.05), lower oropharingeal mucositis rate (25% vs 70%; p < 0.05), but more frequent cGvHD (83.3% vs 30.3%; p < 0.05). A significantly improved (log-rank = 2.39; p < 0.01) overall survival (OS) was obtained in BM-setting.
The results obtained in this study are in accordance with data from analogous clinical trials. Exactly, in the era of the new target therapy (TKI application), allogeneic SCT can be still a convenient therapeutic approach for well-selected CML-patients, especially for those with initial high-risk disease and lower probability of TRM.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the prognostic significance of international prognostic index (IPI), mantle cell lymphoma IPI (MIPI), simplified MIPI (sMIPI), and MIPI biological (MIPIb), as well as their correlation with immunophenotype, clinical characteristics, and overall survival (OS), in a selected group of 54 patients with advanced-stage mantle cell lymphoma (MCL), treated uniformly with CHOP. Seventeen patients had IV clinical stage (CS), while other 37 had leukemic phase at presentation. Diffuse type of marrow infiltration was verified in 68.5% and nodular in remainder patients. Extranodal localization (25.9%) included bowel (20.4%), pleural effusion, sinus, and palpebral infiltration. All of analyzed patients expressed typical MCL immunophenotypic profile: CD19(+)CD20(+)CD22(+)CD5(+)Cyclin-D1(+)FMC7(+)CD79b(+)smIg(+)CD38(+/-)CD23(-)CD10(-). Median OS of the whole group was 23 months, without significant differences between IV CS and leukemic phase patients. Thirty-two patients (59.3%) responded to initial treatment, 9 (16.7%) with complete and 23 (42.6%) with partial remission. Negative prognostic influence on OS had high IPI (P < 0.01), high sMIPI (P < 0.001), MIPI (P < 0.01), MIPIb (P < 0.01), extranodal localization (P < 0.01), and diffuse marrow infiltration (P < 0.01). Testing between randomly selected groups showed that patients with lower proportion of CD5(+) cells (<80%) correlated with cytological blastoid variant and had shorter survival comparing with the group with higher proportion of CD5(+) cells (>80%) (P < 0.01). Using univariate Cox regression, we proved that IPI, sMIPI, MIPI, and MIPIb had an independent predictive importance (P < 0.01) for OS in uniformly treated advanced MCL patients, although sMIPI prognostic significance was the highest (P < 0.001).
Medical Oncology 12/2011; 29(3):2212-9. DOI:10.1007/s12032-011-0136-1 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND/AIM: Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT) with bone marrow transplantation (BMT) on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease--aGvHD) and delayed (chronic GvHD--cGvHD) complications, as well as transplant-related mortality (TRM), transfusion needs, relapses and overall survival (OS). METHODS: We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57), who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML)--39, acute lymphoblastic leukemia (ALL) 47, chronic myeloid leukemia (CML)--32, myelodysplastic syndrome (MDS)--10, Hodgkin's lymphoma (HL)- 2, multiple myeloma (MM) 3, granulocytic sarcoma (GrSa) 3, severe aplastic anemia (sAA)--22. The patients underwent transplantations were divided into two groups: BMT group (74 patients) and PBSCT group (84 patients). Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one "Large Volume Leukapheresis" (after recombinant human granulocyte colony stimulating factor, rHuG-CSF) application (5-12 microg/kgbm, 5 days). Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001) faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (P < 0.01) higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05). There were no significant differences in the incidence of aGvHD and cGvHD between the two groups. The patients who underwent PBSCT had more frequently extensive cGvHD in comparison with the BMT group (29.1% vs 11.29%, p < 0.05). SC source (SCS) had no significant influence on the TRM (21.62% vs 23.8%, p = 0.64) and the incidence of relapses (21.6% vs 29.7%, p = 0.32). Finally, the patients treated by BMT hd a significantly better OS (logrank 2.33, p < 0.05). Conclusion. SCs harvesting from PB resulted in improved cell yield, faster engraftment, as well as in a decrease of immediate transplantation related complications with a reduced treatment cost. Allogeneic PBSCT were associated with more frequent extensive cGvHD, while the influence of SCS in TRM and relapses was not observed. Finally, the long-term OS was better in the patients treated by BMT. To verify impact of SC source on transplantation (PBSCT vs BMT) overall efficacy, more larger randomized clinical studies are needed.