Ofer Shpilberg

Assuta Medical Centers, Tell Afif, Tel Aviv, Israel

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Publications (249)1319.91 Total impact

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    ABSTRACT: Background: The prognosis of elderly patients with acute myeloid leukemia (AML) is poor, and the best treatment is controversial. Since the majority of AML patients are older than 60 years, identification of those who might benefit from intensive treatment is essential. Methods: Data from electronic charts of consecutive AML patients treated in our center were analyzed. Eligibility criteria included newly diagnosed de novo or secondary AML, an age of 60 years or older, and intensive induction treatment. Results: Sixty-two patients were included in the analysis. Forty-six patients (74%) achieved complete remission (CR) after 1-2 intensive induction courses. Twenty of them received consolidation with conventional chemotherapy, 20 proceeded to allogeneic hematopoietic cell transplantation (allo-HCT), and 6 were ineligible for further treatment. The projected overall survival (OS) at 2 and 3 years was 28 and 23%, respectively. A normal karyotype, CR achievement, and allo-HCT were associated with improved OS, while an Eastern Cooperative Oncology Group performance status of 0-1 was borderline associated. The median survival and disease-free survival at 2 years was 18.7 months and 49%, respectively, for patients who underwent allo-HCT in CR1, compared to 12.8 months and 25%, respectively, for those who did not. Conclusion: Based on our data, selected eligible elderly AML patients might benefit from intensive treatment.
    Full-text · Article · Oct 2015 · Acta Haematologica
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    ABSTRACT: Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, the strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted (P<0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs.Bone Marrow Transplantation advance online publication, 14 September 2015; doi:10.1038/bmt.2015.213.
    No preview · Article · Sep 2015 · Bone marrow transplantation
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    Full-text · Dataset · Jul 2015
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    Full-text · Dataset · Jul 2015
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    Full-text · Dataset · Jul 2015
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    ABSTRACT: This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone (VTD) and VTD-cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m(2) ; days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m(2) ; days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64·8 months, median time-to-next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively. Type of subsequent therapy was similar in both arms. After adjusting for asymmetric censoring, median time to progression was not significantly different between VTD and VTDC [35·7 vs. 34·5 months; Hazard ratio (HR) 1·26, 95% confidence interval: 0·76-2·09; P = 0·370]. Five-year survival was 69·1% and 65·3% with VTD and VTDC, respectively. When analysed by minimal residual disease (MRD) status, overall survival was longer in MRD-negative versus MRD-positive patients with bone marrow-confirmed complete response (HR 3·66, P = 0·0318). VTD induction followed by transplantation provides long-term disease control and, consistent with the primary analysis, there is no additional benefit from adding cyclophosphamide. This study was registered at ClinicalTrials.gov (NCT00531453). © 2015 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.
    Full-text · Article · Jul 2015 · British Journal of Haematology
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    ABSTRACT: This study compared the value of several simple laboratory parameters with known prognostic models for predicting survival in patients with diffuse large B-cell lymphoma (DLBCL). The data of 157 adult patients with DLBCL diagnosed at Rabin Medical Center in 2004-2008 and treated with R-CHOP immunochemotherapy were retrospectively reviewed. Main clinical features of the cohort were as follows: mean age 63.0 years, 43% male, 63% stage III/IV disease, 28% ECOG performance status >2, 60% elevated lactate dehydrogenase level. Median duration of follow-up was 6.6 years. The NCCN-International Prognostic Index (IPI) was found to be a more powerful prognosticator than the IPI. Five-year overall survival (OS) was 69.6; 73.6% for patients with intermediate NCCN-IPI and 38.4% for patients with poor NCCN-IPI. On univariate analysis, pretreatment hemoglobin and albumin levels were significantly associated with survival. By albumin level, 5-year OS was 77.6 + 4% in patients with >3.5 g/dl and 53 + 7% in patients with <3.5 g/dl (p < 0.001); 5-year progression-free survival (PFS) was 69.9% and 50.9%, respectively (p = 0.002). By hemoglobin level, 5-year OS was 82.9 + 4.5% in patients with >12 g/dl and 58.8 + 5% in patients with <12 g/dl (p = 0.007); 5-year PFS was 75.5% and 54.1%, respectively (p = 0.008). On multivariate analysis with Cox regression, pretreatment albumin level was a significant independent predictor of OS. Furthermore, 5-year OS of patients with a high NCCN-IPI and albumin < 3.5 g/dl was 29.2% compared with 60% in patients with albumin > 3.5 g/dl (p = 0.022). In conclusion, pretreatment albumin level is a strong prognostic factor for OS in patients with DLBCL and can discriminate high-risk patients for good and poor prognosis. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Jun 2015 · Hematological Oncology

  • No preview · Article · Jun 2015
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    ABSTRACT: R-CHOP-21 has remained the standard chemotherapy for aggressive non-Hodgkin's lymphoma. It was suggested that decreasing the treatment interval from three weeks (CHOP-21) to two weeks (CHOP-14) may improve survival and disease control of patients with aggressive lymphoma. To evaluate the effect of CHOP-like-14 (with or without rituximab) compared to standard CHOP-like -21 on overall survival (OS), disease control and toxicity of patients with aggressive non-Hodgkin lymphoma. Systematic review and meta-analysis of RCTs. In October 2014 we searched The Cochrane Library, MEDLINE, LILACS, conference proceedings, and databases of ongoing trials. Authors were contacted for complementary data. The primary outcome was OS. We identified seven trials (4073 patients), conducted between the years 1999 and 2008. Trials were at low or unclear risk for selection bias, and at low or unclear risk of attrition bias. CHOP-like-14 improved OS of patients with aggressive lymphoma compared to the same regimen given every 21 days (all trials): HR of death 0.86, 95% confidence interval (CI) 0.77-0.97. There was no OS difference between rituximab-CHOP-like 14 to rituximab-CHOP-like-21 (3 trials): HR 0.93 95% CI 0.78-1.10. The rates of progression or death, complete response, treatment-related mortality, grade 3-4 infection, and discontinuation were similar between groups. R-CHOP-21 remains the standard of care for patient with aggressive B-cell lymphoma. CHOP-14 can be considered as in case rituximab is omitted.
    Full-text · Article · May 2015 · Acta oncologica (Stockholm, Sweden)
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    ABSTRACT: Patients with β-thalassemia major (TM) may have tubular dysfunction and glomerular dysfunction, primarily hyperfiltration, based on eGFR. Assessment of GFR based on serum creatinine concentration may overestimate GFR in these patients. This study sought to determine GFR by using inulin clearance and compare it with measured creatinine clearance (Ccr) and eGFR. Patients followed up in an Israeli thalassemia clinic who had been regularly transfused for years and treated with deferasirox were included in the study. They were studied by inulin clearance, Ccr, the CKD Epidemiology Collaboration and the Modification of Diet in Renal Disease equations for eGFR, and the Cockcroft-Gault estimation for Ccr. Expected creatinine excretion rate and tubular creatinine secretion rate were calculated. Nine white patients were studied. Results, given as medians, were as follows: serum creatinine was 0.59 mg/dl (below normal limits); GFR was low (76.6 ml/min per 1.73 m(2)) and reached the level of CKD; Ccr was 134.9 ml/min per 1.73 m(2), higher than the GFR because of a tubular creatinine secretion rate of 30.3 ml/min per 1.73 m(2) (this accounted for 40% of the Ccr); and eGFR calculated by the CKD Epidemiology Collaboration and Modification of Diet in Renal Disease equations and Cockcroft-Gault-estimated Ccr were 133, 141, and 168 ml/min per 1.73 m(2), respectively. These latter values were significantly higher than the GFR, reaching the hyperfiltration range, and indicated that the estimation techniques were clinically unacceptable as a method for measuring kidney function compared with the GFR according to Bland and Altman analyses. Contrary to previous reports, patients in this study with TM had normal or reduced GFR. The estimating methods showed erroneous overestimation of GFR and were clinically unacceptable for GFR measurements in patients with TM by Bland and Altman analysis. Therefore, more accurate methods should be used for early detection of reduced GFR and prevention of its further decline toward CKD in these patients. Copyright © 2015 by the American Society of Nephrology.
    No preview · Article · May 2015 · Clinical Journal of the American Society of Nephrology
  • L Cohen · M Yeshurun · O Shpilberg · R Ram
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    ABSTRACT: We aimed to study the risk factors for first and subsequent cytomegalovirus (CMV) infection among patients who are CMV seropositive and underwent allogeneic hematopoietic cell transplantation (HCT). We performed a historical cohort study of all sequential CMV-seropositive patients who underwent allogeneic HCT at a single center. Between May 2007 and December 2012, 121 patients fulfilled inclusion criteria. Multivariate model identified myeloablative preparative regimen (hazard ratio [HR] = 4.297, P = 0.033) and acute graft-versus-host disease (GVHD) prior to infection (HR = 5.091, P = 0.021) as risk factors for first CMV infection. The cumulative incidences of first CMV infection for patients with 0, 1, and 2 risk factors were 52%, 71%, and 91%, respectively. Multivariate analysis identified the diagnosis of lymphoma/myeloma (HR = 3.5, P = 0.049) and GVHD (HR = 1.280, P = 0.045) as risk factors for subsequent CMV infection. High graft CD3 stem cell dose was associated with a trend of lower rate of subsequent CMV infection (HR = 0.543, P = 0.056). The cumulative incidences for subsequent CMV infection in patients with 0, 1, and 2-3 risk factors were 11%, 41%, and 77%, respectively. In conclusion, in CMV-seropositive patients, myeloablative conditioning and acute GVHD are risk factors for first CMV infection, while lymphoma /myeloma, ongoing GVHD, and low CD3 graft content are risk factors for subsequent infection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · Transplant Infectious Disease

  • No preview · Article · Apr 2015 · Leukemia Research
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    ABSTRACT: Tailoring treatment by patient strata based on the risk of disease progression and treatment toxicity might improve outcomes of patients with posttransplant lymphoproliferative disorder (PTLD). We analysed the cohort of 70 patients treated in the international, multicenter phase II PTLD-1 trial (NCT01458548) to identify such factors. Of the previously published scoring systems in PTLD, the international prognostic index (IPI), the PTLD prognostic index and the Ghobrial score were predictive for overall survival. None of the scoring systems had a considerable effect on the risk for disease progression. Age and ECOG performance status were the baseline variables with the highest prognostic impact in the different scoring systems. Baseline variables not included in the scoring systems that had an impact on overall survival and disease progression were the type of transplant and the response to rituximab at interim staging. Thoracic organ transplant recipients who did not respond to rituximab monotherapy were at particularly high risk for death from disease progression with subsequent CHOP-based chemotherapy. Patients in complete remission after four courses of rituximab and patients in partial remission with low-risk IPI had a low risk of disease progression. We speculate that chemotherapy might not be necessary in this patient cohort. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    No preview · Article · Mar 2015 · American Journal of Transplantation
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    ABSTRACT: Bone marrow (BM) trephine biopsy is a part of routine staging of patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The significance of lymphoid monoclonal population on flow cytometry (FC) of the BM aspirate in the presence of negative BM histology has not been clarified. In this study, we assessed the clinical role of positive FC in predicting outcome of patients with DLBCL and a negative BM histology. We retrospectively analysed 101 patients diagnosed with DLBCL at a single institution between years 1994-2003. Three groups of patients were compared: patients with histologic involvement of the BM (BM+), patients with no histologic involvement of the BM but with positive FC (BM-FC+) and patients with neither histologic or FC evidence of BM involvement (BM-FC-). The BM+ group included 13 patients (13%). The BM-FC+ group 16 patients (16%), and the BM-FC-included 72 patients (71%). Median age of the cohort was 67 years. Disease stage and International Prognostic Index score were significantly higher in the BM+ and BM-FC+ groups compared with the BM-FC- group. Median overall survival (OS) for the BM-FC-, BM-FC+ and BM + groups were 4.6, 2.2 and 0.9 years, respectively. Median progression free survival (PFS) for the BM-FC-, BM-FC+ and BM+ groups were 3.2, 1.4 and 0.6 years, respectively (p=0.01 for both analysis). In multivariable Cox regression models adjusting for age, sex, stage and International Prognostic Index, there was no significant differences in OS or PFS between the BM-FC+ and BM-FC- groups. In conclusion, positive FC in the setting of negative BM histology at diagnosis did not significantly affect OS or PFS. Copyright © 2014 John Wiley & Sons, Ltd.
    No preview · Article · Mar 2015 · Hematological Oncology
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    ABSTRACT: MicroRNAs (miRNAs) are small noncoding RNAs that participate in many biological processes by posttranscriptionally regulating gene expression. Dysregulation of miRNA expression has been shown to be typical of many neoplasms. Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cells carrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL tyrosine kinase fusion gene. While the development of tyrosine kinase inhibitors (TKIs) like imatinib have revolutionized treatment of CML, it has become increasingly clear in recent years that TKIs treatment alone will not be curative in many cases. Thus, further dissection of the regulatory networks that drive BCR-ABL-induced malignant transformation may help to identify other novel therapeutic approaches that complement TKIs treatment. In this study we demonstrate that the expression of miR-424 is markedly low in CML cell lines and patient samples at time of diagnosis. With the aid of bioinformatics analysis we revealed a conserved target site for miR-424 in the 3'-untranslated region (UTR) of the ABL gene. Via luciferase assays, we showed that miR-424 directly targets BCR-ABL. Over expression of miR-424 was shown to suppress proliferation and induce apoptosis of K562 cells as well as sensitize these cells to imatinib treatment. These findings strongly suggest that miR-424 acts as a tumor suppressor by down regulating BCR-ABL expression. Up-regulation of miR-424 in CML cells may therefore have a therapeutic effect against this disease. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Feb 2015 · Cancer Letters
  • I Vaxman · R Ram · A Gafter-Gvili · L Vidal · M Yeshurun · M Lahav · O Shpilberg
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    ABSTRACT: We performed a systematic review and meta-analysis of randomized controlled trials comparing autologous hematopoietic cell transplantation (HCT) with other treatment modalities to analyze the risk for various secondary malignancies (SMs). Relative risks (RR) with 95% confidence intervals were estimated and pooled. Our search yielded 36 trials. The median follow-up was 55 (range 12-144) months. Overall, the RR for developing SMs was 1.23 ((0.97-1.55), I(2)=4%, 9870 patients). Subgroup analysis of trials assessing TBI-containing preparative regimens and of patients with baseline lymphoproliferative diseases, showed there was a higher risk for SMs in patients given autografts (RR=1.61 (1.05-2.48), I(2)=14%, 2218 patients and RR=1.62 (1.12-2.33), I(2)=22%, 3343 patients, respectively). Among all patients, there was a higher rate of myelodysplastic syndrome MDS/AML in patients given HCT compared with other treatments (RR=1.71 (1.18-2.48), I(2)=0%, 8778 patients). The risk of secondary solid malignancies was comparable in the short term between patients given HCT and patients given other treatments (RR=0.95 (0.67-1.32), I(2)=0%, 5925 patients). We conclude that overall the risk of secondary MDS/AML is higher in patients given autologous HCT compared with other treatments. In the subgroup of patients given a TBI-based regimen and in those with a baseline lymphoproliferative disease, there was a higher risk of overall SMs.Bone Marrow Transplantation advance online publication, 9 February 2015; doi:10.1038/bmt.2014.325.
    No preview · Article · Feb 2015 · Bone Marrow Transplantation
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    ABSTRACT: Cytarabine is the backbone of most chemotherapeutic regimens for acute myeloid leukemia (AML), yet the optimal dose for salvage therapy of refractory or relapsed AML (RR-AML) has not been established. Very high dose single-agent cytarabine at 36 g/m(2) (ARA-36) was previously shown to be effective and tolerable in RR-AML. In this retrospective analysis, we aim to describe the toxicity and efficacy of ARA-36 as salvage therapy for patients with AML who are primary refractory to intensive daunorubicin-containing induction or those relapsing after allogeneic stem cell transplant (alloSCT). Fifteen patients, median age 53 years, were included in the analysis. Six patients were treated for induction failure, one had resistant APL, and eight relapsed after alloSCT. Complete remission was achieved in 60% of patients. Surviving patients were followed for a median of 8.5 months. One-year overall survival was 54% (95% CI 30%-86%), and relapse rate from remission (n = 9) was 56%. Grade III/IV pulmonary, infectious, ocular and gastrointestinal toxicities occurred in 26%, 20%, 20% and 20% of patients respectively. Salvage therapy with ARA-36 regimen for RR-AML has considerable efficacy with manageable toxicity in patients with induction failure or post-transplant relapse. Overall survival in these high-risk patients still remains poor. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Feb 2015 · Hematological Oncology
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    ABSTRACT: Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a non-psychotropic ingredient of Cannabis sativa possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a prospective phase II study (NCT01385124). GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low dose anti-T-cell globulin (Fresenius). CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or MDS and 35 patients (73%) were given a myeloablative conditioning. The donor was either an HLA-identical sibling (n=28), a 10/10 matched unrelated donor (n=16) or a one antigen mismatched unrelated donor (n=4). The median follow-up was 16 (range, 7-23) months. There were no grade 3-4 toxicities attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grade 2-4 and grade 3-4 acute GVHD by day 100 were 12.1% and 5%, respectively. Compared to 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grade 2-4 acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was 0.3 (p=0.0002). Rates of non-relapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidence of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double blind controlled study is warranted. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Feb 2015 · Biology of Blood and Marrow Transplantation
  • Ron Ram · Moshe Yeshurun · Ofer Shpilberg · Lirit Cohen

    No preview · Article · Feb 2015 · Biology of Blood and Marrow Transplantation
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    ABSTRACT: Total therapy 3 is an intensified protocol for multiple myeloma (MM). The “real life” outcomes of this protocol were seldom reported. Data was obtained for 81 patients (newly diagnosed, n = 49; progressive MM, n = 32), most of which had high risk parameters. Overall response rate following (V)DT-PACE was 96% and 75% for the newly diagnosed and progressive groups, respectively. Median progression-free survival was 42.5 and 9 months, respectively. The 2 year overall survival was 88% and 40%, respectively. Treatment with (V)DT-PACE achieves high response rate among patients with high-risk disease, which can be translated into long-term remission only for newly diagnosed patients.
    Full-text · Article · Dec 2014 · Leukemia Research

Publication Stats

7k Citations
1,319.91 Total Impact Points


  • 2015
    • Assuta Medical Centers
      Tell Afif, Tel Aviv, Israel
  • 2014-2015
    • Tel Aviv Sourasky Medical Center
      Tell Afif, Tel Aviv, Israel
  • 1989-2015
    • Tel Aviv University
      • • Faculty of Medicine
      • • Felsenstein Medical Research Center
      • • Department of Internal Medicine
      • • Sackler Faculty of Medicine
      Tell Afif, Tel Aviv, Israel
  • 2002-2014
    • Rabin Medical Center
      • Department of Cardiology
      Tell Afif, Tel Aviv, Israel
  • 2002-2012
    • Ben-Gurion University of the Negev
      • Faculty of Health Sciences
      Be'er Sheva`, Southern District, Israel
  • 2010
    • Sapienza University of Rome
      Roma, Latium, Italy
  • 2009
    • Duke University
      Durham, North Carolina, United States
    • Alexandra Regional General Hospital
      Athínai, Attica, Greece
  • 2002-2008
    • Soroka Medical Center
      • • Soroka Medical Center
      • • Department of Pathology
      Be'er Sheva`, Southern District, Israel
  • 2001
    • Technion - Israel Institute of Technology
      H̱efa, Haifa District, Israel
  • 1997-2001
    • University of Pittsburgh
      • Department of Epidemiology
      Pittsburgh, Pennsylvania, United States
  • 1989-2000
    • Sheba Medical Center
      • Department of Pathology
      Gan, Tel Aviv, Israel
  • 1995
    • Hadassah Medical Center
      • Department of Hematology
      Yerushalayim, Jerusalem District, Israel