Irit Avivi

Technion - Israel Institute of Technology, H̱efa, Haifa District, Israel

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Publications (52)283.47 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Therapeutic options for progressive multifocal leukoencephalopathy (PML) caused by reactivation of John Cunningham virus (JCV) are limited and inefficient in preventing neurological progression and death. The current study investigated the course of JCV reactivation resulting in PML in patients undergoing allogeneic stem cell transplantation (allo-SCT) and assessed the feasibility and potential significance of preemptive JCV detection in peripheral blood, enabling early cessation of immunosuppressive therapy and immune restoration. Two allografted patients were diagnosed with PML at 188 and 808 days post-allo-SCT. Stored DNA samples of both patients, originally obtained for quantitative cytomegalovirus PCR analysis since transplantation, were evaluated for JCV. JCV reactivation in peripheral blood was found to precede the appearance of neurological symptoms by 126 and 105 days. JCV blood levels were found to be highly correlated with the steroid dosage administered for treating graft-versus-host disease (GVHD). In one patient, the cessation of immunosuppression, including steroids, led to the disappearance of JCV in peripheral blood, with a remarkable improvement in neurological symptoms. In conclusion, the current study suggests the feasibility of early detection of JCV reactivation in blood. Immune restoration at that point may prevent PML development; however prospective studies are warranted to elucidate these issues.
    International Journal of Infectious Diseases. 07/2014; 26.
  • Irit Avivi, Benjamin Brenner
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    ABSTRACT: Diagnosis of acute leukemia during pregnancy presents significant medical challenges. Pancytopenia, caused by bone marrow substitution with leukemic cells, impairs maternal and fetal health. Chemotherapeutic agents required to be immediately used to save the mother's life are likely to adversely affect fetal development and outcome, especially if administered at an early gestational stage. Patients diagnosed with acute leukemia during the first trimester are, therefore, recommended to undergo pregnancy termination. At later gestational stages, antileukemic therapy can be administered, although in this case, fetal outcome is still associated with increased incidence of growth restriction and loss. Special attention to the issue of future reproduction, adopting a personalized fertility preservation approach, is required. This article addresses these subjects, presenting women diagnosed with acute myeloid and acute promyelocytic leukemia in pregnancy. The rarity of this event, resulting in insufficient data, emphasizes the need for collaborative efforts to optimize management of this complicated clinical condition.
    Future oncology (London, England). 06/2014; 10(8):1407-15.
  • British Journal of Haematology 05/2014; · 4.94 Impact Factor
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    ABSTRACT: Autologous stem cell transplantation (autoSCT) is considered a standard treatment for non-frail patients with mantle cell lymphoma (MCL), but little is known about outcome of MCL patients relapsing after autoSCT. We therefore sought to analyse the outcome after autoSCT failure and the efficacy of a rescue SCT in this setting. Patients with MCL were eligible if they had relapsed after autoSCT performed between 2000 and 2009. 1054 patients could be identified in the EBMT registry. By contacting the transplant centres a full data set could be retrieved for 360 patients. Median overall survival (OS) after relapse of the whole study group was 19 months. A long (>12 months) interval between autoSCT and relapse (p<0.001; HR 0.62), primary refractory disease (p<0.02, HR 1.92), prior high-dose ARA-C treatment (0.04, HR 1.43) and the year of relapse (0.02 HR 0.92) significantly influenced OS from relapse in multivariate analysis.Eighty patients (22%) received a rescue allogeneic SCT (alloSCT). Relapse incidence, non-relapse mortality, and OS 2 years after alloSCT was 33% (CI 21-45%), 30% (CI 19-42%) and 46% (CI 33-59%), respectively. Remission duration after autoSCT was the only variable significantly affecting the outcome of salvage alloSCT. In contrast, rescue autoSCT was not associated with long-term disease control. However, individual patients survived long-term even without salvage transplantation. MCL recurrence within one year after autoSCT has an extremely dismal outcome, whilst the prognosis of patients with longer remission durations after autoSCT is significantly better. AlloSCT may offer the possibility of durable survival when performed for patients with a remission duration of more then 12 months after first autoSCT, but the favourable effect of a salvage alloSCT in this setting needs further validation.
    Annals of Oncology 02/2014; · 7.38 Impact Factor
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    ABSTRACT: The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiving URD-HCT between 2000 and 2007 and reported to the European Group for Blood and Marrow Transplantation, was compared with that of 301 subjects, allografted from sib-HCT. With a median follow-up of 45 months, 3-year PFS approached 35% for both groups; overall survival (OS) was 42% for sib-HCT versus 37% for URD (NS). Multivariate analyses confirmed that donor type was not associated with differences in non-relapse mortality (NRM), relapse rate (RR), PFS or OS. Poor performance status (PS) and refractory disease adversely affected PFS and OS. Prior auto-SCT and multiple previous therapies predicted for shorter PFS. NRM was adversely affected by older age (50 years), poor PS and refractory disease, and RR by time from diagnosis to allo-HCT of <36 months, prior auto-SCT, refractory disease, poor PS and in vivo T-cell depletion with alemtuzumab. This large study shows for the first time that URD-HCT is not inferior to sib-HCT, providing a reasonable therapeutic approach for DLBCL patients, having no HLA-identical sibling available.Bone Marrow Transplantation advance online publication, 10 February 2014; doi:10.1038/bmt.2014.4.
    Bone marrow transplantation 02/2014; · 3.00 Impact Factor
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    ABSTRACT: Abstract FDG-PET/CT scanning is often used for staging and response assessment in Mantle cell lymphoma (MCL); however, the ability of interim and post therapy scans to predict outcome is debatable. We retrospectively evaluated the prognostic impact of interim and post therapy FDG-PET/CT scan on outcome of patients with MCL. Fifty eight consecutive patients diagnosed between 1998 and 2011 were included in the analysis. Scans, performed at diagnosis, mid-therapy, post chemotherapy (prior to ASCT) and post transplantation, were reviewed and outcome was analyzed. Median age was 59. Most patients presented with advanced disease. MIPI was low in 45%, intermediate in 41% and high in 14%. Thirty four patients (58%) received RCHOP or RCHOP-like chemotherapy and 24 (42%) underwent an upfront ASCT. Three years overall (OS) and progression free survival (PFS) were 81% and 45% respectively. No significant differences in OS or PFS between the PET positive and PET negative groups both for interim and post therapy scans were observed. Analysis of chemotherapy only and chemotherapy+ASCT groups separately did not reveal any correlation between interim, post therapy or pre transplant PET result to OS and PFS. We conclude that in patients treated with R-CHOP-21 or R-CHOP- like chemotherapy using the International Harmonization Project criteria to determine whether a scan is positive or negative, there is no role for interim or post therapy PET.
    Leukemia & lymphoma 01/2014; · 2.61 Impact Factor
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    ABSTRACT: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) often present with systemic symptoms such as fatigue, shortness of breath and night sweats, mimicking pregnancy-related features which may result in delayed disease diagnosis. Furthermore, the wish to avoid investigational imaging, aiming to protect the fetus from radiation exposure, may lead to a further delay, which does not often result in significant changes in HL clinical nature and patient outcome. In contrast, a more aggressive behavior (i.e., advanced disease stage and reproductive organ involvement) of most NHL types diagnosed in pregnancy may require urgent therapeutic intervention to prevent disease progression. Current management of pregnancy-associated NHL depends on histological subtype of the disease, gestational stage at diagnosis and the urgency of treatment for a specific patient. Patients diagnosed with indolent lymphoma may often be just followed, whereas those presenting with aggressive or highly aggressive disease need to be urgently treated with chemoimmunotherapy, either after undergoing an elective pregnancy termination if diagnosed at an early gestational stage, or with pregnancy preservation, if diagnosed later. Supportive care of NHL is also important; however, granulocyte colony stimulating factor (G-CSF) which is commonly used outside of pregnancy, should be cautiously employed, considering its established teratogenicity in animals, though this is less proven in humans. In conclusion, given the paucity of studies prospectively evaluating the outcome of pregnant women with NHL, international efforts are warranted to elucidate critical issues and develop guidelines for the management of such patients.
    Blood Reviews. 01/2014;
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    ABSTRACT: Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In attempt to eradicate CRE colonization, we conducted a semirandomized, prospective, controlled trial using oral nonabsorbable antibiotics. Consecutive hospitalized CRE carriers were studied. Patients whose rectal isolates were gentamicin sensitive but colistin resistant were treated with gentamicin. Patients whose isolates were colistin sensitive but gentamicin resistant were treated with colistin. Patients whose isolates were sensitive to both drugs were randomized to 3 groups of oral antibiotic treatment: gentamicin, colistin, or both. Patients whose isolates were resistant to both drugs, and those who did not consent, were followed for spontaneous eradication. One hundred fifty-two patients were included; 102 were followed for spontaneous eradication for a median duration of 140 days (controls), and 50 received 1 of the 3 drug regimens: gentamicin, 26; colistin, 16; both drugs, 8, followed for a median duration of 33 days. Eradication rates in the 3 treatment groups were 42%, 50%, and 37.5%, respectively, each significantly higher than the 7% spontaneous eradication rate in the control group (P < .001, P < .001, and P = .004, respectively) with no difference between the regimens. No significant adverse effects were observed. Oral antibiotic treatment with nonabsorbable drugs to which CRE is susceptible appears to be an effective and safe for eradication of CRE colonization and, thereby, may reduce patient-to-patient transmission and incidence of clinical infection with this difficult-to-treat organism.
    American journal of infection control 12/2013; 41(12):1167-72. · 3.01 Impact Factor
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    ABSTRACT: CXCR4 plays an important role in the retention of stem cells (SCs) within the bone marrow. BKT140 is a 14-residue bio stable synthetic peptide which binds CXCR4 with a greater affinity compared with plerixafor (4nM vs 84nM). Studies in mice demonstrated the efficient and superior mobilization and transplantation of SCs collected with GCSF-BKT140, compared with those obtained when using SCs obtained with each one of these mobilizing agent alone. These results have served as a platform for the present clinical phase I study. Eighteen patients with multiple myeloma (MM) who were preparing for their first autologous stem cell transplantation (ASCT) were included. Patients received a standard MM mobilization regimen, consisting of 3-4 gr/m2 cyclophosphamide (Day 0), followed by G-CSF at 5 μg/kg/d starting on day 5 and administered between 8 and 10 PM until the end of stem cell collection. A single injection of BKT140 (0.006, 0.03, 0.1, 0.3 and 0.9 mg/kg) was administered subcutaneously (SC) on day 10 in the early morning, followed by G-CSF 12 hr later. BKT140 was well tolerated at all concentrations, and none of the patients developed grade III-IV toxicity. A single administration of BKT140 at the highest dose, 0.9 mg/kg, resulted in a robust mobilization and collection of CD34+ cells (20.6± 6.9x106/kg), which were obtained through a single apheresis. All transplanted patients received ~5.3x106 CD34+ cells/kg, which rapidly engrafted (n=17). The median time to neutrophil and platelet recovery was 12 and 14 days, respectively, at the highest dose (0.9 mg/kg).
    Clinical Cancer Research 11/2013; · 7.84 Impact Factor
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    ABSTRACT: Anti-CD20 monoclonal antibodies (MoAbs), employed in treating CD20(+) lymphomas and autoimmune diseases, appear to have broader functions than just eradicating malignant B-cells and decreasing autoantibody production. Rituximab-induced T-cell inactivation, reported both in-vitro and in-vivo, may contribute to the increased risk of T-cell-dependent infections, observed in patients receiving this therapy. T-cell polarization into a suppressive phenotype, often observed in patients receiving rituximab for autoimmune disorders, was reported to be associated with prolonged remissions. Elimination of B-cells serving as antigen-presenting cells, thereby causing impaired T-cell activation, could play a significant role in induction of these changes. Direct binding of rituximab to a CD20(dim) T-cell population, inducing its depletion, may contribute to the decreased T-cell activation following rituximab therapy. Further investigation of the complex network through which rituximab and new anti-CD20 MoAbs act, would advance the employment of these agents in different clinical settings.
    Blood reviews 08/2013; · 7.19 Impact Factor
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    ABSTRACT: In this study we assessed the prognostic significance of absolute monocyte count and elected the best cut-off value at diagnosis, in a large cohort of patients with diffuse large B-cell lymphoma. Data were retrieved for therapy-naive patients with diffuse large B-cell lymphoma followed in Israel and Italy during1993-2010. A final cohort of 1017 patients was analyzed with a median follow up of 48 months and a 5 year overall survival rate of 68%. The best absolute monocyte count cut-off level was< 630/mm3and the 5 years overall survival for these patients was 71% and 59% for those with >630mm3 (p=0.0002). Of the 1017 patients, 521 (51%) were treated with chemo-immunotherapy, and in this cohort, using multivariate analysis, elevated monocyte counte retained a negative prognostic value even when adjusted for IPI (HR 1.54, P=0.009). This large study shows that a simple parameter like absolute monocyte count (>630 /mm3) can easily be used routinely in the evaluation of newly diagnosed diffuse large B-cell lymphoma to identify high-risk patients with a worse survival in the rituximab era.
    Haematologica 08/2013; · 5.94 Impact Factor
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    ABSTRACT: Abstract Methotrexate (MTX), a folate antagonist employed for treating a wide range of malignancies, has an extensive inter-patient variability, resulting in unpredictable toxicity. The current study evaluated the impact of single gene polymorphisms (SNPs: rs1801133 and rs1801131 in the MTHFR gene; rs4149056 and rs11045879 in the SLC01B1 gene; and rs2032582 and rs1045642 in the ABCB1 transporter gene) on MTX blood levels and toxicity in samples from 69 diffuse large-cell lymphoma (DLBCL) patients treated with high dose intravenous (HD IV ) MTX, > 2 gr/m(2). None of the studied genotypes were found to be associated with a statistically significant risk for elevated MTX levels at 24-48 hours after completing therapy with MTX. Ancestral alleles (T) for SLC01B1 rs4149056 (T521C) and SLC01B1 rs11045879 (intron C21273886T) were found to be associated with an increased risk for MTX-related toxicity (p<0.05 and p=0.07, respectively), emphasizing the potential importance of employing pharmacogenetic assessment for personalized medicine.
    Leukemia & lymphoma 07/2013; · 2.61 Impact Factor
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    ABSTRACT: Data for pregnancy-associated non-Hodgkin lymphoma are limited to case reports, making it difficult to define this disorder. We did a systematic search for articles published between 1967 and 2011 with the aim to determine the characteristics, management, and outcome of pregnancy-associated non-Hodgkin lymphoma. We identified 121 patients from 74 papers. Most patients with stage information available presented with stage IV disease (75%, 82 of 108 patients). Patients were classified into three clinical groups; those with indolent lymphomas accounted for 5% (five of 108), aggressive lymphomas (diffuse large B-cell lymphoma and T-cell lymphomas) made up 48% of patients (52 of 108), and highly aggressive lymphomas (Burkitt's lymphoma, immunoblastic lymphoma, and unspecified highly aggressive lymphomas) accounted for 47% of patients (51 of 108). Reproductive organ involvement (breast, ovary, uterus, placenta) was reported in 49% of 110 patients with information available on extranodal involvement, and prevailed in endemic Burkitt's lymphoma (100%, 19 of 19), followed by non-endemic Burkitt lymphoma (70%, 14 of 20), immunoblastic lymphoma (67%, two of three), peripheral T-cell lymphoma (46%, six of 13), and indolent (40%, two of five) and diffuse large cell lymphoma (23%, nine of 40). Most patients received antepartum (45%, 55 of 121) or postpartum therapy (45%, 54 of 121), resulting in 6-month survival of 53% for mothers and a livebirth rate of 83%. Pregnancy-associated non-Hodgkin lymphoma has unique clinical characteristics with frequent reproductive organ involvement. Collaborative prospective studies are needed to further characterise pathophysiological and clinical aspects of this complication.
    The Lancet Oncology 06/2013; 14(7):e275-e282. · 25.12 Impact Factor
  • Clinical Cancer Research 05/2013; · 7.84 Impact Factor
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    ABSTRACT: Background: A multiple myeloma (MM) vaccine has been developed whereby patient derived tumor cells are fused with autologous dendritic cells (DCs), creating a hybridoma that stimulates a broad anti-tumor response. We report on the results of a phase II trial in which patients underwent vaccination following autologous stem cell transplantation (ASCT) to target minimal residual disease. Methods: Twenty-four patients received serial vaccinations with DC/myeloma fusion cells following post-transplant hematopoietic recovery. A second cohort of 12 patients received a pre-transplant vaccine followed by post-transplant vaccinations. DCs generated from adherent mononuclear cells cultured with GM-CSF, IL-4 and TNFα were fused with autologous bone marrow-derived MM cells using polyethylene glycol (PEG). Fusion cells were quantified by determining the percentage of cells that co-express DC and MM antigens. Findings: The post-transplant period was associated with reduction in general measures of cellular immunity; however, an increase in CD4 and CD8+ myeloma specific T cells was observed after ASCT that was significantly expanded following post-transplant vaccination. Seventy-eight percent of patients achieved a best response of CR+VGPR and 47% achieved a CR/nCR. Remarkably, 24% of patients who achieved a partial response following transplant were converted to CR/nCR after vaccination and at over 3 months post-transplant, consistent with a vaccine-mediated effect on residual disease. Interpretation: The post-transplant period for patients with multiple myeloma provides a unique platform for cellular immunotherapy in which vaccination with DC/MM fusions resulted in the marked expansion of myeloma specific T cells and cytoreduction of minimal residual disease.
    Clinical Cancer Research 05/2013; · 7.84 Impact Factor
  • Benjamin Brenner, Irit Avivi
    Women s Health 03/2013; 9(2):127-9.
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    ABSTRACT: Predictive value (PV) of surveillance fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy-rituximab (R) versus chemotherapy only, remains unclear. The aim of the current study was to compare the performance of surveillance PET in DLBCL patients receiving CHOP (cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine and prednisone) alone versus CHOP-R. Institutional database was retrospectively searched for adults with newly diagnosed DLBCL, receiving CHOP or CHOP-R, who achieved complete remission and underwent surveillance PETs. Follow-up (FU) PET was considered positive for recurrence in case of an uptake unrelated to physiological or known benign process. Results were confirmed by biopsy, imaging and clinical FU. 119 patients, 35 receiving CHOP and 84 CHOP-R, who underwent 422 FU-PETs, were analyzed. At a median PET-FU of 3.4 years, 31 patients relapsed (17 vs 14, respectively; p=0.02). PET detected all relapses, with no false-negative studies. Specificity and positive PV (PPV) were significantly lower for patients receiving CHOP-R vs CHOP (84% vs 87%, p=0.023; 23% vs 74%, p<0.0001), reflecting a higher false-positive (FP) rate in subjects receiving CHOP-R (77% vs 26%, p<0.001). In the latter group, FP-rate remained persistently high upto 3 years post-therapy. Multivariate analysis confirmed rituximab to be the most significant predictor for FP-PET. In conclusion, routine surveillance FDG-PET is not recommended in DLBCL treated with rituximab; strict criteria identifying patients in whom FU-PET is beneficial are required. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Hematology 02/2013; · 4.00 Impact Factor
  • Noa Lavi, Benjamin Brenner, Irit Avivi
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    ABSTRACT: Myeloproliferative neoplasms (MPNs) are generally considered to be diseases of elderly population; however, 20% of subjects diagnosed with ET are younger than 40 years.Increase in gestational age in the Western world and improved diagnostic tools raise MPN incidence during pregnancy. MPNs are associated with a remarkable risk for thrombosis and the hypercoagulability milieu associated with pregnancy increases that risk even further. Pregnancies of women diagnosed with MPNs may be complicated with placental thrombosis, fetal growth restriction or loss, and increased risk for maternal thrombosis. The live birth rate in ET and PV is as low as 60 %, with first-trimester loss occurring in 20–30% of pregnancies and an increase in late placenta-mediated complications. Major maternal complications (thromboembolic events and bleeding) are more frequent in PV compared with ET. Therapeutic options range from no therapy, aspirin alone, low-molecular weight heparin (LMWH) to cytoreductive therapy, tailored according to patient-specific risk factors.
    Thrombosis Research 01/2013; 131:S11–S13. · 3.13 Impact Factor
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    ABSTRACT: Difficulty in segregating graft-versus-tumor effect (GvT) from graft-versus-host disease (GvHD) remains a major limitation of allogeneic stem cell transplantation (Allo SCT). Naturally occurring regulatory T cells have been suggested to suppress alloreative T cells involved in GvHD; however, their non-selective suppressive effect raises concern regarding probable attenuation of the GvT effect. Recent studies suggested inducible CD8 (iCD8) cells to be useful in suppressing autoimmune reactions, although their function in the Allo SCT setting has not been fully explored. The current study assessed in-vitro the properties of iCD8 T cells, generated in response to allogeneic dendritic cells (DCs), imitating the Allo SCT conditions. CD25(-) peripheral blood mononuclear cells (PBMCs) were stimulated with allogeneic DCs in mixed lymphocyte culture (MLC). The resultant iCD8(+)CD25(+) population was isolated and assessed for phenotypic markers, cytokine expression profile, cell proliferation, inhibitory capacity and anti-viral response. The generated CD8(+)CD25(+)FOXP3(+) T cells selectively inhibited the primary allogeneic response, without attenuating T cell response against other stimuli, such as mitogens or a cytomegalovirus (CMV) recall antigen. In conclusion, iCD8(+)CD25(+)cells suppress allogeneic stimulation, while maintaining the capacity to respond to infectious pathogens. These cells could be potentially efficient in the Allo SCT setting, where GvHD prevention is required.
    Transplant Immunology 11/2012; · 1.52 Impact Factor
  • The Lancet 05/2012; 379(9830):1949. · 39.06 Impact Factor

Publication Stats

453 Citations
283.47 Total Impact Points

Institutions

  • 2007–2014
    • Technion - Israel Institute of Technology
      H̱efa, Haifa District, Israel
    • Tel Aviv Sourasky Medical Center
      Tell Afif, Tel Aviv, Israel
  • 2005–2014
    • Rambam Medical Center
      H̱efa, Haifa District, Israel
  • 2011
    • Wroclaw Medical University
      Vrotslav, Lower Silesian Voivodeship, Poland
  • 2003–2011
    • Ministry of Health (Israel)
      Yerushalayim, Jerusalem District, Israel
  • 2004
    • University College London
      • Department of Haematology
      London, ENG, United Kingdom