Irit Avivi

Tel Aviv Sourasky Medical Center, Tell Afif, Tel Aviv, Israel

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Publications (99)503.97 Total impact

  • Irit Avivi, Andre Goy
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    ABSTRACT: Although mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma, proactive research efforts fueled by challenges in the management of MCL have led to an increase in median overall survival (OS) of 2.5 years in the mid 1990s to beyond 5 years nowadays. This improvement is due mostly to the use of dose-intensive strategies, particularly cytarabine-containing regimens (with or without high-dose therapy [HDT] followed by autologous stem cell transplantation [ASCT] consolidation), which are associated with deeper remission (and higher molecular complete response rate), as well as better salvage therapies. Along this line, MCL became the first lymphoma for which 4 novel agents have been approved in the relapsed/refractory setting: temsirolimus, lenalidomide, ibrutinib, and bortezomib (the last agent approved both in relapsed/refractory disease and firstline combination therapy). In addition, the use of rituximab maintenance has helped reduce relapse rates and improve outcome. However, in routine practice (i.e., outside clinical trials), the outcome of MCL remains overall unchanged with standard immunochemotherapy, and even after HDT-ASCT, most patients still relapse and frequently develop chemoresistance. The persistent lack of consensus for the treatment of MCL explains the rather impressive variability in management of these patients. The integration of newer therapies, either in combination with immunochemotherapy or as consolidation/maintenance post-induction, offers new opportunities for MCL patients. This review highlights how such developments can help refine the current MCL paradigm. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 06/2015; DOI:10.1158/1078-0432.CCR-15-0488 · 8.19 Impact Factor
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    ABSTRACT: A multicenter retrospective analysis of a cohort of patients in Israel treated with any bendamustine containing regimen between 2010 and 2014 was performed in order to determine the incidence and predictors for infection. The Kaplan Meier Model, employing log rank analysis, was used to assess time-to-infection. The Cox Proportional Hazards model was used to analyze multivariate effects of risk and 234 patients were included in the analysis. One hundred and nine (46.6%) developed at least one infection, and 33.76% had severe infections. Seventy six (41.5%) developed bacterial infection, 9 (3.8%) fungal infection and 26 (11.5%) had viral infections. Factors significantly associated with time to infection on multivariable analysis were: bendamustine-combinations [hazard ratio (HR) of 0.589 (95% CI 0.374-0.926), p = 0.022], Hb level [HR 0.791 (95% CI 0.716-0.875), p<0.0001] and ischemic heart disease [HR 1.828 (95% CI 1.165-2.868), p=0.009]. Infections were associated with a higher mortality and hospitalization rate.
    Leukemia & lymphoma 05/2015; DOI:10.3109/10428194.2015.1046862 · 2.61 Impact Factor
  • Value in Health 05/2015; 18(3):A300-A301. DOI:10.1016/j.jval.2015.03.1750 · 2.89 Impact Factor
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    ABSTRACT: Patients with mantle cell lymphoma (MCL) generally respond to first-line immunochemotherapy, but often show chemoresistance upon subsequent relapses, with poor outcome. Several studies of the immunomodulator, lenalidomide, have demonstrated its activity in MCL including the MCL-001 study in relapsed/refractory patients who had failed defined prior therapies of anthracyclines or mitoxantrone, cyclophosphamide, rituximab and also bortezomib. We present here the long-term efficacy follow-up of the prospective phase II MCL-001 study (N = 134), including new exploratory analyses with baseline Ki-67 (MIB1), a biological marker of tumour proliferation. With longer follow-up, lenalidomide showed a 28% overall response rate [ORR; 8% complete response (CR)/CR unconfirmed (CRu)]. Median duration of response (DOR), progression-free survival and overall survival were 16·6, 4·0 and 20·9 months, respectively. Myelosuppression continued to be the most common grade 3/4 toxicity. Several studies of MCL patients treated with chemotherapy, rituximab and bortezomib have shown an inverse association between survival and Ki-67. Ki-67 data in 81/134 MCL-001 patients showed similar ORRs in both low (<30% or <50%) versus high (≥30% or ≥50%) Ki-67-expressing groups, yet lower Ki-67 levels demonstrated superior CR/CRu, DOR and survival outcomes. Overall, lenalidomide showed durable efficacy with a consistent safety profile in heavily pretreated, relapsed/refractory MCL post-bortezomib. © 2015 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.
    British Journal of Haematology 04/2015; DOI:10.1111/bjh.13456 · 4.96 Impact Factor
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    ABSTRACT: Extended application of allogeneic stem cell transplantation (alloSCT) is expected to increase the frequency of JC polyomavirus (JCPyV)-related progressive multifocal leukoencephalopathy (PML). The aim of this study was to assess frequency, risk factors and course of JCPyV reactivation in allografted hematology patients. This retrospective study included consecutive adult patients, treated with alloSCT between January 2008 and December 2011. Quantitative JCPyV-PCR analysis was performed on whole blood DNA samples, originally drawn for cytomegalovirus detection since transplant date. The study included 164 patients diagnosed with hematological malignancies. Patients received reduced-intensity conditioning (n=74) or myeloablative conditioning (n=90), followed by alloSCT. Twenty patients developed transient and 20 had persistent JCPyV reactivation. Two of the patients with persistent reactivation showed a gradual increase in JCPyV levels, preceding PML development by 96 and 127 days. Cessation of immunosuppression resulted in complete resolution of neurological symptoms in one patient, while the other died of PML. Seventy percent of the 'persistently reactivating' patients died. Multivariate analysis confirmed age to be the only significant predictive factor for JCPyV reactivation. In conclusion, JCPyV reactivation occurs in a quarter of allografted patients. Preemptive detection of JCPyV reactivation in high-risk subjects and early discontinuation of immunosuppressive therapy may prevent development of lethal PML.Bone Marrow Transplantation advance online publication, 13 April 2015; doi:10.1038/bmt.2015.68.
    Bone marrow transplantation 04/2015; DOI:10.1038/bmt.2015.68 · 3.47 Impact Factor
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    ABSTRACT: Light chain amyloidosis (AL) is associated with low survival rates, particularly in patients with cardiac involvement. We evaluated the outcome of 73 consecutive, non- selected 'real-world' AL patients, treated with first line bortezomib-based induction, focusing on the benefit of concurrent administration of alkylating agents. Most patients had renal (77%), cardiac (66%), or multi-organ (74%) involvement. 68% (n=50) received alkylating agent (mostly cyclophosphamide). Severe adverse events were seen in 45%, most evident in patients with cardiac involvement, with no increased toxicity in patients receiving an alkylator agent. Haematological response (HaemR) was obtained in 77% of patients, including 33% very good partial responses and 19% complete responses. Age <70 years, lack of cardiac and peripheral neurologic involvement and co-administration of an alkylating agent, were associated with significantly improved HaemR. NYHA cardiac failure staging was the only independent factor affecting overall survival. Administration of an alkylating agent and the achievement of both HaemR and organ response, were associated with a statistically significant improved survival in those surviving the first 6 months of induction. First line bortezomib- based regimen resulted in favorable response and survival in newly diagnosed patients. Co-administration of an alkylating agent improved outcome without increasing treatment related toxicity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal Of Haematology 03/2015; DOI:10.1111/ejh.12558 · 2.41 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S152. DOI:10.1016/j.bbmt.2014.11.215 · 3.35 Impact Factor
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    ABSTRACT: Gaucher disease (GD) is characterized by glucocerebroside (GC) accumulation due to defective activity of the glucocerebrosidase (GlcCerase) enzyme. Monocytes and macrophages exhibit the highest GlcCerase activity and are most prominently affected by GC engorgement. As GD patients tend to exert various immune system-related changes, this study was designed to investigate potential effects of monocyte dysfunction on these alterations. Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of untreated GD patients and healthy volunteers. Monocyte migration capacity towards SDF1α was assessed. The GD patients exhibited reduced numbers of monocytes and decreased capability of SDF1α-dependent monocyte migration. Evaluation of CXCR4, the SDF1α receptor, revealed reduced expression of surface CXCR4 on GD-derived monocytes, despite similar CXCR4 mRNA transcript levels in the monocytes of healthy volunteers and GD patients. Reduction of surface CXCR4 was accompanied by increased intracellular CXCR4 levels in patient monocytes. This elevated intracellular CXCR4 might reflect significantly increased SDF1α concentrations characterizing patients' serum and the lysosomal impairment of GD, resulting in decreased degradation of CXCR4. Different distributions of CXCR4 expression observed in the two groups explain impaired SDF1α-dependent monocyte migration. Reduced numbers and impaired migration capacity of GD-derived monocytes could contribute to abnormal inflammation and GD-associated immune alterations seen in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.
    Blood Cells Molecules and Diseases 12/2014; DOI:10.1016/j.bcmd.2014.12.003 · 2.33 Impact Factor
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    ABSTRACT: ImMucin, a 21-mer cancer vaccine encoding the signal peptide domain of the MUC1 tumour-associated antigen, possesses a high density of T- and B-cell epitopes but preserves MUC1 specificity. This phase I/II study assessed the safety, immunity and clinical response to 6 or 12 bi-weekly intradermal ImMucin vaccines, co-administered with human granulocyte-macrophage colony-stimulating factor to 15 MUC1-positive multiple myeloma (MM) patients, with residual or biochemically progressive disease following autologous stem cell transplantation. Vaccination was well tolerated; all adverse events were temporal grade 1 2 and spontaneously resolved. ImMucin vaccination induced a robust increase in γ-interferon (IFN-γ-producing CD4+ and CD8+ T-cells (≤80-fold), a pronounced population of ImMucin multimer CD8+ T-cells (>2%), a 9·4-fold increase in peripheral blood mononuclear cells proliferation and 6·8-fold increase in anti-ImMucin antibodies, accompanied with T-cell and antibody-dependent cell-mediated cytotoxicity. A significant decrease in soluble MUC1 levels was observed in 9/10 patients. Stable disease or improvement, persisting for 17·5-41·3 months (ongoing) was achieved in 11/15 patients and appeared to be associated with low-intermediate PDL1 (CD274) bone marrow levels pre- and post-vaccination. In summary, ImMucin, a highly tolerable cancerous vaccine, induces robust, diversified T- and B-cell ImMucin-specific immunity in MM patients, across major histocompatibility complex-barrier, resulting in at least disease stabilization in most patients.
    British Journal of Haematology 12/2014; 169(1). DOI:10.1111/bjh.13245 · 4.96 Impact Factor
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    ABSTRACT: The recognition that the development of cancer is associated with acquired immunodeficiency, mostly against cancer cells themselves, and understanding pathways inducing this immunosuppression, has led to a tremendous development of new immunological approaches, both vaccines and drugs, which overcome this inhibition. Both "passive" (e.g. strategies relying on the administration of specific T cells) and "active" vaccines (e.g. peptide-directed or whole-cell vaccines) have become attractive immunological approaches, inducing cell death by targeting tumor-associated antigens. Whereas peptide-targeted vaccines are usually directed against a single antigen, whole-cell vaccines (e.g. dendritic cell vaccines) are aimed to induce robust responsiveness by targeting several tumor-related antigens simultaneously. The combination of vaccines with new immuno-stimulating agents which target "immunosuppressive checkpoints" (anti-CTLA-4, PD-1, etc.) is likely to improve and maintain immune response induced by vaccination.
    10/2014; 5(4):e0024. DOI:10.5041/RMMJ.10158
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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 09/2014; 28(5). DOI:10.1016/j.blre.2014.06.004 · 5.45 Impact Factor
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    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. DOI:10.1016/j.ijid.2014.03.1381 · 2.33 Impact Factor
  • 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 06/2014; 10(8):1407-15. DOI:10.2217/fon.14.64 · 2.61 Impact Factor
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    ABSTRACT: This two-stage phase IB study investigated the pharmacokinetics and safety of subcutaneous (SC) versus intravenous (IV) administration of rituximab as maintenance therapy in follicular lymphoma. In stage 1 (dose finding), 124 patients who responded to rituximab induction were randomly assigned to SC rituximab (375 mg/m(2), 625 mg/m(2), or an additional group at 800 mg/m(2)) or IV rituximab (375 mg/m(2)). The objective was to determine an SC dose that would yield a rituximab serum trough concentration (Ctrough) in the same range as that of IV rituximab. In stage 2, 154 additional patients were randomly assigned (1:1) to SC rituximab (1,400 mg) or IV rituximab (375 mg/m(2)) given at 2- or 3-month intervals. The objective was to demonstrate noninferior rituximab Ctrough of SC rituximab relative to IV rituximab 375 mg/m(2). Stage 1 data predicted that a fixed dose of 1,400 mg SC rituximab would result in a serum Ctrough in the range of that of IV rituximab. Noninferiority (ie, meeting the prespecified 90% CI lower limit of 0.8) was then confirmed in stage 2, with geometric mean Ctrough SC:Ctrough IV ratios for the 2- and 3-month regimens of 1.24 (90% CI, 1.02 to 1.51) and 1.12 (90% CI, 0.86 to 1.45), respectively. Overall safety profiles were similar between formulations (in stage 2, 79% of patients experienced one or more adverse events in each group). Local administration-related reactions (mainly mild to moderate) occurred more frequently after SC administration. The fixed dose of 1,400 mg SC rituximab predicted by using stage 1 results was confirmed to have noninferior Ctrough levels relative to IV rituximab 375 mg/m(2) dosing during maintenance, with a comparable safety profile. Additional investigation will be required to determine whether the SC route of administration for rituximab provides equivalent efficacy compared with that of IV administration.
    Journal of Clinical Oncology 05/2014; 32(17). DOI:10.1200/JCO.2013.52.2631 · 17.88 Impact Factor
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    British Journal of Haematology 05/2014; 167(1). DOI:10.1111/bjh.12930 · 4.96 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; 25(5). DOI:10.1093/annonc/mdu097 · 6.58 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; 49(5). DOI:10.1038/bmt.2014.4 · 3.47 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; DOI:10.3109/10428194.2014.882506 · 2.61 Impact Factor
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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. DOI:10.1016/j.ajic.2013.04.018 · 2.33 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; 20(2). DOI:10.1158/1078-0432.CCR-13-1302 · 8.19 Impact Factor

Publication Stats

1k Citations
503.97 Total Impact Points

Institutions

  • 2007–2015
    • Tel Aviv Sourasky Medical Center
      • Hematology
      Tell Afif, Tel Aviv, Israel
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2002–2014
    • Rambam Medical Center
      • • Department of Anesthesiology
      • • Department of Hematology
      H̱efa, Haifa, Israel
  • 1996–2014
    • Technion - Israel Institute of Technology
      • • Ruth and Bruce Rappaport Faculty of Medicine
      • • Rambam Medical Center
      H̱efa, Haifa, Israel
  • 2010
    • London Health Sciences Centre
      • Department of Anesthesia and Perioperative Medicine
      London, Ontario, Canada
  • 2004
    • University College London
      • Department of Haematology
      Londinium, England, United Kingdom
  • 2003
    • Ministry of Health (Israel)
      Yerushalayim, Jerusalem District, Israel