Irit Avivi

18F-FDG Avidity in Lymphoma Readdressed: A Study of 766 Patients

PET/CT with 18F-FDG is an important noninvasive diagnostic tool for management of patients with lymphoma, and its use may surpass current guideline recommendations. The aim of the present study is to enlarge the growing body of evidence concerning 18F-FDG avidity of lymphoma to provide a basis for future guidelines. Methods: The reports from 18F-FDG PET/CT studies performed in a single center for staging of 1,093 patients with newly diagnosed Hodgkin disease and non-Hodgkin lymphoma between 2001 and 2008 were reviewed for the presence of 18F-FDG avidity. Of these patients, 766 patients with a histopathologic diagnosis verified according to the World Health Organization classification were included in the final analysis. 18F-FDG avidity was defined as the presence of at least 1 focus of 18F-FDG uptake reported as a disease site. Nonavidity was defined as disease proven by clinical examination, conventional imaging modalities, and histopathology with no 18F-FDG uptake in any of the involved sites. Results: At least one 18F-FDG–avid lymphoma site was reported for 718 patient studies (94%). Forty-eight patients (6%) had lymphoma not avid for 18F-FDG. 18F-FDG avidity was found in all patients (100%) with Hodgkin disease (n = 233), Burkitt lymphoma (n = 18), mantle cell lymphoma (n = 14), nodal marginal zone lymphoma (n = 8), and lymphoblastic lymphoma (n = 6). An 18F-FDG avidity of 97% was found in patients with diffuse large B-cell lymphoma (216/222), 95% for follicular lymphoma (133/140), 85% for T-cell lymphoma (34/40), 83% for small lymphocytic lymphoma (24/29), and 55% for extranodal marginal zone lymphoma (29/53). Conclusion: The present study indicated that with the exception of extranodal marginal zone lymphoma and small lymphocytic lymphoma, most lymphoma subtypes have high 18F-FDG avidity. The cumulating evidence consistently showing high 18F-FDG avidity in the potentially curable Burkitt, natural killer/T-cell, and anaplastic large T-cell lymphoma subtypes justifies further investigations of the utility of 18F-FDG PET in these diseases at presentation.

Vaccination with Dendritic Cell/Tumor Fusions following Autologous Stem Cell Transplant Induces Immunologic and Clinical Responses in Multiple Myeloma Patients

Purpose: A multiple myeloma vaccine has been developed whereby patient-derived tumor cells are fused with autologous dendritic cells, creating a hybridoma that stimulates a broad antitumor 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. Experimental Design: Twenty-four patients received serial vaccinations with dendritic cell/myeloma fusion cells following posttransplant hematopoietic recovery. A second cohort of 12 patients received a pretransplant vaccine followed by posttransplant vaccinations. Dendritic cells generated from adherent mononuclear cells cultured with granulocyte macrophage colony-stimulating factor, interleukin-4, and TNF-α were fused with autologous bone marrow–derived myeloma fusion cells using polyethylene glycol. Fusion cells were quantified by determining the percentage of cells that coexpress dendritic cell and myeloma fusion antigens. Results: The posttransplant 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 posttransplant vaccination. Seventy-eight percent of patients achieved a best response of complete response (CR)+very good partial response (VGPR) and 47% achieved a CR/near CR (nCR). Remarkably, 24% of patients who achieved a partial response following transplant were converted to CR/nCR after vaccination and at more than 3 months posttransplant, consistent with a vaccine-mediated effect on residual disease. Conclusions: The posttransplant period for patients with multiple myeloma provides a unique platform for cellular immunotherapy in which vaccination with dendritic cell/myeloma fusion fusions resulted in the marked expansion of myeloma-specific T cells and cytoreduction of minimal residual disease. Clin Cancer Res; 19(13); 3640–8. ©2013 AACR.

Haematological cancers in pregnancy

Haematological cancer in pregnancy, although rare, poses a substantial risk to both mother and fetus. Hodgkins lymphoma is the most common, followed by non-Hodgkin lymphoma and acute leukaemia. Diagnosis of haematological cancers is challenged by an overlap of the disease and gestation-related symptoms and limitations of imaging studies in pregnancy. Data for safety and effectiveness of therapy are scarce and mostly retrospective. This report provides updated guidance for management, focusing on chemotherapy and biological agents. The primary goal of treatment is to preserve the mothers health; hence, pregnancy termination is often advisable at early stages, allowing delivery of adequate therapy. However, at later gestational stages treatment is often feasible. Pregnancy-related hypercoagulability, augmented by cancer, often necessitates thromboprophylaxis. The consequences and complex management of haematological cancer during pregnancy emphasise the need for collaborative research, focusing on basic mechanisms of disease and prospective epidemiological studies.

A randomized study comparing yttrium‐90 ibritumomab tiuxetan (Zevalin) and high‐dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma

High‐dose chemotherapy combined with autologous stem‐cell transplantation (ASCT) is the standard therapy for refractory/relapsed aggressive lymphoma. In the era of rituximab‐containing frontline regimens, it is becoming more challenging to salvage patients in this setting, and novel approaches are required. This is a randomized study evaluating the safety and efficacy of standard‐dose ibritumomab tiuxetan (Zevalin) combined with high‐dose BEAM chemotherapy (Z‐BEAM) and ASCT in refractory/relapsed aggressive lymphoma.

Respiratory virus infections in transplant recipients after reduced‐intensity conditioning with Campath‐1H: high incidence but low mortality

Summary. Respiratory virus infections can cause serious morbidity and mortality after conventional allogeneic stem cell transplantation. However, the incidence and outcome of these infections after reduced intensity conditioning has not been reported. Between 1997 and 2001, 35 episodes of respiratory virus infections were noted in 25 of 83 transplant recipients conditioned with fludarabine, melphalan and Campath‐1H, and 80% of them received early antiviral therapy. Parainfluenza virus (PIV) 3 was the commonest isolate (45·7%) followed by respiratory syncytial virus (37%). Patients with myeloma were more susceptible to these infections [odds ratio (OR) 4·1, P = 0·01] which were often recurrent in patients with severe acute or chronic graft‐versus‐host disease (GVHD) (OR 10·6, P = 0·03). Infection within the first 100 d (OR 5·0, P = 0·05) and PIV 3 (OR 9·2, P = 0·01) isolation were risk factors for developing lower respiratory infection. Although more than half of the episodes progressed to lower respiratory infection, the mortality was only 8%. This could have been due to early initiation of antiviral therapy, but the attenuation of pulmonary damage due to the reduced‐intensity conditioning, low incidence of GVHD and, paradoxically, the low CD4+ T‐cell subset in this setting might also have been contributory factors.

Soluble plasma HLA peptidome as a potential source for cancer biomarkers

The HLA molecules are membrane-bound transporters that carry peptides from the cytoplasm to the cell surface for surveillance by circulating T lymphocytes. Although low levels of soluble HLA molecules (sHLA) are normally released into the blood, many types of tumor cells release larger amounts of these sHLA molecules, presumably to counter immune surveillance by T cells. Here we demonstrate that these sHLA molecules are still bound with their authentic peptide repertoires, similar to those of the membranal HLA molecules (mHLA). Therefore, a single immunoaffinity purification of the plasma sHLA molecules, starting with a few milliliters of patients’ blood, allows for identification of very large sHLA peptidomes by mass spectrometry, forming a foundation for development of a simple and universal blood-based cancer diagnosis. The new methodology was validated using plasma and tumor cells of multiple-myeloma and leukemia patients, plasma of healthy controls, and with cultured cancer cells. The analyses identified thousands of sHLA peptides, including some cancer-related peptides, present among the sHLA peptidomes of the cancer patients. Furthermore, because the HLA peptides are the degradation products of the cellular proteins, this sHLA peptidomics approach opens the way for investigation of the patterns of protein synthesis and degradation within the tumor cells.

Myelodysplastic syndrome and associated skin lesions: a review of the literature.

The skin involvement of the myelodysplastic syndrome (MDS) can take the form of either a neoplastic infiltration or various non specific lesions. The occurrence of these lesions may be the presenting feature of the disease (MDS) or may herald its progression to acute leukemia. Recognition and early diagnosis have therapeutic and prognostic significance.

Strikingly high false positivity of surveillance FDG-PET/CT scanning among patients with diffuse large cell lymphoma in the rituximab era

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. One hundred nineteen 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 up to 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. 88:400–405, 2013.

Nosocomial outbreak of Legionella pneumophila serogroup 3 pneumonia in a new bone marrow transplant unit: evaluation, treatment and control

A nosocomial outbreak of pneumonia caused by Legionella pneumophila serogroup 3 occurred in four patients following hematopoietic stem cell transplantation (HSCT) in a new bone marrow transplantation (BMT) unit during a 2 week period. The causative organism was recovered from the water supply system to the same unit just before the outbreak. Nineteen other BMT patients were hospitalized in the same unit at the same time, giving a frequency of proven infection of 4/23 = 17%. Immediately after recognition of the outbreak, use of tap water was forbidden, humidifiers were disconnected, and ciprofloxacin prophylaxis was started for all patients in the unit, until decontamination of the water was achieved. No other cases were detected. In conclusion, contamination of the hospital water supply system with legionella carries a high risk for legionella pneumonia among BMT patients. Early recognition of the outbreak, immediate restrictions of water use, antibiotic prophylaxis for all non-infected patients, and water decontamination, successfully terminated the outbreak.

Eradication of carbapenem-resistant Enterobacteriaceae gastrointestinal colonization with nonabsorbable oral antibiotic treatment: A prospective controlled trial

BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In attempt to eradicate CRE colonization, we conducted a semirandomized, prospective, controlled trial using oral nonabsorbable antibiotics. METHODS 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. RESULTS 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. CONCLUSION 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.