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Objective To determine the rate of lymphoproliferative disease (LPD) in women undergoing routine breast cancer screening (BCS). BCS can reveal pathologies other than carcinoma that involve the breast and lymph tissue. The few studies that have described cases in which BCS led to the diagnosis of LPD were based on small series and focused on imaging rather than clinical characteristics. Setting and Methods A multi-center retrospective study in Israel, investigating LPD rate and characteristics among women diagnosed with LPD via BCS. Results Thirty-four patients out of 14,400 consecutive women undergoing BCS at Tel Aviv Sourasky Medical Center during the study period were diagnosed with LPD, suggesting a diagnosis rate of 0.24%. The enlarged cohort (n = 45), including 11 patients that were retrieved from the databases of three other centers, demonstrates a predominant histological diagnosis of non-aggressive LPD (n = 33). Thirty-four (76%) had a suspicious axillary lymph node, and 11 had a breast lesion. The median maximal lesion size was 1.95 cm (range 0.8–6.5). Disease was localized in 60% of patients (stage 1 and 1E). Univariate analysis revealed that lymphocyte count was inversely associated with aggressive histology. At median follow-up of 39 months, all but three patients were alive. These three had been diagnosed with non-aggressive LPD which had never been treated and died from unrelated causes. Conclusions The LPD detection rate via BCS was 2.36 per 1000 screens. The majority of LPDs were non-aggressive. Nearly a third were aggressive, most detected at an early stage, and the clinical outcome was generally favorable.

Polatuzumab (Pola)-based regimens and chimeric antigen receptor T (CAR T) cells provide superior outcome compared to conventional chemoimmunotherapy in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL). Choosing between these strategies remains controversial. The efficacy of CAR T versus Pola-rituximab(R) /Pola-bendamustine(B)-R in R/R DLBCL patients after failing ≥2 lines of treatment was compared in a retrospective, 'real-world' study. Propensity score matching, for age, lymphoma category (de-novo/transformed), number of prior lines, Eastern Cooperative Oncology Group performance status and lactate dehydrogenase level, was applied to control for differences in patients' characteristics. Response rate, progression-free survival (PFS) and overall survival (OS) were analyzed. A total of 82 patients, treated with CAR T (n=41) or Pola-based regimens (n=41), were included. No treatment-related deaths occurred with CAR T vs. 3 (7.3%) with Pola. The overall and complete response rates were 83% and 58% with CAR T vs. 66% and 44% with Pola-based-regimens (p=0.077 and p=0.18, respectively). At a median follow-up of 9 months (range 1-19.2) and 16 months (range 0.7-25.3) for the CAR T and Pola arm respectively, the median PFS has not been reached for CAR T vs. 5.6 months for Pola (95% CI 3.6-7.6, p=0.014). Median OS has not been reached for CAR T vs. 10.8 months (95% CI 2.2-19.4) for Pola (p=0.026). To conclude, in a real-world setting, treatment with CAR T achieved superior PFS and OS compared to Pola-based regimens in patients with R/R DLBCL.

Cytomegalovirus (CMV) is a ubiquitous virus that infects people worldwide. CMV is known to trigger thrombocytopenia, but this association is probably underdiagnosed since CMV infection in healthy adults is usually either asymptomatic or causes only mild symptoms. A systematic literature review was carried out and yielded 23 publications that reported 25 patients. All haematology centres in Israel were searched for adult immunocompetent patients with CMV-associated thrombocytopenia, and five new cases were identified. The median age of the combined 30 patients was 33 years (range 18-80), 73% were men, 77% presented with CMV-related symptoms, 48% had enlarged spleens, 95% had atypical lymphocytes in peripheral blood and 68% had elevated transaminase levels. The response rate to first-line steroid-containing regimens was only 31%, whereas 11 patients who were treated with an anti-CMV agent had a response rate of 82%. Moreover, four patients received thrombopoietin receptor agonists (TPO-RA) to which three (75%) responded. Taken together, these distinctive features of a case with thrombocytopenia should alert to CMV infection as the source. While steroids were effective in less than one-third of the cases, both anti-CMV therapy and TPO-RA exhibited excellent efficacy, suggesting that those agents should be introduced earlier in the therapeutic course.

Mantle cell lymphoma (MCL) is a B-cell malignancy, comprising between 3% and 10% of all adult-onset non-Hodgkin lymphomas. MCL is considered incurable with current treatment modalities and most patients require multiple lines of treatment during their lifetime. MCL is very sensitive to radiotherapy (RT), even when delivered in low doses. In limited-stage MCL, RT can enable the de-escalation of systemic therapy. RT monotherapy is a valid option for frail patients. In advanced-stage disease, RT is very potent mode of palliation, even in heavily pretreated and chemo-resistant patients. Furthermore, it can provide a respite during which systemic treatment is unnecessary. In general, RT has a favorable toxicity profile and can be repeated as necessary for local relapse or distant disease. This effective, safe, and relatively inexpensive modality of therapy has been underutilized for patients with MCL. In this review, we will outline the use of RT for limited and advanced-stage disease and its potential application in combination with novel drugs.

This national Israeli multicenter retrospective study aimed to characterize the clinical course of COVID-19 infection among patients with hematological malignancies, with special emphasis on treatment efficacy and outcome. Clinical and laboratory data from haemato-oncological patients diagnosed with COVID-19 from 16 medical centers were centrally reported. Multivariate regression analyses were used to determine variables associated with severe disease, hospitalization, and mortality. In total, 313 patients were included: 103 (35.7%) developed severe/critical respiratory infection, 178 (61.4%) were hospitalized, and 60 (20.0%) died. Age > 70 years was associated with severe/critical disease (p = 0.036) and mortality (p = 0.023), hypertension with severe/critical disease (p = 0.046) and hospitalization (p = 0.001), active haemato-oncological treatment with hospitalization (p = 0.009), and remdesivir treatment was associated with decreased mortality (p = 0.021). Convalescent plasma, enoxaparin, and corticosteroids resulted in no clinical benefit. In conclusion, COVID-19 infection seems particularly severe in patients with hematological malignancies, and of all examined therapies, remdesivir appears to be the most effective.

The incidence of systemic diffuse large B cell lymphoma (DLBCL) concurrently involving the central nervous system (CNS) at diagnosis, is very low and data regarding the clinical course of these patients are scarce. We investigated characteristics, efficacy of treatment regimens including consolidative autologous stem cell transplantation and outcome of patients presenting with concomitant systemic and CNS DLBCL. The records of 44 patients, diagnosed between 2004 and 2017, who fulfilled the inclusion criteria, were retrospectively reviewed. CNS involvement was diagnosed as solely parenchymal in 41%, solely leptomeningeal in 43%, and paranchymal with leptomeningeal in 11% of the patients. Induction regimens were anthracycline-based combined with high-dose methotrexate (HD-MTX) in 80% (n = 35) of patients, anthracycline-based combined with intrathecal MTX in 3, cytarabine-based (without antracyclines) in 2, HD-MTX in 1 and palliative in three. Five of 41 patients treated with chemotherapy died of treatment-related toxicity, all due to infections. Nineteen patients had consolidative autologous transplantation. Overall response rate following induction was 80% (complete responses 66% and partial responses 15%). All relapses (n = 11) occurred within less than 2 years. Within a median follow-up of 26.8 months, 3-years projected overall survival (OS) and progression free survival rates for the entire cohort were 56% ± 8.3 and 42% ± 8.9, respectively. In multivariate analysis, RCHOP-HD MTX-based induction [HR = 0.228, (0.054-0.964)], administration of 3.5 g/m2 MTX [HR = 0.735 (0.620-0.871)], and attaining CR following induction [HR = 0.185, (0.051-0.667)] predicted longer OS. RCHOP-HD MTX can provide prolonged remissions in DLBCL patients presenting with concomitant systemic and CNS involvement whereas role of autograft remains uncertain.

Data regarding efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in the elderly, geriatric population are insufficient. In 2019, tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory diffuse large B-cell lymphoma. From May 2019 onwards, 47 relapsed/refractory diffuse large Bcell lymphoma patients, ≥70 years underwent lymphopharesis in three Israeli centers. Elderly (n=41, mean age 76.2 years) and young (n=41, mean age 55.4 years) patients were matched based on ECOG performance status and lactose dehydrogenase levels. There were no differences in CD4/CD8 ratio (P=0.94), %CD4 naive (P=0.92), %CD8 naive (P=0.44) and exhaustion markers (both HLA-DR and PD-1) between CAR-T cell products in both cohorts. Forty-one elderly patients (87%) received CAR-T cell infusion. There were no differences in the incidence of grade ≥3 cytokine-release-syndrome (P=0.29), grade≥3 neurotoxicity (P=0.54), and duration of hospitalization (P=0.55) between elderly and younger patients. There was no difference in median D7-CAR-T cell expansion (P=0.145). Response rates were similar between the two groups (complete response 46% and partial response 17% in the elderly group, P=0.337). Non-relapse mortality at 1 and 3 months was 0 in both groups. With a median follow-up of 7 months (range, 1.3-17.2 months), 6- and 12-months progression-free and overall survival in elderly patients were 39% and 32%, and 74% and 69%, respectively. EORTC QLQ-C30 questionnaires, obtained at 1 month, showed worsening of disability and cancer-related-symptoms in elderly versus younger patients. We conclude that outcomes of CAR-T cell therapy are comparable between elderly, geriatric and younger patients, indicating that age as per se should not preclude CAR-T cell administration. Longer rehabilitation therapy is essential to improve disabilities and long-term symptoms.

The efficacy of polatuzumab vedotin in relapsed/refractory diffuse large B-cell lymphoma outside clinical study are undetermined. This retrospective study examined the efficacy and safety of polatuzumab vedotin administered in real life settings. Forty-seven patients, 31 with

Primary central nervous system lymphoma (PCNSL) is a rare disease with a dismal prognosis compared to its systemic large B-cell lymphoma counterpart. Real world data are limited, when considering a uniform backbone treatment.A retrospective study of all adult patients treated sequentially with a high-dose methotrexate (HD MTX)-based regimen in a single tertiary medical center between 2003 and 2019.The 2015-2019 period differed from its predecessor in that most patients were treated with an HD MTX-based polychemotherapy regimen as opposed to HD MTX monotherapy (81% vs. 13%, P .001), rituximab was given as standard of care (100% vs. 56%, P .01), and most induction-responsive patients received consolidation treatment (70% vs. 18%, P = .01). The median progression-free and overall survival (OS) for the entire cohort (n = 73, mean age 64 years) was 9.9 and 29.8 months, respectively. Patients diagnosed between 2015 and 2019 had superior OS (P = .03) compared to those treated earlier. An interim partial response (PR) state, documented after two cycles of chemotherapy, was associated with increased incidence of progression, with only 33% of those patients achieving end-of-induction complete response. Twenty-three percent of patients developed thrombotic events and 44% developed grade 3-4 infections. HD MTX-based polychemotherapy induction was associated with both increase in thrombotic and infection incidence.Contemporary HD MTX-based combination therapies suggestively improved the outcomes for PCNSL, but at a cost of increased incidence of toxicity. Patients who achieve an interim PR status are at a high risk for treatment failure.

Patients with inflammatory bowel disease (IBD) on immunosuppression are at risk of developing lymphoma, particularly primary gastrointestinal (GI) tract non-Hodgkin lymphoma. Primary GI Hodgkin lymphoma (HL) in this setting, however, is rare and poorly defined. Here we review the available literature and also report a patient with Crohn's disease (CD) who developed GI HL. Our search yielded 12 single case studies and 7 case series involving 22 patients published between 1978-2016. Twenty-one (91%) patients had CD, and 2 had ulcerative colitis. The median age at lymphoma diagnosis was 39 years, and 18 (78%) patients were males. HL was diagnosed at a median of 8 years after IBD detection and 2 years after commencing immunosuppression. HL had a predilection (80%) to involve the inflamed GI site and the histological subtype was mixed cellularity in 65% of cases. In-situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was positive in all documented cases. HL was diagnosed in stages I, II, IV in 35%, 20% and 45% of the patients, respectively. Notably, 66% of patients with advanced disease had liver involvement. Immunosuppression was stopped in most (69%) patients at HL diagnosis. Treatment used was either chemotherapy only, surgery followed by chemotherapy, or surgery alone in 50%, 33% and 16% of cases, respectively. Four patients had an IBD flare during HL remission. Patients with IBD who develop GI HL have distinct characteristics; male sex, predominance of CD, preference to develop in inflamed sites, mixed cellularity histology, EBV positivity, and a unique spread to the liver pattern.

Patients with diffuse large B-cell lymphoma (DLBCL) presenting with intestinal involvement are prone to develop perforation. Identification of those who are at high risk for this complication would enable a rational-based decision regarding preemptive surgery. Although computed tomography (CT) is widely used at diagnosis, data regarding its ability to predict intestinal perforation are scanty. We performed a retrospective single-center study, including all consecutive DLBCL patients presented with intestinal involvement, assessing predictors for perforation with an emphasis on CT-related parameters. Forty-nine patients were included, 43 (88%) underwent CT scan at diagnosis. Ten patients (20%) developed intestinal perforation. A univariate regression analysis found increased risk among patients with a concentric, transmural lesion, and a longer involved intestinal segment. In conclusion, CT scan results can define patients with DLBCL and intestinal involvement who are at risk for perforation, suggesting that a preemptive surgical resection should be considered in these cases.

Introduction: Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase, is an established therapeutic agent in a variety of B-cell lymphoproliferative disorders. Ibrutinib induces platelet dysfunction and concurrent treatment with ibrutinib and warfarin was shown to significantly increase the risk of bleeding. The current study was designed to investigate the safety of direct oral anticoagulants (DOACs) in patients receiving ibrutinib, considering their expanding employment together with the lack of data regarding their safety in patients receiving ibrutinib. Methods: We conducted a retrospective cohort study to evaluate risks of major bleeding in patients with B-cell lymphoproliferative disorders (CLL, MCL, DLBCL, MZL or WM) that were treated with ibrutinib and DOACs but without concurrent antiplatelet therapy, between January 2010 and October 2018 in 5 participating centers. Patient medical charts were reviewed for demographic parameters, comorbidities, ibrutinib dosage, DOACs dosage (including the adjustment for renal function), blood count and chemistry tests, bleeding site and grade. Results: The study included 30 patients, median age at starting concurrent administration of ibrutinib and DOACs was 71.58 years (range 50.9-88.2). Most patients were treated for CLL (n=18, 60%) and MCL (n=8, 26%). The most common daily doses of ibrutinib were 420 mg and 560 mg in 63.3% and 30% of patients respectively. None of the patients received an additional antiplatelet agent. Twenty-three patients were treated with apixaban (76.7%), 4 with rivaroxaban (13.3%) and 3 (10%) with dabigatran. The main indications for DOACs were atrial fibrillation and VTE (venous thromboembolism). The median follow-up after initiation of the ibrutinib-DOAC combination was 13.4 months (range 1.8-47.9 months). Bleeding was reported in 22 patients (73.3%), mostly mucocutaneous (n=12, 40%) and gastrointestinal tract (n=7, 23.3%), followed by CNS bleeding (n=4, 13.3%). Mucocutaneous bleedings were all grade 1-2 and gastrointestinal tract and CNS bleeding events were grade 1-4. Major bleeding events, defined as grade 3 or 4, occurred in 5 patients (16.6%) and did not result in death of any of the patients. The median time for bleeding following ibrutinib-DOAC initiation was 5.6 months. Over a follow-up period of 21 months of combined treatment, the incidence of bleeding events (of all grades) increased to 75% (Figure 1). Incidence of bleeding events (including all grades) was quite similar between all DOAC subtypes (73.9% with apixaban, 75% with rivaroxaban and 66.7% with dabigatran). No statistically significant predictors for increased risk of bleeding in patients receiving ibrutinib combined with DOACs were detected. Ibrutinib was stopped in 8 patients (26.7%) due to grade 1 to 4 bleeding events and was re-initiated in 6 patients, resulting in recurrent grade 3 and 4 bleeding events in 2 patients. Conclusions: Concurrent administration of DOACs and ibrutinib appears to be feasible. However, risk of bleeding is not neglectable, and treatment resumption in patients that experienced a significant bleeding event should be considered with caution. Disclosures Arnason: Celgene/Juno: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy. Herishanu:Roche: Honoraria; AbbVie: Honoraria; Janssen: Honoraria.

The risk of developing non-Hodgkin lymphoma increases with age, yet elderly patients are under-represented in clinical trials. Here, we evaluate a combination regimen including ifosfamide, carboplatin and etoposide with or without rituximab (ICE ± R) in 32 fit elderly patients (median age 75.6 years) with relapsed or refractory diffuse large B-cell lymphoma. ICE ± R was generally administered in reduced doses and was well tolerated. The overall response rate (ORR) was 53.1% with a complete response (CR) rate of 40.6%. The median progression free survival (PFS) and overall survival (OS) were 3.9 and 17.0 months, respectively. Patients who responded to ICE ± R achieved median PFS of 47.2 months and OS of 78.9 months. Patients ineligible for autologous transplantation who responded to ICE ± R were treated with additional cycles, and achieved a median PFS of 18.9 months and OS of 21.7 months. Previous response to first-line therapy was the strongest predictor of response, PFS and OS to second-line treatment.

Hodgkin lymphoma (HL) is one of the most curable malignancies. Despite its effectiveness, chemotherapy is often associated with adverse events (AEs) such as nausea, anorexia, and impairment of general well-being. Our objective was to assess the extent of medical cannabis use among HL patients and evaluate its efficacy in controlling chemotherapy-related AEs. Patterns of medical cannabis use and efficacy were evaluated using physician-completed application forms, medical files, and patient-completed questionnaires, for all consecutive adult HL patients treated at the Tel-Aviv Medical Center between June 2010 and November 2016. One-hundred and thirty-three patients met the inclusion criteria. The median age of the cohort was 37 years, 53% were male, 46% were diagnosed at an early stage, and 88% achieved a complete response to treatment. Fifty-one patients (38%) used medical cannabis. There were no significant differences in baseline characteristics between cannabis users and nonusers. Cannabis users reported improvement in pain, general well-being, appetite, and nausea in 94, 87, 82, and 79% of cases, respectively. Importantly, 81.5% reported a high overall efficacy of cannabis in relieving symptoms. AEs related to cannabis use itself were mild. Thus, medical cannabis use is prevalent in this HL cohort, and appears to be effective in ameliorating chemotherapy-related AEs.

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. Patients with stage I disease are usually treated with radiotherapy (RT). In previous studies, mostly from the pre positron emission tomography-computed tomography (PET-CT) era, the 5 year progression-free survival (PFS) and overall survival (OS) rates of stage I disease were 60-80% and 80-93%, respectively. This study retrospectively evaluated the outcome of stage I FL which was treated with involved field RT in the PET-CT era between 2002 and 2015. Ninety-one patients were enrolled. Five year PFS and OS rates were 73% and 97%, respectively. Relapse occurred in 19 (21%) patients, 74% occurring outside the radiation field. In conclusion, PET-CT staging of clinical stage I FL may contribute to the improved prognosis in patients treated with RT compared to historical cohorts, possibly due to better identification of "genuine" stage I disease.

This study aimed to compare the real-life results of TECAM, a thiotepa-based conditioning regimen consisting of thiotepa (40 mg/m2 days −5 to −2), etoposide (200 mg/m2 days −6 to −3), cytarabine (200 mg/m2 days −4 to −1), cyclophosphamide (60 mg/kg day −3), and melphalan (60 mg/m2 days −2 to −1) with that of the conventional carmustine-based regimen BEAM. We reviewed 125 consecutive patients who underwent a first autologous transplantation (ASCT) for B-cell lymphomas at a large tertiary transplantation center between 1999 and 2014. TECAM (n=65) and BEAM (n=60) had comparable results (3yPFS 49 vs 62%, P=0.16; 3yOS 64 vs 71%, P=0.44; TRM 1.6 vs 5%, P=0.35) without a difference in toxicity or time to engraftment. Notably, comparable outcomes were observed even though patients treated with TECAM were older (55 vs 44) and had a trend towards more prior lines of therapy (>2 prior lines: 43 vs 27%, P=0.08). In this regard, 23% of TECAM patients were over the age of 65 yet could withstand therapy with similar results to younger patients. We conclude that, replacing carmustine by thiotepa and cyclophosphamide for ASCT conditioning, has comparable efficacy and safety profiles with a possible advantage in older patients.

[Figure][1] A 72-year-old man presented in an acutely confused state. He had been diagnosed with immunoglobulin A κ, 17p-deleted multiple myeloma (MM) 3 years prior. He had since received numerous lines of treatment, including several immunomodulatory agents (thalidomide, lenalidomide

Follicular lymphoma (FL) is the 2nd most common type of lymphoma diagnosed in the Western World. Bone marrow (BM) involvement is an adverse prognostic factor in FL, routinely assessed by an arbitrary biopsy of the iliac crest. This study was aimed to investigate the role of positron emission tomography/computed tomography (PET/CT) in identifying BM involvement by FL. In this retrospective, single-center study we reviewed the records of consecutive patients with FL at diagnosis or relapse who underwent staging/restaging workup visual assessment of BM uptake was categorized as either normal, diffusely increased, or focally increased. Quantitative BM fluorine-18-fluro-deoxyglucose (FDG) uptake was measured using mean standardized uptake value (BM-SUVmean). The diagnosis of BM involvement was based on either BM histological findings or disappearance of increased uptake at end-treatment PET/CT in patients who responded to treatment. Sixty eight cases with FL were included. Sixteen (23.5%) had BM involvement, 13 (19.1%) had a biopsy proven involvement, and 3 (4.4%) had a negative BM biopsy, but increased medullary uptake that normalized post-treatment. BM FDG uptake in these patients was diffuse in 8 (50%) and focal in 8 (50%). Focal increased uptake was indicative of BM involvement; however, diffuse uptake was associated with 17 false positive cases (32.7%). Overall, visual assessment of BM involvement had a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 48.5%. On a quantitative assessment, BM-SUVmean was significantly higher in patients with BM involvement (SUVmean of 3.7 [1.7–6] vs 1.4 [0.4–2.65], P 2.7 had a PPV of 100% for BM involvement (sensitivity of 68%), while BM-SUVmean

Acute myeloid leukemia (AML) with a complex karyotype (CK) has frequent alterations in TP53 and a very poor prognosis. We examined whether a prompt and simple fluorescence in situ hybridization (FISH) analysis for 17p13 deletion at diagnosis has a predictive value for response to therapy and overall survival in subgroups of AML. In 15 patients with a normal karyotype the TP53 FISH analysis was normal, whereas in 16 patients with CK 75% had only one copy of the TP53 allele. The deletion was also detected in 33% of six patients with monosomy or partial monosomy of chromosome 5, 7, 9, or 12. This loss of TP53 correlated significantly with a poor response to chemotherapy, and the median survival time of these patients was shorter. TP53 FISH analysis carried out at diagnosis has a predictive value with respect to chemotherapy response and can therefore facilitate a rapid decision on treatment strategies.

Janus kinase-2 (JAK2) is mutated in a high proportion of patients with polycythemia vera and in a smaller number with essential thrombocythemia and primary myelofibrosis. Mutated JAK2 is an important diagnostic marker for myeloproliferative neoplasm (MPN) and may also play a major role in the pathogenesis of MPN.To evaluate the prevalence of mutated JAK2 (JAK2-V617F) among patients with major intraabdominal vein thrombosis who had normal blood counts at diagnosis of the initial event.The medical records of patients who presented with a major intraabdominal venous thrombosis and normal peripheral blood counts were obtained. JAK2-V617F mutation status was determined by real-time polymerase chain reaction.Twenty-two patients were available for this analysis and 9 (41%) were found to have JAK2-V617F. Patients with positive JAK2-V617F were younger and had more frequent clinical splenomegaly than those with wild-type JAK2.A high proportion of patients presenting with "idiopathic" major intraabdominal vein thrombosis and normal blood counts carry JAK2-V617F. We recommend searching for the mutation in this clinical setting to detect patients with occult MPN.

Recent studies have reevaluated whether gemtuzumab ozogamicin (GO) improves the outcome of acute myeloid leukemia (AML) in elderly patients. Over 5 years, we treated 16 elderly patients with AML with GO and cytarabine. A high response rate, prolonged survival, and low toxicity were observed in the favorable and intermediate-I genetic groups of AML. Our study raises the issue about the optimal protocol for these patients. Background: The benefit of gemtuzumab ozogamicin (GO) in combination with chemotherapy as frontline therapy in patients with acute myeloid leukemia (AML) is still debated. Patients and Methods: We evaluated the safety and efficacy of low-dose GO with cytarabine in elderly patients with newly diagnosed AML. Over the past 5 years, we have treated 16 elderly patients with AML (64-82 years) with GO (3 mg/m 2 ) followed by continuous infusion of cytarabine (100 mg/m 2 ) for 7 days. Results: Complete remission (CR) was achieved in 68.8% of patients; however, this was true only in patients in the favorable or intermediate-I cytogenetic risk groups. Of the 12 patients with AML in the favorable and intermediate-I genetic groups, 11 (91.7%) achieved CR. By comparison, of all 4 patients in the intermediate-II or adverse genetic groups, none of the patients achieved CR (P .003). The median disease-free survival and overall survival (OS) was 10.9 and 18.8 months, respectively, for patients who achieved CR. The estimated median survival was 15 months in the favorable and intermediate-I cytogenetic groups and only 4.4 months in the intermediate-II and unfavorable risk groups (P .008). The toxicity profile was also manageable in patients with AML who were mainly older than 70 years with good performance status (PS). The 8-week mortality rate was 6.25%, which is relatively low in this high-risk group of patients. These data are in line with results from 2 randomized trials suggesting that the addition of low-dose GO should be further investigated to reevaluate its role in selected elderly patients with AML and raises the issue of the optimal protocol.

Cefepime is a broad-spectrum cephalosporin with enhanced coverage against Gram-positive and Gram-negative bacteria. We did a systematic review of randomised trials that compared cefepime with another beta-lactam antibiotic, alone or with the addition of a non-beta-lactam antibiotic to both study groups. We searched Central, PubMed, Embase, Lilacs, new US Food and Drug Administration drug applications, conference proceedings, and references of the included studies. Two reviewers independently did the search and data extraction. 57 trials were included. All-cause mortality-the primary outcome-was higher with cefepime than other beta-lactams (risk ratio [RR] 1.26 [95% CI 1.08-1.49]). Sensitivity analyses by the trials' methodological quality revealed higher RRs for trials reporting adequate allocation-sequence generation (1.52 [1.20-1.92]) and allocation concealment (1.36 [1.09-1.70]). Baseline risk factors for mortality were similar. No significant differences between groups in treatment failure, superinfection, or adverse events were found. This Review provides evidence and offers possible explanations for increased mortality among patients treated with cefepime in randomised trials.