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Purpose The aim of this study was to assess the impact of the 3 types of initial respiratory support (noninvasive positive pressure ventilation vs invasive positive pressure ventilation vs supplemental oxygen only) in hematological patients with acute hypoxemic respiratory failure (ARF). Materials and Methods This study is a retrospective analysis of a cohort of hematological patients admitted to the intensive care unit (ICU) of a tertiary care hospital between January 1, 2002, and June 30, 2006. Results One hundred thirty-seven hematological patients were admitted at the ICU with ARF (defined as Pao2/Fio2 <200): within the first 24 hours, 24 and 67 patients received noninvasive positive pressure ventilation and invasive positive pressure ventilation, respectively, and 46 received supplemental oxygen only. Intensive care unit mortality in the 3 patient categories was 71%, 63%, and 32%, respectively (P = .001), and in-hospital mortality was 75%, 80%, and 47%, respectively (P = .001). In multivariate regression analysis, increasing cancer-specific severity-of-illness score upon admission and more organ failure after 24 hours of ICU admission, but not the type of initial respiratory support, were significantly associated with ICU or in-hospital mortality. Conclusions Intensive care unit and in-hospital mortality in our population of hematological patients with hypoxemic ARF was determined by severity of illness and not by the type of initial respiratory support. © 2010 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

Purpose: Glofitamab is a T-cell-engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells. This phase I study evaluated glofitamab in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Data for single-agent glofitamab, with obinutuzumab pretreatment ( Gpt ) to reduce toxicity, are presented., Methods: Seven days before the first dose of glofitamab (0.005-30 mg), all patients received 1,000 mg Gpt . Dose-escalation steps were determined using a Bayesian continuous reassessment method with overdose control. Primary end points were safety, pharmacokinetics, and the maximum tolerated dose of glofitamab., Results: Following initial single-patient cohorts, 171 patients were treated within conventional multipatient cohorts and received at least one dose of glofitamab. This trial included heavily pretreated patients with R/R B-NHL; most were refractory to prior therapy (155; 90.6%) and had received a median of three prior therapies. One hundred and twenty-seven patients (74.3%) had diffuse large B-cell lymphoma, transformed follicular lymphoma, or other aggressive histology, and the remainder had indolent lymphoma subtypes. Five (2.9%) patients withdrew from treatment because of adverse events. Cytokine release syndrome occurred in 86 of 171 (50.3%) patients (grade 3 or 4: 3.5%); two (1.2%) patients experienced grade 3, transient immune effector cell-associated neurotoxicity syndrome-like symptoms. The overall response rate was 53.8% (complete response [CR], 36.8%) among all doses and 65.7% (CR, 57.1%) in those dosed at the recommended phase II dose. Of 63 patients with CR, 53 (84.1%) have ongoing CR with a maximum of 27.4 months observation., Conclusion: In patients with predominantly refractory, aggressive B-NHL, glofitamab showed favorable activity with frequent and durable CRs and a predictable and manageable safety profile., Competing Interests: Martin HutchingsConsulting or Advisory Role: Takeda, Roche, GenmabResearch Funding: Celgene, Genmab, Roche, Takeda, Novartis Franck MorschhauserConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Celgene, Bristol Myers Squibb, AbbVie, Epizyme, ServierSpeakers' Bureau: RocheExpert Testimony: Roche/Genentech Gloria IacoboniHonoraria: Gilead Sciences, Novartis, Roche/Genentech, Celgene/Bristol Myers Squibb, JanssenConsulting or Advisory Role: Novartis, Celgene/Bristol Myers Squibb, Gilead SciencesTravel, Accommodations, Expenses: Gilead Sciences, Novartis, Celgene/Bristol Myers Squibb Carmelo Carlo-StellaHonoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca, Celgene, Takeda, Incyte, Gilead SciencesConsulting or Advisory Role: Sanofi, ADC Therapeutics, Roche, Karyopharm Therapeutics, Celgene/Bristol Myers Squibb, IncyteResearch Funding: ADC Therapeutics, Sanofi, RocheTravel, Accommodations, Expenses: Roche, Janssen, Takeda, ADC Therapeutics Anna SuredaHonoraria: Takeda, Bristol Myers Squibb, Merck Sharp & Dohme, Celgene, Janssen, Sanofi, Roche, Novartis, Gilead Sciences, Janssen-CilagConsulting or Advisory Role: Takeda, Bristol Myers Squibb, Gilead Sciences, Celgene, Janssen, NovartisSpeakers' Bureau: TakedaOther Relationship: Sanofi, Takeda, Roche, Celgene, Gilead Sciences Gilles SallesHonoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSysConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, Velosbio, Bristol Myers Squibb, BeiGene, Incyte, Miltenyi Biotec Joaquín Martínez-LopezSpeakers' Bureau: Roche, Janssen-Cilag, BMSiResearch Funding: Astellas Pharma, Bristol Myers Squibb Michael CrumpHonoraria: Gilead Sciences, Servier/PfizerConsulting or Advisory Role: Servier, Gilead Sciences, Novartis Canada Pharmaceuticals IncResearch Funding: Roche Canada Denise N. ThomasEmployment: Roche TCRC, Genmab, Cellectis Peter N. MorcosEmployment: Roche/Genentech, BayerStock and Other Ownership Interests: Roche/Genentech, Bayer Cristiano FerliniEmployment: Roche/Genentech, AstraZenecaStock and Other Ownership Interests: AstraZeneca, Roche Ann-Marie E. BröskeEmployment: RocheStock and Other Ownership Interests: Roche, BioNTech AG Anton BelousovEmployment: Roche Marina BacacEmployment: RocheStock and Other Ownership Interests: RocheResearch Funding: RochePatents, Royalties, Other Intellectual Property: Coinventor in Roche patentsTravel, Accommodations, Expenses: Roche Natalie DimierEmployment: RocheStock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Roche David J. CarlileEmployment: Roche, AstraZenecaStock and Other Ownership Interests: AstraZeneca, Roche Linda LundbergEmployment: F. Hoffmann LaRocheStock and Other Ownership Interests: F. Hoffmann LaRoche David Perez-CallejoEmployment: RocheStock and Other Ownership Interests: Roche Pablo UmañaEmployment: RocheLeadership: RocheStock and Other Ownership Interests: RochePatents, Royalties, Other Intellectual Property: Co-inventor in Roche-owned patents on glofitamab and obinutuzumabTravel, Accommodations, Expenses: Roche Tom MooreEmployment: RocheStock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Roche Martin WeisserEmployment: RocheStock and Other Ownership Interests: RochePatents, Royalties, Other Intellectual Property: I hold patents for biomarkers and drug combinations. These are not related to the present study. I do not receive royalties Michael J. DickinsonHonoraria: Roche, Amgen, MSD, Janssen, Bristol Myers Squibb, NovartisConsulting or Advisory Role: Novartis, Bristol Myers Squibb, Gilead Sciences, Roche, JanssenSpeakers' Bureau: NovartisResearch Funding: Novartis, Roche, Takeda, Celgene, MSDTravel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

Purpose: Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma., Patients and Methods: A total of 175 patients with relapsed CD20(+) indolent lymphoma requiring therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m(2)). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab maintenance therapy every 2 months for up to 2 years., Results: Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab (44.6% v 26.7%; P = .01). However, this difference did not translate into an improvement in progression-free survival. No new safety signals were observed for obinutuzumab, and the incidence of adverse events was balanced between arms, with the exception of infusion-related reactions and cough, which were higher in the obinutuzumab arm., Conclusion: Obinutuzumab demonstrated a higher ORR without appreciable differences in safety compared with rituximab. However, the clinical benefit of obinutuzumab in this setting remains unclear and should be evaluated within phase III trials., Competing Interests: Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

Objectives: The randomized phase 3 PRIMA trial established that 2 years of rituximab maintenance therapy after attaining disease response to immunochemotherapy as first-line treatment of follicular lymphoma, reduced the risk of disease progression, compared with observation, without adversely affecting patient-reported quality of life (QoL). We now report additional analyses of symptom burden and toxicity., Methods: Symptom burden was measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items. The proportion of patients with worsening, no change, or improvement in symptoms from maintenance baseline was compared between rituximab maintenance and observation groups with Pearson χ(2) tests. Improvement in symptoms after 1 and 2 years of maintenance was further analyzed using generalized mixed models. The adverse event (AE) rate was calculated from the toxicity checklist at each visit to explore the frequency and timing of the toxicity AE in each treatment arm. The study protocol was approved by local ethics committees and is registered at ClinicalTrials.gov under NCT00140582., Results: Being tired, needing to rest, feeling weak, and trouble sleeping were the most frequently reported symptoms at the end of immunochemotherapy. By the end of maintenance, notable improvement was seen for fatigue symptoms, trouble sleeping, shortness of breath, lack of appetite, and nausea, with no significant difference in QoL symptoms between the rituximab maintenance and observation groups. The rate of AEs was low, and hematologic toxicity induced during chemotherapy treatment improved in both rituximab maintenance and observation groups., Discussion: These results indicated that rituximab maintenance did not negatively impact disease- or treatment-related symptoms.

Aspiration pneumonia is rarely considered in the differential diagnosis of respiratory failure in patients suffering from haematologic malignancies in daily practice. We describe four patients who were admitted with severe respiratory failure in the ICU over a one-year-period prospective survey (a total of 72 patients with haematological malignancies of which 34 presented with respiratory failure). All of these patients had chemotherapy-induced severe oral mucositis (WHO grade ILL-IV) for which three of them received opioids. All had a history of cough after oral rinsing and two of them experienced sudden brief desaturation in the days before ICU referral. Two of these patients, both in allogeneic bone marrow transplant setting, died. With this data, we want to draw the attention to the diagnosis of aspiration pneumonia in this group of patients.

Purpose: To compare evolution in organ dysfunction (OD) between hematologic malignancy patients with and without bacterial infection (BI) precipitating intensive care unit (ICU) admission, and to assess its impact on mortality., Methods: Retrospective analysis of prospectively collected data was performed. Sequential Organ Failure Assessment (SOFA) scores from day 1 to 5 were calculated in all consecutive hematologic malignancy patients admitted to the ICU (2000-2006). Patients were categorized according to the presence or absence, the diagnostic certainty, and the site of BI., Results: Of the 344 patients admitted, 258 were still in the ICU at day 3 and 164 at day 5. Patients admitted because of BI had more severe OD on day 1 (SOFA 9.7 ± 4.0 vs. 8.4 ± 4.0, p = 0.008) but a more rapidly reversible OD within the first 3 days (ΔSOFA -1.12 ± 3.10 vs. 0.03 ± 3.40, p = 0.013) and a lower in-hospital (43.2% vs. 62.9%, p < 0.001) and 6-month mortality (52.1% vs. 71.7%, p < 0.001) than patients with other complications. In a multivariate analysis, BI remained associated with a lower risk of death (OR 0.20, 95% CI 0.1-0.4, p < 0.001) even after adjustment for the SOFA on day 1 (OR 1.36, 95% CI 1.22-1.52, p < 0.001) and the ΔSOFA (OR 1.48, 95% CI 1.29-1.68, p < 0.001). These findings remained significant regardless of the site and the diagnostic certainty of BI., Conclusion: BI is associated with a more severe initial but a more rapidly reversible OD and a subsequent lower mortality compared to other complications in ICU patients with hematologic malignancies. These findings further support the recommendation that these patients should certainly benefit from advanced life support, and in the case of an uncertain long-term prognosis due to the underlying malignancy, at least from a 3-day ICU trial.

Purpose: The aim of this study was to assess the impact of the 3 types of initial respiratory support (noninvasive positive pressure ventilation vs invasive positive pressure ventilation vs supplemental oxygen only) in hematological patients with acute hypoxemic respiratory failure (ARF)., Materials and Methods: This study is a retrospective analysis of a cohort of hematological patients admitted to the intensive care unit (ICU) of a tertiary care hospital between January 1, 2002, and June 30, 2006., Results: One hundred thirty-seven hematological patients were admitted at the ICU with ARF (defined as Pao(2)/Fio(2) <200): within the first 24 hours, 24 and 67 patients received noninvasive positive pressure ventilation and invasive positive pressure ventilation, respectively, and 46 received supplemental oxygen only. Intensive care unit mortality in the 3 patient categories was 71%, 63%, and 32%, respectively (P = .001), and in-hospital mortality was 75%, 80%, and 47%, respectively (P = .001). In multivariate regression analysis, increasing cancer-specific severity-of-illness score upon admission and more organ failure after 24 hours of ICU admission, but not the type of initial respiratory support, were significantly associated with ICU or in-hospital mortality., Conclusions: Intensive care unit and in-hospital mortality in our population of hematological patients with hypoxemic ARF was determined by severity of illness and not by the type of initial respiratory support., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To compare the characteristics and outcome of patients with hematological malignancies referred to the ICU with severe sepsis and septic shock who had or had not received recent intravenous chemotherapy, defined as within 3 weeks prior to ICU admission., Design and Setting: Retrospective observational cohort study on prospectively collected data in a medical ICU of a university hospital., Patients: 186 ICU patients with hematological malignancies with severe sepsis or septic shock (2000-2006)., Measurements and Results: There were 77 patients admitted with severe sepsis and 109 with septic shock; 91 (49%) had received recent intravenous chemotherapy. Patients with recent chemotherapy more often had a high-grade malignancy and were more often neutropenic, less often had pulmonary infiltrates, and less often required mechanical ventilation. ICU, 28-day, in-hospital, and 6-month mortality rates were 33% vs. 48.4%, 40.7% vs. 57.4%, 45.1% vs. 58.9%, and 50.5% vs. 63.2% in patients with and without recent chemotherapy, respectively. Logistic regression identified four variables independently associated with 28-day mortality: SOFA score at ICU admission, pulmonary site of infection, and fungal infection were associated with worse outcome whereas previous intravenous chemotherapy was protective at borderline significance. After adjustment with a propensity score for recent chemotherapy, chemotherapy was not associated with outcome., Conclusions: Patients referred to the ICU with severe sepsis and septic shock complicating active chemotherapeutic treatment have better prognosis than commonly perceived.

Objective: To assess the outcome in severely ill patients with hematological malignancies who receive intravenous chemotherapy in an intensive care unit (ICU) for a life-threatening malignancy-related complication., Design: Retrospective observational study of prospectively collected data., Patients: All 37 critically ill patients with hematological malignancies who received intravenous chemotherapy in the ICU between January 1997 and March 2005 (mean age 46+/-19 years; mean APACHE II 23+/-7)., Measurements and Results: Thirty-seven (69%) patients received chemotherapy because of extensive disease with organ involvement (54%), extensive disease without organ involvement (19%), severe disseminated intravascular coagulation (11%), and other reasons (16%). In 41% there was concomitant infection when chemotherapy was initiated, in 86% a high-grade malignancy, and 30% relapsing disease. Twenty-three (62%) patients received mechanical ventilation at the moment of or soon after initiation of chemotherapy for a median duration of 5 days (1-67), and 24% underwent renal replacement therapy during ICU stay. Only ventilation was associated with in-hospital mortality (odds ratio 9.3). ICU, in-hospital, and 6-month mortality rates in nonventilated vs. ventilated patients were 7% and 48%, 14% and 61%, and 54% and 74%, respectively., Conclusions: Starting chemotherapy in the ICU for a life-threatening malignancy related complication can be lifesaving even when infection or organ failure is present.

Objective: To assess the impact of documented and clinically suspected bacterial infection precipitating ICU admission on in-hospital mortality in patients with hematological malignancies., Design and Setting: Prospective observational study in a 14-bed medical ICU at a tertiary university hospital., Patients: A total of 172 consecutive patients with hematological malignancies admitted to the ICU for a life-threatening complication over a 4-year period were categorized into three main groups according to their admission diagnosis (documented bacterial infection, clinically suspected bacterial infection, nonbacterial complications) by an independent panel of three physicians blinded to the patient's outcome and C-reactive protein levels., Results: In-hospital and 6-months mortality rates in documented bacterial infection (n=42), clinically suspected bacterial infection (n=40) vs. nonbacterial complications (n=90) were 50.0% and 42.5% vs. 65.6% (p=0.09 and 0.02) and 56.1% and 48.7% vs. 72.1% (p=0.11 and 0.02), respectively. Median baseline C-reactive protein levels in the first two groups were 23 mg/dl and 21.5 mg/dl vs. 10.7 mg/dl (p<0.001 and p=0.001) respectively. After adjustment for the severity of critical and underlying hematological illness and the duration of hospitalization before admission documented (OR 0.20; 95% CI 0.06-0.62, p=0.006) and clinically suspected bacterial infection (OR 0.18; 95% CI 0.06-0.53, p=0.002) were associated with a more favorable outcome than nonbacterial complications., Conclusions: Severely ill patients with hematological malignancies admitted to the ICU because of documented or clinically suspected bacterial infection have a better outcome than those admitted with nonbacterial complications. These patients should receive advanced life-supporting therapy for an appropriate period of time.

Background: Starting renal replacement therapy (RRT) for acute renal failure in critically ill patients with haematological malignancies is controversial because of the poor outcome and high costs. The aim of this study was to compare the outcome between critically ill medical patients with and without haematological malignancies who received RRT for acute renal failure., Methods: We retrospectively collected data on all consecutive patients who received RRT for acute renal failure at the Medical Intensive Care Unit (ICU) of a University Hospital between 1997 and 2002, and assessed the impact of the presence of a haematological malignancy on the survival within 6 months after ICU admission by Cox proportional hazard models., Results: Fifty of the 222 (22.5%) consecutive patients with haematological malignancies admitted to the ICU over the study period received RRT for acute renal failure compared with 248 of the 4293 (5.8%) patients without haematological malignancies (P<0.001). Among patients who received RRT, those with haematological malignancies had higher crude ICU (79.6 vs 55.7%, P=0.002) and in-hospital (83.7 vs 66.1%, P=0.016) mortality rates, and a higher mortality at 6 months (86 vs 72%, P=0.018) by Kaplan-Meier estimates compared with those without haematological malignancies. However, after adjustment for the severity of illness and the duration of hospitalization before ICU admission, haematological malignancy by itself was no longer associated with a higher risk of death (hazard ratio 1.04; 95% confidence interval, 0.73-1.54, P=0.78)., Conclusions: Medical ICU patients with haematological malignancies have a higher rate of occurrence of acute renal failure treated with RRT and a higher mortality, compared with those without haematological malignancies. However, the presence of a haematological malignancy by itself is not a reason to withhold RRT in medical ICU patients with acute renal failure.

Background: In the medical community, little is known regarding bone marrow necrosis (BMN) as a clinicopathologic entity, although to the authors' knowledge it was described for the first time more than 50 years ago. To identify the rate of prevalence, the symptoms and signs, the underlying disease associations, and the usefulness of diagnostic procedures, an extensive literature search was made., Methods: Only cases identified as extensive necrosis and diagnosed during life were selected. Two hundred forty cases met these criteria., Results: Bone pain (75%) and fever (68.5%) were the most important symptoms, whereas anemia (91%) and thrombocytopenia (78%), associated with a leukoerythroblastic picture (51%), were the most frequent hematologic abnormalities. Nearly 50% of patients showed elevated lactate dehydrogenase and alkaline phosphatase levels. In 90% of the patients an underlying malignancy was identified., Conclusions: Bone marrow necrosis is caused by hypoxemia after failure of the microcirculation. Given the high rate of malignancy as an underlying disease association, an extensive search for neoplastic disease is justified whenever BMN is diagnosed. Pancytopenia and embolic processes are major complications that should be managed with supportive measures until effective treatment of the underlying disease has been administered. When necrosis resolves, repopulation of the bone marrow cavity with normal hematopoiesis is observed., (Copyright 2000 American Cancer Society.)

The cloning of hematopoietic growth factors has allowed their application in clinical medicine. This review deals with clinical studies on GM-CSF and G-CSF in bone marrow insufficiency (primary or secondary to chemotherapy), myelodysplastic syndromes, AIDS and bone marrow transplantation.