A 35-year old woman developed Burkitt's lymphoma and was treated with rituximab and CHOP therapy early during pregnancy. Monitoring of rituximab concentrations and B-cell counts in the child revealed ...a transient complete B-cell depletion associated with high rituximab cord blood concentrations. B-cell recovery was fast, showing a regular immunophenotype without loss of CD20 antigen, no functional deficits and adequate vaccination IgG titers.
The influence of a number of factors, including age and particularly seating position, on the injury severity of restrained occupants was examined for 41 front-seat occupants seated adjacent to the ...impact (near side) and 38 sitting opposite the impacted side (far side) in car-to-car side collisions (center of impact: front door and B-pillar). Above an energy equivalent speed of 40 km/h all near-side occupants and about half of the far-side occupants sustained severe injuries. A logistic regression analysis showed that within range of 30–60 km/h (delta ν 20–60 km/h) the probability of severe injuries increased dramatically from approximately 20% to more than 90%; in these cases, far-side occupants had the same injury probability as near-side occupants only when the speed was 10 km/h higher. The main cause of death for 27 occupants seated on both sides was polytrauma, this was accompanied in two-thirds of the cases by serious head injuries. The second most frequent cause of death was head injury.
We investigated subclonal cytogenetic aberrations (CA) detected by interphase fluorescence in situ hybridization (iFISH) in patients with newly diagnosed multiple myeloma (MM) enrolled in the Haemato ...Oncology Foundation for Adults in the Netherlands (HOVON)–65/German-Speaking MM Group (GMMG)–HD4 phase 3 trial. Patients were either treated with 3 cycles of vincristine, Adriamycin, and dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide or bortezomib maintenance after tandem autologous transplantation. Subclones were defined either by presence of different copy numbers of the same chromosome loci and/or CA present in at least 30% less and maximally 2/3 of cells compared with the main clone CA. Patients with subclones harbored more frequently high risk (31.0%) or hyperdiploid main clone aberrations (24.8%) than patients with t(11;14) in the main clone (10.1%). Gains and deletions of c-MYC were the only CA that occurred more frequently as subclone (8.1%/20.5%) than main clone (6.2%/3.9%, respectively). Treatment with bortezomib completely overcame the negative prognosis of high-risk CA in patients without subclones, but not in patients with additional subclonal CA. High-risk patients treated without bortezomib showed dismal outcome whether subclones were present or not. Cytogenetic heterogeneity defined by subclonal CA is of major prognostic significance in newly diagnosed MM patients treated with bortezomib within the HOVON-65/GMMG-HD4 trial.
•Clonal heterogeneity detected by iFISH is common in newly diagnosed MM.•Treatment with bortezomib overcomes the negative impact of high-risk cytogenetic abnormalities if no further subclones are detected.
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Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen ...remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-d-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.
Background:
Signaling Lymphocyte Activation Marker Family member 7 (SLAMF7) is highly expressed on human plasma cells and malignant myeloma cells, which is a therapeutic target for the anti‐SLAMF7 ...antibody elotuzumab. Lower expression of SLAMF7 is found in NK cells, NK‐like T cells, CD8+ T cells, activated monocytes and dendritic cells. With the exception of plasmablastic lymphoma and multiple myeloma, SLAMF7 was never been reported to be expressed in other malignant hematological diseases.
Aims:
This prompted us to examine the expression of SLAMF7 also in T‐cell lymphoma, NK/T‐cell lymphoma, NK cell derived large granular lymphocyte (NK‐LGL) and T‐cell LGL.
Methods
We examined in biopsy tissue or blood samples of 11 patients with histologically proven NK/T‐cell lymphomas, T‐cell lymphoma, T‐ALL, non‐malignant Kikuchi necrotizing lymphadenitis, NK‐LGL and T‐LGL SLAMF7 expression by immunohistochemistry (IHC) or flow cytometry. We defined SLAMF7 as positive if we detected SLAMF7 expression in at least 20% of lymphoma cells by IHC or 10% by flow cytometer. As positive controls for SLAMF7 expression we used biopsy tissue from patients with multiple myeloma.
Results:
Here we found a strong expression of SLAMF7 by IHC in all 3 patients with NK/T‐cell lymphoma, whereas no expression by IHC was found on T‐cell lymphoma biopsy tissue of 3 patients with T‐cell lymphoma and of 1 patient with T‐ALL. Another patient who was suspected with T‐cell lymphoma but later diagnosed as non‐malignant Kikuchi necrotizing lymphadenitis, was tested weak positive for SLAMF7 expression by IHC as shown in table 1. Strong SLAMF7 expression was specific to lymphoma tissue in a patient with NK/T‐cell lymphoma but not found in the surrounding healthy tissue of nasal epithelial cells as shown in figure 1, which identifies SLAMF7 as a suitable biomarker for NK/T‐cell lymphoma. We detected SLAMF7 also in a patient with CD3‐/CD56+/CD16+ NK‐LGL cells and a further patient with CD3+/CD56+/CD8+ T‐LGL by flow cytometer. Interestingly, 100% of NK‐LGL cells (38,9% of all mononucleated cells in peripheral blood) and all T‐LGL cells (17,2% of all mononucleated cells in peripheral blood) were SLAMF7 positive.
Summary/Conclusion:
Here we report for the first time expression of SLAMF7 in NK/T‐cell lymphoma and NK‐LGL and T‐LGL, which has clinical relevance because it extends possible immunotherapy to SLAMF7 inhibitor elotuzumab. SLAMF7 might also be a suitable target for CAR‐T cell therapies as already used successfully in multiple myeloma trials. Nevertheless, it might be useful as a biomarker for NK/T‐cell lymphomas and LGL, too.
Background:
Induction failure of standardchemotherapy with anthracycline and cytarabine occur frequently in AML.
Aims:
The aim of this retrospective single centre study was to investigate risk ...factors for induction failure (IF) of standard chemotherapy with anthracycline and cytarabine (DA) in 108 patients with acute myeloid leukemia (AML), who were consecutively treated between 2013 and 2018 at our institution
Methods:
We evaluated in all patients at diagnosis CMV igG status, LDH‐value, Platelet counts, peripheral blood blast number and blast count in bone marrow, Sorror comorbidity score (range 0–6), age (under 70 years or above), and cytogenetic risk factors according to the ELN classification (favourable n = 15, intermediate n = 55, or high risk n = 38). Furthermore we evaluated if the occurrence of biclonal AML detected by flow cytometer and extramedullary manifestation of AML are risk factors for IF of standard chemotherapy with DA. IF was defined as non‐responsiveness of one induction therapy with ≥ 30% blasts regardless of cellularity or non‐achievement of complete remission after two induction therapies. The primary study objective was to identify risk factors for IF after DA therapy in our study cohort. Further, second study objectives were to evaluate rate of overall survival (OS) after salvage chemotherapy and allogeneic transplant in patients with IF.
Results:
55 male and 53 female patients were evaluated for IF after DA therapy. In 42 (39%) of 108 patients an IF was observed. Total 37 of these patient received a salvage therapy with idarubicin and fludarabine (n = 29) or allotransplant (n = 8), whereas 5 patients received no further intensive therapy but only best supportive care. Consolidation therapies were in 6 patients high dose cytarabine and in 68 patients allogeneic transplant. By flow cytometer detectable biclonal AML was found in 10 (9,3%) cases, whereas extramedullary manifestation of AML was reported in 8 (7,3%) patients. Both had statistically no influence on the occurrence of IF. Only age above 70‐years (p = 0.04, odd ratio 2.5), cytogenetic adverse risk classification according to ELN (p = 0.006; odd ratio 3.21), Sorror comorbidity score of 2 or higher (scores 2–6), (p = 0.019, odd ratio 2.72), and more than 40% blasts in bone marrow (p = 0.01; odd ratio 3.64), had influence on the occurrence of IF after DA. We used for calculation of p‐value Mann‐Whitney U‐test and one‐sided Fisher‐exact test. Gender, platelet counts under 40.000/nl, peripheral blood blast counts over 20%, positive CMV immunoglobuline G status, LDH above norm at diagnosis had no influence statistically for the occurrence of IF. PFS and OS did not differ statistically between responders and non‐responders of induction therapy when an allogeneic transplant subsequently was performed. Patients with IF and without subsequent transplant had a worse prognosis (2‐year OS 20% versus 85%, p < = .02). Further reduced OS was found for patients >70 years (2‐year OS 50% versus 75%, p < 0.05)
Summary/Conclusion:
In our study cohort we identify age over 70 years, adverse cytogenetic risk classification according to ELN, Sorror morbidity score of 2 or higher and blast count > 40% in bone marrow as risk factors for primary induction failure after DA chemotherapy in AML. The occurrence of IF had no influence on outcome for patients when after salvage therapy a subsequently an allogeneic transplant was performed.
We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/ doxorubicin/dexamethasone (PAd) induction therapy with respect to very good ...partial response rates or better (≥ VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma patients. VCD was found to be non-inferior to PAd with respect to > VGPR rates (37.0 versus 34.3%, P = 0.001). The rates of progressive disease (PD) were 0.4% (VCD) versus 4.8% (PAd; P = 0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine ≥ 2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leukocytopenia/neutropenia (greater than or equal to 3°) occurred more frequently in the VCD arm (35.2% versus 11.3%, P < 0.001). Neuropathy rates (≥ 2°) were higher in the PAd group (14.9 versus 8.4%, P = 0.03). Serious adverse events, both overall and those related to thromboembolic events, were higher in the PAd group (32.7 versus 24.0%, P = 0.04 and 2.8 versus 0.4%, P = 0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving ≥ VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy. Leukemia (2015) 29, 1721-1729; doi:10.1038/leu.2015.80
Patients with relapsed multiple myeloma (MM) have been shown to respond to a combination therapy consisting of vincristine, Adriamycin (doxorubicin) and high-dose dexamethasone (VAD). Because of the ...low hematological toxicity of the VAD regimen, this combination is frequently chosen for tumor reduction prior to high-dose therapy and blood stem cell transplantation. This study was designed to examine the efficacy and complications of outpatient VAD treatment. Over a period of 6 years, 103 outpatients with MM were treated with VAD chemotherapy administered by microprocessor-controlled infusion pumps via intravenous polyurethane catheters equipped with a safety valve. Response to treatment, treatment-associated complications and infections were documented and analyzed. In 85 of the 103 patients, tumor reduction by more than 25% was found. In 8 patients an occlusion occurred as a result of kinking of the central venous catheter in the subcutaneous segment. In two treatment cycles the infusions had to be stopped because of irreversible catheter occlusion. Twenty patients were hospitalized because of complications, which were infectious in 12 and noninfectious in 8. Severe infectious complications (> or =WHO grade III) occurred in 5.6% of the treatment cycles. Thus, continuous infusion of VAD over 96 h can be performed on an outpatient basis with a low complication rate.
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