Quality of life gains in frail and intermediate-fit patients with multiple Myeloma: Findings from the prospective HOVON123 clinical trial.

BACKGROUND: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. METHODS: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). RESULTS: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. CONCLUSION: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.

Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study.

Allogeneic stem cell transplantation (alloSCT) remains the only curative option for CLL patients. Whereas active disease at the time of alloSCT predicts poor outcome, no standard remission-induction regimen exists. We prospectively assessed outcome after cisplatin-containing immune-chemotherapy (R-DHAP) followed by alloSCT in 46 patients (median age 58 years) fulfilling modified European Society for Blood and Marrow Transplantation (EBMT) CLL Transplant Consensus criteria being refractory to or relapsed (R/R) <1 year after fludarabine or <2 years after fludarabine-based immunochemotherapy or R/R with del(17p). Twenty-nine patients received ⩾3 cycles of R-DHAP and sixteen <3 cycles (4 because of disease progression, 8 for toxicity and 4 toxic deaths). Overall rate of response to R-DHAP was 58%, 31 (67%) proceeded to alloSCT after conditioning with fludarabine and 2 Gy TBI. Twenty (65%) remained free from progression at 2 years after alloSCT, including 17 without minimal residual disease. Intention-to-treat 2-year PFS and overall survival of the 46 patients were 42 and 51% (35.5 months median follow-up); del(17p) or fludarabine refractoriness had no impact. R-DHAP followed by alloSCT is a reasonable treatment to be considered for high-risk CLL patients without access or resistance to targeted therapies.

Diffuse large B-cell lymphoma with MYC gene rearrangements: Current perspective on treatment of diffuse large B-cell lymphoma with MYC gene rearrangements; case series and review of the literature.

In the past decade, patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. Standard treatment is now changing as a result of deeper understanding of underlying biologic differences of such lymphomas. One of the most powerful predictors of an adverse outcome on R-CHOP therapy is the presence of a MYC gene rearrangement (MYC+ lymphoma). Determination of MYC gene rearrangement by FISH (fluorescent in situ hybridisation) has recently become a standard diagnostic procedure. In this paper, an overview of current literature on MYC function and MYC+ lymphoma patient outcome is presented. Furthermore, we present 26 patients from our tertiary referral centre who were diagnosed with MYC+ lymphoma between 2009 and 2014. In our patient series, we confirm the dismal prognosis of MYC+ lymphoma patients. Intensification of classical chemotherapy does not lead to better overall survival, justifying new treatment modalities. First line therapy should be more specifically targeted against MYC and the genes and proteins that are deregulated by MYC. To this end, the first clinical trial in which MYC+ patients will be offered targeted treatment has recently been launched.

Levofloxacin vs. ciprofloxacin plus phenethicillin for the prevention of bacterial infections in patients with haematological malignancies.

An open-label randomised clinical trial was designed to compare the efficacy and tolerance of levofloxacin and ciprofloxacin plus phenethicillin for the prevention of bacterial infections in patients with high-risk neutropenia, and to monitor the emergence of antimicrobial resistance. Adult patients (n = 242) scheduled to receive intensive treatment for haematological malignancies were assigned randomly to receive oral prophylaxis with either levofloxacin 500 mg once-daily (n = 122), or ciprofloxacin 500 mg twice-daily plus phenethicillin 250 mg four-times-daily (n = 120). The primary endpoint was failure of prophylaxis, defined as the first occurrence of either the need to change the prophylactic regimen or the initiation of intravenous broad-spectrum antibiotics. This endpoint was observed in 89 (73.0%) of 122 levofloxacin recipients and in 85 (70.8%) of 120 ciprofloxacin plus phenethicillin recipients (RR 1.03, 95% CI 0.88-1.21, p 0.71). No differences were noted between the two groups with respect to secondary outcome measures, including time to endpoint, occurrence of fever, type and number of microbiologically documented infections, and administration of intravenous antibiotics. A questionnaire revealed that levofloxacin was tolerated significantly better than ciprofloxacin plus phenethicillin. Surveillance cultures indicated the emergence of viridans group (VG) streptococci resistant to levofloxacin in 17 (14%) of 122 levofloxacin recipients; in these cases, the prophylactic regimen was adjusted. No bacteraemia with VG streptococci occurred. It was concluded that levofloxacin and ciprofloxacin plus phenethicillin are equally effective in the prevention of bacterial infections in neutropenic patients, but that levofloxacin is tolerated better. Emergence of levofloxacin-resistant VG streptococci is of concern, but appears to be a manageable problem.

Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies.

Gram-positive breakthrough infections pose a major drawback to the use of quinolones for antibacterial prophylaxis in neutropenic patients. Levofloxacin offers the advantage of an augmented Gram-positive spectrum and may potentially overcome this problem. In an open-label, clinical pilot study, we investigated the effects on throat and bowel microflora and pharmacokinetics of a once-daily oral dose of 500 mg levofloxacin, during neutropenia in 20 patients with haematological malignancies. Gram-negative bowel flora and Staphylococcus aureus were successfully eradicated. No Gram-negative infections occurred. Minimal inhibitory concentration values for viridans group (VG) streptococci tended to increase, in four patients over 8 mg/l, indicating resistance to levofloxacin. Four patients developed blood-stream infections with levofloxacin-resistant Gram-positive cocci. No significant changes in numbers of anaerobic microorganisms were observed. Pharmacokinetic parameters of levofloxacin, including the maximum serum concentration (C(max)), time to C(max) (T(max)), area under the concentration-time curve (AUC), volume of distribution at steady state (V(ss)/F) and clearance (CL/F) were not statistically different at first dose and during neutropenia. In conclusion, levofloxacin eradicates Gram-negative microorganisms and S. aureus and spares the anaerobic flora. Its pharmacokinetic profile is unaltered during neutropenia. However, prolonged administration of levofloxacin as antibacterial prophylaxis may be hampered by the emergence of levofloxacin-resistant VG streptococci.

Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial.

We conducted an open label, randomised clinical trial to compare amphotericin B colloidal dispersion (ABCD, Amphocil) 2 mg/kg/day intravenously with fluconazole 200 mg/day orally, for the prevention of fungal disease in neutropenic patients with haematological malignancies. In the event of unresolved fever after 4 days of empirical antibacterial therapy, patients in both treatment groups were to receive ABCD, 4 mg/kg/day. However, the study had to be stopped in an early phase, due to severe side-effects of ABCD. A total of 24 patients were enrolled, 12 patients were randomly assigned to receive prophylactic ABCD, which was administered for a mean of 13.9 days. Fluconazole prophylaxis was given to 12 patients for a mean of 21.2 days. Therapeutic ABCD, 4 mg/kg, was initiated in four patients because of suspected fungal infection, all of whom had initially received fluconazole. A high rate of infusion-related toxicity of ABCD was observed. Chills occurred in 15/16 ABCD recipients (94%), accompanied by a temperature rise of >/=2 degrees C in 4/16 patients and of >/=1 degrees C but <2 degrees C in 10/16 patients. Other ABCD-related adverse events were hypotension (4/16), nausea with vomiting (5/16), tachycardia (7/16), headache (3/16) and dyspnoea (3/16). For premedication patients received: antihistamines (12/16), hydrocortisone (9/16) and/or morphine (6/16). ABCD was discontinued in 8/16 patients (50%) due to side-effects, which ultimately dictated early termination of the study. We conclude that ABCD is not suitable for antifungal prophylaxis in neutropenic patients due to severe infusion-related side-effects. Subject numbers were too low for conclusions on variables of antifungal efficacy.

Deep vein thrombosis as a presenting symptom of congenital interruption of the inferior vena cava.

Infrahepatic interruption of the inferior vena cava is a congenital anomaly, resulting in venous drainage of the lower extremities by way of a compensatory enlarged vena azygos system. We report the case of a 37-year-old male who presented with symptoms of deep vein thrombosis of the entire right lower extremity. A right-sided mediastinal mass on the chest X-ray was mistaken for a haematological malignancy but proved later to represent an enlarged azygos vein. The case illustrates that in a case of deep vein thrombosis, especially in younger patients, interruption of the inferior vena cava should be considered. A right-sided paratracheal mass on the chest X-ray may give a clue in making the correct diagnosis.

[Hypertension in the Negro patient]. / Hypertensie bij de negroïde patiënt.

Essential hypertension appears to be more prevalent among blacks than among whites and has an earlier onset in blacks. Many data in this field come from studies in the African-American population. Hypertension-related complications, e.g. ischaemic heart disease, (end stage) renal failure and cerebrovascular disease, are encountered more often among blacks and frequently run a more severe course. Factors that might explain the racial difference in prevalence of hypertension and hypertensive complications include both genetic and environmental variables. Hypertension in blacks is characterized by salt sensitivity, a tendency towards expanded plasma volume and low plasma renin levels. Socioeconomic factors, the higher prevalence of obesity and insulin resistance may contribute to the high prevalence of hypertension in blacks. Aggressive antihypertensive therapy appears mandatory in the black hypertensive, possibly with lower goal blood pressures than the 140/90 mmHg generally recommended. Diuretic monotherapy proves to be the first-line therapy, calcium channel blockers are an attractive alternative. Black patients are frequently less responsive to monotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta-blocking agents. This black/white difference in therapeutic response can, however, be eliminated by addition of a diuretic.