Rebound Thrombocytosis after Induction Chemotherapy is a Strong Biomarker for Favorable Outcome in AML Patients

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Nitrogen Oxides and Ozone in the Tropopause Region of the Northern Hemisphere: Measurements from Commercial Aircraft in 1995/96 and 1997

Measurements of nitrogen oxides (NO and NO2) and ozone (O3) were performed from a Swissair B-747 passenger aircraft in two extended time periods (May 1995 to May 1996, August to November 1997) in the framework of the Swiss NOXAR and the European POLINAT 2 project. The measurements were obtained on a total of 623 flights between Europe and destinations in the United States and the Far East. NO2 measurements were obtained only after December 1995 and were less precise than the NO measurements. Therefore daytime NO2 values were derived from measured NO and O3 concentrations assuming photostationary equilibrium. The completed NOx data set (measured NO, measured NO2 during night, and calculated NO2 during day) includes a complete annual cycle and is the most extensive and representative data set currently available for the upper troposphere (UT) and the lower stratosphere (LS) covering a significant proportion of the northern hemisphere between 15°N and 65°N. NOx concentrations in midlatitudes (30°−60°N) showed a marked seasonal variation both in the UT and the LS with a maximum in summer (median/mean values of 159/264 pptv in UT, 199/237 pptv in LS) and a minimum in winter (51/99 pptv in UT, 67/91 pptv in LS). Mean NOx concentrations were generally much higher than the respective median values, in particular in the UT, which reflects the important contribution from comparatively few very high concentrations observed in large-scale convection/lightning and small-scale aircraft plumes. Seasonal mean NOx concentrations in the UT were up to 3–4 times higher over continental regions than over the North Atlantic during summer. Lightning production of NO and convective vertical transport from the polluted boundary layer thus appear to have dominated the upper tropospheric NOx budget over these continental regions, particularly during summer. Ozone concentrations at aircraft cruising levels typically varied by an order of magnitude due to the strong vertical gradient in the LS. Seasonal mean values were dominated by large-scale dynamical processes controlling the altitude of the tropopause and the O3 abundance in the LS. O3 in the UT in midlatitudes showed a broad maximum between June and August, typical of observations in the free troposphere

High incidence of reversible renal toxicity of dose-intensified bendamustine-based high-dose chemotherapy in lymphoma and myeloma patients

INTRODUCTION High-dose chemotherapy (HDCT)/autologous stem cell transplantation (ASCT) is the standard for patients with relapsed/refractory lymphomas and multiple myeloma (MM), thereby improving DFS and OS. Relapse after HDCT/ASCT remains the major cause of death in patients with lymphomas or MM after melphalan-based HDCT. Dose-intensified bendamustine by replacing carmustine in the BEAM regimen (BeEAM) or by combining it with melphalan (BenMel) is a promising strategy to lower the relapse rates.Renal toxicity after BeEAM emerges as a major concern. METHODS We investigated renal toxicity in consecutive lymphoma patients treated with BeEAM and in consecutive MM patients treated with the same dose of 400 mg/m2 bendamustine (split into 200 mg/m2 on two consecutive days) together with full-dosed (200 mg/m2) melphalan. Patients with a history of renal impairment before HDCT were included. We assessed renal damage summarized as acute kidney injury (AKI) by measuring renal parameters on a daily basis starting from the first day of HDCT until the last day of hospitalization for HDCT/ASCT. AKI: rise of s-creatinine 6526.5 \u3bcmol/L in 48 hours or increase to more than or equal to twofold compared to baseline s-creatinine within 7 days (Kidney Disease International Global Organization, KDIGO, criteria). Grading of AKI: KDIGO. Treatment-related AKI (rAKI): occurred within 10 days from the last administration of bendamustine; no relation to sepsis. Consequently, we defined as treatment-unrelated AKI (uAKI) all renal damage occurring because of sepsis or later than 10 days since the last administration of bendamustine. Statistical Analysis Subgroup differences: Chi-squared test, Fisher Exact test. IBM SPSS software version 21. RESULTS Patient characteristics and therapy regimen: 122 consecutive patients with lymphomas or MM who underwent high- dose bendamustine regimen before ASCT in 01/2013-06/2016. Factors related to rAKIOccurrence of rAKI: correlated (p<0.05) with age >60 years, previous AKI, cardiovascular comorbidities and concomitant nephrotoxic drugs. In addition, rAKI correlated (p=0.004) with cardiovascular complications during hospitalization; details of subgroups analysis: Table 2.No differences in the incidence of rAKI MM (n=7/15; 46.7%) and lymphoma patients (n=44/107; 41.1%), p=0.683. Acute kidney Injury related to High Dose Bendamustine is reversible and manageable \u2022 Acute kidney injury related to bendamustine (rAKI): in 51 patients (41.8%); completely reversible in n=50/51 (98.0%). \u2022 rAKI: mild to moderate in 90% of affected patients; did not increase TRM after ASCT. \u2022 3/51 patients (5.9%) with rAKI required transient renal dialysis to enable recovery from renal damage, whereas approaches such as additional hydration were sufficient in the vast majority (n=48 with rAKI; 94.1% of this subgroup). \u2022 The median duration of rAKI was 7 days (range, 1-22). \uad According to Cox ZL et al., Adverse Drug Events during AKI and its recovery, Clin J Am Soc Nephrol 2013; 8:1070-1078. CONCLUSION \u2022 Our data suggest that treatment-related acute renal toxicity is common in lymphoma and MM patients receiving dose-intensified bendamustine HDCT before ASCT. \u2022 However, renal impairment is reversible and manageable. \u2022 Our data identify a subgroup of patients at increased risk for the development of renal damage following bendamustine-based HDCT. \u2022 Such patients should be strictly monitored during hospitalization, and a generous hydration strategy before, during and after administration of bendamustine is recommended. \u2022 Assessing the pre-transplant renal risk profile may help to identify those patients, which may not be candidates for bendamustine-based HDCT thereby avoiding prolonged hospitalization due to rAKI and eventual transient dialysis treatment. \u2022 Our results may contribute to design appropriate selection criteria for dose-intensified bendamustine as part of the conditioning regimens preceding HDCT/ASCT in lymphoma and MM patients

Rebound Thrombocytosis after Induction Chemotherapy is a Strong Biomarker for Favorable Outcome in AML Patients

Abstract. Whereas the molecular events underlying acute myeloid leukemia (AML) are increasingly identified, dynamics of hematologic recovery following induction chemotherapy remain mysterious. Platelet recovery may vary between incomplete and excess recovery among patients achieving remission. We analyzed platelet recovery after the first induction cycle in 291 consecutive AML patients. We defined excess platelet rebound (EPR) as platelet increase above 500 G/L. We observed EPR in 120 (41.2%) patients. EPR+ patients had lower platelets at diagnosis, higher marrow infiltration, more frequently NPM1 mutations, and were associated with ELN favorable risk. Absence of EPR correlated with complex karyotypes, ELN intermediate-I and adverse risk, and therapy-related AML. Overall survival was better in EPR+ patients than EPR- (median 125 vs 41 months; p = 0.04), as was disease-free survival. By multivariate analysis, EPR+ was an independent parameter associated with favorable survival. Plasma thrombopoietin (TPO) levels at diagnosis indicated EPR+ (p < 0.0001), while GATA-1, GATA-2, and MPL mRNA expression did not differ between EPR+ and EPR- patients. Finally, transcription factors blocking early megakaryopoiesis were upregulated in EPR- patients, while NFE2 involved in late megakaryocyte differentiation was increased in EPR+ patients. Our work identifies mechanisms involved in platelet recovery after induction chemotherapy

NSAID treatment with meloxicam enhances peripheral stem cell mobilization in myeloma.

Chemotherapy with G-CSF is used to mobilize peripheral stem cells in multiple myeloma (MM) patients, with plerixafor as a rescue strategy for poorly mobilizing patients. Preclinical studies suggested that the nonsteroidal anti-inflammatory drug meloxicam enhances the mobilization of CD34+ cells. In this single-center study, we evaluated whether adding meloxicam to chemotherapy/G-CSF mobilization increases peripheral hematopoietic CD34+ cell levels and reduces the need of using plerixafor. We prospectively compared two consecutive cohorts of MM patients in first remission mobilized with G-CSF and non-myelosuppressive chemotherapy with vinorelbine or gemcitabine. The second cohort additionally received oral meloxicam. The cohorts comprised 84 patients without meloxicam (-M) and 66 patients with meloxicam (+M). Meloxicam was well tolerated and associated with similar hematologic engraftment after transplantation and equal survival rates. However, the meloxicam group had higher CD34+ cell levels on day 8 of the mobilization procedure (53 200 versus 35 600 CD34+ cells/mL; P=0.007), and fewer patients needed >1 collection day (+M: 6 (9%) patients versus -M: 16 (19%) patients; P=0.04). This resulted in reduced plerixafor administrations (+M: 7 (11%) patients versus -M: 18 (21%) patients; P=0.03) and less costs. Our data suggest that meloxicam enhances the mobilization of hematopoietic CD34+ blood cells in MM patients.Bone Marrow Transplantation advance online publication, 23 October 2017; doi:10.1038/bmt.2017.234