Prospective long-term follow-up after first-line subcutaneous cladribine in hairy cell leukemia: a SAKK trial.

Hairy cell leukemia (HCL) remains an incurable disease. However, first-line treatment with either intravenous or subcutaneous cladribine generally leads to long-lasting remissions. Although there are excellent long-term data for intravenous application, similar data regarding subcutaneous administration are lacking. We therefore analyzed the long-term outcome of 3 prospective multicenter clinical trials on subcutaneous cladribine performed by the Swiss Group for Clinical Cancer Research (SAKK), which recruited 221 patients with classical HCL between 1993 and 2005. Median overall survival from start of treatment was not reached. Pretreatment anemia, higher Eastern Cooperative Oncology Group score, and higher age were associated with poorer overall survival in multivariable analysis, whereas early progression at 24 and 36 months had no significant impact on overall survival. Second-line treatment was necessary in 53 (23.7%) patients after a median of 5 (range, 0.2-20.4) years, and first retreatment was mainly monotherapy with cladribine (66%) or rituximab (15.1%) or a combination of these drugs (15.1%). A total of 44 (19.9%) patients developed second primary malignancies with a median time to occurrence of 5.7 (range, 0.01-17.5) years. Second primary malignancies were the main cause for death (14; 27.5%). Compared with a matched normal Swiss population, the incidence of second primary malignancies was not increased. However, survival of patients with HCL was slightly inferior by comparison (P = .036). In conclusion, the outcome of HCL patients treated with subcutaneous cladribine is excellent, and in most patients, 1 cycle of subcutaneous cladribine is sufficient for long-term disease control.

A blind passenger: a rare case of documented seroconversion in an Angiostrongylus cantonensis induced eosinophilic meningitis in a traveler visiting friends and relatives.

BACKGROUND: Eosinophilic meningitis (EOM) is a rare condition that is caused by various communicable and non-communicable factors. The rat-lungworm Angiostrongylus cantonensis, which is associated with consumption of raw or undercooked paratenic or intermediate hosts, is the most common cause of parasitic eosinophilic meningitis worldwide. While the majority of A. cantonensis cases are reported from endemic regions, cases in travelers pose a challenge to clinicians in non-endemic countries. Here we report a rare case of eosinophilic meningitis caused by A. cantonensis in a Swiss traveler who was diagnosed after returning from Thailand. CASE PRESENTATION: A 33-year old woman with a travel history to rural north-eastern Thailand presented to an emergency department in Switzerland with severe headache and vomiting. Eosinophilic meningitis was confirmed as the cause of the symptoms; however, serologic investigations failed to confirm an A. cantonensis infection on the first evaluation. Nevertheless, empirical treatment with an anthelminthic and steroid regimen led to a rapid alleviation of symptoms. Repeated serology confirmed seroconversion 2 weeks after treatment initiation. DISCUSSION: Parasitic etiology must be considered in returning travelers who present with symptoms compatible with a central nervous system infection. A thorough medical history, including types of food consumed, is paramount and can often suggest differential diagnosis. Neuroangiostrongyliasis is rare and might be missed if serology does not cover possible seroconversion.

Standardization of 8-color flow cytometry across different flow cytometer instruments: A feasibility study in clinical laboratories in Switzerland.

The EuroFlow Consortium developed a fully standardized flow cytometric approach from instrument settings, through antibody panel, reagents and sample preparation protocols, to data acquisition and analysis. The Swiss Cytometry Society (SCS) promoted a study to evaluate the feasibility of using such standardized measurements of 8-color data across two different flow cytometry platforms - Becton Dickinson (BD) FACSCanto II and Beckman Coulter (BC) Navios, aiming at increasing reproducibility and inter-laboratory comparability of immunophenotypic data in clinical laboratories in Switzerland. The study was performed in two phases, i.e. a learning phase (round 1) and an analytical phase (rounds 2 and 3) consisting of a total of three rounds. Overall, 10 laboratories using BD FACSCanto II (n=6) or BC Navios (n=4) flow cytometers participated. Each laboratory measured peripheral blood samples from healthy donors stained with a uniform antibody panel of reagents - EuroFlow Lymphoid Screening Tube (LST) - applying the EuroFlow standardized protocols for instrument setup and sample preparation (www.EuroFlow.org). All data files were analyzed centrally and median fluorescence intensity (MedFI) values for individual markers on defined lymphocyte subsets were recorded; variability from reference MedFI values was assessed using performance scores. Data troubleshooting and discussion of the results with the participants followed after each round at SCS meetings. The results of the learning phase demonstrated that standardized instrument setup and data acquisition are feasible in routine clinical laboratories without previous experience with EuroFlow. During the analytical phase, highly comparable data were obtained at the different laboratories using either BD FACSCanto II or BC Navios. The coefficient of variation of MedFI for 7 of 11 markers performed repeatedly below 30%. In the last study round, 89% of participants scored over 90% MedFI values within the acceptance criteria (P-score), in line with the results of the EuroFlow quality assessment rounds performed by the EuroFlow expert laboratories(Kalina et al., 2015). Central analysis of data allowed identification of deviations from the standardized procedures and technical issues (e.g. failure to perform correct instrument setup and improper compensation). In summary, here we show that inter-laboratory cross-platform standardization of 8-color flow cytometric measurements in clinical laboratories is feasible and allows for fully comparable MedFI results across BD FACSCanto II and BC Navios instruments. However, adherence to standardized protocols is crucial. Thus, training of the laboratory personnel in the EuroFlow standardized procedures is highly recommended to prevent errors in instrument setup and sample preparation.

Optimised radiological diagnosis of hepatic fungal infection during the treatment of leukemia.

Hepatic fungal infection is a frequent complication in patients receiving intensive chemotherapy for acute leukaemia. Hepatic lesions may be detected using computerised tomographic (CT) scans, but there is no standardised CT protocol for the diagnosis and follow-up of hepatic fungal infection. We therefore retrospectively analysed the number and the volume of hepatic fungal lesions in 24 CT of 20 consecutive patients treated for acute leukaemia during late-arterial and porto-venous phase. The mean number of lesions per patient was 31 (range: 3-105) in the late-arterial and 26 (3-81) in the porto-venous CT (P = 0.026). The mean total volume of all lesions was 6.45 ml in the late-arterial and 4.07 ml in the porto-venous CT representing a 1.6fold difference between the two CT scans (P = 0.008). The total volume of the lesions negatively correlated to the absolute contrast difference between liver parenchyma and liver vein (Pearson correlation, r = -0.62; P = 0.002). In conclusion, the late-arterial CT provides a superior distinction of hepatic lesions due to a delayed perfusion of the outer rim of the fungal lesions resulting in an extended visibility. The late-arterial CT is superior to the porto-venous CT for initial diagnosis and follow-up of hepatic fungal infection.

Significant reduction of red blood cell transfusion requirements by changing from a double-unit to a single-unit transfusion policy in patients receiving intensive chemotherapy or stem cell transplantation.

BACKGROUND: Traditionally, single-unit red blood cell transfusions were believed to be insufficient to treat anemia, but recent data suggest that they may lead to a safe reduction of transfusion requirements. We tested this hypothesis by changing from a double- to a single-unit red blood cell transfusion policy. DESIGN AND METHODS: We performed a retrospective cohort study in patients with hematologic malignancies receiving intensive chemotherapy or hematopoietic stem cell transplantation. The major end-points were the reduction in the total number of red blood cell units per therapy cycle and per day of aplasia. The study comprised 139 patients who received 272 therapy cycles. Overall 2212 red blood cell units were administered in 1548 transfusions. RESULTS: During the periods of the double- and single-unit policies, one red blood cell unit was transfused in 25% and 84% of the cases and the median number of red blood cell units per transfusion was two and one, respectively. Single-unit transfusion led to a 25% reduction of red blood cell usage per therapy cycle and 24% per aplasia day, but was not associated with a higher out-patient transfusion frequency. In multivariate analysis, single-unit transfusion resulted in a reduction of 2.7 red blood cell units per treatment cycle (P = 0.001). The pre-transfusion hemoglobin levels were lower during the single-unit period (median 61 g/L versus 64 g/L) and more transfusions were administered to patients with hemoglobin values of 60 gl/L or less (47% versus 26%). There was no evidence of more severe bleeding or more platelet transfusions during the single-unit period and the overall survival was similar in both cohorts. CONCLUSIONS: Implementing a single-unit transfusion policy saves 25% of red blood cell units and, thereby, reduces the risks associated with allogeneic blood transfusions.

Optimal preprocedural platelet transfusion threshold for central venous catheter insertions in patients with thrombocytopenia.

BACKGROUND: Patients with severe thrombocytopenia are at risk for bleeding during insertion of central venous catheters (CVCs). Although most guidelines recommend preprocedural platelet (PLT) transfusions at a threshold of less than 50 × 10(9) /L, there is only weak evidence supporting such recommendations. STUDY DESIGN AND METHODS: The current study aimed to establish a safe PLT transfusion trigger in patients with CVC placements. We performed a retrospective single-center analysis of 604 CVC insertions in 193 patients with acute leukemia receiving intensive chemotherapy or stem cell transplantation. RESULTS: A total of 48% of the patients had a bleeding risk during CVC insertions, mostly due to thrombocytopenia. The bleeding incidence was 32% with 96% Grade 1 and 4% Grade 2 bleedings requiring prolonged local compression. There were no Grade 3 to 4 bleedings. Hemoglobin levels were similar before and 24 and 48 hours after the CVC insertion in the bleeding and nonbleeding group and there was no difference in the red blood cell (p = 0.72) and PLT transfusion requirements (p = 0.057) after CVC insertion. In multivariate analysis, only patients with PLT counts of less than 20 × 10(9) /L were at higher risk for bleeding before (p = 0.015) and after preprocedural PLT transfusions (p =0.006) compared to patients with PLT counts of 100 × 10(9) /L or more. CONCLUSION: CVC placements can safely be performed in patients with PLT counts of 20 × 10(9) /L or more without preprocedural PLT transfusions.