Central venous catheter-related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter-related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.

Chemotherapy-Based Stem Cell Mobilization Does Not Result in Significant Paraprotein Reduction in Myeloma Patients in the Era of Novel Induction Regimens.

Novel induction agents markedly improved remission rates in multiple myeloma (MM), and the continued use of chemotherapy for CD34+ stem cell mobilization (SCM) has been questioned. We examined the additional effect of chemotherapy in SCM regarding remission status/morbidity. We reviewed 236 consecutive MM patients (aged 36 to 75 years) with first autologous stem cell transplantation from January 2009 to March 2016 after chemotherapy-based SCM. Responses were measured by changes in intact Ig and free light chain levels before and after chemomobilization (International Myeloma Working Group [IMWG] criteria). Most patients (225/236, 95.3%) received novel induction regimens, which were bortezomib-based (n = 223) and/or lenalidomide-based (n = 19). Most patients (170/190, 89.5%) achieved at least partial remission postinduction and pre-SCM. Stem cells were mobilized with granulocyte colony-stimulating factor and cyclophosphamide-based (212/227, 93.4%) or etoposide-based (15/227, 6.6%) regimens. There were insignificant changes in serum Ig and free light chain levels before and after chemomobilization either in the whole cohort or subgroups. Significant improvements of the IMWG remission status were documented in only 7 of 236 patients (3.0%). Sixty-seven patients (28.4%) developed chemotherapy-related complications (neutropenic fever, sepsis, and others), resulting in 9 hospitalizations (3.8%). Our study suggests that although causing significant morbidity, chemotherapy-based mobilization fails to improve remission status. The value of incorporating additional chemotherapy for SCM is thus not evident.

Collection of peripheral blood progenitor cells on Day 4 is feasible and effective while reducing granulocyte-colony-stimulating factor exposure to healthy donors.

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are the most common stem cell source for allogeneic transplantations. Analysis of our collection data obtained with a Spectra Optia device (Terumo) for apheresis demonstrated collection efficacies (CEs) exceeding our internal target levels of 5 × 10(6) CD34+ cells/kg body weight of the recipient when collected on Day 5. We thus aimed to investigate whether collection on Day 4 would lead to adequate amounts of PBPCs while minimizing granulocyte-colony-stimulating factor (G-CSF) exposure in healthy donors. STUDY DESIGN AND METHODS: We compared feasibility and effectiveness of Day 5 versus Day 4 collections with data obtained from 23 and 18 allogeneic procedures, respectively. RESULTS: Both groups were comparable with regard to donor and collection characteristics. Product characteristics as well as platelet loss, CE, throughput, and collection rate did not differ between both protocols. A higher contamination with white blood cells (WBCs; ×10(9) /L) was observed in products collected on Day 5 compared to Day 4 (231 [range, 181-299] vs. 203 [range, 165-239]; p = 0.004). A second apheresis procedure was required in three of 23 patients and three of 18 patients, respectively (p = 0.6) to obtain the required PBPC dose. CONCLUSIONS: PBPC apheresis on Day 4 seems as feasible and effective as collection on Day 5. Collection on Day 4 produces lower WBC content in the product and allows a reduction in G-CSF exposure to healthy donors.

Outcome of non-mold effective anti-fungal prophylaxis in patients at high-risk for invasive fungal infections after allogenic stem cell transplantation.

Patients who develop severe graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (alloSCT) have a higher risk for invasive fungal infection (IFI). At our center, fluconazole prophylaxis is standard and upfront mold-effective prophylaxis performed only in patients with specific risk constellations. A total of 290 patients undergoing alloSCT between May 2002 and August 2011 were analyzed. Patients were regarded as high-risk if they suffered from acute GvHD II-IV° or extensive chronic GvHD. The 2-year incidence of an IFI after alloSCT was 8.97% (26/290) in the entire cohort and 7.78% (7/90) in the high-risk group. Mortality due to IFI was 3.85% (1/26) without including a high-risk patient. In the multivariate analysis a pre-transplant fungal infection was the only significant risk factor for developing an IFI after alloSCT (HR = 5.298; p = .001). A fluconazole prophylaxis in patients with GvHD after alloSCT is feasible in facilities with HEPA filtration and high awareness of clinical signs for IFI.

Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia.

PURPOSE: Imatinib induces sustained remissions in patients with chronic myelogenous leukemia (CML), but fails to eradicate CML stem cells. This is of major concern regarding the issues of cure, long-term imatinib tolerability, and imatinib resistance. We therefore asked whether interferon alfa-2a (IFN) alone could maintain molecular remissions achieved by a prior combination therapy with imatinib and IFN. PATIENTS AND METHODS: Imatinib therapy was stopped in 20 patients who had concomitantly been pretreated with imatinib and IFN for a median of 2.4 years (range, 0.2 to 4.8 years) and 2.5 years (range, 0.2 to 4.9 years), respectively. After imatinib discontinuation, remission status was monitored monthly by quantitative analysis of the peripheral-blood BCR-ABL mRNA levels using real-time polymerase chain reaction. Proteinase-3 expression and proteinase-3-specific cytotoxic T cells (CTLs) were longitudinally measured to assess putative markers of IFN response. RESULTS: With a median time of 2.4 years after imatinib withdrawal (range, 0.5 to 4.0 years), 15 (75%) of 20 patients remained in remission. The number of patients in complete molecular remission increased under IFN from two patients at baseline to five patients after 2 years. Relapses occurred in five patients within 0.4 years (range, 0.2 to 0.8 years), but patients underwent rescue treatment with imatinib, re-establishing molecular remission. IFN therapy was associated with an increase in the expression of leukemia-associated antigen proteinase 3 and induction of proteinase-3-specific CTLs. CONCLUSION: Treatment with IFN enables discontinuation of imatinib in most patients after prior imatinib/IFN combination therapy and may result in improved molecular response. Induction of a proteinase-3-specific CTL response by IFN may contribute to this effect.