Treatment of acute myeloid leukaemia in older patients – scope of intensive therapy? – A retrospective analysis

ABSTRACTPurpose: Therapeutic regimens and outcome of acute myeloid leukaemia (AML) patients substantially improved over the past decades. However, AML in older patients is still widely understudied and therapeutic standards are far less well defined. This study provides a retrospective analysis of a cohort of AML patients above 65 years of age treated at a single university centre in Germany.Methods: Treatment regimens including intensive chemotherapy with or without subsequent allogenic stem cell transplantation (allo-SCT), hypomethylating agent (HMA) or low-dose cytarabine (LD-AraC) based therapy or best supportive care (BSC) were evaluated and compared to patient-specific variables, comorbidities indices such as Haematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) or Charlson Comorbidity Index (CCI), or Eastern Cooperative Oncology Group (ECOG) performance status to assess their potential impact on outcome.Results: 229 patients ≥ 65 years with newly diagnosed AML were included in this study. Patients received either intensive chemotherapy (IT) without (n = 101, 44%), or followed by allo-SCT (n = 27, 12%), HMA (n = 29, 13%), LD-Ara-C (n = 16, 7%) or best supportive care (BSC) only (n = 56, 24%). Of interest, ECOG performance status predicted overall survival in patients treated with IT, and combinatorial assessment of ECOG and HCT-CI was particularly useful to predict outcome in this subgroup of patients.Conclusion: Subsets of AML patients above 65 years of age benefit from intensive chemotherapy and allogenic stem cell transplantation. Combined assessment of ECOG scores and HCT-CI might help to objectively identify suitable patients, and this concept should be further investigated in a prospective manner in future studies

Utility of a Commercially Available Multiplex Real-Time PCR Assay To Detect Bacterial and Fungal Pathogens in Febrile Neutropenia ▿

Infection is the main treatment-related cause of mortality in cancer patients. Rapid and accurate diagnosis to facilitate specific therapy of febrile neutropenia is therefore urgently warranted. Here, we evaluated a commercial PCR-based kit to detect the DNA of 20 different pathogens (SeptiFast) in the setting of febrile neutropenia after chemotherapy. Seven hundred eighty-four serum samples of 119 febrile neutropenic episodes (FNEs) in 70 patients with hematological malignancies were analyzed and compared with clinical, microbiological, and biochemical findings. In the antibiotic-naïve setting, bacteremia was diagnosed in 34 FNEs and 11 of them yielded the same result in the PCR. Seventy-three FNEs were negative in both systems, leading to an overall agreement in 84 of 119 FNEs (71%). During antibiotic therapy, positivity in blood culture occurred only in 3% of cases, but the PCR yielded a positive result in 15% of cases. In six cases the PCR during antibiotic treatment detected a new pathogen repetitively; this was accompanied by a significant rise in procalcitonin levels, suggestive of a true detection of infection. All patients with probable invasive fungal infection (IFI; n = 3) according to the standards of the European Organization for Research and Treatment of Cancer had a positive PCR result for Aspergillus fumigatus; in contrast there was only one positive result for Aspergillus fumigatus in an episode without signs and symptoms of IFI. Our results demonstrate that the SeptiFast kit cannot replace blood cultures in the diagnostic workup of FNEs. However, it might be helpful in situations where blood cultures remain negative (e.g., during antimicrobial therapy or in IFI)

Epidemiology of invasive aspergillosis and azole resistance in patients with acute leukaemia: the SEPIA Study

Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azoleresistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acutemyeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Caseswere documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acuteleukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved