Search

In vivo T-cell depletion with anti-thymocyte globulin (ATG) can attenuate GvHD but may increase infection and relapse risks. ATG-Fresenius (ATG-F) at a dose of 60 mg/kg was standard GvHD prophylaxis in unrelated donor hematopoietic stem cell transplantation (HSCT) at our institution. We changed to an incremental reduced dose regimen of 35 mg/kg and extended ATG prophylaxis to include older matched-related donor transplants considered to be at higher risk of GvHD. A total of 265 adults with hematological malignancies receiving a first allogeneic HSCT after myeloablative conditioning between 2009 and 2014 were analyzed in this cohort study. Patients had either received higher dose (n=32) or lower dose ATG-F (n=88) or no ATG (n=145). ATG-F was associated with slower engraftment and less chronic GvHD, whereas no effect was noted on acute grade II-IV GvHD and relapse incidence. Transplant-related mortality (TRM) was lower and survival higher with lower dose, but not with higher dose ATG-F. Both ATG-F groups were associated with more viral reactivation, viral disease and bacterial blood stream infection, but not invasive fungal infection, and with slower immune reconstitution. The recently adopted strategy of using lower doses of ATG-F in unrelated and older age-related donor HSCT appears to reduce TRM without increasing disease relapse, leading to slightly enhanced survival.

Induction/consolidation chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies are associated with treatment-related risks such as infections. The predominant types of infections are blood stream infections (BSIs) and respiratory tract infections. We prospectively compared infectious complications after induction/consolidation chemotherapy versus allogeneic HSCT in a directly comparable setting with both groups being hospitalized on the same ward. From July 2003 until June 2008, 492 hospitalizations of 321 patients took place; 237 chemotherapies and 255 HSCTs were performed. We observed 49 (20.7%) BSIs, 70 (29.5%) pneumonias and 11 (4.6%) probable or proven invasive mould infections in the chemotherapy group. In the HSCT group we detected 70 (27.5%) BSIs, 71 (27.8%) pneumonias and 14 (5.4%) probable or proven invasive mould infections. There was a trend toward more transfers to the intensive care unit (OR 1.61; 95%CI 0.95-2.72; P=0.074) and BSIs (OR 1.45; 95%CI 0.95-2.22; P=0.079) after HSCT; 44 (13.7%) patients died. In-hospital mortality was significantly higher in the HSCT group (OR 2.39; 95%CI 1.22-4.68; P=0.010). We conclude that the risk of pneumonia and invasive mould infection is comparable after induction/consolidation chemotherapy and allogeneic HSCT. However, there was a trend for more BSIs and intensive care unit stays and a higher mortality in the latter.

We have read with great interest the recent article by Martino et al. about lower respiratory tract virus infections as a risk factor for invasive aspergillosis. The established risk factors for aspergillosis in patients after allogeneic hematopoietic SCT (HSCT) include duration of neutropenia, use of steroids, donor type, underlying disease, age, and presence and treatment of GVHD. The authors of this study analyzed the incidence and risk factors for the occurrence of invasive aspergillosis among 219 recipients of allogeneic HSCT after a reduced-intensity conditioning regimen. They showed that steroid therapy for GVHD and the occurrence of a lower respiratory tract infection caused by a respiratory virus were independent risk factors for the development of invasive aspergillosis. Here we report the case of a 45-year-old woman with a history of extensive chronic GVHD of the lungs (bronchiolitis obliterans), gastrointestinal tract, liver and skin following myeloablative allogeneic HSCT for AML 3 years earlier. She was under triple immunosuppression with prednisolone, tacrolimus and mycophenolate when she developed rhinitis, productive cough and chest pain. Influenza A virus was isolated from a nasopharyngeal swab and treatment with oseltamivir and i.v. Igs was initiated. A computed tomography (CT) of the chest done at this time was normal. However, treatment symptoms persisted and another CT scan was performed 1 week later. The picture was suggestive of pulmonary aspergillosis (Figure 1a). Treatment with voriconazole was added and the symptoms improved. The follow-up CT 2 weeks later revealed the formation of a massive cavitation (Figure 1b). Treatment was empirically changed to liposomal amphotericin B and meropenem, and partial resection of the right lower pulmonary lobe was performed. Histological and microbiological investigations showed a polymicrobial infection with the presence of zygomyceteRhizopus microsporus (Figures 2a and b), Enterococcus faecium and coagulasenegative staphylococci. On treatment with liposomal amphotericin B and antibiotics, the infections resolved. This case is in line with the paper by Martino et al. and illustrates how influenza virus triggered this rapidly progressive polymicrobial disease in a severely immunocompromised patient with active chronic GVHD late

A recent study in this journal1 raised the issue of prolonged hypogammaglobulinemia in patients receiving autologous hematopoietic stem cell transplantation (HSCT) for high-risk B-cell lymphoma and maintenance therapy with rituximab. Despite significant hypogammaglobulinemia, these patients did not experience significant infectious complications. With the following case report, we aim to increase the awareness of the potential for severe infectious complications associated with the hypogammaglobulinemia observed in lymphoma patients given lymphocytotoxic chemotherapy in combination with rituximab before allogeneic HSCT.2