Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a patient with acute myeloid leukemia and HIV-1 infection. The patient remained without viral rebound 20 months after transplantation and discontinuation of antiretroviral therapy. This outcome demonstrates the critical role CCR5 plays in maintaining HIV-1 infection.
In conclusion, combination of standard induction and consolidation therapy with sorafenib in the schedule investigated in our trial is not beneficial for elderly patients with AML.
Toxoplasmosis is a rare but often fatal complication that occurs after patients undergo allogeneic hematopoietic stem cell transplant. At our institution, toxoplasmosis was diagnosed in 8 of 301 patients who received stem cell transplants. Disseminated toxoplasmosis with a rapid fatal course was observed in 2 patients. Six patients had cerebral toxoplasmosis diagnosed on the basis of neurological signs and observation of the patients' mental confusion, seizures, and typical lesions (which were assessed by computed tomography, magnetic resonance imaging, or both). Seroconversion of antitoxoplasma immunoglobulin and a discovery of toxoplasma deoxyribonucleic acid in the cerebrospinal fluid (confirmed by use of polymerase chain reaction) were documented in all patients. Treatment consisted of clindamycin therapy (for 2 patients) and of pyrimethamine-clindamycin therapy, sulfadiazine therapy, or both (for 5 patients). Patients showed improvement after therapy, as assessed by clinical and radiological means. Three of 8 patients survive-1 without any residual neurological symptoms and 2 with minimal neurological symptoms.
Infections of the central nervous system (CNS) are increasingly reported in patients with malignancies. Heavily immunocompromised patients like those after allogeneic stem cell transplantation (SCT) or previous T cell depleting treatment regimens (e.g. with fludarabine or alemtuzumab) are at highest risk for cerebral infections. The spectrum of causative organisms may vary greatly, depending on the underlying malignancy, its treatment and various other factors. Toxoplasma gondii and fungi are the leading causative organisms in patients after allogeneic SCT, but also viruses such as herpes simplex virus or JC virus may be detected in these patients. Definitive diagnosis of cerebral infection still remains a high challenge, although diagnostics have improved by the wide availability of imaging techniques and polymerase chain reaction in recent years. Novel therapeutic options are arising, particularly for fungal CNS infections. Here, we summarise aspects on epidemiology, clinical symptoms and prognosis of CNS infections in patients with malignancies. Additionally, we give an overview on the diagnostics and management of cerebral infections in these patients including evidence evaluation of efficacy of treatment.
BackgroundPrimary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML.MethodsThe current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.ResultsHSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality.ConclusionsHSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0498-8) contains supplementary material, which is available to authorized users.
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