In Europe, most reported human cases of babesiosis have been attributed, without strong molecular evidence, to infection with the bovine parasite Babesia divergens. We investigated the first known human cases of babesiosis in Italy and Austria, which occurred in two asplenic men. The complete 18S ribosomal RNA (18S rRNA) gene was amplified from specimens of their whole blood by polymerase chain reaction (PCR). With phylogenetic analysis, we compared the DNA sequences of the PCR products with those for other Babesia spp. The DNA sequences were identical for the organism from the two patients. In phylogenetic analysis, the organism clusters with B. odocoilei, a parasite of white-tailed deer; these two organisms form a sister group with B. divergens. This evidence indicates the patients were not infected with B. divergens but with an organism with previously unreported molecular characteristics for the 18S rRNA gene.
We evaluated the toxicity and efficacy of nonpegylated liposomal doxorubicin (Myocet) when substituted for conventional doxorubicin in the CHOP-21 regimen in the treatment of frail elderly patients with aggressive non-Hodgkin lymphoma. Twenty frail patients (median age, 73 years), as defined by Balducci et al., with diffuse large B cell or grade IIIb follicular lymphoma, either at diagnosis (15 patients) or relapsed (five patients), were prospectively enrolled. Nine out of 20 (45%) had a World Health Organisation (WHO) performance status > or =2. Fifteen out of 20 patients (75%) had an International Prognostic Index (IPI) score > or =3. Thirteen out of 20 (65%) evaluable patients obtained a complete response. Five additional patients (25%) achieved a partial response. With a median follow-up of 24 months (range 18-27), 15/18 responding patients (83%) are alive and disease free, as well as 3/18 are alive with active disease. Toxicity was mainly hematological with grade 3/4 neutropenia in 26% of cycles and febrile neutropenia in 5%. However, 3/20 patients presented a grade III-IV WHO toxicity (one fatal pulmonary embolism, one congestive, and one ischemic heart failure) while receiving R-COMP chemotherapy. In conclusion, R-COMP-21 is an effective regimen with promising response rates for frail and elderly patients with aggressive non-Hodgkin lymphoma.
Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma.Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs).Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL.Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development.
The role of autologous hematopoietic SCT (autoHSCT) in the treatment of high-risk (HR) adult ALL is controversial. In this study, we retrospectively analyzed the results of autoHSCT according to the status of minimal residual disease (MRD) at transplantation, as a joint analysis of the European Study Group for Adult ALL (EWALL). Data on 123 recipients of autoHSCT, aged 31 (16-59) years, with B-lineage (n=77) or T-lineage (n=46) ALL were included. In a cohort of Ph-negative ALL, the probability of leukemia-free survival at 5 years was higher for patients with MRD <0.1% compared with those with MRD > or = 0.1% (57 vs 17%, P=0.0002). The difference was significant for T-lineage ALL (62 vs 8%, P=0.001), and a tendency was observed for B-lineage ALL (54 vs 26%, P=0.17). In a multivariate analysis, adjusted for other potential prognostic factors, high MRD level remained the only independent factor associated with increased risk of failure (risk ratio, 2.8; P=0.0005). We conclude that MRD determines the outcome of autoHSCT in HR adult ALL. Our results suggest the need to reevaluate the role of this treatment option in prospective trials.
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