Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy.

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

Polymer coated liposomes for dental drug delivery--interactions with parotid saliva and dental enamel.

The interactions between pectin coated liposomes and parotid saliva and dental enamel were studied to investigate their potential to mimic the protective biofilm formed naturally on tooth surfaces. Different pectin coated liposomes with respect to pectin type (LM-, HM- and AM-pectin) and concentration (0.05% and 0.2%) were prepared. Interactions between the pectin coated liposomes and parotid saliva were studied by turbidimetry and imaging by atomic force microscopy. The liposomes were adsorbed to hydroxyapatite (HA) and human dental enamel using phosphate buffer and parotid saliva as adsorption media. A continuous flow was imposed on the enamel surfaces for various time intervals to examine their retention on the dental enamel. The results were compared to uncoated, charged liposomes. No aggregation tendencies for the pectin coated liposomes and parotid saliva were revealed. This makes them promising as drug delivery systems to be used in the oral cavity. In phosphate buffer the adsorption to HA of pectin coated liposomes was significantly lower than the negative liposomes. The difference diminished in parotid saliva. Positive liposomes adsorbed better to the dental enamel than the pectin coated liposomes. However, when subjected to flow for 1h, no significant differences in the retention levels on the enamel were found between the formulations. For all formulations, more than 40% of the liposomes still remained on the enamel surfaces. At time point 20 min the retention of HM-pectin coated and positive liposomes were significantly higher. It was concluded that pectin coated liposomes can adsorb to HA as well as to the dental enamel. Their ability to retain on the enamel surfaces promotes the concept of using them as protective structures for the teeth.

Rapid emergence of echinocandin resistance during Candida kefyr fungemia treatment with caspofungin.

Echinocandin drugs are widely used for the treatment of candidemia. Resistance is considered rare, and only a few cases of breakthrough candidiasis in patients receiving echinocandin have been reported worldwide. We report here for the first time a Candida kefyr isolate that acquired echinocandin resistance very rapidly after the initiation of caspofungin treatment for candidemia. We characterized the FKS gene mutation responsible for the resistance via the comparison of isolates sampled before and during treatment.

Ethmoid sinus carcinomas: results and prognosis after neoadjuvant chemotherapy and combined surgery--a 10-year experience.

From June 1982 to June 1992, 144 ethmoido-sphenoido-orbital tumors have been referred to the neurosurgical department of Ste Anne Hospital. One hundred five of them were malignant lesions, among which 83 were included into our therapeutic protocol (1) neo-adjuvant chemotherapy (CDDP + 5-FU), (2) combined surgical procedure (subfrontal and transfacial), (3) postoperative radiotherapy. Fifty nine percent of the patients had no response to chemotherapy; 19% had a partial response (reduction of the tumoral volume > 50% and < 100%), 22% had a complete response. One patient had an immediate and transient postoperative rhinorrhea responsible for meningitis (acinetobacter) that was cured after a 3-day treatment. Four patients had postoperative meningitis without any cerebrospinal fluid leakage; they were also cured. Five patients had a local suppuration that was treated by subcutaneous drainage (n = 1) or the removal of the cranial basis graft (n = 4). Oncologic results are presented for only adenocarcinomas (n = 63) because they represent the only population of this series large enough to assure significant statistical figures. The global actuarial survival rate was 53% at 3 years and 42.5% at 5 years. The 5-year actuarial survival rate was 80% for T1 tumors, 60% for T2, 40% for T3, and 25% for T4. Patients with an intracranial extension had a 3-year survival rate of 19%; none survived after 4-year follow-up. Neo-adjuvant chemotherapy seemed to influence the survival: 100% survival rate at 5 and 10 years for the complete responders. We discuss the opportunity of intraorbital exenteration, the indications, and the limits of combined surgery. We emphasize the importance of neo-adjuvant chemotherapy and of combined surgical procedures, even when the patients are complete responders to chemotherapy: complete responders who had only a transfacial approach have a 5-year actuarial survival rate of 80% (instead of 100% when a combined procedure was performed). Those who were not operated primarily recurred within 3 years and then had to be operated. We propose to follow such a combined surgery for all large ethmoidal cancers (T3 and T4) and for small tumors (T1 and T2) developed superiorly and posteriorly. Anterior T1 and T2 tumors should be operated through a single transfacial route.