Impact of disease status and stem cell source on the results of reduced intensity conditioning transplant for Hodgkin’s lymphoma: a retrospective study from the French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

The role of reduced intensity allogeneic stem cell transplantation for the treatment of relapsed/refractory Hodgkin’s lymphoma remains controversial. We retrospectively analyzed 191 patients who underwent reduced intensity allogeneic stem cell transplantation between 1998 and 2008 for relapsed or refractory Hodgkin’s lymphoma and whose data were reported to the French registry. The median follow-up was 36 months. The estimated 3-year overall survival rate, progression-free survival rate, cumulative incidence of relapse and cumulative incidence of non-relapse mortality were 63%, 39%, 46%, and 16%, respectively. There was no difference in outcome between patients in complete response and in partial response at the time of transplantation with regards to overall survival (70% versus 74%, no significant difference) and progression-free survival (51% versus 42%, no significant difference). Patients with chemoresistant disease had a shorter overall survival (39% at 3 years; P=0.0003) and progression-free survival (18% at 3 years; P=0.001) than patients in complete remission. The use of umbilical cord blood as the source of stem cells was associated with a poor outcome with an increased risk of death with a hazard ratio of 3.49 (95% confidence interval: 1.26 to 9.63; P=0.016). The use of peripheral blood was associated with a better outcome for patients who where alive 1 year after transplantation with a hazard ratio of 0.38 (95% confidence interval: 0.17 to 0.83; P=0.016). Disease status at transplantation remains the most important risk factor for outcome. Our data suggest that the use of peripheral blood should be preferred whereas umbilical cord blood should be used with caution.     

Transplantation for Fanconi's anaemia: long-term follow-up of fifty patients transplanted from a sibling donor after low-dose cyclophosphamide and thoraco-abdominal irradiation for conditioning

We describe the long-term follow-up of 50 Fanconi's anaemia patients who were transplanted from a related donor with a median follow-up of >6 years. The survival estimate was 74.4% at 54 months and 58.5% at 100 months. All patients were conditioned with low-dose cyclophosphamide and thoraco-abdominal irradiation. Acute graft-versus-host disease (GvHD) of grade II or more developed in 26 patients and chronic GvHD developed in 30/43 (69.9%) patients. The survival of patients without chronic GvHD ( n  = 13) was 100%. In addition to chronic GvHD, 20 pre-transplant transfusions was shown to have an adverse impact on survival by multivariate analysis (relative risk = 7.08, P  = 0.0003). Prospective follow-up of growth and endocrine function could be performed in 31 patients. Of 20 boys, six have already reached normal puberty within the expected time. Among the 11 girls, three were at the pubertal age at the time of analysis. Growth retardation was common, whereas late complications (e.g. peripheral hypothyroidism, cataract) were rare. However, the most important long-term complication was the occurrence of cancer in seven patients (8-year projected incidence 24%).
Among the 32 survivors, 27 (84.5%) had a normal and four a moderately reduced performance status, and all achieved complete engraftment with donor cells. Therefore transplantation was able to cure these patients who remain at high risk for developing late complications. Clearly, a genetic predisposition and chronic GvHD could have led to the development of these cancers. However, we cannot completely rule out irradiation as a cofactor in the genesis of these cancers, and therefore no longer use irradiation for the conditioning of Fanconi's anaemia patients.     

Life-threatening gastrointestinal bleeding after liver transplatation due to hepatic artery pseudoaneurysm perforating into the common bile duct. A case report

A 54-year-old male presented with acute rejection and life-threatening gastrointestinal bleeding 2 months following orthotopic liver transplantation. Since no bleeding was identified in the entire gastrointestinal (GI) tract, hematobilia was first suspected and an arteriocholedochal fistula angiographically confirmed. Two days after resection of a pseudoaneurysm of the hepatic artery (HA) with primary repair and closure of the bile duct fistula, hepatic artery thrombosis (HAT) occurred. Various attempts to revascularize the HA eventually failed. Two weeks later, a CT scan showed necrotic areas within the two left lateral segments. At relaparotomy, major parts of the bile duct were found to be necrotic, and the biliary anastomosis was therefore abandoned and necrotic tissue removed. HAT was otherwise well tolerated by the graft and, at a further relaparotomy some weeks later, a hepaticojejunostomy was performed. Two years after transplantation the patient is well with a normally functioning graft.     

Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer

Huntingtin-interacting protein 1 (HIP1) is frequently overexpressed in prostate cancer. HIP1 is a clathrin-binding protein involved in growth factor receptor trafficking that transforms fibroblasts by prolonging the half-life of growth factor receptors. In addition to human cancers, HIP1 is also overexpressed in prostate tumors from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model. Here we provide evidence that HIP1 plays an important role in mouse tumor development, as tumor formation in the TRAMP mice was impaired in the Hip1null/null background. In addition, we report that autoantibodies to HIP1 developed in the sera of TRAMP mice with prostate cancer as well as in the sera from human prostate cancer patients. This led to the development of an anti-HIP1 serum test in humans that had a similar sensitivity and specificity to the anti-alpha-methylacyl CoA racemase (AMACR) and prostate-specific antigen tests for prostate cancer and when combined with the anti-AMACR test yielded a specificity of 97%. These data suggest that HIP1 plays a functional role in tumorigenesis and that a positive HIP1 autoantibody test may be an important serum marker of prostate cancer.     

Effects of Between-Set Interventions on Neuromuscular Function During Isokinetic Maximal Concentric Contractions of the Knee Extensors

The presents study investigated the effects of between-set interventions on neuromuscular function of the knee extensors during six sets of 10 isokinetic (120°·s^-1) maximal concentric contractions separated by three minutes. Twelve healthy men (age: 23.9 ± 2.4 yrs) were tested for four different between-set recovery conditions applied during two minutes: passive recovery, active recovery (cycling), electromyostimulation and stretching, in a randomized, crossover design. Before, during and at the end of the isokinetic session, torque and thigh muscles electromyographic activity were measured during maximal voluntary contractions and electrically-evoked doublets. Activation level was calculated using the twitch interpolation technique. While quadriceps electromyographic activity and activation level were significantly decreased at the end of the isokinetic session (-5.5 ± 14.2 % and -2.7 ± 4.8 %; p < 0.05), significant decreases in maximal voluntary contractions and doublets were observed after the third set (respectively -0.8 ± 12.1% and -5.9 ± 9.9%; p < 0.05). Whatever the recovery modality applied, torque was back to initial values after each recovery period. The present results showed that fatigue appeared progressively during the isokinetic session with peripheral alterations occurring first followed by central ones. Recovery interventions between sets did not modify fatigue time course as compared with passive recovery. It appears that the interval between sets (3 min) was long enough to provide recovery regardless of the interventions.

Key points

• Allowing three minutes of recovery between sets of 10 maximal concentric contractions would help the subjects to recover from the peripheral fatigue induced by each set and therefore to start each new set with a high intensity.
• During this type of session, with three minutes between sets, passive recovery is sufficient; there is no need to apply complicated recovery interventions.

Key words: Electromyography, electromyostimulation, stretching, recovery, maximal strength     

Detection of HIV-1 in injection paraphernalia: risk in an era of heightened awareness

Links between AIDS and self-injection of drugs were first recognized more than 20 years ago, but identification of a specific pathogen and ways to neutralize it has not led to complete success in preventing transmission of HIV-1 infection among injecting drug users (IDUs). A street ethnographer identified active risk locales (places where IDUs go to inject drugs) and recruited their proprietors into a study of contaminated injection paraphernalia. Collected paraphernalia from locales were analyzed for contamination by HIV-1 using real-time polymerase chain reaction (PCR). Proprietors and clientele of 16 risk locales participated by contributing used paraphernalia and/or agreeing to a blood test (0.5-1 mL drawn by finger stick). Realtime PCR was the primary measure used to determine contamination of injection paraphernalia and blood samples with HIV-1. Of 130 samples collected at baseline, a total of 8 were found to have evidence of HIV-1 contamination by detection of either HIV-1 RNA or DNA. The most serious contamination (up to 600,000 copies per milliliter) was found in ancillary paraphernalia, rather than needle/syringe (N/S) specimens. Only 4 of 74 N/S specimens had any evidence of HIV-1 contamination at all (with very low viral loads), and none had both HIV-1 DNA and RNA. Although IDUs in risk locales in Miami/Dade appear to be taking care of their N/S with regard to contamination by HIV-1, important evidence of contamination in ancillary paraphernalia, especially cookers and cottons, indicates that IDUs may still incur serious risk regardless of how well they care for their N/S. Our observations indicated that IDUs rinsed their N/S before returning them to the proprietors, from whom we eventually collected them, and this rinsing would have masked the contamination to which they were exposed through use of unrinsed cookers and reused cottons.