Efficacy of haematopoietic stem cell boost as a rescue for poor graft function after haematopoietic stem cell transplantation: A multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

Haematopoietic stem cell reinjection may be a curative option for poor graft function after haematopoietic stem cell transplantation; however, literature supporting its use remains limited. We conducted a multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, including 55 patients. We demonstrated response rates of nearly 40% and two-year survival of more than 60% in the context of an otherwise deadly complication and we observed that the timing of injection and the degree of cytopenia are strongly associated with outcomes. This study shows the feasibility of the procedure informing on its epidemiology, outcomes and prognostic factors, setting the stage for future guidelines.

Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients.

BACKGROUND: Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. METHODS: We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. RESULTS: Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II-IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II-IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). CONCLUSION: The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity.

BACKGROUND: According to the National Institutes of Health classification of chronic graft-versus-host disease (cGVHD), skin ulcers after allogeneic haematopoietic stem-cell transplantation (HSCT) are recorded as having the maximal severity score but published data are scarce. OBJECTIVES: To describe skin ulcers related to cGVHD with an emphasis on clinical findings, associated morbidity, management and evolution. PATIENTS AND METHODS: A multicentre retrospective analysis was carried out of patients with a diagnosis of cGVHD skin ulcers. RESULTS: All 25 patients included in the study had sclerotic skin cGVHD and 21 had lichenoid skin lesions associated with the sclerotic skin lesions. Thirteen patients had severe cGVHD without considering the skin, because of the involvement of an extracutaneous organ by cGVHD. The median time from HSCT to the onset of ulcers was 44 months. In addition to scleroderma, initial skin lesions at the site of ulcers were bullous erosive lichen in 21 patients and bullous erosive morphoea in four patients. Fifteen patients had an inaugural oedema. Ulcers were mostly bilateral with a predilection for the lower limbs. They were frequently colonized but few infections occurred. Four patients died during a median follow-up period of 55 months. CONCLUSIONS: Chronic graft-versus-host disease skin ulcers occur in patients with sclerodermatous skin cGVHD, are associated with severe cGVHD, often start with bullous lichenoid lesions or bullous morphoea and seem to cause more morbidity than mortality, given the low rate of mortality observed in our series of patients.

[Allogeneic stem cell transplantation from an HLA-haploidentical related donor: SFGM-TC recommendations (Part 1)]. / Greffes de cellules souches hématopoïétiques à partir d'un donneur haplo-identique : recommandations de la SFGM-TC (première partie).

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part one of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.

[Allogeneic stem cell transplantation from an HLA-haploidentical related donor: SFGM-TC recommendations (part 2)]. / Greffes de cellules souches hématopoïétiques à partir d'un donneur haploidentique : recommandations de la SFGM-TC (deuxième partie).

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part two of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.

Teaching cardiopulmonary resuscitation using virtual reality: A randomized study.

BACKGROUND: The main functions of healthcare professionals include training and health education. In this sense, we must be able to incorporate new technologies and serious game to the teaching cardiopulmonary resuscitation. METHODS: a multicenter, comparative and cross-sectional study was carried out to assess the learning of resuscitation of a group that was trained with the use of serious gaming with virtual reality, as compared to a control group trained with conventional classroom teaching. RESULTS: the mean quality obtained in chest compressions for the virtual reality group was 86.1 % (SD 9.3), and 74.8 % (SD 9.5) for the control group [mean difference 11.3 % (95 % CI 6.6-16.0), p < 0.001]. Salivary Alpha-Amylase was 218.882 (SD 177.621) IU/L for the virtual reality group and 155.190 (SD 116.746) IU/L for the control group [mean difference 63.691 (95 % CI 122.998-4.385), p = 0.037]. CONCLUSION: using virtual reality and serious games can improve the quality parameters of chest compressions as compared to traditional training.

[Vaccination post hematopoietic stem cell transplantation: which vaccines and when and, how to vaccinate? An SFGM-TC report]. / Vaccinations post-allogreffe de cellules souches hématopoïétiques: lesquels? Quand? Comment?

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding vaccination post Hematopoietic Stem Cell Transplantation with practical focus on which vaccines to use and when and how to vaccinate?

Extraosseous plasmacytoma of the lacrimal duct.

OBJECTIVE: Extraosseous plasmacytoma (EOP) is a rare plasma cell proliferative disorder that commonly affects the head and neck region. We report the first case of a plasmacytoma of the lacrimal duct. METHODS: A 66-year-old man presented with an isolated plasmacytoma of the right lacrimal duct and was treated surgically. RESULTS: The tumour grew slowly for a few months. CT scan and MRI showed a right lateral nasal mass extending from the right lacrimal duct toward the floor of the right maxillary sinus. The lesion was removed completely by endoscopic nasal surgery. DISCUSSION: EOP accounts for up to 3% of all plasma cell tumours. Management of this rare lesion involves surgery and radiotherapy with or without adjuvant chemotherapy. Guided by a literature review, we discuss the diagnostic and therapeutic management of EOP.

Enteropathy-associated T-cell lymphoma: a review on clinical presentation, diagnosis, therapeutic strategies and perspectives.

INTRODUCTION: Enteropathy-associated T-cell lymphoma (EATL) is a rare complication of celiac disease (<1% of lymphomas) and has a poor prognosis. METHODS: International literature review with PubMed search (up to January 2009) of pathophysiological, clinical and therapeutic data. RESULTS: EATL is found in patients with a mean age of 59 years, often with a complication that signals its diagnosis. Refractory celiac disease (RCD), equivalent to low-grade intraepithelial T-cell lymphoma, could be an intermediary between celiac disease and high-grade invasive T-cell lymphoma. The median survival is 7 months, with no significant difference between stages; the cumulative 5-year survival is less than 20%. The poor prognosis is determined by disease that has often spread before it is diagnosed (50%), multifocal involvement of the small bowel (50%), poor general health status and undernutrition, and recurrence of complications (infections, perforations, gastrointestinal haemorrhages, occlusions), thus delaying the chemotherapy and contributing to frequent chemotherapy resistance. There is currently no effective and consensual treatment: preventive surgery for complications is controversial, and the results of chemotherapy are disappointing. The classic CHOP protocol (combination of doxorubicin-cyclophosphamide-vincristine-prednisone) does not have satisfactory results and survival remains poor, especially in patients with underlying RCD. High-dose chemotherapy with autotransplantion seems to only improve the prognosis in localised forms. Allogeneic bone marrow transplantation was not evaluated. In all, 1/3 of patients, being unfit for treatment, die before 3 months and half of treated patients stop chemotherapy prematurely due to inefficacy, intolerance and/or complications. CONCLUSION: Improvement of the prognosis requires collaboration in order to compose a national cohort, to evaluate new diagnostic and therapeutic strategies and to define prognostic factors.

Detection of circulating Aspergillus fumigatus DNA by real-time PCR assay of large serum volumes improves early diagnosis of invasive aspergillosis in high-risk adult patients under hematologic surveillance.

Detection of galactomannan antigen (GMA) in serum is the standard assay for the diagnosis of invasive aspergillosis (IA) in high-risk patients with hematological disorders. Detection of Aspergillus DNA in serum has been proposed, but its sensitivity is lower than that of GMA when small serum volumes (SSV) are used. In this study, we investigated whether extraction of DNA from large serum volumes (LSV) improves diagnostic yield. In a 13-month prospective study, we compared the performances of twice-weekly screening of serum for GMA by an enzyme immunoassay and weekly screening for Aspergillus fumigatus DNA by a real-time PCR (RT-PCR) assay of 1.0 ml (LSV) or 100 mul (SSV) of serum. We included 124 patients (138 treatment episodes), with 17 episodes of EORTC (European Organization for Research and Treatment of Cancer)/MSG (Mycoses Study Group)-documented IA. In all, 1,870 samples were screened for GMA. The sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV and NPV, respectively) of GMA for IA were 88.2%, 95.8%, 75%, and 98.3%, respectively. We screened 938 samples for Aspergillus DNA by using LSV; 404 of these samples were also tested with SSV. The Se, Sp, PPV, and NPV of RT-PCR were 100%, 96.7%, 81%, and 100%, respectively, with LSV and 76.5%, 96.7%, 81.3%, and 95.6%, respectively, with SSV. DNA detection gave a positive result when performed on LSV in two cases of IA where the GMA assay result remained negative. Furthermore, in four IA cases, DNA was detected earlier than GMA. The use of LSV for extraction improved the performance of the RT-PCR, which appears highly sensitive and specific for the early diagnosis of IA in high-risk patients with hematological disorders.

Seasonality of reproduction in mammals: intimate regulatory mechanisms and practical implications.

Farm mammals generally express seasonal variations in their production traits, thus inducing changing availability of fresh derived animal products (meat, milk and cheese) or performances (horses). This is due to a more or less marked seasonal birth distribution in sheep and goats, in horses but not cattle. Birth peak occurs at the end of winter-early spring, the most favourable period for the progeny to survive. Most species show seasonal variations in their ovulation frequency (presence or absence of ovulation), spermatogenic activity (from moderate decrease to complete absence of sperm production), gamete quality (variations in fertilization rates and embryo survival), and also sexual behaviour. The intimate mechanism involved is a complex combination of endogenous circannual rhythm driven and synchronized by light and melatonin. Profound and long-term neuroendocrine changes involving different neuromediator systems were described to play a role in these processes. In most species artificial photoperiodic treatments consisting of extra-light during natural short days (in sheep and goats and mares) or melatonin during long days (in sheep and goats) are extensively used to either adjust the breeding season to animal producer needs and/or to completely overcome seasonal variations of sperm production in artificial insemination centres. Pure light treatments (without melatonin), especially when applied in open barns, could be considered as non-invasive ones which fully respect animal welfare. Genetic selection could be one of the future ways to decrease seasonality in sheep and goats.

Prediction of relapse by day 100 BCR-ABL quantification after allogeneic stem cell transplantation for chronic myeloid leukemia.

Chronic myeloid leukemia (CML) relapse after allogeneic stem cell transplantation (SCT) is a relatively frequent situation, which is correlated to disease status, time from diagnosis to transplant and T-cell depletion. We evaluated the potential for early minimal residual disease (MRD) BCR-ABL quantification to predict relapse of CML patients receiving allogeneic SCT. Minimal residual disease was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) at day 100 (d100) in 38 patients with >1 year follow-up after conventional non-T-cell-depleted SCT. Normal ABL control values from 1724 follow-up blood samples were used to define an RQ-PCR amplifiability index and the limits of reliable use of BCR-ABL ratios. We then compared the 14 patients with a high-level d100 BCR-ABL/ABL ratio (> or = 10(-4)) to that of the 24 patients with a negative/low-level ratio (<10(-4)). Despite being comparable for all classical parameters, the incidence of relapse was significantly higher in the high MRD group (11/14 (79%)) compared to that of the low/negative MRD group (7/24 (29%)) (P = 0.009), with d100 MRD values representing an independent risk factor of relapse and disease-free survival, but not of overall survival, in multivariate analysis. These data should facilitate risk-adapted post-transplant immunosuppression and/or tyrosine kinase inhibitor therapy based on an early evaluation of MRD.

Scleral lenses for severe chronic GvHD-related keratoconjunctivitis sicca: a retrospective study by the SFGM-TC.

Chronic GvHD-related keratoconjunctivitis sicca (cGvHD-related KCS) can significantly alter the quality of life of patients after allogeneic hematopoietic stem cell transplantation. The aim of this work was to assess the efficacy and tolerability of scleral lenses to treat severe cGvHD-related KCS. In this retrospective, multicenter study, we included 60 consecutive patients diagnosed with cGvHD-related KCS and fitted with scleral lenses. Patients were evaluated at baseline and at 2 months with the following tests: the Ocular Surface Disease Index (OSDI) to assess quality of life, the Oxford score to grade corneal damage and the logarithm of minimal angle of resolution (Log MAR) scale to determine visual acuity. We observed improvement in quality of life in 58 patients (97%). All parameters improved at 2 months. We observed significant differences at 2 months compared with baseline for the mean OSDI (86 versus 30, respectively, P<0.001), the mean Oxford score (3.2 versus 1.3, respectively, P<0.001) as well as visual acuity (Log MAR of 0.33 versus 0.10, respectively, P<0.001). Treatment with scleral lenses was discontinued in only 5 patients (8%) with a median follow-up of 20.5 months (range: 2-125 months). Scleral lenses were very efficient and well tolerated in patients with severe cGvHD-related KCS.

Pre-transplant donor CD4- invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease.

Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34+, NK, conventional T, regulatory T and invariant natural killer T (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4- iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4- iNKT expansion capacity was predictive in PBSC grafts. Receiver operating characteristic analyses determined the CD4- iNKT expansion factor as the best predictive factor of aGVHD. Incidence of grade II-IV aGVHD was reduced in patients receiving a graft with an expansion factor above versus below 6.83 (9.7 vs 80%, P<0.0001), while relapse incidence at two years was similar (P=0.5).The test reached 94% sensitivity and 100% specificity in the subgroup of patients transplanted with human leukocyte antigen 10/10 PBSCs without active disease. Analysis of this CD4- iNKT expansion capacity test may represent the first diagnostic tool allowing selection of the best donor to avoid severe aGVHD with preserved graft-versus-leukemia effect after peripheral blood allo-SCT.

The impact of allogeneic-hematopoietic stem cell transplantation on patients' and close relatives' quality of life and relationships.

PURPOSE: Although evidence suggests considerable disruption to families, the impact of allo-Hematopoietic Stem Cell Transplantation (HSCT) on patients' partners and close relatives has not been sufficiently explored. The present mixed-methods study aimed to enlighten allo-HSCT effects on patients' and close relatives' quality of life (QOL) and their relationships. METHODS: Patients who received allo-HSCT between 2007 and 2010 (N = 58) and their close relatives (parents, partners and/or adult children) were asked to respond to an anonymous questionnaire including socio-demographic data, Likert-scale of the impact of HSCT on sexual, couple, family, professional and social life, as well as on perceived support. QOL of patients and close relatives was evaluated (by the FACT-BMT and by WHO-QOL-bref) as were the adjustments of the couples (patients/partners by the DAS). In-depth interviews were performed with patients and partners who consented to this proposition. RESULTS: Patients (N = 28) and close relatives (N = 48) reported fatigue, sleep and sexual problems, emotional distress and relationship difficulties. Patients were mainly concerned with « being a burden ¼ to their close relatives. Close relatives' main concerns were changes in marital and family dynamics, disruptions in daily routine tasks and the responsibility for being the main provider of physical and emotional care. These difficulties increased after HSCT - notably when patients have to face the long-term consequences of the procedure. CONCLUSION: HSCT has a negative impact on patients' partners and other close relatives' QOL. Data on this topic is still scarce and this study might pave the way for future research in this field and notably guide psychosocial interventions.

Risk model for severe anemia requiring red blood cell transfusion after cytotoxic conventional chemotherapy regimens. The Elypse 1 Study Group.

PURPOSE: Cancer patients frequently experience anemia as a consequence of myelosuppressive therapy or bone marrow invasion. PATIENTS AND METHODS: A risk model for chemotherapy-induced severe anemia requiring RBC transfusions (SARRT) within 31 days after the administration of chemotherapy was delineated in the cohort of cancer patients treated with chemotherapy in the Department of Medicine of Centre Léon Bérard in 1996 (CLB-1996). The risk model was tested on a series of 797 patients treated in 1997 (CLB-1997) and on 295 patients included in a multicenter prospective series (ELYPSE 1). RESULTS: One hundred seven of the 1,051 patients of the CLB-1996 cohort (10%) experienced SARRT. In univariate analysis, only female sex, performance status greater than 1, hemoglobin level less than 12 g/dL before chemotherapy on day 1 (d1), and d1 lymphocyte count < or = 700/microL significantly correlated with the risk of SARRT. Using logistic regression, d1 hemoglobin level less than 12 g/dL (odds ratio [OR] = 14.0; 95% confidence interval [CI], 7 to 30), performance status greater than 1 (OR = 2.2; 95% CI, 1.4 to 3.5), and d1 lymphocyte count < or = 700/microL (OR = 1.7; 95% CI, 1. 1 to 2.6) were identified as independent risk factors for SARRT. These three factors were given arbitrary risk coefficients of 3, 1, and 1 respectively, and a risk score for each individual patient was obtained by adding the coefficients. The calculated probability of RBC transfusions was 30% for patients with a score > or = 4, and 11%, 4%, and 1% in patients with a score of 2 or 3, 1, and 0 respectively. This model was then tested and validated in the CLB-1997 and ELYPSE 1 series. CONCLUSION: This risk index could be useful to identify patients at high risk for chemotherapy-induced SARRT who might be appropriate candidates for prophylactic erythropoietin treatment.

[Evolution of the epidemiological characteristics of tuberculosis in Navarra (1994-2003)]. / Evolución en las características epidemiológicas de la tuberculosis en Navarra (1994-2003).

AIM: To describe the changes in the incidence and the epidemiological profile of tuberculosis in Navarra. METHODS: The cases of tuberculosis in the 1994-2003 period were analysed. Cases reported to the system of obligatory notifiable diseases, completed with the microbiological diagnoses and the cases collected in other health registers. RESULTS: The incidence of tuberculosis fell from 21 per 100,000 inhabitants in the five-year period 1994-1998 to 16 per 100,000 in 1999-2003. In both periods the number of cases in men doubled that in women, and the maximum incidence occurred in the age groups from 25 to 44 and over 65 years of age. The diagnoses of tuberculosis in persons with HIV infection fell from 15.1% to 6.6% and those in immigrants rose from 2.2% to 21.3%. Somewhat over 3% of the cases had received prior anti-tuberculosis treatment and about 6% showed resistance to some medicine, without significant differences between periods. The proportion of potentially transmissible tuberculosis (73%) underwent no significant changes, nor did that of those with positive sputum bacilloscopy. The number of outbreaks (groupings of two or more cases) rose from 18 to 26 and the percentage of cases secondary to another recent case rose from 3.6% to 10.1% (p<0,001). In the 1999-2003 period, pulmonary localisation occurred in isolated form in 67.7% of the patients, and in combination with other localisations in another 5.1%. The isolated pleural form appeared in 9.9% and the meningeal form in 1.5%. CONCLUSION: There has been an advance in the control of tuberculosis although its incidence is still high with respect to other European countries. Control of imported cases is one of the challenges to be faced in coming years, without neglecting control measures in the autochthonous population.

HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome A prospective study on behalf of SFGM-TC and GFM.

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only a curative treatment in patients with higher risk myelodysplastic syndrome (MDS), although demethylating agents (DMA) have been reported to improve survival. The advantage of HSCT over other treatment comes from retrospective studies and the aim of the current study was to prospectively test this hypothesis, analyzing in particular patients from the pre-transplant period to avoid the selection bias of performing transplantation. This study was conducted to compare overall survival in MDS patients candidates to transplantation according to donor availability. The majority of patients (76%) received a treatment with DMA after registration, 69% had a human leukocyte antigen (HLA)-identical donor, 70% of whom were transplanted. Baseline patient and disease characteristics were similar according to donor availability. Four-year overall survival was significantly better in patients with an HLA matched donor (37%) compared to patients without donor (15%). There was also evidence that this overall survival advantage was because of transplantation. Mortality risk was decreased after transplantation but it became significant only after the second year post transplant, because of early transplant-related mortality. Our results appear to justify, in higher risk MDS, a transplantation approach in all potential candidates who have an HLA identical donor.