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International audience; Primary antibody deficiency (PAD) is characterized by a defective immunoglobulin production and recurrent infections, mostly involving respiratory and gastrointestinal tracts. Chronic or recurrent diarrhea is reported in up to 23%. Campylobacter infection is a common cause of infectious diarrhea, reported in 1.2% to 7.5% of patients with common variable immunodefi-ciency (CVID), the most frequent PAD. The aim of this study was to describe Campylobacter infection in patients with PAD included in a large nationwide study and analyze factors associ-ated with susceptibility to this pathogen. The DEFI (DEFicit Immunitaire) study is an ongoing large cross-sectional French multicentric study of adults with PAD, with retrospective collection of clinical data. All patients with a history of bacteriologically documented Campylobacter infection were identified, and clinical data were collected for each episode. Factors associated with recurrent infection were assessed as oddsratio (OR) and 95% confidence interval (CI), calculated by means of simple regression analysis. In patients with available material, strains of each episode were characterized using molecular analysis and compared (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). A com-parison of immunodeficiency-related characteristics of patients with and without Campylobacter infection was performed in the homogeneous group of patients with CVID. The control group included patients with CVID from DEFI centers who confirmed that patients did not develop Campylobacter infection after enrollment (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). After correction for multiple comparisons, P

International audience; BACKGROUND:In 2014, the European Society for Immune Deficiencies (ESID) revised the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new clinical and biological markers. The new definition appeared more restrictive but had not yet been evaluated in a large cohort of patients.OBJECTIVE:The objective of this study was to evaluate the impact of this new definition in a large cohort of patients with primary hypogammaglobulinemia.METHODS:Evaluation of 3 different CVID definitions (ESID/Pan-American Group for Immunodeficiency [PAGID] 1999, ESID 2014, DEFI 2015) in 521 patients included in the French DEFI study with a diagnosis of primary hypogammaglobulinemia.RESULTS:Using the ESID/PAGID 1999 definition, 351 patients were classified as CVID. The new ESID 2014 definition excluded 62 (18%) patients. Most of them (n = 56; 90%) had a less severe disease, whereas 6 (10%) presented with a severe disease with major T-cell defect. We propose different criteria (occurrence of opportunistic infection or very low naive CD4+ T-cell count) to define this population with severe T-cell defect. Sixty-two patients fulfilled these criteria, represented 20% of the initial CVID population but accounted for 77% of the deaths, with a 5-year overall survival of 67.6% (95% confidence interval, 51.0-79.6), and were considered as late onset combined immunodeficiency (LOCID).CONCLUSIONS:The new ESID definition for CVID still fails to exclude a large number of patients with severe T-cell defect. We propose a new definition (DEFI 2015) that excluded more patients with a T-cell defect and consider these patients as LOCID. This population has a poor outcome and should be considered as a distinct group requiring specific care.

Observation of schistocytes on the peripheral blood following haematopoietic stem cell transplantation (SCT) is a common finding. As their presence is not specific to the onset of SCT-related thrombotic microangiopathy, we evaluated the interest of schistocyte measurement twice a week during the entire follow-up of 195 patients undergoing SCT, particularly focussing on the 125 allogeneic SCT.Schistocytes were strickly defined as triangular-, crescent- or helmet-shaped red blood cells according to consensus standards and were checked blindly under the microscope and with computer image analysis.Mean schistocyte percentage was 0.7% (±0.5%, reference value ≤0.5). High schistocyte percentage was observed after allografts (0.79%) when compared to autologous SCT (0.47, P0.001). All but one patients undergoing allogenic SCT had schistocytes ≥0.6%. Conversely, significant schistocytosis was observed in 20% of the autologous SCT. Initial diagnosis [chronic myelocytic leukaemia, acute lymphoblastic leukaemia (ALL)], high-risk status, unrelated transplant and conditioning regimen including total body irradiation influenced higher schistocyte percentage (≈0.9%). Significant rise in the schistocyte percentage was observed during acute/chronic graft-versus-host disease, veno-occlusive disease (VOD), cholestatic hepatitis, haemorrhagic cystitis (HC) and pulmonary complications. Multivariate analysis showed a significant association between thrombotic microangiopathy (TM), renal impairment and delayed thrombopaenia after day 50, and schistocyte1.2%. SCT-TM grade ≥2 occurred in nine patients. A marked rise in schistocyte4.5% was observed, which was not reached during the other SCT-related complications. Children with ALL, undergoing unrelated allogeneic SCT, with early acute graft-versus-host disease refractory to steroids were prone to present SCT-TM, associated with VOD, interstitial pneumopathy and HC, resulting in a high mortality rate (six of seven patients). Our data confirmed that schistocytosis was common after SCT. Mild percentages were likely concomitant with extensive endothelial damage but higher percentage should have prompted to a close monitoring with SCT-TM investigation.In our experience, systematic schistocyte count after HSCT proved to be useful: the occurrence of an increased percentage was a surrogate marker for complications even if unspecific for TM.

A fatal case of disseminated Scopulariopsis brevicaulis infection in an allogeneic stem cell transplant recipient is described. The patient was initially thought to have pulmonary aspergillosis, on the basis of clinical signs and antigenaemia, but Aspergillus was not isolated by culture. Scopulariopsis brevicaulis was subsequently isolated from skin and then from sputum and stool. Further investigation revealed that the infection had spread from a primary pulmonary site to the skin. A review of the literature underscores the difficulty of diagnosing infections caused by such emerging fungal pathogens and the poor outcome of immunocompromised patients with non-Aspergillus mould infections.

Antihistone antibodies were detected in the sera of a randomly selected group of patients with rheumatoid arthritis (RA) and juvenile chronic arthritis (JCA) by an enzyme-linked immunosorbent assay (ELISA) with the five individual histones and by immunoblotting. In ELISA, the overall frequency of antihistone antibodies in RA and JCA was 51 and 44%, respectively. Antibodies present in these serum samples were further studied by ELISA by means of 17 core histone synthetic peptides. The fragment 1–21 of H3 was recognized by 60% of RA sera and by 62% of JCA sera. In addition, at least four terminal or internal peptides of H3 and H4 were recognized by more than a third of JCA sera, while only two of these peptides reacted with 20% of RA sera. Many of the sera that did not show any reactivity with the whole histone reacted with various histone peptides. This finding demonstrates the usefulness of synthetic peptides for identifying autoantibodies.

Show the contribution of imaging to the diagnosis and follow-up of serious mucormycosis in immunodepressed patients.Retrospective analysis of the 5-year radiological data in serious forms of mucormycosis occurring in patients with bone marrow allografts who are in refractory chronic graft-versus-host disease after bone marrow transplantation from 2002 to 2005. The positive diagnosis was bacteriologically and pathologically positive in all cases.This study involved three patients with isolated pulmonary involvement and two cases of disseminated mucormycosis. Areas of pulmonary condensations were found in all cases, one of whom had a low-attenuation zone and parenchymal nodules. The kidney, liver, and spleen lesions were clearly limited, hypoechogenic, hypodense, and homogenous with no peripheral contrast material uptake. There was thyroid involvement in the form of hypoechogenic nodules. Rapid growth of the lesions was observed on follow-up CT (n=3) and despite surgical treatment (n=2) and intensive medical management, all cases ended in death.Mucormycosis is an integral part of the differential diagnosis of infectious syndromes in immunodepressed patients during the period after bone marrow transplantation. Imaging can assist in the diagnosis but pathological confirmation remains indispensable.

The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy.A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide).Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases).The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.

Thrombocytopenia occurs frequently. We will illustrate, through the presentation of a clinical case, the difficulties encountered to identify and characterize thrombocytopenia. The clinicobiological validation of a low platelet count implies, at the same time, the biologist, who must assume the validation of numeration while mentioning the morphological characteristics of the platelets and other blood cells, as well as the clinician who must interpret these data according to the clinical context. Firstly, we will detail the basic rules to correctly ensure this validation. Secondly, we will see which are the arguments which that make it possible to direct the diagnosis towards an acquired or inherited thrombocytopenia. Lastly, we will approach the classification of inherited thrombocytopenias.

Over an eight-month period from October 1997 to May 1998, four patients who had received bone marrow transplant (BMT) from unrelated donor presented with severe mucosal cutaneous infections involving aciclovir resistant herpes simplex virus 1 (HSV-1). The four isolates were aciclovir (ACV) resistant, three of which were also foscarnet resistant as determined by the dye uptake method. The sequencing of the thymidine kinase (TK) gene did not permit to establish a relation between mutations and resistance to ACV. Three patients were considered as clinically cured of their HSV infection by replacement of ACV or foscarnet with either valaciclovir (one case) or cidofovir (two cases) but eventually two of them died of graft vs host disease. One patient died of extensive HSV infection despite administration of cidofovir. This study emphasizes the importance of monitoring the herpes virus resistance to antiviral drugs in bone marrow transplant recipients and the usefulness of the evaluation of novel antiviral drug for treatment of infections due to strains of HSV resistant to ACV and foscarnet that occur in about 5% of immunocompromised patients.

In this retrospective multicentre study, we analysed the results of 82 consecutive second early allogeneic transplants for primary (n = 28) or secondary ([n = 54) graft failures performed between 1985 and 1997 in patients with acute leukaemia (n = 33), aplastic anaemia (n = 29) or chronic myeloid leukaemia (n = 20). HLA-matched siblings were used in 64 cases. The same donors were used for both transplants in 56 cases and the first transplant was T-cell depleted in 30 cases. The median age at transplant was 25 years and the median intertransplant time interval was 2 months. Estimates of the 3-year overall survival and day 100 transplant-related mortality were 30% and 53% respectively. A recipient age34 years at transplant, an intertransplant time intervalor = 80 d and a positive recipient cytomegalovirus serology were predictors of a better outcome. The use of cyclosporin A (CsA) after second transplant had a dramatic impact on outcome, the best results being observed with CsA alone. The day 40 probability of neutrophil recovery was 73%. The use of peripheral blood progenitor cells (PBPCs) was associated with a higher and faster neutrophil recovery. Other factors associated with neutrophil recovery were an intertransplant time intervalor = 80 d and a positive recipient cytomegalovirus serology. Therefore, second early allogeneic transplantation for graft failure is an effective treatment, especially if patients can receive CsA for graft-versus-host disease prevention and are retransplanted more than 80 d from first transplant.

Diamond-Blackfan anemia (DBA) is a constitutional disease characterized by a specific maturation defect in cells of erythroid lineage. We have assembled a registry of 229 DBA patients, which includes 151 patients from France, 70 from Germany, and eight from other countries. Presence of malformations was significantly and independently associated with familial history of DBA, short stature at presentation (before any steroid therapy), and absence of hypotrophy at birth. Two hundred twenty-two patients were available for long-term follow-up analysis (median, 111.5 mo). Of these individuals, 62.6% initially responded to steroid therapy. Initial steroid responsiveness was found significantly and independently associated with older age at presentation, familial history of DBA, and a normal platelet count at the time of diagnosis. Severe evolution of the disease (transfusion dependence or death) was significantly and independently associated with a younger age at presentation and with a history of premature birth. In contrast, patients with a familial history of the disease experienced a better outcome. Outcome analysis revealed the benefit of reassessing steroid responsiveness during the course of the disease for initially nonresponsive patients. Bone marrow transplantation was successful in 11/13 cases; HLA typing of probands and siblings should be performed early if patients are transfusion dependent, and cord blood should be preserved. Incidence of DBA (assessed for France over a 13-y period) is 7.3 cases per million live births without effect of seasonality on incidence of the disease or on malformative status. Similarly, no parental imprinting effect or anticipation phenomenon could be documented in families with dominant inheritance.

We determined the proportion of survival variability explained by the usual prognostic factors in childhood acute lymphoblastic leukaemia (ALL) during a prognostic study of 1552 patients enrolled in three consecutive Fralle group protocols (Fralle 83, Fralle 87 and Fralle 89). The event-free survival rates at 5 years were 54.8% (SD 1.9), 43.1%) (SD 2.7) and 55.6% (SD 2.2), respectively. In the univariate analysis the following variables were predictive of poor outcome: male gender, elevated leucocytosis (50 x 10(9)/l), circulating blastosis. haemoglobin12 g/dl, platelet count100 x 10(9)/l, age under 1 year or over 9 years, enlarged mediastinum, nodes, spleen and liver, T phenotype, absence of CD10+ cells; testicular and meningeal involvement, poor response to induction therapy (CCSG M3), and LDH400 U/l. Among the cytogenetic features, hyperdiploidy had a protective effect, whereas hypodiploidy, translocation and other structural abnormalities had a negative influence, particularly in cases of t(9;22) or t(4;11). Multivariate analysis summarized the prognostic information in terms of four variables: age, gender, leucocytosis and cytogenetic features. Missing data had little influence on the results. However, despite their significance in the multivariate analysis, these four variables each had very low predictive power (1.1% for gender, 2.0% for age, 3.5% for leucocytosis, and 1.6% for cytogenetic features). Thus, the most significant prognostic factors in childhood ALL each explain no more than 4% of the variability in prognosis. This may explain the disappointing practical value of these factors and underlines the need for prognostic tools in childhood ALL.

Autologous peripheral blood stem cell (PBSCs) are frequently used to reconstitute hematopoiesis following administration of megatherapy in children with advanced stage IV neuroblastoma. Some centers prefer the use of autografts enriched for CD34+ progenitor cells because the positive selection procedure is believed to reduce indirectly tumor cell contamination.In this study, we monitored the efficiency of tumor cell purging following CD34 selection in PBSCs from seven patients with advanced neuroblastoma by using a highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, Amplification of tissues-specific mRNA transcript of tyrosine hydroxylase gene with nested primers enabled the detection of residual neuroblastoma cells with a sensitivity of one malignant-cell per 10(6) normals.Using this method, contaminating tumor cells were detected in seven of nine leukapheresis products of the patients. After positive immunoselection of CD34+ cells on Ceprate column, only one of nine enriched stem cell fraction still contained tumor cells detectable by RT-PCR. In six cases, PCR positive PBSCs became PCR negative after selection.We conclude that tumor cell contamination may be frequently detected in PBSC harvests of stage IV neuroblastoma patients by sensitive molecular analysis. The load of contaminating malignant cells might be reduced following CD34 selection.

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy mainly rely upon prognostic factors, and their importance is constantly reassessed. To examine the impact of time from diagnosis to transplant on survival and leukemia-free survival (LFS), we analyzed 109 patients from the database of the SFGM comprising patients who had all received an HLA-identical allogeneic BMT for a diagnosis of AML in first complete remission (CR1) between January 1987 and December 1992. All patients were conditioned with cyclophosphamide (CY) and total body irradiation (TBI) (CYTBI), and methotrexate (MTX) + cyclosporin A (CsA) were used as graft-versus-host disease (GVHD) prophylaxis. Patient characteristics were: age = 33 +/- 9, M/F = 64/45, white blood cell count (WBC) at diagnosis = 27 +/- 42 x 10(9)/l, FAB distribution: M1 and M2 = 55; M3 = 15, M4 and M5 = 33, M0, M6 and M7 = 6. Karyotyping was carried out for 64 patients: 32 had a normal karyotype, 16 had good prognosis abnormalities (t(8;21), t(15;17), inv 16) and 16 patients had other abnormalities. Eleven patients needed two courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64-287) days. Forty-nine patients developed gradeor = 2 acute GVHD (actuarial probability = 46%). With a median follow-up of 50 months (27-100), the 5-year probabilities for transplant-related mortality (TRM), relapse, overall survival and LFS are respectively 25%, 26%, 59% and 55%. A multivariate analysis showed that survival is adversely influenced by three independent factors: time to transplant (120 days vsor = 120 days), acute GVHD (grade 2-4 vs grade 0-1) and age (33 vsor = 33). LFS is only influenced by the first two of these factors. The favorable impact of a shorter time from diagnosis to transplant should lead to performing the transplant as early as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should begin immediately and transplant be performed as soon as possible.

The PRimed IN Situ synthesis is a method for rapid identification of chromosomes in metaphase or interphase on cytological preparations and frozen tissue sections, using oligonucleotide primers derived from chromosome specific subsets of repeated DNA families. PRINS technique is an alternative to fluorescence in situ hybridization, as sensitive as FISH but faster and more specific. This technique is potentially of great interest for pathologists involved in transplantation pathology or cytogenetic interphasic oncology.

Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was undertaken to assess one strategy of marrow graft rejection prevention when alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives were used. Results have been compared with two matched groups of children with the same risks factors and disease status who underwent HLA-genoidentical or autologous BMT. The conditioning regimen was the same for the three groups of patients; in the study group anti-LFA-1 and anti-CD2 monoclonal antibodies combined with T-cell depletion of the marrow was added to prevent graft rejection and graft-versus-host disease. Nineteen patients were included and followed for a median of 25 months (14 months to 3 years). Bone marrow engraftment occurred in 83% of the evaluable patients. Post-transplantation infectious diseases were the most frequent causes of death in the study group, occurring in 31% of patients. No fatal infections occurred in the two control groups. Post-transplantation relapse of leukaemia occurred in 26% of study group's patients, in 58% of autologous BMT control group's patients and 5% of HLA-genoidentical allogeneic group's patients. The event-free survival was 83% in the HLA-genoidentical control group, and 30% and 24% in the study group and in the autologous control group, respectively. In conclusion, a high rate of engraftment was achieved by the use of anti-LFA-1 and anti CD2 antibodies. Occurrence of a long-lasting immunodeficiency, however, led to a high incidence of lethal infections and relapses. Combined approaches are therefore to be investigated accelerating immune reconstitution after transplantations of T-depleted HLA partially incompatible marrow.

Patients with lysosomal storage disorders have visceral, skeletal, and neurological abnormalities and a limited life expectancy. Bone marrow transplantation has been used to correct the metabolic defects and leads to metabolic improvements in most patients. However, the long-term effect of such therapy is uncertain. We analysed the data from 63 patients transplanted for lysosomal storage diseases. The transplant-related mortality was 10% if an HLA-identical sibling marrow donor was available (n = 40) and 20-25% if mismatched tissue was used. Data on the effect of bone marrow transplantation on biochemical and clinical disease variables were available in 29 of the 63. 28 had a follow-up duration of 1.0-10.2 years; 1 patient died of disease progression in the first year after stable engraftment. 13 patients who had severe neurological symptoms at the time of transplantation showed disease progression. Engraftment of bone marrow in 5 patients with non-neuronopathic Gaucher's disease led to complete disappearance of symptoms. 11 patients had skeletal symptoms because of various mucopolysaccharidoses (MPSs). There was stabilisation of the skeletal lesions during the observation period of 1.4-6.4 years, but none of the patients showed significant regression of the skeletal symptoms. The visceral features (hepatosplenomegaly, cardiac hypertrophy, and upper airway obstruction) in these patients abated after transplantation. We could not evaluate the biochemical and clinical variables in 34 patients because of graft rejection, transplant-related mortality, or follow-up of less than 1 year. There were significant beneficial effects of bone marrow transplantation in patients with non-neuronopathic Gaucher's disease. Stabilisation of disease was observed in patients with MPS-I and MPS-II; this potential benefit needs to be confirmed by longer follow-up. Bone marrow transplantation was not effective if severe neurological symptoms were already present at the time of transplantation.

Ganciclovir which has proved effective in the treatment of cytomegalovirus (CMV) infection was given prophylactically to 40 bone marrow transplant (BMT) patients pre and post-transplant in seropositive patients and post-transplant in seronegative patients with a seropositive donor. All patients were transfused with screened blood products and 33 received CMV hyperimmune globulin. They were compared with an historical control group consisting of 39 patients who had received significantly more unscreened blood products (p = 0.01) and less HLA-mismatched marrow transplants (p = 0.05). Toxicity of ganciclovir was hematological-neutropenia was responsible for cessation of the drug in seven patients and transfusion requirements were significantly higher in the ganciclovir group. Non-hematological toxicity did not occur in any patient. Only one patient (2.5%) experienced symptomatic CMV infection and no patient developed CMV pneumonitis. In contrast, in the control group, 23 (59%) patients had clinical symptoms of CMV infection (p0.0001) and 4 (10%) experienced CMV pneumonitis (p0.01). Ganciclovir significantly reduced the incidence of positive CMV antigenemia (7.5% in the treated group vs 72% in the control group; p0.01). However, ganciclovir delivery did not result in an improved overall survival due to a higher rate of regimen-related deaths and chronic GVHD mostly in patients transplanted from an HLA-mismatched donor. The prophylactic administration of ganciclovir abrogates CMV pneumonitis and considerably reduces the incidence of CMV infection in BM recipients at high risk of developing this disease after transplantation.

Bone marrow transplants are being increasingly used to treat a broadening spectrum of serious pediatric conditions including hematologic, metabolic, and immune disorders. A common adverse effect is slowing of statural growth which, according to the author's experience, reaches 0.4 SD a year on average in the highest risk group with progressive graft-versus-host disease after whole body irradiation and transplantation of an allograft. Growth was normal in autograft recipients treated by moderate-intensity chemotherapy. High-dose chemotherapy, in particular with busulfan and cyclophosphamide, has been reported to cause growth retardation. The mechanism of failure to gain height is complex. Partial growth hormone deficiency is rare. Relative resistance of growth plates is the most likely mechanism. The role and efficacy of growth hormone replacement therapy is unclear. Conditioning regimens can affect ovarian and testicular function. Peripheral thyroid resistance can occur after whole body irradiation and transplantation of an allograft. The high rate of growth and endocrine disorders warrants close monitoring including full evaluations of growth and pubertal development as well as periodic endocrinologic investigations.

Fifteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (3/y) vaso-occlusive crises (VOC) associated with recurrent acute chest syndrome episodes (n = 10), osteitis (n = 3), osteonecrosis (n = 3), strokes (n = 3) or frequent massive deglobulisation (n = 2). Two children undergone splenectomy, two were chelated and two had an erythroid allo-immunization. Ethnic origins were from various countries in Africa (n = 11), North-Africa (n = 3) or West Indies (n = 1). At BMT, they were 2y 3m to 14y 9m old (mean: 8y 7m). Donors were AS (n = 11) or AA (n = 4). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n = 13) or 260 mg/kg (n = 2); BU: 14 mg/kg (n = 1), 16 mg/kg (n = 9),16 mg/kg (n = 5); one patient received also TLI and the last two anti-thymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n = 4) or CSA plus short-term MTX (n = 11). Median follow-up is 28 months (5 m to 53 m). All patients had an engraftment (d12 to d32) with a stable total chimerism in 10/14 patients. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (35 m follow-up) without any manifestation of SCD, with a high stable 22% Hb F level.(ABSTRACT TRUNCATED AT 250 WORDS)

Fourteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (4/y) vasoocclusive crises (VOC) and recurrent acute chest syndrome episodes (n:10), osteitis (n:3), osteonecrosis (n:3), strokes (n:3) or frequent massive deglobulisation (n:2). Two children undergone splenectomy, 2 were chelated and 2 had erythroid allo-immunization. Ethnic origins were from various countries in Africa (n:10), North-Africa (n:3) or West Indies (n:1). At BMT, they were 2y 3m to 14y 9m old (mean:8y 7m). Donors were AS (n:11) or AA (n:3). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n:12) or 260 mg/kg (n:2); BU:14 mg/kg (n:1), 16 mg/kg (n:9),16 mg/kg (n:4); 1 patient received also TLI and one other antithymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n:4) or CSA plus short-term MTX (n:10). Median follow-up was 23 months (8 m. to 48 m.). All patients had an engraftment (d13 to d32) with a stable total chimerism in 10/14 patients who are cured. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (28 m. follow-up) without any manifestation of SCD, with a high stable 22% Hb F level. One patient developed an aplastic anaemia 15 m after BMT: a second BMT was achieved 21 m after the first one with engraftment and total chimerism. Two patients have a relatively stable partial chimerism with still undergoing CSA therapy (11 m. and 23 m. follow-up).(ABSTRACT TRUNCATED AT 250 WORDS)

We report the case of a young woman whose son had X-linked chronic granulomatous disease (CGD) while she was gene transmitter and presented with erythematous-squamous dermatosis predominant in unprotected regions, photosensitivity and oral ulcerations. The diagnosis of discoid lupus erythematosus, suggested by the clinical complex, was not confirmed by paraclinical examinations. CGD is an X-linked or, less often, autosomal recessive disease underlain by a selective deficiency of intraleucocytic bactericidal ability. Its clinical manifestations are repeated and severe infections involving most of the body organs. A review of the literature yielded 20 cases resembling that of our patient; all concerned mothers or sisters of children with X-linked CGD. The skin disease usually begins during childhood. The authors describe cutaneous manifestations as a photosensitive infiltrating erythema, frequently suggestive of lupus erythematosus, and oral ulcerations. At light microscopy, these skin lesions show a lymphohistiocytic infiltrate which sometimes erodes the basement membrane or remains at a distance from it. Such images suggest lupus erythematosus or, for some authors, a Jessner-Kanoff syndrome or a lichenoid infiltrate. Direct immunofluorescence was negative in all but one case, and there was usually no laboratory evidence of autoimmunity. In women who transmit the X-linked form of the disease, the bactericidal activity of granulocytes is reduced by 50 p. 100, but infection is not a major problem. The pathogenesis of these disorders is not yet fully understood. However, we would like to draw attention to the studies by Roberts et al. who demonstrated a defective degradation of bacterial DNA by circulating monocytes in patients with systemic or discoid lupus erythematosus.(ABSTRACT TRUNCATED AT 250 WORDS)

Seventy-four children with juvenile chronic arthritis were entered into a 6-month, multicenter, comparative double-blind study of the efficacy of D-penicillamine versus placebo. The results were evaluated in 70 patients, 55 of whom completed 6 months of the study. Improvement was observed in the total number of stiff joints, total number of painful joints, and total severity index measuring joint pain. There was also a significant reduction in the concurrent use of nonsteroidal anti-inflammatory drugs. D-penicillamine was well-tolerated in all but 2 patients. Some children in the placebo group exhibited definite improvement; however, relapses that were observed were mainly in that group. These results confirm the efficacy of D-penicillamine for the treatment of joint involvement in juvenile chronic arthritis.

The case of a 14 year-old adolescent girl presenting with paroxysmal nocturnal hemoglobinuria (PNH) associated with aplastic anemia is reported. This disease, rare in children, is characterized by an acquired hemolytic anemia, with abnormal sensitivity to complement: PNH actually affects the bone marrow stem cell. This explains its possible association with any type of malignant blood disease and with aplastic anemia. When aplastic anemia is the first sign of the disease, diagnosis is delayed, due to the possible negative response of the specific Ham's test. Therefore, the proper complications of PNH, especially thromboses, may be misappreciated and poorly managed.

A 5-yr experience of massive therapy and autologous bone marrow transplantation (ABMT) for Burkitt's lymphoma is reviewed. Thirty courses were given to 28 patients. Three patients were in resistant relapse and all three died before day 54 post ABMT. Thirteen patients were in non-resistant relapse and seven are alive with non-evidence of disease (NED). All three patients grafted in partial remission (PR) are alive NED including two with initial central nervous system (CNS) disease. Nine patients were grafted in 1st complete remission (CR) either because of long delay to achieve CR [3] or as consolidation in those with initial CNS involvement [5] or leukaemia [1]. Three of these nine are alive including 2 3 with a long delay to CR and 1 5 initial CNS. The overall survival NED for the 28 patients is 46%. The median observation time post ABMT, 22 months. Clear indications for ABM T in BL are in our opinion restricted to about 20% of the patients: non-resistant relapses and PR after initial induction therapy. Massive therapy as consolidation of 1st CR after initial CNS involvement and in resistant relapses should still be considered as experimental. In 14 patients whose marrow was purged there is laboratory evidence suggesting that the purging procedures used in this study may have been incomplete. Purging techniques still require perfection at a laboratory level and their rationale should not be judged on the basis of incomplete procedures.

Lymphocytes from five children suffering from ataxia telangectasia or various unclassified immune deficiencies were tested in vitro for their sensitivity to synthetic serum thymic factor (FTS). The percentages of cells bearing T cell markers were elevated after incubation with FTS at graded concentrations (0.25, 2.5 and 25 ng/ml), by microlymphocytotoxicity or indirect immunofluorescence, using monoclonal anti-Lyt1 antibodies. In four cases, more than 30% of the non-T non-B cells acquired the Lyt1 T cell marker. These four children had low levels of circulating FTS. In the fifth child, who had a normal serum FTS level, and in two age-matched controls, there was no significant increase in the percentage of cells bearing the T marker.

Bone marrow cultures in semi-solid medium provide an estimate of progenitors in granulopoiesis and also in erythropoiesis. They are available data in leukemias and in bone marrow grafts. The cytogenetic studies of the abnormal clones show numeric and structural-abnormalities depending from the different types of leukemias and from the course of the disease.

Seventy-four children with juvenile chronic arthritis were admitted to a 6-month multicentric double blind comparative study of the efficiency of D-Penicillamine or placebo. The results evaluated in 55 patients who completed the study, indicated an improvement in the total number of stiff joints and in the total index of severity measuring joint pain and inflammation. A significant reduction of the concurrent use of non steroidal antiinflammatory drugs was also observed. The tolerance was good except in two patients. Some children in the placebo group exhibited a definite improvement.

Sixty-five children with acute lymphoblastic leukemia (ALL) underwent allogenic bone marrow transplantation (BMT) from an HLA identical donor, following cytoreduction with cyclophosphamide and total body irradiation (TBI): 15 were transplanted in 1st remission, 43 in 2nd and 7 in 3rd or in 4th. The Kaplan Meier estimate of surviving disease free at 4 years post BMT was 49.9% and the probability of continued remission at 4 years was 63.3%. Fourteen patients relapsed between 90 and 690 days (mean: 240 +/- 88) post BMT. The other causes of BMP failure included: graft versus host disease, veno-occlusive disease and sepsis. No interstitial pneumonitis has been reported. Patients who had a relapse while on chemotherapy had a higher probability of relapse than those who had a relapse while off therapy (p less than 0.01). We conclude that allogeneic BMT is the treatment of choice for children with ALL in second hematologic remission, the interval between diagnosis and first relapse being the most significant prognostic factor. Patients with poor prognosis might benefit from a more intensive chemotherapy/total body irradiation schedule or a BMT earlier in the course of their disease.

After recalling the main studies about the fragile sites, a fra (2) (q11) in a girl with familial lymphohistiocytosis is described. The influence of medicine, inducers, mutagenic agents are analysed.

BACKGROUND Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs). METHODS The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. RESULTS Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count