Long-Term Observational Study of Chronic Granulomatous Disease About 41 Patients From Tunisia and Comparison to Other Long-Term Follow-Up Studies.

Chronic granulomatous disease (CGD) is an inherited autosomal recessive or X-Linked primitive immunodeficiency (PID), due to a defective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex impairing anti-infectious and anti-inflammatory role of peripheral blood mononuclear cells. It is characterized by severe bacterial and fungal infections and by excessive inflammation leading to granulomatous complications. This work was made over a period of 34 years on 41 Tunisian patients suffering from CGD. Cumulative follow-up of patients was 2768.5 months, median 31 months. Survival was studied by survival curves according to Kaplan-Meier method. Lymphatic nodes, pulmonary and cutaneous infections predominate as revealing manifestations and as infectious events during patients' monitoring. At study end 12 patients died mainly of invasive pulmonary aspergillosis and septicemia. Median age of death was 30 months. CGD remains compatible with a decent quality of life. Early diagnosis, anti-infectious prophylaxis, and initiation of adequate management, as soon as complication is perceived, promote pretty good evolution.

Autoimmune polyglandular syndrome type II after bone marrow transplant: real transfer or acceleration of a programmed disease?

We report a case of autoimmune polyglandular syndrome type II that developed in an 11-year-old boy with homozygous sickle cell disease after allogeneic bone marrow transplant; the donor was his father, who was human leukocyte antigen identical and had vitiligo. On day 24 after transplant, the patient developed grade 1 acute graft-versus-host disease, which was controlled over a period of 3 months with corticosteroid-induced immunosuppression. Full donor engraftment was documented on day 31 after transplant, and this was further confirmed on days 59, 231, 321, 472, 549, and 720. Three months after transplant, the recipient developed adrenal insufficiency, and at 13 months, he developed vitiligo. Seventeen months after transplant, autoimmune thyroid disease, positive for thyroid peroxidase and thyroglobulin autoantibodies, was diagnosed. At the same time, we identified adrenal insufficiency in the donor. We analyzed a serum sample from the recipient for autoantibody markers for type 1 autoimmune diabetes mellitus. The sample was positive for antiglutamic acid decarboxylase. Antibody against 21-hydroxylase enzyme was also found (261 U/mL; normal value, < 1 U/mL). We conclude that the recipient developed autoimmune polyglandular syndrome type II after bone marrow transplant from his father, who was probably affected by the same syndrome.

Generalized allergy due to zinc in insulin treated with zinc-free insulin.

Allergy to insulin became a rare complication due to the introduction of recombinant human insulin preparations. Nevertheless, allergic reactions to components of such preparations can occur. We report a case of a 61-year-old man with an atopic background and affected by diabetes mellitus type 2 since 27 years, who experienced generalized allergy to insulin at the moment of switching oral anti-diabetics to insulin. Prick tests revealed an allergy specifically to zinc, and the patient was treated with zinc-free glulisine insulin. After 8 months of such treatment, patient's glucose is stable and he never experienced allergic reactions to insulin injections. Even insulin allergy due specifically to zinc is rare, such complication must be assessed especially in a patient suffering from multiple allergies.

Successful treatment of Fusarium solani ecthyma gangrenosum in a patient affected by leukocyte adhesion deficiency type 1 with granulocytes transfusions.

BACKGROUND: Ecthyma gangrenosum (EG) manifests as a skin lesion affecting patients suffering extreme neutropenia and is commonly associated with Pseudomonas aeruginosa in immunocompromised patients. Leukocyte adhesion deficiency I (LAD I) which count among primary immunodeficiency syndromes of the innate immunity, is an autosomal recessive disorder characterized in its severe phenotype by a complete defect in CD18 expression on neutrophils, delayed cord separation, chronic skin ulcers mainly due to recurrent bacterial and fungal infections, leucocytosis with high numbers of circulating neutrophils and an accumulation of abnormally low number of neutrophils at sites of infection. CASE PRESENTATION: We report at our knowledge the first case of a child affected by LAD-1, who experienced during her disease course a multi-bacterial and fungal EG lesion caused by fusarium solani. Despite targeted antibiotics and anti-fungi therapy, the lesion extended for as long as 18 months and only massive granulocytes pockets transfusions in association with G-CSF had the capacity to cure this lesion. CONCLUSION: We propose that granulocytes pockets transfusions will be beneficial to heal EG especially in severely immunocompromised patients.

Switch from beta-thalassemia major to beta-thalassemia intermedia after secondary graft failure.

In this article, we report a switch of beta-thalassemia major to intermedia beta-thalassemia after allogeneic bone marrow transplant of a 6-year-old girl from her HLA-matched brother. After stable mixed chimerism, the patient had a secondary graft rejection and returned to total recipient chimerism as assessed by real-time polymerase chain reaction assay. Nonetheless, with a medium hemoglobin rate of 89 g/L, she did not need further transfusions for 60 months after rejection. We conclude that complete loss of donor cells after bone marrow transplant for beta-thalassemia major is compatible with a stable clinical state, probably due to a gamma-globin gene demethylation that enhances gamma-globin chain production and further allows constitution of a fetal hemoglobin rate compatible with free transfusion survival.

Hemophagocytic syndrome after hematopoietic stem cell transplantation: a prospective observational study.

The aim of this prospective observational study was to evaluate the incidence of hemophagocytic syndrome (HPS) after hematopoietic stem cell transplantation (HSCT). Between July 2006 and December 2007, all patients who received a HSCT in our institution were included in this study. All the following criteria were needed for the diagnosis of HPS: sustained fever over 7 days; cytopenia (neutropenia and/or thrombocytopenia); presence of more than 3% mature macrophages in bone marrow; hyperferritinaemia (>1,000 ng/mL). During this study, 171 patients received a HSCT (68 allogeneic and 103 autologous). The median age was 32 years (3-62). We observed six cases of HPS (6/68; 8.8%) after allogeneic stem cell transplantation (ASCT): one case of EBV-related HPS, two cases of CMV-related HPS, and three cases with no evidence of bacterial, fungal or viral infections. We observed only one case of CMV-related HPS (1/103; 0.9%) after autologous stem cell transplantation. Four patients died despite aggressive supportive care. To our knowledge, this is the first prospective observational study conducted with the aim to evaluate the incidence of HPS after HSCT. This study provides a relatively high incidence of HPS after ASCT. When sustained fever with progressive cytopenia and hyperferritinaemia are observed, HPS should be suspected, and bone marrow aspirate considered. The rapid diagnosis of HPS and the early initiation of an appropriate treatment are essential for patient management.

Possible transfer of vitiligo by allogeneic bone marrow transplantation: a case report.

Among the cases yet published of development of vitiligo after BMT, only two can claim as possible adoptive transfer of such disease. We report a case of a patient with sickle cell disease in whom vitiligo developed after allogeneic BMT from his HLA identical father affected by vitiligo. We reviewed and searched for some particularities in the reported cases of post-BMT vitiligo.

Transmission of type 1 diabetes by bone marrow transplantation: a case report.

T1D after BMT constitutes a human model of autoimmune disease transmission. This case report refers to T1D onset after allogeneic HLA-matched BMT in a six-yr-old recipient affected by aplastic anemia. The donor was his sister who had T1D. The recipient had a complication free course apart from grade 1 acute GVHD, which was resolved spontaneously. With the predictive value and significance of T1D-associated autoantibodies, we tried to consolidate the T1D transfer possibility based on our patient characteristics and a literature review.

Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial.

From April 2003 to December 2006, 195 patients with de novo symptomatic myeloma and younger than 60 years of age were randomly assigned to receive either tandem transplantation up front (arm A, n = 97) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide (day + 90, 100 mg per day during 6 months) (arm B, n = 98). Patients included in arm B received a second transplant at disease progression. In both arms, autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m(2)) and granulocyte colony stimulating factor. Data were analyzed on an intent-to-treat basis. With a median follow-up of 33 months (range, 6-46 months), the 3-year overall survival was 65% in arm A and 85% in arm B (P = .04). The 3-year progression-free survival was 57% in arm A and 85% in arm B (P = .02). Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide (with second transplant in reserve for relapse or progression) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to tandem transplant in this setting. This study was registered at www.ClinicalTrials.gov as (NCT 00207805).

Bone marrow transplantation without conditioning regimen in Omenn syndrome: a case report.

OS is a non-SCID immunodeficiency characterized by a poor outcome even after BMT. We report here a case of BMT without preparative conditioning regimen, and with a successful engraftment in a five-month-old infant with OS. The patient was transplanted with 15 x 10(8) bone marrow mononuclear cells/kg, from his HLA matched brother, without preparative regimen and GVHD prophylaxis. Immunological status was assessed before and after the BMT, and the engraftment was monitored with microchimerism analysis. Six days after BMT, an acute GVHD involving first the skin, then the liver and gut, complicated the post-transplantation course. An excellent engraftment was confirmed by donor chimerism over 95% respectively at day post-transplantation 30, 60, 90, and 150. The cellular immunity of the patient was restored, and infectious complications decreased after BMT. Later the patient experienced chronic GVHD, and he died on day post-transplantation 246 from GVHD. BMT without conditioning regimen for OS is feasible, but there must be a megadose cell transplantation, and appropriate prophylactic immunosuppressive treatment to prevent acute GVHD.

[Recurrent pregnancy loss related to immune disorders]. / Pertes foetales et avortements spontanés à répétition d'origine immunologique.

Progress in immunologic methods and diagnostic assays over the last two decades has led the description of an association between some cases of recurrent fetal loss and recurrent spontaneous abortion of unknown cause to immunological factors. Some causal immunological diseases or dysregulations have been identified in pregnant women. These abnormalities may precede or be triggered by the pregnancy, or occasionally result from an impairment of the mother's allogeneic response to the fetus. In this article we review the principal immunological factors and abnormalities implicated in recurrent pregnancy loss and focusing on those generally accepted by the majority of authors.