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Genetic changes associated with Acute Lymphoblastic Leukaemia (ALL) provide diagnostic and prognostic information with a direct impact on patient management. We report the cytogenetic analysis of 298 Tunisian patients with ALL, including 183 children and 115 adults. Chromosome abnormalities have been detected in 68.2% of our patients associating clonal numerical and/or structural rearrangements. Some chromosomal abnormalities especially hyperdiploidy, 19p13 abnormalities, 8q24 translocations, 12p, 6q deletions and TCR rearrangements occur at a lower incidence compared to that reported in other populations. ALL cases (5.7%) had miscellaneous clonal abnormalities. We also found in our Tunisian series a higher incidence for T-lineage ALL more than usually described. Among structural chromosomal abnormalities, t(9;22)(q34;q11) resulting in the BCR/ABL fusion and the t(12;21)(p13;q22) resulting in the TEL/AML1 fusion were studied by FISH providing additional diagnostic and prognostic information. We conclude that although the incidence of our cytogenetic results are slightly different, their clinical significance is similar to that described in the literature.

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).

Purpose: To discuss, through a retrospective study, the epidemiologic and anatomo-clinic aspects of paediatric Hodgkin disease (HD) in south Tunisia and to study the faisability of the French protocol MDH 90 for our patients., Patients and Methods: Between January 1995 and December 2000, we treated 23 children with HD. Initial work-up included clinical examination, radiological explorations (chest X ray, abdomen ultrasonography and computed tomography scan of chest, abdomen and pelvis), biological explorations (full blood count, erythrocyte sedimentation rate, serum albumin, liver functions tests) and a bone marrow biopsy. Treatment was inspired from the SFOP MDH 90 protocol. Overall survivals and disease free survivals were estimated with Kaplan-Meier method and compared with the log-rank test., Results: Mean age was 8.6 years (4-14 years), sex-ratio was 3.6. Histological subtypes 2 and 3 had the same frequency. Localised stages (I-II) were as frequent as advanced stages (III-IV). At the end of the treatment, the 18 evaluables patients were in complete remission. The 5-year overall survival (OS) and disease free survival (DFS) were 82 and 76% respectively. Localised stages and advanced stages had the same 5-year overall survival (82%). There were no statistical differences in term of OS between the different prognosis factors studied., Conclusions: The particularity of our study was the identical frequency of the two histological subtypes 2 and 3 and of localised and advanced stages. The MDH 90 protocol is feasable for our patients with satisfactory results similar to those found in the literature.

Purpose: the aim of this study was to determine the prevalence of cobalamin (vitamin B12) deficiency in different populations of patients with clinical manifestations associated or secondary to cobalamin or folates deficiency and to analyse the demographic, clinical, paraclinical investigations in cobalamin deficient patients in Tunisia., Methods: it was a prospective (1999-2001) multicenter study of 604 patients divided into four groups. The first group is composed of 478 consecutive patients with anaemia and/or macrocytosis with megaloblastic haemopoiesis on bone marrow examination without myelodyslasic or malignancy signs. The second group is made up of 34 patients with unexplained neurological symptoms without the presence of anaemia. The third group was composed of 82 invidious with isolated psychiatric disorders and the 10 patients with Hashimoto thyroïditis constituted the last group., Results: serum cobalamin level was low in 98 %, 23%, 14% of cases, respectively, in the first three groups. Only one case of patients with Hashimoto thyroiditis has serum cobalamin deficiency. Pernicious anaemia (Biermer's disease) was established by dual isotope schilling examination in 103 patients among a sample of 120 serum cobalamin deficient patients (86%). The median age at presentation was 45.5 years. Severe chronic atrophic gastritis was diagnosed in 97.5% of patients with Biermer's disease. Serum antibodies against intrinsic factor and gastric parietal cells were detected in (42.5%) and (60.6%) patients, respectively; (25.5%) patients had the both types of antibodies. 23.4% patients were positive for antithyroid antibodies. Anti-nuclear antibodies were detected in 3% patients., Conclusion: an interesting finding of our study was the high frequency of cobalamin deficiency in Tunisia, particularly in relative young patients. Our patients had classic features of florid cobalamin deficiency (severe haematological manifestations and neuro-psychiatric disorders). The main underlying causes of such deficiencies were Biermer's disease. Subtle clinical manifestations should be recognized and investigated even in young patients at risk.

Unlabelled: Based on a case report of aplastic anemia associated with malformation, we discuss the diagnostic criteria and the nosologic problem between the 2 principal aplastic anemia accompanied with malformation: Fanconi disease and dyskeratosis congenita., Case Report: A 19-year-old girl, issued from a third degree consanguineous marriage, was admitted because of anemic and hemorrhagic syndrome. Physical examination showed several malformations: microphtalmia, brownish spots, generalized hyperpigmentation and ungueal dystrophy without mucosal leucoplasia. Statural and ponderal retardation were noted. On the hemogram there was a pancytopenia and on biopsy, the bone marrow was desertic. The caryotype performed on peripheral blood lymphocytes after sensibilisation with mitomycin C revealed chromosomal instability aspects. Based on these clinical and biological features, the diagnosis of hereditary aplastic anaemia was retained. The patient was given norethandrolone. She died 3 months later by septic shock., Discussion: Coexistence of aplastic anemia with a malformative syndrome suggests most probably an hereditary form of aplastic anemia. Fanconi anemia is the most frequent. It associates characteristic anomalies of the face, with microphtalmia, brownish spots, statural and ponderal retardation, and thumb anomalies. Ungueal dystrophy, mucosal leucoplasia are almost pathognomonic of congenital dyskeratosis. When the malformative syndrome is not characteristic, the cytogenetic study may also fail to make the differential diagnosis, as was the situation in our case.

Factor XIII deficiency is a rare autosomal recessive congenital disorder of haemostasis characterised by a plasmatic factor XIII level less than 1% in homozygote and bleeding as of the youth. We report a study about ten patients with congenital factor XIII deficiency from seven south-Tunisian families, there are seven females. Umbilical bleeding was common and only two patients had intracranial bleeding. The standard screening tests are normal. Factor XIII activity was less than 1% in all patients. A sub-unit A deficit was detected for the ten patients. Out hemorrhagic context, five patients receive regular prophylactic transfusion with fresh frozen plasma.

Subacute necrotizing lymphadenitis or Kikuchi-Fujimoto disease is a benign pathological entity diagnosed chiefly in young adults. We report a case in a 20-year-old woman who presented with swollen lymph nodes and a fever. Disseminated lymphadenopathy with nodes measuring up to 6 cm in diameter was found upon physical examination. The erythrocyte sedimentation rate was elevated to 40 mm/h and the lactic dehydrogenase level to 593 IU/l. Findings were negative from serological tests for rubella, hepatitis B, hepatitis C, HIV, and toxoplasmosis, as well as from tests for tuberculosis. A biopsy of a cervical lymph node showed nonsuppurative necrosis, karyorrhexis, and a marked histiocytic reaction consistent with Kikuchi-Fujimoto disease. No treatment was given, and a full recovery was achieved within 3 months. In this patient, the disseminated lymphadenopathy and constitutional symptoms strongly suggested a hematological malignancy and more specifically a lymphoproliferative disease.

The purpose of this study was to examine the effects of long-term rugby participation on bone mineral content (BMC) and density (BMD) of male rugby players and to determine if the diverse stimuli elicited by the actions of forwards and backs affect their skeleton differently. Dual energy X-ray absorptiometry (DXA) scans were obtained from 20 male rugby players (10 Forwards and 10 Backs) who actively participated in rugby for the past 13 yr, and from 29 age matched non active subjects of the same ethnic origin. Both groups (rugby players and controls) had comparable age (23.6 +/- 3.7 yr vs. 25.6 +/- 3.4 yr), height (178.1 +/- 4.0 cm vs. 178.3 +/- 6.0 cm), and body fat percentage (14.2 +/- 4.4 vs. 16.5 +/- 5.1). Rugby players showed greater total body mass, and greater total lean and fat body masses than control subjects (p < 0.01). Whole spine BMC and BMD were 52 % and 15 % higher, respectively, in the rugby players than in the control subjects (p < 0.001). Furthermore, rugby players displayed higher skeletal BMC (40 %, 37 % and 58 % for legs, arms and pelvis, respectively) and BMD (16 %, 21 % and 17 %, respectively) than controls. Within the rugby group, forwards were taller, heavier and had greater body fat percentage, and greater total lean and fat body masses than backs (p < 0.05 to p < 0.001). Likewise, BMC, BMD and bone area for the whole body and at specific sites such as arms, spine and legs were also greater in the forwards (p < 0.05 to p < 0.001). Long-term rugby participation, starting at pubertal age, is associated with markedly increased BMC, BMD and bone size at all skeletal sites, except at the head. The musculo-skeletal adaptations, greater in forwards than in backs, could mimic training responses and therefore explain the bone features, localized in specific stressed regions.

The molecular analysis of chromosomal abnormalities associated with hematological malignancies allowed the identification of genes involved in theses rearrangements as well as of some recurrent mechanisms. Polymerase chain reaction (PCR) tools are now available to detect these rearrangements, allowing a better follow-up of these diseases. Chronic myeloid leukemia is a myeloproliferative disorder characterized by a reciprocal translocation t(9;22)(q34;q11) which results in a bcr-abl fusion gene. Retro-transcription polymerase chain reaction (RT-PCR) is used to detect bcr-abl to establish diagnosis and to monitor patients. We report here the results of 30 patients samples tested in the hematology laboratory at Pasteur Institute, diagnosed as chronic myeloid leukemia and monitored with RT-PCR. Our results highlight the interest of molecular tools to diagnose and monitor patients mainly when cytogenetic techniques are irrelevant such as cases with complex chromosomal rearrangements or when patients achieve Philadelphia negativity after treatment.

Objective: To investigate the response of the somatotrope axis (insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3)) to intense exercise in relation to tiredness., Methods: The study involved 11 rugby players who completed a questionnaire intended to evaluate fitness or, conversely, overtraining and who agreed to plasma samples being taken before and after an international rugby match., Results: The main finding of our study is that we observed strong negative correlations between IGF-1 (r = 0.652) and IGFBP-3 (r = 0.824) levels and the overtraining state estimated using the French Society of Sport Medicine questionnaire. In particular, there was a fall (of up to 25%) in IGFBP-3 levels after the match in the more fatigued subjects compared to an increase (of up to 40%) in fit subjects., Conclusions: A fall in IGFBP-3 in response to an intense bout of exercise may represent an index of tiredness in highly trained sportsmen, as indicated by the scores obtained from the overtraining questionnaire.

Thalidomide-dexamethasone therapy was given in patients (<61 years) with previously untreated symptomatic multiple myeloma. The aim of this study was to assess the efficacy and toxicity of this combination as first-line therapy, and to determine its effect on stem cell collection and engraftment. During first-line therapy, thalidomide and dexamethasone were administered for 75 days (200 mg/day) and 3 months, respectively. The monthly dose of dexamethasone was 20 mg/m2/day for 4 days, with cycles repeated on days 9 to 12 and 17 to 20 on the first and the third month of therapy. After first-line therapy, a collection of peripheral blood stem cells (PBSC) was performed. Between May 2003 and September 2004, 60 patients were included. On an intent-to-treat basis, the overall response (> or =partial response) rate was 74%, including 24% of patients who obtained a complete remission. Grade 3-4 toxicities consisted of infections (12%), deep-vein thrombosis (3%), constipation (5%), and neuropathy (5%). A total of 58 patients (96%) proceeded to PBSC mobilisation and yielded a median number of 8 x 10(6) CD34+ cells/kg. First-line thalidomide-dexamethasone therapy is effective and relatively well tolerated in young patients with symptomatic multiple myeloma. This combination does not affect PBSC mobilisation.

We report the case of a 8-year-old girl diagnosed with myelodysplastic syndrome. This case was morphologically characterized by the presence of bundle of Auer rods in the neutrophils. The evolution of the disease was marked by a quick transformation in a acute myeloid leukaemia with t(8;21) refractory to treatment. We reviewed the literature for clinical, biological and therapeutic features of this rare childhood hemopathy.

Introduction: Glanzmann's thrombasthenia (GT) is a rare congenital thrombopathy, with a recessive autosomal transmission. We present here the genealogic study of a series of patients suffering from GT., Patients and Methods: This is a retrospective study about all the GT patients treated in Sfax hematology department during 18 years. Final diagnosis was established by agregometry. Genealogic study was based on clinical history., Results: 17 cases of GT from 11 families from the south of Tunisia wen collected. The disease was paricularly frequent in the region of Moulares-Gafsa (7 patients). The percentage of consanguinity was also very high (82%), with a third degree consanguinity of 86%. Family investigation revealed 6 previously unknown cases, and 10 deaths subsequent to hemorrhagic manifestations., Conclusion: The high rate of consanguinity, the absence of clinical or biological manifestations in the parents, and the ratio of ill to normal subjects in the same family which was about one to four, are suggestive of an autosomal recessive mode of transmission.

From July 1992 to December 2000, 288 cases of monoclonal gammapathy (MG) were collected at the university hospital of Sfax. The middle age of the patients at the time of the diagnosis was 62 years and 7 months with extremes to 18 months and 99 years and median to 64 years. One hundred and eighty-two patients were men and 106 women. Among the 270 observations for which aetiology has been established, 73 were classified MG of undetermined significance (MGUS), 160 myeloma (or plasmocytoma) and 37 other malignant MG (Waldenstrom's macroglobulinemia: 13, lymphoma: 9, alpha heavy chains disease: 6, primary amyloidosis: 5, chronic lymphocytic leukaemia: 4). Rheumatological affections (19.2%), infections and renal failure (10% each), haematological and autoimmune diseases (9.6% each) were pathologies most often associated with MGUS. Agarose gel electrophoresis did not show a monoclonal peak in 16% of the cases. In the 242 patients with a peak on electrophoresis, the peak was in the beta zone in 22% of cases and in the gamma zone in 78% of cases. The IgG isotype represents more than the half of the cases of our set (51.7%). IgG is even more predominant in the MGUS group (65.8%). The IgA isotype counts for 20.8% of the cases in our set and the free light chains (kappa or lambda) for 13.6% of the cases whereas the IgM represents 8.7% only of the 288 cases of our set which involves three cases of IgD myeloma and six cases of biclonal gammapathy.

We report on the effectiveness of molecular studies regarding Fanconi anemia (FA) for a better selection of bone marrow graft donors and for post-transplant follow up. Ten unrelated FA patients and their families were analyzed by microsatellite markers. In 9 cases, the cytogenetic investigation of potential human leukocyte antigen (HLA)-identical related donors was normal, and the molecular analyses confirmed that they were also either normal or heterozygous carriers. For 1 patient, cytogenetic analysis of an HLA-identical sibling donor yielded ambiguous results with a relatively high number of chromosomal breakages using cross-linking agents. However, genotyping of this potential donor demonstrated his heterozygous state. Nine patients have received allogeneic bone marrow transplantation from HLA-matched related donors. Microsatellite analysis showed complete chimerism (CC) in all cases. The median follow up was 54 months (range 8-144 months). One patient out of 9 with CC rejected her graft without prior detection of a transitional mixed chimerism. Among these patients, 1 died 25 months after the transplantation of a chronic graft-versus-host-disease (GVHD). We conclude that, when the cytogenetic studies are not conclusive, molecular analyses are crucial to distinguish heterozygous carriers from asymptomatic FA Tunisian patients. Molecular analyses also allowed the evaluation of hematopoietic chimerism after allogeneic bone marrow transplantation and might be of value to identify patients with a high risk for graft rejection.

Gaucher's disease is an uncommon inborn recessive autosomal disease, due to a deficient activity of the lysosomal enzyme beta glucocerebrosidase. This disease is usually diagnosed in the first or second decade of life with the arising of bone pains, splenomegaly and hemorragic manifestations due to thrombocytopenia. When the enlarged spleen is not evident, or after splenectomy, patients may be mis-identified as having Gaucher's disease. We present here two cases of elderly patients aged 70 and 46 years respectively, in whom the disease was a surprising finding of bone marrow examination, during check up for pancytopenia.

Unlabelled: Gaucher's disease is one of the rare lysosomial disease that could receive substitutive enzymatic treatment which may improve considerably the prognosis of certain forms. The purpose of this work is to study the epidemiology of the disease in Tunisia, to highlight the diagnostic and therapeutic difficulties and also to precise our subsequent needs for substitutive medication., Patients and Methods: We have conducted a retrospective survey of the hospital wards that were susceptible to take care of patients having Gaucher's disease. These wards are the paediatric, neonatology, internal medicine, haematology, neurology and cardiology wards., Results: In this study we have observed 27 cases of Gaucher's disease over a period of 18 years (1983-2001). The age at onset ranges from birth to 73 years of age, with an average age of 14.5 years. According to the age at onset and the clinical presentation, we classify our patients into: 20 cases of type 1 (74%), three cases of type 2 (12%), and three cases of type 3 (12%), and one case of unspecified type.Gaucher's disease type 1: The age at onset ranged from 10 months to 73 years with an average of 19 years. The main clinical signs that we have observed were splenomegaly, hepatomegaly, pallor, haemorrhagic appearance and also osteoporosis and bone pain observed in 40% of the cases. The diagnosis was based on histology showing the Gaucher's cells in various tissues while the diagnosis obtained by the dosage of glucocerebrosidase took place only in 50% of the cases. The treatment has always been symptomatic (analgesics, transfusion). A splenectomy was performed in 47% of the cases and none of the patients received a specific treatment. The follow-up period ranged from 1 month to 18 years with an average follow-up of 4 years. Among the 12 patients having a follow-up of at least 1 year, we have noticed an improvement after splenectomy in three cases, a stability in three cases and two worsening cases dealing mainly with bone problems. One patient aged 73 died from respiratory problem and three were lost to follow-up. Gaucher's disease type 2: We have observed three cases of Gaucher's disease type 2 diagnosed at 1 day, 45 days and 3 months of age. The visceral manifestations were serious and the neurological features included seizures, hypertony, ocular-nerve palsies and psychometric decline. The three patients died. Gaucher's disease type 3: Three patients were probably suffering from Gaucher's disease type 3 with visceral manifestations observed at the ages of 9 months, 1 year and 3 years, and also neurological signs observed at respective ages of 2.5 and 3 years. Two patients died and the remaining one was lost to follow-up., Conclusion: Gaucher's disease is not exceptional in Tunisia. Type 1 is by far the most common one. We have noticed some insufficiency in the diagnosis as the glucocerebrosidase enzymatic dosage was performed only in 50% of the cases as well as therapeutic insufficiency with no prescription of the specific treatment.

Competition is a more demanding situation than other strenuous exercise of equivalent duration; it results in stronger physiological changes. The object of this study was to get information on the duration of the recovery period by measuring changes of saliva cortisol [C], testosterone [T] and their ratio T/C in a group of international rugby players ( n=20) during the week following a rugby match (6 days). Using non-invasive saliva assays, we were able to take samples during the day of competition and the post-competitive days. Hormone levels were assayed with a routine in-house radioimmunoassay (RIA) method. Throughout the competition, C levels increased sharply (about 2.5-fold compared resting values) and returned to basal values within 4 h. Conversely, the T level decreased slightly. During the recovery period, C levels were lower and T levels were higher than basal values, resulting in a very high T/C ratio until the 5th day. This high post-competitive T/C ratio phase is probably required to restore the break-down of homeostasis induced by the very hard mental and physical strain associated with a rugby match. Thus, a period of 1 week recovery appears to be the minimal duration between two competitions.

Introduction: Progressive multifocal leukoencephalitis (PML) must be evoked in patients presenting with a systemic disease during which multiple neurological deficiencies rapidly worsen., Observation: A 17 year-old girl suffering from histologically confirmed polymyositis was treated with corticosteroids. Two years after the diagnosis she exhibited global signs of cerebral damage with fever and magnetic resonance imaging evoked leukoencephalitis., Comments: An affection of the central nervous system, PML is characterised by the existence of multiple areas of demyelination in the hemispheric white substance of the cerebral trunk and sometimes the cerebellum, whereas the grey substance is usually spared. This entity occurs more frequently in HIV-infected patients, but also in patients in whom the immunodeficiency may have other causes, such as the treatment for a systemic disease for example.

Stickler syndrome, also called hereditary arthro-ophthalmopathy is a dominant disorder, with poly-epiphyseal dysplasia resulting in early osteoarthritis. It usually includes bilateral myopia, that changes little during the follow up period, but can lead to retinal detachment. Children with Stickler syndrome can show facial dysmorphism that may improve with age, but severe anomalies may exist such as Pierre Robin sequence. Our case, a woman, 20-year-old, presents chronic polyarthritis which is an unusual feature of this disease. The diagnosis of Stickler's syndrome is based on polyepiphyseal dysplasia in skeletal radiography and bilateral myopia. Otherwise, this patient has no facial dysmorphism.

In this report, we studied the frequency, the types and the prognosis value of the Durie and Salmon's classification of radiological bone lesions in multiple mycloma. Our study concerned 52 patients presenting multiple myeloma, defined according to South West Oncology Group criteria, collected during nine years (1988-1996). Radiological anomalies were noted in 89% of the cases. When we compared the medial survival and the 5 years survival rate in the different groups, we found a statistically significant difference with a better survival for groups 0,1,2 considered all together as compared to group 3 patients (p = 0.0155), (71% versus 37%). According to our series, prognostic value is obviously significant when comparing groups 0, 1, and 2 to group 3.

A group of 139 patients with de novo acute myeloid leukemia were investigated to determine the prognostic significance of karyotype on early death, complete remission, continuous complete remission and survival. There were 27 children and 112 adults. Mean age was 32 years. t(15;17) was found associated with a high rate of early death and a diploid karyotype with long continuous complete remission. The presence of a structural change was predictive of shorter survivals. The study of the prognostic impact of recurrent anomalies reveals a good prognostic impact for normal karyotype (1 year survival probability: 40%), followed by t(8;21) (1 year survival probability: 24%), and by t(15;17) (1 year survival probability: 9%).

Cytogenetic studies were performed on 117 Tunisian patients with de novo myelodysplastic syndromes (MDS). According to the French-American-British (FAB) criteria 40 patients presented with refractory anaemia (RA, 34%), eight with refractory anaemia with ringed sideroblasts (RARAS, 7%), 19 with refractory anaemia with excess of blasts (RAEB, 16%), 16 with refractory anaemia with excess of blasts in transformation (RAEB-t, 14%), 18 had chronic myelomonocytic leukaemia (CMML, 15%) and 16 unclassifiable MDS (14%). Seventy-five were men and forty-two were women. Five were children and 112 were adults with a median age of 58 years. Fifty-five per cent of the patients presented clonal chromosome abnormalities. Rates of abnormality varied from one FAB subtype to the other: 55% in RA, 75% in RARAS, 63% in RAEB, 75% in RAEB-t and 28% in CMML. The most frequent chromosome abnormalities were del(5q) (22 cases), monosomy 7 (12 cases), del(12p) (6 cases), and trisomy 8 (5 cases). Rare abnormalities were also found: ring of chromosome 12 and trisomy 15. Conventional cytogenetics remains the basic technique in identifying chromosomal abnormalities associated with MDS.

Through a national retrospective study, the authors report the clinical and hematological characteristics of 124 acute lymphoblastic leukemia of the adult diagnosed during 5 years (1993-1997). The national prevalence is of 0.28/100.000 inhabitants/year. The sex-ratio is of 1.3. Sixty six per cent of patients were 16-35 years of age, and only 10% of them were more than 60 years of age. A tumoral syndrome was present at 71% of the cases with peripheral adenopathies in 55%, splenomegaly in 40%, hepatomegaly in 19% and a mediastinal tumor in 18% of the cases. The bone pain were rarely signaled (10%) and neuro-meningeal affection was found in only 3% of cases. There was no testicular lesions. The white blood cells count was less than 30.000/mm3 in 60% whereas an important hyperleucocytosis superior than 100.103/mm3 was observed in 20% of the cases. Anemia and thrombopenia were noted in 94% and 90% of the cases respectively. Acute lymphoblastic leukemia typing by cytological study of Bone marrow according to the Fransh-American-Britain criteria (FAB) had found 43%, 48% and 4% for type 1,2 and 3 respectively. In 5% of the cases the type of the acute lymphoblastic leukemia was not precised (diagnosis based on the Bone biopsy).

This paper presents the results of a cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia (AML), including 27 children aged 1-15 years and 112 adults. Mean age was 32 (range 1-75) and the M/F ratio was 1.43. Of our patients, 45% had apparently normal karyotypes. Acquired chromosome aberrations were found in 77 (55% ) patients. t(8;21) was identified in 27 patients (19%); t(15;17) in 13 patients (9%); deletion 7q or monosomy 7 in seven patients (5%); +8 in seven patients (5%); abnormal 16 in four patients (3%); 11q23 rearrangements in two patients (2%) and del(5q), in one patient (1%). The remaining 16 patients had miscellaneous clonal abnormalities. Specific translocations associated with the FAB type were found: t(8;21) with AML2 and t(15;17) with AML3. We concluded that our study in a Tunisian population confirmed the relation between some specific abnormalities and the FAB classification. We found a higher incidence for t(8;21) than usually described.

A hundred and eight patients less than 60 years old with de novo acute myeloid leukemia were treated between 1982 and 1994 by protocols including final intensification with a transplant using autologous bone marrow purged by mafosfamide in first remission in the absence of an HLA-matched sibling donor available for allograft. From 1989, we attempted to improve tumor control by using high-dose anthracyclines in induction, by increasing from one to two the number of consolidation courses pre-transplant and by introducing intermediate doses of cytarabine in the first consolidation course. The CR rate was 77% (33/43) before 1989 and 90% (59/65) after 1989 (P = 0.06). Forty-five out of the 59 patients (76%) who achieved CR after 1989 could undergo bone marrow grafting in CR1 vs 16/33 (48%) before 1989 (P = 0.01). In spite of the higher proportion of patients above 50 years after 1989 (32%) toxicity was mild and an adequate graft was obtained more frequently after one collection. The principal factor relating to improvement in graft feasibility was the post-1989 modification of induction and consolidation regimens. This improvement in graft feasibility was associated with a better disease-free survival (DFS) (48 +/- 7% vs 32 +/- 8%, P = 0.04) and overall survival (OS) (53 +/- 6% vs 30 +/- 7%, P = 0.007) at 5 years. By multivariate analysis four factors were associated with overall survival (OS): karyotype, white blood cell count at diagnosis, treatment regimen and bone marrow grafting in CR1. This global approach should be prospectively compared with intensive chemotherapy.

Pleural effusion caused by plasma cell involvement in multiple myeloma has been reported unfrequently, and has been described at a frequency below 1% of multiple myeloma. In this study, we report an observation with pleural effusion as first symptom of multiple myeloma. The analysis of the pleural liquid showed plasma cells with a monoclonal IgG Kappa immunoglobulin. In addition, there was a bone marrow infiltration by plasma cells, a serum monoclonal immuno-globulin of the same type and osteolytic lesions. Our patient has received one course of chemotherapy with: vincristine, melphalan, cyclophosphamide and prednisone. The patient did not respond to the therapy and died one month later. Pleural effusion seems to be an expression of aggressive myeloma. Survival exceeds rarely 4 months.

We report a retrospective study of 42 cases of lymph node tuberculosis. We noted symptoms of tuberculosis impregnation in 92%, cervical localization in 71%, positive tuberculin intra-dermo-reaction in 77%, and accelerated erythrocyte sedimentation rate in 73% of the cases. Koch bacillus was detected in expectoration, urine or gastric liquid at the rate of 11% of the cases. Lymph node function was suggestive in 4 out of 12 patients, showing giant cells with or without caseum. Lymph node biopsy, performed in 32 patients, was contributive in 94% of them. Another tuberculous localization was found in 14 cases mainly pulmonary (8 cases).

Background: Hemoglobin abnormalities constitute a public health problem in many countries in the world. In Tunisia, these disorders were thought to affect only the North-western population. However, the existence of hemoglobinosis concentration in Kebily in south Tunisia has been suggested by previous work. In order to estimate their frequencies, we performed a screening of hemoglobin abnormalities in the North-Kebili region, to establish a prevention program of the homozygous forms., Methods: This screening concerned all 1st and 2nd grade primary school pupils in North Kebily. After a questionnaire, a blood sample was drawn from every child. Hemogram, sickling test, and hemoglobin electrophoresis at alkaline pH were performed for all children. Hemoglobin electrophoresis at acid pH and a specific hemoglobin A2 titration were performed for some children., Results: The study concerned 1,400 children, aged between 5 and 12 years, the mean age was 7 years and 7 months +/- 10 months. Consanguinity rate and coefficient were respectively 44% and 2249 x 10(5). Endogamy was very high. The global rate of hemoglobin abnormalities was 9.4%. Drepanocytosis with a rate of 4.9% was the most frequent, followed by beta thalassemia (3.1%) and C hemoglobinosis (1.6%). These abnormalities were unequally distributed; very frequent in some localities, they were quite absent in others., Conclusions: This study revealed a hemoglobinosis concentration in Tunisia, which can be classified second after that of Beja in North-western Tunisia. The heterogeneous distribution of the hemoglobin abnormalities in North-Kebili region and the high consanguinity and endogamy rates constitute factors that promote homozygous and double heterozygous forms to arise and justify the elaboration of a preventive strategy.

Background: To report the epidemiologic, clinical, biological features and course of Fanconi's anemia in southern Tunisia., Patients and Methods: During a period of 12 years we observed 43 cases. For each patient, careful clinical, biological (hemogram, myelogram, bone marrow biopsy, hemoglobin electrophoresis, karyotype) and radiological (skeleton X-rays, abdominal echography and intravenous urography) examinations were performed. All the patients who were at a pancytopenia stage were given androgens. None had a bone marrow allograft., Results: There were 24 girls and 19 boys. The mean age at diagnosis was 10 years and 9 months. The familial character was present in 53% of the cases. The most frequent initial complaint was anemic syndrome (69%). In ten cases (24%), the diagnosis has been established during a familial investigation. Malformations were present in all cases (abnormal pigmentation: 86%; skeletal maturation retardation: 83%; facial dysmorphy: 76%; statural hypotrophy: 65%; bone abnormalities: 53%; renal malformations: 44%). Anemia was present in 88% of the cases, thrombocytopenia and neutropenia in all cases. Bone marrow was hypoplastic or aplastic in all cases on biopsies. Spontaneous chromosomal breaks were found in 79% of the studied cases. Fetal hemoglobin was increased in 80% of the studied cases with a mean level of 20.5%. Actuarial survival rate at 5 years was 48%, but long survival durations were rare (eight out of 43 patients)., Discussion: This disease, rare in the world, seems to be frequent in southern Tunisia. A normal karyotype (with classical techniques), found in five patients, could not discard the diagnosis; for this reason, the use of sensitizing agents should improve the sensitivity of the test. Besides, an increased level of fetal hemoglobin enabled us to suggest the diagnosis in some cases. Androgenotherapy increased the survival duration to more than 5 years in eight patients. However, bone marrow allograft remains the only possibility of cure.

Between January 1994 and June 1995, 19 cases of nasopharyngeal carcinoma, classified N2-N3 (AJC/UICC 1987) were treated by neoadjuvant chemotherapy including cisplatin 100 mg/m2 on day 1 and epirubicin 80 mg/m2 on day 1. Following course started on day 21. A clinical and scannographic evaluation was made after 3 courses of chemotherapy. Fifty-eight percent of the patients were N3. Seventy-four percent were T3-T4. Tolerance to chemotherapy was good in 100% of the cases. A functional improvement was obtained in 14 among 16 patients who were initially symptomatic. For lymph nodes, an objective response (OR) was observed in all patients. The response was complete (CR) in 53%. A regression of primary tumor was obtained in 68% of the patients, but it was complete in 16% only. Sixty-nine percent of the patients has have a tumoral OR have a lymph node CR. Ninety percent of the patients with a complete lymph node response have a tumoral regression more than 50%. A correlation seems likely between the importance of the tumoral and the lymph node responses.

This is a retrospective study on the use of cytarabine at low doses in acute myeloid leukemias in 41 patients. Four groups of AML are included: group A: 19 cases of de novo AML in elderly patients; group B: ten cases of AML in relapse; group C: five cases of AML refractory to previous treatment and group D: seven cases of secondary AML. Cytarabine was given subcutaneously at the dose of 10 mg/m2 of body surface, for 21 days per month for the first course; then 15 days per month for the following courses. The response rates were 42, 20, 0, and 43% respectively for the A, B, C, and D groups. A complete remission was attained in only 15% (six patients). Extra haematological tolerance was excellent. Infection complications were noted in 66%, whereas a severe neutropenia was observed in 34% of patients. Hemorrhagic complications were more rare (20% of patients). The mean duration of complete remission was 10 months. The median survival was 10.5 months (2 to 31 months) for the responder patients, and 2.4 months (1 to 7 months) for the non-responders. Cytarabine at low doses seems to be a good indication for first intention treatment of AML in elderly patients. It does not give a bone marrow aplasia, the infection and hemorrhagic episodes are less numerous than with conventional dose chemotherapy, the life quality is improved, and treatment at home is often possible.

Aplastic anaemia is a potentially fatal haematopoietic disorder whose aetiology is not yet clarified. In our preliminary study we have introduced cyclosporin in the aplastic anaemia treatment to evaluate its effect on the disease evolution. Ten aplastic anaemia patients, mean age 33.33 +/- 20.01 years, were treated with cyclosporine (9 +/- 2.35 mg/kg/d), prednisolone (0.5 mg/kg/d) and androgens (1 mg/kg/d). The prednisolone was always combined with cyclosporine. The androgens were administered concomitantly with the cyclosporine or alternately. Seven patients responded to the treatment after a median remission delay of 6 weeks (2-12 weeks). They became independent of blood requirements at a median of 36 weeks (8-108 weeks); the three other patients died during the first trimester without showing any improvement. Among the seven responders, two relapsed early and transiently. The rate of actuarial survival was 70 per cent. The median duration of survival was 10.5 months. The side effects observed included one case of malignant lymphoma, six cases of liver toxicity and five cases of kidney toxicity. This toxicity was reversible after dose adjustment of the cyclosporine. In our study, the introduction of cyclosporin in the aplastic anaemia treatment resulted in improved therapeutic response. Androgens should be used to maintain the haematologic response. This therapeutic protocol associated with drug monitoring seems promising and the side effects should not limit its use because of the severity of the underlying disease.