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Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, mainly the C677T, have been implicated as risk factors for several cancers as the acute lymphoblastic leukemia (ALL). In addition, a potential effect of such variant on the efficacy of methotrexate (MTX) has been reported.In this study, we evaluated the impact of the C677T variant of MTHFR on MTX-related toxicity in ALL patients from Tunisia; to provide new insights for a personalized therapy based on the human genotype.Genotyping was carried out with restriction fragment length polymorphism (RFLP) on blood samples from a total of 35 younger patients; suffering from ALL.In the ALL patients, the MTHFR 677CT genotype confers a greater risk of toxicity with 1.3 times as relative risk mainly the hepatic toxicity when compared with MTHFR 677CC.Our findings suggest that C677T polymorphism of MTHFR seems to be a good marker for MTX-related toxicity in ALL.

The aim of the present study was to evaluate in patients with acute lymphoblastic leukemia (ALL), the oxidative status and antioxidant defense and its involvement in the relapse of ALL. The plasmatic levels of malondialdehyde, advanced oxidation of protein products and reduced glutathione (GSH), and the plasmatic activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase were determined in 34 patients who were newly diagnosed with ALL and compared with 92 healthy individuals. The plasmatic concentrations of malondialdehyde and advanced oxidation of protein products were higher in ALL patients than in controls and increased during chemotherapy. A decrease in glutathione peroxidase activity and an increase in catalase and SOD activities and GSH plasma levels were observed in ALL patients, as compared with sex-matched controls. Moreover, SOD activity and GSH levels were significantly correlated with the relapse of ALL patients. These data suggest the involvement of oxidative stress in acute lymphoid leukemias and leukemic relapse.

Background Methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy, but it is associated with serious toxicities in a considerable number of patients. Objectives The aim of the current study was to determine which variables were associated with MTX toxicity in children, adolescents and young adults with ALL. Material and methods In this prospective study, 35 patients with newly diagnosed ALL, treated according to the 58951 European Organization for Research and Treatment of Cancer - Children's Leukemia Group (EORTC-CLG) protocol, were prospectively enrolled. Toxicity data was collected objectively after each high-dose methotrexate (HD-MTX) course. The risk factors of MTX toxicity were determined using multiple linear regression analysis, with age, gender, immunophenotype, risk group, plasma MTX levels, plasma homocysteine (HCY) levels, and MTHFR C677T included as independent variables. Results Twenty-five (71.4%) patients experienced toxicity on at least 1 course of HD-MTX. In the univariate linear regression, the global toxicity score was associated with a significant rise in plasma HCY concentrations within 48 h after MTX administration (β = 0.4; R2 = 0.12; p = 0.02). In the multiple regression model, the global toxicity score was significantly associated with a higher MTX plasma levels at 48 h (β = 0.5; R2 = 0.38; p = 0.001) and CT 677 MTHFR genotype (β = 0.3; R2 = 0.38; p = 0.01). Conclusions Routine monitoring of plasma MTX concentrations is essential to detect patients at a high risk of MTX toxicity. MTHFR C677T genotyping may be useful for predicting MTX toxicity.

Apres traitement d’un lymphome hodgkinien (LH), plusieurs types de tumeurs peuvent survenir dont les lymphomes non hodgkiniens. Nous rapportons le cas d’un lymphome gastrique B diffus a grandes cellules, diagnostique chez une patiente, sept ans apres sa guerison d’un LH.

Resume Objectif Evaluer les taux d’immunisation anti-erythrocytaire dans les hemoglobinopathies. Patients et methodes Etude prospective (1990–2009) portant sur 84 patients : 44 drepanocytaires homozygotes, un drepanocytaire heterozygote S/C, 30 thalassemiques et neuf drepano-thalassemiques. L’âge moyen a ete de 10,13 ans (extremes : 1–45). Les concentres de globules rouges ont ete ABORH1 compatibles au debut puis phenotypes RH-KEL a partir de 2006 et phenotypes RH-KEL et dans les autres systemes apres immunisation. Les concentres de globules rouges ont ete compatibilises en test de Coombs indirect. La recherche d’agglutinines irregulieres a ete realisee avant chaque episode transfusionnel et le test de Coombs direct lorsque l’indication s’imposait. Resultats Le nombre de concentres de globules rouges transfuses a ete de 3545 (42,2/patient). Le nombre des recherches d’agglutinines irregulieres et des tests de Coombs direct ont ete, respectivement, de 1474 (17,5/patient) et de 272 (3,2/patient). Nous avons identifie 27 anticorps (32,1 %) : 14 allo-anticorps, soit 16,6 % (16,6 % chez les drepanocytaires, 16,6 % chez les thalassemiques, p = 1), 16 auto-anticorps, soit 19,04 % (11,1 % chez les drepanocytaires, 33,3 % chez les thalassemiques, p = 0,018) dont trois cas d’association auto- et allo-anticorps. Les allo-anticorps ont ete essentiellement de specificite anti-RH secondaires a la transfusion de concentres de globules rouges standard. Il n’existait pas de relation significative entre le sexe et l’immunisation, ni entre la consommation de concentres de globules rouges et l’allo-immunisation. En revanche, il existait une relation significative entre auto-immunisation et consommation de concentres de globules rouges chez les thalassemiques (p Conclusion Cette etude confirme l’interet de systematiser la transfusion de concentres de globules rouges RH KELL compatible chez les hemoglobinopathes polytransfuses afin de reduire le taux d’allo-immunisation aux antigenes erythrocytaires les plus immunogenes.

Resume La prise en charge therapeutique des tumeurs pelviennes depend de leur nature histologique. Certaines ne necessitent qu’un traitement medical sans recours a une chirurgie. Nous rapportons deux cas de tumeurs pelviennes rares survenant chez des adultes jeunes. Dans un cas, la nature actinomycosique a ete portee sur l’etude histologique des biopsies chirurgicales. Dans le second cas, la nature lymphomateuse d’une tumeur du bas rectum a ete retenue sur l’etude immunohistochimique des biopsies endoscopiques. L’evolution etait favorable dans les deux observations, respectivement apres un traitement medical a base de penicilline G ou d’une chimiotherapie. Nous discutons a l’occasion de ces deux observations les difficultes diagnostiques et les modalites therapeutiques de ces affections rares.

The mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct clinical pathologic entity that develops in diverse anatomic locations such as the stomach, salivary gland, thyroid, lung, skin and breast. However, colorectal involvement is extremely rare. To our knowledge, only ten cases of primary rectal MALT lymphoma have been reported in the literature. We report a 46-year-old woman with rectal MALT lymphoma, which regressed after radiotherapy. The patient had rectal bleeding. Colonoscopy showed a pseudonodular and ulcerated big fold in the rectum. Microscopic and immunohistologic studies of the biopsy specimen showed typical features of low grade MALT lymphoma. Upper endoscopy showed chronic gastritis with lymphoid follicles but without any infiltration of lymphoma cells. Helicobacter pylori infection was confirmed by histology. No extra-intestinal involvement was found on the staging evaluation, which included computed tomography (CT) of the abdomen, chest, pelvis and a bone marrow biopsy. We attempted to eradicate H. pylori with a 7-day course of omeprazole, amoxycillin, and metronidazole. Eradication was proved successful by endoscopy. Repeated colonoscopy 4 months after the end of treatment showed that the rectal tumor had not regressed. Biopsy specimens confirmed the persistent infiltration of lymphoma cells. The patient was considered to be a non-responder to eradication therapy and was indicated for radiotherapy. He underwent a total of 34 Gy. Complete regression was confirmed by colonoscopic and histologic examination at 2 months after the end of treatment. He was followed up closely with colonoscopy, but no relapse of these lesions was detected after 12 months.

Acute myeloid leukemia philadelphie positive (Ph+ AML) is a rare aggressive acute leukemia with poor prognosis. We report a patient with ph positive AML (FAB5), the transcript bcr/abl was not performed at diagnosis. She achieved complete remission after conventional induction chemotherapy. The consolidation therapy was based on Imatinib only due to infectious complications. She was in complete hematologic and cytogenetic remission for 19 months, and after she exhibited an isolated meningeal relapse. A second remission was achieved with intrathecal chemotherapy and cranial irradiation. Imatinib was switched to second generation Tyrosine kinase Inhibitor which had better diffusion into cerebrospinal fluid. She is in complete hematologic, cytogenetic and meningeal remission after 14 months of treatment. Imatinib monotherapy affords insufficient protection from CNS relapse. Second generation Tyrosine kinase Inhibitor seems to have better efficiency. Ph+ AML with monoblastic differentiation should be considered, like Ph+ ALL, at high risk of meningeal leukemia and should receive central nervous system prophylaxis.

Introduction Le lymphome de Hodgkin (LH) est une hemopathie maligne pouvant etre associee a une atteinte cutanee (17 a 53 %), le plus souvent paraneoplasique. L’association a une papulose lymphomatoide (PL) est rarement rapportee. Observations Une femme de 51 ans, sans antecedents pathologiques particuliers, nous a consultes pour des lesions des membres et du tronc, evoluant par poussees depuis quelques mois avec une regression spontanee. A l’examen, elle avait une eruption de lesions papuleuses erythemato-violines infiltrees, d’âges differents, a centre ulcero-necrotique par endroit alternees avec des lesions pigmentees cicatricielles, un etat general conserve et des aires ganglionnaires libres. Elle avait une anemie inflammatoire a 9,6 g/dL, une vs. a 105 mm/1re h, une LDH a 263 UI/L (normale) et une hypergammaglobulinemie a 19 g/L. Sur differentes biopsies cutanees, l’examen histologique montrait un epiderme d’epaisseur variable avec un infiltrat dermique en bande avec extension en periannexiel et perivasculaire majoritairement lymphocytaire fait de petits lymphocytes (noyaux hyperchromatiques irreguliers), avec quelques histiocytes et polynucleaires neutrophiles. L’immunohistochimie (IHC) etait positive pour CD3, CD5, CD4 et surtout CD8 et negative pour CD15 et CD30. Le diagnostic de PL CD30 (−) etait ainsi evoque. Un scanner thoraco-abdomino-pelvien etait sans anomalies. L’evolution etait marquee par une aggravation des lesions cutanees, plus infiltrees, de plus grande taille, largement ulcerees et plus nombreuses, et l’apparition 3 mois plus tard d’une adenopathie inguinale fixee, indolore, dont la biopsie a confirme le diagnostic de LH. L’evolution sous chimiotherapie (ABVD puis BEACOOP) etait bonne avec regression rapide des lesions cutanees et des adenopathies. La patiente est encore sous traitement ( Fig. 1 ). Discussion Dans 10 a 20 % des cas, la PL est precedee, associee ou suivie par un autre lymphome, le plus souvent un mycosis fongoide, un LH ou un lymphome CD30 (+). Notre observation est originale, car elle associe une clinique typique de PL et une histologie discordante. Classiquement, l’histologie de la PL est soit de type A (infiltrat mixte avec quelques grandes cellules CD30 + ), de type C (riche en grandes cellules CD30+, mimant un lymphome), plus rarement de type B (mimant un mycosis fongoide) ou encore plus rarement de type D (infiltrat epidermotrope lymphocytaire T CD8+ cytotoxique, ± CD30 + ), E et F (infiltrat lymphocytaire T perifolliculaire CD8+ cytotoxique, ± CD30 + ). La biopsie montre dans notre cas un infiltrat non epidermotrope lymphocytaire T CD8 (+) et CD30 (−) sans atypies (type B ou F dans leurs variantes CD8 + ). La negativite de CD30 est a l’origine d’une difficulte diagnostique et son association a une positivite de CD8 est connue. Conclusion L’association d’un LH a une PL est rarement rapportee. La confrontation anatomoclinique est essentielle pour porter le diagnostic de PL.

Resume Les Trichosporon sont des levures de plus en plus incriminees dans la survenue d’infections profondes, notamment chez les patients d’oncohematologie. Nous rapportons deux observations de septicemie a Trichosporon asahii diagnostiquees au laboratoire de parasitologie et mycologie du CHU Habib-Bourguiba de Sfax, Tunisie. Notre premier patient presentait une leucemie aigue myeloide avec une fievre persistante malgre la mise en place d’une antibiotherapie a large spectre. Le second cas avait une anemie avec une fievre resistante aux antibiotiques. T. asahii a ete isole des hemocultures dans les deux cas. Les patients ont ete mis sous amphotericine B mais l’evolution etait fatale. Les trichosporonoses sont rares mais particulierement graves chez les sujets immunodeprimes avec un pronostic souvent pejoratif malgre le traitement antifongique.

We report here the case of a 35-year-old woman. She was diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia. Because of primary infertility, she received imatinib without contraception. Complete cytogenetic response was not obtained with 800mg/day. As a result, the patient was switched to nilotinib at 400 mg twice a day. An accidental pregnancy was identified at a term of 9 weeks while the patient was on imatinib during the first 4 weeks then nilotinib between 5th and 9th weeks of gestation. Because the patient elected to continue the pregnancy to term, nilotinib was discontinued; no further treatment was given until delivery. A follow-up with ultrasound scans was unremarkable. She successfully gave birth to female twins at 38 weeks with no malformation until 13 months post- partum. This experience provides a useful contribution for counselling patients exposed to nilotinib during pregnancy. The introduction of the tyrosine kinase inhibitors TKI since 1998 indisputably advanced the clinical management of chronic myeloid leukemia CML. As a result, patients who are of childbearing age and are currently being treated with TKI now find themselves contemplating reproductive opportunities that would not have otherwise been possible. Because imatinib was teratogenic in rats, in addition to general safety concerns surrounding the use of any new drug in pregnancy and the limited data available in the public domain on the outcome of pregnancies of patients exposed to imatinib, it was strongly advised that effective contraception be used during therapy to prevent pregnancy [1-4] . Moreover, there is still very insufficient data on the second generation TKIs to warrant their safety in pregnant women with CML [5, 6] . We report the outcome of a patient with CML who became pregnant while receiving imatinib then nilotinib.

To estimate the rate of red cell immunization in hemoglobinopathies.Prospective study (1990-2009) about 84 patients: 44 homozygous sickle cell anemia, one heterozygous sickle cell anemia S/C, 30 thalassemia and nine sickle cell anemia-thalassemia. The mean age was 10.13 years (extremes: 1-45). The red cell units transfused were ABORH1 compatible, then RH-KELL phenotyped after 2006 and phenocompatible after alloimmunisation. The cross-match was realized using indirect antiglobuline test. Irregular red cell antibody screening was realized before every transfusional episode and the direct antiglobuline test was done when there was a poor transfusional efficiency.The number of red blood cells units transfused was 3545 (42.2/patient). The number of red cell antibody screening and the number of direct antiglobulin test were respectively 1474 (17.5/patient) and 272 (3.2/patient). Twenty-seven antibodies were identified (32.1%): 14 alloantibodies (16.6%, 16.6% in sickle cell disease, 16.6% in thalassemia, P=1), 16 antoantibodies (19.04%, 11.1% in sickle cell disease, 33.3% in thalassemia, P=0.018). There were three cases of association of allo- and autoantibodies. The most frequent alloantibodies were anti-RH3 and anti-KEL1 and were developed after transfusion of standard red cell units. There was no significant relation, neither between sex and risk of immunization, nor between the number of red cell units transfused and alloimmunization. On the other hand, there was a significant relation between autoimmunization and the number of red cell units transfused in thalassemia (P0.001).This study proves the interest of using RH-KELL red cell units compatible in patients with hemoglobinopathies in order to reduce alloimmunisation rates.

The treatment of the pelvic tumors depends of their histological nature. Some of them require only one medical treatment without recourse to surgery. We report two rare cases of pelvic tumors occurring in young adults. For the first case, actinomycosic nature was related to the histological study of the surgical biopsies. Concerning the second case, the lymphatic nature of a tumor of the low rectum was retained on the immunohistochimic study of the endoscopic biopsies. The evolution was uneventful in the two cases after a medical treatment containing penicillin G or a chemotherapy. We discuss at the time of these two observations the diagnostic difficulties and the therapeutic methods of these rare affections.

The mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct clinical pathologic entity that develops in diverse anatomic locations such as the stomach, salivary gland, thyroid, lung, skin and breast. However, colorectal involvement is extremely rare. To our knowledge, only ten cases of primary rectal MALT lymphoma have been reported in the literature. We report a 46-year-old woman with rectal MALT lymphoma, which regressed after radiotherapy. The patient had rectal bleeding. Colonoscopy showed a pseudonodular and ulcerated big fold in the rectum. Microscopic and immunohistologic studies of the biopsy specimen showed typical features of low grade MALT lymphoma. Upper endoscopy showed chronic gastritis with lymphoid follicles but without any infiltration of lymphoma cells. Helicobacter pylori infection was confirmed by histology. No extra-intestinal involvement was found on the staging evaluation, which included computed tomography (CT) of the abdomen, chest, pelvis and a bone marrow biopsy. We attempted to eradicate H. pylori with a 7-day course of omeprazole, amoxycillin, and metronidazole. Eradication was proved successful by endoscopy. Repeated colonoscopy 4 months after the end of treatment showed that the rectal tumor had not regressed. Biopsy specimens confirmed the persistent infiltration of lymphoma cells. The patient was considered to be a non-responder to eradication therapy and was indicated for radiotherapy. He underwent a total of 34 Gy. Complete regression was confirmed by colonoscopic and histologic examination at 2 months after the end of treatment. He was followed up closely with colonoscopy, but no relapse of these lesions was detected after 12 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).