Investigation of Azole Resistance Involving cyp51A and cyp51B Genes in Clinical Aspergillus flavus Isolates.

This study aimed to investigate azole resistance mechanisms in Aspergillus flavus, which involve cyp51A and cyp51B genes. Real-time Reverse Transcriptase qPCR method was applied to determine the overexpression of cyp51A and cyp51B genes for 34 A. flavus isolates. PCR sequencing of these two genes was used to detect the presence of gene mutations. Susceptibility test found sensitivity to voriconazole (VOR) in all strains. 14.7% and 8.8% of isolates were resistant to itraconazole (IT) and posaconazole (POS), respectively, with a cross-resistance in 5.8%. For the double resistant isolates (IT/POS), the expression of cyp51A was up to 17-fold higher. PCR sequencing showed the presence of 2 mutations in cyp51A: a synonymous point mutation (P61P) in eight isolates, which did not affect the structure of CYP51A protein, and another non synonymous mutation (G206L) for only the TN-33 strain (cross IT/POS resistance) causing an amino acid change in the protein sequence. However, we noted in cyp51B the presence of the only non-synonymous mutation (L177G) causing a change in amino acids in the protein sequence for the TN-31 strain, which exhibits IT/POS cross-resistance. A short single intron of 67 bp was identified in the cyp51A gene, whereas three short introns of 54, 53, and 160 bp were identified in the cyp51B gene. According to the models provided by PatchDock software, the presence of non-synonymous mutations did not affect the interaction of CYP51A and CYP51B proteins with antifungals. In our study, the overexpression of the cyp51A and cyp51B genes is the primary mechanism responsible for resistance in A. flavus collection. Nevertheless, other resistance mechanisms can be involved.

Impact of CYP1A1 variants on the risk of acute lymphoblastic leukemia: evidence from an updated meta-analysis.

OBJECTIVE: Our study aimed to investigate the association between cytochrome P450 1A1 (CYP1A1) polymorphisms (T3801C and A2455G) and acute lymphoblastic leukemia (ALL) risk, considering genetic models and ethnicity. MATERIALS AND METHODS: PubMed, Embase, Web of Knowledge, Scopus, and the Cochrane electronic databases were searched using combinations of keywords related to CYP1A1 polymorphisms and the risk of ALL. Studies retrieved from the database searches underwent screening based on strict inclusion and exclusion criteria. RESULTS: In total, 2822 cases and 4252 controls, as well as 1636 cases and 2674 controls of the C3801T and A2455G variants of CYP1A1, respectively, were included in this meta-analysis. The T3801C polymorphism of CYP1A1 significantly increases the risk of ALL, particularly those observed in Asian and Hispanic populations, independent of age. Similarly, the A2455G polymorphism of CYP1A1 plays a significant role in the susceptibility to ALL in all genetic models, except the heterozygous form. This association was observed mainly in mixed populations and in both children and adults (except in the heterozygous model). CONCLUSION: Our comprehensive analysis indicates that the T3801 and A2455G polymorphisms of CYP1A1 may increase the risk of ALL depending on ethnicity. Therefore, both variants should be considered promising biomarkers for ALL risk. Further large-scale investigations are necessary to assess other factors, such as gene-gene or gene-environment interactions.

The interest of intranasal clonidine in the prevention of perioperative children's anxiety: a prospective randomized trial.

Introduction: perioperative anxiety in children may lead to psychological and physiological side effects. Clonidine is in increasing use in the pediatric population as an anxiolytic, sedative, and analgesic because of its central alpha2-adrenergic agonist effect. Our study aimed to evaluate the effect of clonidine in the prevention of perioperative children´s anxiety. Methods: we conducted a prospective controlled randomized double-blinded clinical trial including children aged between 2 and 15 years undergoing tonsillectomy surgery. The patients were randomly allocated to receive either an intranasal dose of clonidine (4 µg/kg) (clonidine group) or an equal volume dose of saline solution (control group) 30 minutes before entering the operating room. The level of anxiety assessed using the m-YPAS score was recorded before premedication, at the time of parent-child separation, and at the time of installation in the operating room. Acceptance of premedication, degree of sedation on entering the operating room as well as agitation on awakening, and sedation on arrival post-anesthesia care unit were noted. Adverse effects were recorded during the surgical procedure and in the postoperative recovery room. Results: the number of patients analyzed was 78 with 39 patients in each group. There were no signification differences in demographic data and premedication acceptance between the two groups. Levels of anxiety before any premedication were similar in the two groups. However, the anxiety level 30 minutes after premedication and in the operating room was significantly lower in the clonidine group (p<0.001). Children who received clonidine showed better sedation on entering the operating room (p=0.002) as well as postoperatively on entering the post-anesthesia unit care (p=0.006). The hemodynamic and respiratory parameters recorded were statistically comparable. Conclusion: intranasal clonidine is an interesting premedication to prevent perioperative children´s anxiety with few side effects.

Imatinib mesylate-induced acute hepatotoxicity.

INTRODUCTION: Imatinib is a first-line selective tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia. Although imatinib-induced hepatotoxicity may aggravate the patient's clinical condition and alter the treatment plan, the mechanism of imatinib-induced hepatotoxicity has rarely been investigated. CASE REPORT: We report a 51-year-old man, suffering from acute toxic hepatitis after 5 months of imatinib treatment for chronic myeloid leukemia. MANAGEMENT AND OUTCOME: The outcome was favorable after discontinuation of treatment with normalization of biological liver function after 12 weeks. The treatment was switched to nilotinib without any incidents. DISCUSSION: Regular liver function test monitoring is recommended during imatinib treatment. In fact of acute hepatic toxicity, treatment with imatinib should be stopped in the case of cytolysis more than five times the upper limit of normal.

The presence of two light chain bands on immunofixation is associated with poor outcomes in newly diagnosed multiple myeloma patients.

We aimed to describe the clinical and biological characteristics and the prognosis of patients presenting with an additional light chain (LC) band along with a complete monoclonal protein on immunofixation (IF).An 8-year descriptive study was conducted to assess all cases with confirmed monoclonal gammopathies (MG). We studied those with an entire M-protein with 2 bands of LC of the same isotype based on the results of IF. Data were collected from patients' files.Among 548 cases of MG, we found 32 cases (5.8%) with an additional LC band. We included 28 patients (5%) with a confirmed diagnosis of multiple myeloma (MM). The m/f ratio was 2.5 with a median age of 63 years [32-80 years]. All MM patients had anemia, 16 (57%) had renal failure, 14 (50%) had lytic lesions, 9 (32%) received hemodialysis, and 7 (25%) had hypercalcemia. The free-kappa-lambda ratio was abnormal in all cases: median = 0.07 [0.002-58.57]. The mean overall survival (OS) was 22 months ± 38.76.Fifteen MM patients (48%) received chemotherapy, and 7 (22%) autologous stem cell transplants (SCT). Patients who received SCT had an OS higher than those who received other treatments (p = 0.038). OS was low in patients with high ß2microglobulin levels (rho = -0.791; p = 0.001), and abnormally low free-kappa-lambda ratio (rho = -0.852;p = 0.04).The presence of an additional LC band with a complete monoclonal protein seems to identify newly diagnosed MM patients with poor outcomes and frequent renal impairment.

Biclonal Gammopathies in South Tunisia: Clinical and Biological Characteristics.

OBJECTIVE: Biclonal gammopathies (BGs) are rare situations characterized by the production of 2 monoclonal proteins. There are no available data on BGs in North Africa. We aimed to estimate the prevalence of BGs in our population and describe their clinical and laboratory features. METHODS: We conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis. RESULTS: A total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ±â€…10.87 years [range, 45-90 years]) were included. The main associated conditions were multiple myeloma (MM) (40%), BG of undetermined significance (BGUS) (34%), and lymphoproliferative diseases (23%). Only one-third of the patients had 2 monoclonal spikes on serum protein electrophoresis. The most common paraprotein combinations were immunoglobulin (Ig)G-IgG (25%) and IgG-IgA (23%) with different light chains in one-half of the cases. The mean follow-up was 25.6 months (median, 12 months). No BGUS evolved into a malignant disease. CONCLUSION: BGs are rare in clinical laboratory routine but must be accurately identified by the pathologist. Our cohort is characterized by a high prevalence of BGUS compared with MM.

Non-Hodgkin's lymphoma developed during imatinib mesylate treatment of chronic myeloid leukemia.

INTRODUCTION: Non-Hodgkin lymphoma induced by imatinib, as a tyrosine kinase inhibitor, is a rare complication. CASE REPORT: A 54-year-old female with a history of chronic myeloid leukemia (CML) was treated with imatinib as first-line therapy. The patient achieved a profound molecular response with treatment-free remission after five years but lost major molecular responses. A second deep molecular remission was again achieved. Nine years after imatinib therapy, the patient developed odynophagia and rhinorrhea. Physical examination revealed enlarged tonsils with a tumor-like appearance without palpable lymph nodes. Immunohistochemical examination of the tonsils revealed a large B-cell lymphoma. According to Naranjo's algorithm, the causality relationship with the drug is possible with a score of 3. MANAGEMENT AND OUTCOME: Imatinib was discontinued. The lymphoma was treated with rituximab and chemotherapy. DISCUSSION: Non-Hodgkin's lymphoma is a rare side effect of tyrosine kinase inhibitors and highlights the importance of follow-up CML patients.

Life threatening hepatotoxicity induced by Nilotinib.

INTRODUCTION: Tyrosine kinase inhibitor had changed the prognosis of chronic myeloid leukemia (CML) and the overall survival had reached 95%. Unfortunately, adverse events (AEs) remain an obstacle to following successful treatment in CML impairing the quality of life and sometimes endangering the lives of patients. To this end, we show this clinical case to discuss strategies to deal with rare AEs in a way to preserve the patient's life and to maintain not only a good response to treatment but also confidence and compliance of the patient. CASE REPORT: We report the case of a 57-year-old woman diagnosed with CML at the chronic phase who developed rare life-threatening hepatotoxicity (major cytolysis and prothrombin time fall) secondary to Nilotinib used as second-line treatment. This complication settled despite an optimal molecular response. MANAGEMENT AND OUTCOME: We discuss below the follow-up and management in our center and according to the literature with more sophisticated pharmacological methods. DISCUSSION: Although we used to monitor disease molecular response to treatment, we need solutions and manuscripts for monitoring drug dose parameters to avoid unusual dangerous effects risking the patient life. We conclude that monitoring the disease as well as the treatment pharmacokinetics is mandatory to better carry on CML patients.

Complexity of diagnosing and treating langerhans cell sarcoma: A case report.

INTRODUCTION: Langerhans cell sarcoma (LCS) is a very rare malignant tumor of Langerhans cells that may metastasize to many organs. The diagnosis of this tumor is difficult and its prognosis is poor. AIM: To report the difficulty to diagnose LCS, and discuss therapeutic management of this rare entity. CASE PRESENTATION: We report a case of LCS in a 52-year-old man who presented with an axillar lymphadenopathy. The diagnosis of nodular sclerosis type Hodgkin's disease was established after histologic examination. The patient was treated with chemotherapy (ABVD regimen: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine) and radiotherapy with a partial response. However, disease recurrence was observed and histological analysis confirmed the diagnosis of Langerhans cell sarcoma. A revision of the initial histological examination concluded to the diagnosis of sarcoma from the beginning. We chose the ESHAP (Etoposide, Methylprednisolone, Aracytine, Cisplatin) regimen and clinical improvement of LCS was obtained after 2 cycles but the patient had a fatal outcome and died by disease progression. CONCLUSION: Because of its rarity, diagnosis is difficult and an optimal treatment strategy for this disease has not yet been identified. Polychemotherapy can be an effective modality for the treatment of LCS.

Cerebral venous thrombosis after first Methotrexate administration by lumbar puncture in a patient with large B cell lymphoma.

Cerebral venous thrombosis is a rare consequence of lumbar punctures for intrathecal therapy. We report a patient treated for diffuse large B cell lymphoma with cerebral venous thrombosis after intrathecal Methotrexate administration. In this patient, intrathecal treatment was discontinued and he was successfully treated with high-dose low-molecular-weight heparin subcutaneously. Haematologist must be aware about neurological symptoms of cerebral venous thrombosis as a complication of lumbar puncture especially among patients with high coagulopathy state. If neurological symptom occurs, patient should be referred early to neurologist to avoid fatal outcome and neurological deficit.

Primary plasma cell leukemia: what role does flow cytometry play? / La leucémie à plasmocytes primitive : quelle place pour la cytométrie en flux ?

Primary plasma leukemia is defined by the presence of more than 20% plasma cells in the peripheral blood or number of circulating plasma cells greater than 2G/L. It has points in common with multiple myeloma and has certain characteristics, in particular its aggressiveness and poor prognosis. Through 02 cases diagnosed in the flow cytometry laboratory, the authors present the clinical, cytological and especially immunophenotypic features of this disease, with the emphasis on the role of flow cytometry in the diagnosis.

La leucémie à plasmocytes primitive, observée de novo, est définie par la présence de plus de 20 % de plasmocytes de la formule leucocytaire ou un nombre de plasmocytes circulants supérieur à 2 G/L. Elle a des points communs avec le myélome multiple et possède certaines caractéristiques, en particulier son évolution très rapide et son mauvais pronostic. A travers 02 cas diagnostiqués à l'unité de cytomètrie en flux du laboratoire d'hémo-biologie, les auteurs présentent les particularités cliniques, cytologiques et notamment immunophénotypiques de cette affection en mettant l'accent sur la place de la cytométrie en flux dans le diagnostic.

Hemophilia in the south of Tunisia.

Hemophilia is a rare constitutional hemorrhagic disorder. There is insufficient epidemiological data on hemophilia in Tunisia. To describe the epidemiological, clinical, therapeutic, and outcome of a cohort of patients with hemophilia in southern Tunisia. A retrospective study was conducted on patients with hemophilia at the Hemophilia Treatment Center of Southern Tunisia in Sfax over 38 years (from January 1982 to December 2020). Data were collected in a regional hemophilia registry of the South Tunisian center. We collected 141 cases of hemophilia, 85% of whom had hemophilia A and 15% had hemophilia B. The severe form represented 65%, followed by the moderate form at 25%. The prevalence of hemophilia was 4.4 in 100 000 population. Family history of hemophilia was found in 70%. The mean age of patients at diagnosis was 28 months. Hemophilia was detected in 87% of cases after hemorrhagic syndrome. Bleeding occurred mainly in hemarthrosis (73%), hematoma (70%), and visceral bleeding (28%). Intracranial bleeding occurred in 6% of cases. Thirty-six percent of patients were on prophylactic therapy. Hemophilic arthropathy was the most important orthopedic complication in our patients (38%). Inhibitory antibodies occurred in 16% of PWH. Transfusion-transmitted infections with HIV and hepatitis C were in 2 and 31% of cases, respectively. The prevalence of hemophilia is still underestimated in our center. The severe form of hemophilia is the most frequent. Hemophilic arthropathy was the most important complication in our patients. This showed that hemophilia is still a disabling disease in our country.

Aplastic anemia secondary to tyrosine kinase inhibitor therapy in a patient with chronic myeloid leukemia.

INTRODUCTION: Nilotinib, as the second generation of tyrosine kinase inhibitor, has significant efficacy in patients with chronic myeloid leukemia resistant or intolerant to Imatinib. Aplastic anemia induced by tyrosine kinase inhibitors is an uncommon complication. CASE REPORT: A 34-year-old female case with CML in the chronic phase was treated with Imatinib in first-line therapy. Nilotinib was switched because of failure to achieve complete cytogenetic response at 6 months following Imatinib. Three years with Nilotinib, the patient developed a persistent pancytopenia grade 4 while a major molecular response was achieved. MANAGEMENT & OUTCOME: Nilotinib was discontinued. However, the hematologic finding of the patient had not recovered after three months. A bone marrow biopsy showed marked hypocellularity and fatty tissue without evidence of myelofibrosis. Immunosuppressive therapy was started. Unfortunately, the patient died due to septic and hemorrhagic shock nine months after Nilotinib interruption. According to Naranjo's algorithm, the causality relationship with the drug is probable with a score of 5. DISCUSSION: Aplastic anemia is an uncommon adverse event of tyrosine kinase inhibitors but it can be a fatal complication. The early diagnosis of aplastic anemia related to Nilotinib therapy is needed to avoid further detrimental effects of the drug.

Prospective observational study of palliative care in hematological malignancies: Report of one year of practice.

INTRODUCTION: Palliative care is an approach that improves the quality of life of patients with advanced disease. OBJECTIVE: The aim of this study is to evaluate the process of palliative care in patients with hematologic malignancies. METHODS: In this prospective observational study, we included patients with hematologic malignancies who received palliative care over a 12 month period from June 1, 2019, to May 31, 2020 at the day care hospital of the hematology department in University Hospital of Sfax, Tunisia. Blood transfusion was used to relieve symptoms of anemia and bleeding. RESULTS: Fifty-five patients were included. The median age was 68 years. Forty-three percent of patients were diagnosed with acute leukemia and 41.8% with myelodysplastic syndrome. Red cell and platelet transfusions were indicated in 94.5% and 36.3% of cases respectively. Patients reported improvement after blood transfusion in 50% of cases. Twenty-five transfusion reactions (45%) were noted. Fever was noted in 33 patients (60%), with documented sites of infection in 84.8% of them. Pulmonary infection was frequently noted (50%). Antimicrobial treatment was prescribed in all febrile cases. Pain was reported in 22 patients and in 77.5% of these cases, it was nociceptive. Patients who received analgesics showed clinical improvement in pain in 81% of cases. Anorexia with malnutrition was reported in 23% of cases which was treated with enteral nutrition in 75% of cases. Sleep disturbance (20 patients), anxiety (7 patients), and depression (4 patients) were mentioned respectively. CONCLUSION: Palliative care in hematology should be a multidisciplinary care approach with a global management of the various physical, psychological and sociological complications.

MTHFR 677T-1298C haplotype in acute lymphoblastic leukemia: Impact on methotrexate therapy.

INTRODUCTION: Functional variants of the Methylenetetrahydrofolate reductase (MTHFR) gene, the C677T and A1298C, have largely investigated in pharmacogenomics of Methotrexate (MTX) in acute lymphoblastic leukemia (ALL), yet the conclusions are inconsistent. In addition; most of these studies do not analyze haplotypes. Here, we investigate the MTHFR 677/1298 genotypes and the 677-1298 haplotype and characterize the MTX response in Northern African ALL patients. METHODS: Genomic DNA was extracted from whole venous from a total of 28 patients with ALL. Genotyping were carried out with restriction fragment length polymorphism (RFLP). A toxicity score (TS) is calculated for each patient and correlate to the haplotype. RESULTS: The allelic frequency of MTHFR 677T-1298C haplotype was 10.7% in ALL patients. According to the toxicity's score (TS) there was no significant differences between haplotype groups (p = 0.79): TS was higher with wild type of MTHFR (TS = 3.43; SEM ± 0.85) followed by combined genotype (677T-1298C) (TS = 2.67; SEM ± 0.88) and isolated variant (C677T or A1298C) (TS = 2.64; SEM ± 0.92). CONCLUSION: Despite the limitation of this study; our results suggest that the MTHFR 677T-1298C haplotype is common in ALL and may be a promising HD-MTX chemotherapy-related adverse effects biomarker.

Assessment of molecular response to tyrosine kinase inhibitors in Tunisian Patients with Chronic Myeloid Leukemia.

AIM: This study was carried out to assess the minimal residual disease in Tunisian patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors in routine clinical practice, to recognize potentially eligible carrier for treatment discontinuation, based on a molecular response (MR). PATIENTS AND METHODS: A retrospective study was carried out in the Hospital University of Sfax, south of Tunisia from January 2016 to October 2020, including all CML patients in the chronic phase at diagnosis, treated with TKI (tyrosine kinase inhibitors) for a minimum duration of 6 months. Quantitative assessment of the BCR-ABL transcript was performed using the Cepheid Xpert BCR-ABL ultra-assay. Molecular response and outcome were evaluated, according to the European Leukemia Net guidelines. RESULTS: A total of 162 CML patients were carried out. The median age was 50 years, the sex ratio M/F was 1.62. The rate of cumulative EMR; MMR and DMR was 80.8%; 73.8% and 55.9% respectively. According to the ELN criteria, 141 CML patients were evaluable. Optimal, suboptimal response and failure were noted in 81 (57.4%), 33(23.4%), and 27(19.1%) patients, respectively. Overall survival (OS) and progression-free survival (PFS) were 96.3% and 85%. Risk factors for an event (death/progression) were lack of EMR, MMR, and DMR (P < 0.05). Among 149 patients with sustained DMR; 14 (8.6%) CML patients have discontinued TKI therapy. CONCLUSION: Despite the limit of our study (duration and size), the available real-life molecular responses with TKI therapy should be considered to identify potentially CML patients eligible for discontinuation of TKI therapy.

Co-existence of BCR-ABL and JAK2V617F mutation in resistant chronic myeloid leukemia in the imatinib era: Is there a correlation?

INTRODUCTION: Diagnoses of myeloproliferative disorder is based on molecular marker. Chronic Myeloid Leukemia and Myeloproliferative neoplasms were considered mutually exclusive and co-existence of BCR/ABL1 and JAK2 mutation is a rare phenomenon. CASE REPORT: Here, we present two cases of co-existence of BCR-ABL and JAK2V617F positivity. We characterize the course of the disease, mainly the minimal residual disease.Management and outcome: The two cases was initially managed as Chronic Myeloid Leukemia and treated by TKI inhibitors. The first one was diagnosed in 2010. He started the first line of TKI, and then switched to second line without obtaining a major molecular response. Hence he was tested for JAK2V617F mutation and positivity was diagnosed. The second patient showed Chronic Myeloid Leukemia phenotype with coexistence of BCR/ABL1 and JAK2 mutation at diagnosis. Molecular monitoring reveals a high BCR-ABL1 transcript level (20%) at the last follow-up (12 months). DISCUSSION: Ours results highlight that JAK2V617F/BCR-ABL double positivity may be a potential marker of resistance in Chronic Myeloid Leukemia and clonal molecular analysis is mandatory to elucidate the mechanism. Moreover, the combination of JAK and TKI inhibitors might be effective and potentially be guided by molecular monitoring of minimal residual disease.

Involvement of MTHFR rs1801133 in the Susceptibility of Acute Lymphoblastic Leukemia: A Preliminary Study.

BACKGROUND: Acute lymphoblastic leukemia (ALL), a common blood cancer, is characterized by the interaction between genetic and environmental factors. Several variants of the Methylenetetrahydrofolate reductase (MTHFR), mainly the C677T (rs1801133), may affect susceptibility to ALL. AIM OF THE STUDY: The authors conducted this case-control study to evaluate the relationship between this variant of the MTHFR gene and the risk of ALL. MATERIALS AND METHODS: Forty-one patients with ALL and 35 non-ALL controls recruited in this study were genotyped utilizing polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The MTHFR 677CT genotype was significantly more frequently found in patients with ALL having a 2-fold increase in risk (P <0.01). CONCLUSION: Our results suggest that rs1801133 of MTHFR is a predictive risk marker to ALL in Tunisian ALL.

Involvement of C677T MTHFR variant but not A1298C in methotrexate-induced toxicity in acute lymphoblastic leukemia.

BACKGROUND: Methotrexate (MTX) is a key drug in acute lymphoblastic leukemia (ALL) treatment; it inhibits DNA replication by blocking the conversion of 5, 10 Methylenetetrahydrofolate to 5-methylene tetrahydrofolate by methylenetetrahydrofolate reductase (MTHFR). Variants of the Methylenetetrahydrofolate reductase (MTHFR) and MTX related toxicities were largely investigated in several populations, nevertheless, the results are conflicting. OBJECTIVE: This study aimed to assess the prevalence of MTHFR SNVs: C677>T and A1298>C in Tunisian patients with ALL and the relation to the frequency of drug-induced complications. METHODS: 28 ALL patients were included in the study. They were treated according to EORTOC, in which a high dose of MTX (HDMTX) was prescribed. A toxicity score (ST) is calculated for each patient, summing the grades of toxicities. Genotyping of MTHFR variants was done with a PCR-based restriction fragment length polymorphism assay. RESULTS: The toxicity's score (TS) was higher with C677T variant compared to wild genotype (C677C) (TS = 4; IC95% [-2.65-13.32] versus TS = 2.5; IC95% [1.65-4.55], respectively; p = 0.2); but lower with the A1298C mutation compared to those with the wild genotype (A1298A) (TS = 2.5; IC95% [0.48-4.77], versus TS =3; IC95% [1.9-5.69], p = 0.4). HDMTX-related toxicity is associated with the 677CT genotype in ALL patients (RR = 1.41, p = 0.2); not for the A1298C [OR = 0.46, [0.08-2.61], p = 0.18]. CONCLUSION: Our preliminary findings highlight the impact of the C677T variant of MTHFR, but not the A1289C; in HD-MTX chemotherapy-related adverse effects in younger Tunisian ALL.

Hypersensitivity pneumonitis related to imatinib mesylate therapy in a patient with chronic myeloid leukemia.

INTRODUCTION: Pulmonary toxicity causally related to Imatinib (IM) therapy is uncommon in patients with chronic myeloid leukemia. CASE REPORT: A 61-year-old patient with chronic myeloid leukemia was treated with IM at 400 mg daily dose. One month within IM, he developed skin lesions and then acute dyspnea and non-productive cough. Chest radiograph and high-resolution lung computed tomography (CT) revealed bilateral reticulonodular infiltration in both lungs. According to Naranjo's algorithm, the causality relationship with the drug is probable with a score of 7. The pharmacovigilance investigation was carried out and implicated IMManagement & outcome: IM was discontinued and started steroid therapy (Prednisolone®) at 1 mg/kg daily. Two weeks after, the dyspnea, and abnormal X-ray and CT findings are improved. DISCUSSION: The early diagnosis of pulmonary toxicity related to IM therapy is needed to avoid further determinal effects of the drug.