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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.

Langerhans Cell Histiocytosis (LCH) is a rare clinical condition of the mononuclear phagocyte system caused by abnormal clonal proliferation of aberrant histiocytes or Langerhans cells . We describe this by reporting a case of a 28-year-old male patient presenting multi-system LCH with pituitary and bone involvement.

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.

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.

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.

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.

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.

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 IM Management & 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.

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 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.

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.

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 Conclusion Our results suggest that rs1801133 of MTHFR is a predictive risk marker to ALL in Tunisian ALL.

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.

Resume Objectif de l'etude Etude retrospective des resultats therapeutiques de la radiotherapie pour les lymphomes du mucosa-associated lymphoid tissue (MALT) gastriques. Patients et methodes Entre fevrier 1993 et decembre 2014, 11 patients atteints d’un lymphome primitif gastrique de type MALT ont ete pris en charge. Les patients atteints d’un lymphome de bas grade avec echec de la tritherapie ont recu exclusivement une radiotherapie externe. En cas de transformation en un lymphome de haut grade, la prise en charge a associe une chimiotherapie a une radiotherapie externe. La radiotherapie a ete delivree a la dose de 30 a 40 Gy selon un etalement et un fractionnement classiques. Resultats Toutes les tumeurs etaient de stade IE. Sept etaient de bas grade et ont ete prises en charge par une radiotherapie externe, quatre etaient transformees en haut grade et ont ete prise en charge par une chimiotherapie suivie d’une radiotherapie externe. Dix patients etaient en situation de remission complete. Le suivi moyen etait de 127 mois. Le taux de survie sans recidive a 5 et a 10 ans etait de 100 %. Aucune toxicite severe n’a ete observee le long du suivi. Conclusion Le traitement du lymphome du MALT gastrique repose sur l’eradication d’Helicobacter pylori. La radiotherapie externe est une modalite therapeutique efficace et sure assurant un excellent controle sans toxicite.

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.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.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.

This paper proposes a novel software architecture for developing disease registries. Our proposal consists of five horizontal layers and two transversal layers. It takes into account several aspects of disease registries, such as various sources of data acquisition, security and privacy issues, data analytics, and user management tasks. Several use cases are presented: the Tunisian Fanconi Anemia Registry (TFAR), the Tunisian Gaucher Disease Registry (TGDR), the Tunisian Non-Hodgkin Lymphoma Registry (TNHLR), and the Tunisian Registry of Diabetes Type 1 (TRD-T1).

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.

Background The P‐glycoprotein (P‐gp) is one of the mechanisms of Imatinib (IM) resistance in chronic myeloid leukemia (CML). P‐gp has been identified as an efflux pump involved in releasing of IM outside CML cells. To date, the P‐gp involvement in the IM resistance development was not completely understood. Therefore, the present study aimed at measuring the P‐gp expression level on lymphocytes from Tunisian patients with CML and correlating this level with a molecular response to IM. Method The expression of P‐gp on peripheral blood lymphocytes from 59 Tunisian patients with CML (27 IM responder patients vs 32 IM non‐responder patients) was evaluated by flow cytometry. Result Our finding showed significantly positive expression of P‐gp in the lymphocytes from the IM non‐responder group when compared to the IM‐responder group (P = .001). In IM non‐responder CML patients, the comparison between CCyR achievers and non‐achievers showed a high mean fluorescence intensity (MFI) of P‐gp expression in patients who did not achieve their CCyR (P = .001). The comparison between patients with primary and secondary resistance to IM showed an increasing MFI value in patients with primary resistance to IM (P = .001). Besides, the comparison between nilotinib‐treated and dasatinib‐treated patients proved a high value of MFI in nilotinib‐treated patients (P = .001). Conclusion The overexpression of P‐gp on lymphocytes has significantly correlated with the failed molecular response to IM in patients with CML.

Supplemental material, sj-pdf-1-opp-10.1177_1078155220984239 for Hypersensitivity pneumonitis related to imatinib mesylate therapy in a patient with chronic myeloid leukemia by Faten Kallel, Olfa Kassar, Imen Maaloul, Maha Charfi, Kamilia Ksouda and Moez Elloumi in Journal of Oncology Pharmacy Practice

Optic nerve infiltration is relatively rare in acute lymphoblastic leukemia. We present a case of a -53 year-old-man who was diagnosed with T- acute lymphoblastic leukemia (ALL). The patient was treated with ALL national protocol and the central nervous system (CNS) prophylactic management. On treatment, the patient presented with sudden severe vision deterioration of both eyes. Fundoscopic examination of the eye and magnetic resonance imaging of the orbits were in favor of an infiltration of the optical nerve. An isolated extramedullary relapse of the optical nerve was retained. The patient was treated with salvage chemotherapy systematic and intrathecal. Waiting forthe beginning of radiotherapy, the patient presented a bone marrow relapse. He died of a severe hemorrhagic syndrome. Conclusion: Optic nerve leukemic infiltration has a severe prognosis. Ophthalmic assessment is essential in patients with ALL in order to diagnose an early ocular involvement and the patient's vision can be preserved if treatment is initiated promptly.

Background This work aimed to evaluate oxidative stress in chronic myeloid leukemia (CML) patients treated with tunisian (IM) vs controls and in CML patients with resistance to IM vs patients without resistance to IM. Methods The study included 40 CML patients and 34 controls. Of 40 patients with CML, 26 patients were developed in resistance to IM. The oxidant/antioxidant markers were evaluated by spectrophotometric methods for all used samples. Results For CML patients, increased malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels were found compared to controls (P, High malondialdehyde and advanced oxidation of protein products levels were evidenced in chronic myeloid leukemia. Disturbed enzymatic and no enzymatic defenses were found in plasma of chronic myeloid leukemia patients. Patients with resistance to imatinib revealed more pronounced oxidant/antioxidant markers than no‐resistant chronic myeloid leukemia patients. Hydrogen peroxide was incriminated in the disturbed oxidative profile in chronic myeloid leukemia patients with resistance to imatinib.

Resume Introduction En Tunisie, la prise en charge du lymphome de Hodgkin de l’adulte est standardisee depuis 1999. Nous rapportons les resultats du protocole national de traitement du lymphome de Hodgkin de l’adulte (MDH2008). Patients et methodes Notre etude prospective et multicentrique a interesse 444 patients pris en charge pour un lymphome de Hodgkin entre juillet 2008 et juin 2013 et traites selon le protocole MDH2008. L’âge median de nos patients etait de 30 ans et 62,8 % avaient des symptomes B. La repartition selon la classification d’Ann-Arbor etait la suivante : stade I (3 %), II (42 %), III (26 %) et stade IV (29 %). Le protocole MDH2008 est base sur une strategie therapeutique adaptee a la reponse a deux cycles de chimiotherapie. Resultats Une reponse ≥ 75 % a deux cycles a ete obtenue chez 43 % des patients et le taux de reponse en fin de traitement etait de 92,1 %. Le taux d’echec primaire etait a 11,4 %. L’existence d’un gros mediastin (IMT ≥ 0,35) etait le seul facteur predictif independant d’echec primaire (p = 0,000). Dix-neuf deces toxiques (4,35 %) ont ete constates. Le taux des rechutes etait a 7,8 %. Les taux de survie sans evenement, de survie sans rechute et de survie globale a cinq ans etaient respectivement de 75 %, 89 % et 90 %. L’adaptation du traitement a la reponse a deux cycles etait efficace dans les stades localises defavorables et les stades etendus. Conclusion Compare au MDH2002, ce protocole a permis de diminuer le taux d’echec primaire, le taux de deces toxique au BEACOPP renforce et le taux des rechutes chez nos patients.

Context: Discontinuation of tyrosine kinase inhibitor (TKI) treatment for chronic phase (CP) chronic myeloid leukemia (CML) patients with a deep molecular response (DMR) has entered standard practice. Objective: In this study, we characterize the treatment-free remission in Tunisian CML patients. Design: This retrospective study collected data for CML patients who had discontinued TKI treatment as part of daily clinical practice in Sfax, Tunisia. Setting: Department of Medical Genetics in University Hospital. Patients or Other Participants: Patients with CML who discontinued their TKI were enrolled. Interventions: Quantitative assessment of the BCR-ABL transcript was performed using the Cepheid Xpert BCR-ABL ultra-assay. Main Outcome Measures: We investigated reasons for discontinuation, duration of TKI treatment before discontinuation, molecular response (MR) status at TKI discontinuation, and treatment-free remission (TFR) duration. Molecular recurrence is defined as the loss of major molecular response (MMR). Results: A total of 17 patients who discontinued treatment were enrolled in this study. Reasons for interruption were deep molecular response (n=13), adverse events (n = 1), and pregnancy (n = 3). TFR was maintained in 10 (64.7%) patients with a median follow-up of 26 months (8–127). The minimum treatment duration before discontinuation was 86 months. Five patients with sustained DMR (38.4%) had a molecular recurrence and re-initiated TKI. Conclusions: Our study highlights that TKI discontinuation was safe and effective in CML patients who are in sustained deep molecular response with longer TKI treatment duration. A larger study is mandatory for a comprehensive analysis of molecular recurrence in CML patients.