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.

Lack of FLT3-ITD in Tunisian childhood acute lymphoblastic leukemia.

Background: The fms-like tyrosine kinase 3 (FLT3) gene belong to the class III receptor tyrosine kinases witch is predominantly expressed on hematopoietic progenitor cells, and plays an important role in haematopoiesis. Targeting the FMS-like tyrosine kinase receptor-3 (FLT3) in acute leukemia is mainly important. Therefore, activating mutations in FLT3, primarily the FLT3-internal tandem duplication (FLT3-ITD), was used as a prognostic marker especially in myeloid leukemia; however, in ALL, the prognostic relevance of FLT3 mutations is less clear. Objectives: This study was conducted to evaluate the frequency of FLT3-ITD mutation in Tunisian childhood acute lymphoblastic leukemia, and to correlate this mutation with prognostic parameters. Methods: Genomic DNA was extracted from EDTA-anticoagulant blood samples from a total of 25 children suffering from acute lymphoblastic leukemia (ALL). After DNA extraction, the polymerase chain reaction using specific primers was conducted to screen the FLT3-ITD. Results: In acute lymphoblastic leukemia (ALL), 9 cases with LAL-B were detected and the median age is 13 years. Chromosome abnormalities were detected in 5 with ALL and are correlated with worse prognosis (very high risk and relapse). At molecular lever, never FLT3-ITD was detected. Conclusions: Our findings suggest that FLT3 mutations are not common in Tunisian childhood ALL and thus do not affect clinical outcome.

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.

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.

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.

Isolated optic nerve infiltration as a site of relapse of acute lymphoblastic leukemia.

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.

Spontaneous Fracture and Migration of a Totally Implanted Port Device to Pulmonary Artery in Acute Leukemia Child.

Totally implanted port devices are important for the administration of fluid and chemotherapeutic agents. However, their use may be associated with serious complications, such as catheter fracture and embolism. Most data on port catheter embolization consist of isolated case reports. We report a 6-year-old boy with relapse of an acute lymphoblastic leukemia. He presented with dysfunction of his totally implanted port device. Radiologic examination revealed a catheter fracture. Echocardiography showed the catheter embolized into the right ventricle. The catheter was successfully removed from the right ventricle by percutaneous endovascular intervention. During the procedure, it was observed that the catheter fragment was located in the pulmonary artery. Catheter embolism may go undiagnosed for a prolonged period; however, severe systemic clinical signs may develop. Any implanted catheter should be removed after completion of treatment, or should be checked regularly for this complication by periodic standard chest x-ray monitoring.

[Primary manifestation of small Lymphocytic Lymphoma in the Prostate: A case report].

We report a case of Lymphocytic Lymphoma presenting with primary manifestation in the prostate. A 82 year-old man presented to emergency department with acute urinary retention. Digital rectal examination revealed a voluminous and firm prostate. Histology confirmed involvement of the prostate by small B Lymphocytic Lymphoma. The patient was treated with chlorambucil. Lymphocytic infiltration of prostate is a rare manifestation. However this may also be the first sign of an undiagnosed lymphoma. This observation shows that the prostatic lymphoma must be considered among the causes of low urinary retention.

Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia.

Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patient and conservative treatment was attempted in the other patient. None treatment measures were effective and two patients died. Acute acalculous cholecystitis is a serious complication in neutropenic patients. Earlier diagnosis could have expedited the management of these patients.

[Primary immune thrombocytopenia in childhood: a regional study in the south of Tunisia]. / Thrombocytopénie immune primaire de L'Enfant: etude régionale dans le sud Tunisien.

BACKGROUND: the primary immune thrombocytopenia (ITP) in children has a favorable evolution in most of cases. aim: describe the epidemiological and therapeutic data and the outcome of primary immune thrombocytopenia in our patients and propose a treatment plan to standardize the management of this disease in our region. methods: We conducted a retrospective study of 140 cases of primary immune thrombocytopenia collected in department of pediatrics and hematology of Hedi Chaker hospital during a period of 15 years. Patients who had a platelet count ≤ 20 000 and / or mucosal or troublesome lifestyle hemorrhage were treated. results: The mean age was 6 years 7 months with extremes varying from 3 months to 15 years. The bleeding manifestations were dominated by cutaneous bleeding in the form of petechiae or bruise (100%). Epistaxis and gingivorragia were noted in 32,9% and 25,7% of the cases respectively. The most of patient were treated with corticosteroids (79%). Intravenous immunoglobulin was associated with corticosteroids in 7%. An acute ITP occurred in 94 cases (67%) and a chronic ITP in 30 cases (21%). CONCLUSION: In the recently diagnosed ITP, the response delay under association Intravenous immunoglobulin and corticoids is shorter than that of corticoids alone, but the high cost of Intravenous immunoglobulin associated with their immediate side effects compels us to recommend corticoids as a first line of treatment.