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Coronavirus disease 2019 (COVID-19) has been associated with a significant fatality rate and persistent evolution in immunocompromised patients. In this prospective study, we aimed to determine the duration of excretion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 37 Tunisian patients with hematological malignancies (40.5% with lymphoma and 37.8% with leukemia). In order to investigate the accumulation of viral mutations, we carried out genetic investigation on longitudinal nasopharyngeal samples using RT-PCR and whole-genome sequencing. Patients' samples were collected until the RT-PCR results became negative. SARS-CoV-2 infection was symptomatic in 48.6% of cases with fever, and cough was symptomatic in 61% of cases; the mortality rate was estimated to be 13.5%. The duration of viral RNA shedding ranged from 7 to 92 days after onset; it exceeded 18 days in 79.4% of cases. An intermittent PCR positivity was observed in two symptomatic patients. Persistent PCR positivity, defined as the presence of viral RNA for more than 30 days, was found in 51.4% of cases. No significant differences were observed for age, sex, type of hematological malignancy, or COVID-19 evolution between this group and a second one characterized by non-persistent PCR positivity. Lymphopenia was an independent predictor of prolonged SARS-CoV-2 RNA detection (p = 0.04). Three types of variants were detected; the most frequent was the Omicron. Globally, the mean intra-host variability in the SARS-CoV-2 genome was 1.31 × 10−3 mutations per site per year; it was 1.44 × 10−3 in the persistent group and 1.3 × 10−3 in the non-persistent group. Three types of mutations were detected; the most frequent were nucleotide substitutions in the spike (S) gene. No statistically significant difference was observed between the two groups as to the type and mean number of observed mutations in the whole genome and the S region (p = 0.650). Sequence analysis revealed the inclusion of one to eight amino acid-changing events in seventeen cases; it was characterized by genetic stability from the third to the twentieth day of evolution in six cases. For the two patients with intermittent PCR positivity, sequences obtained from samples before and after negative PCR were identical in the whole genome, confirming an intra-host evolution of the same viral strain. This study confirms the risk of persistent viral shedding in patients with hematological malignancies. However, persistence of PCR positivity seems to be correlated only with a continuous elimination of viral RNA debris. Additional studies based on cell culture analysis are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal hematological disorder that requires urgent treatment. Once the diagnosis has been made, plasma exchange (PE) must be started immediately and until a response is obtained., Aim: Evaluate PE in terms of responses and complications in the treatment of TTP., Methods: This was a monocentric, descriptive, retrospective study including patients in whom TTP was diagnosed and treated with plasmapheresis in the clinical hematology department at Aziza Othmana Hospital, between January 2010 and December 2020., Results: Our study included 26 patients. PE was initiated within a median of 1 day. The rhythm of exchanges was daily in 22 patients. Twenty PE-related complications were noted, hypocalcemia being the most frequent (30%). CR was achieved in 15 patients after PE alone. Nine patients were refractory, and six received 2nd-line treatment, with CR achieved in five patients. Relapse was noted in six patients (40%). They were treated by PE and only one patient received rituximab. Four patients had a response. The overall response rate was 69% and overall mortality was 30%. OS at 2 years was 68,3% and RFS was 84,4%. Factors associated with the achievement of CR were the fall in LDH at D5 of treatment (p=0,027,OR=0,59 ;IC 95%[0,32-1,08]) and the daily rhythm of PE (p=0,005, OR=0,35; IC 95%[0,14-0,91])., Conclusion: Our results were comparable to those of the literature, but the rate of refractory disease was higher. Rituximab may enhance our results.

Background: bcr-abl fusion gene is the hallmark of chronic myeloid leukemia (CML). RQ-PCR provides an accurate measure of the total leukemia cell mass and the degree to which bcr-abl transcripts are reduced by therapy correlates with progression free survival., Aim: We report molecular assessment of residual disease in CML Tunisian patients., Methods: Between June 2003 and December 2014 we measured bcr-abl mRNA levels in peripheral blood from all Tunisian patients by quantitative real time polymerase chain reaction (RQ-PCR)., Results: A total of 708 patients with a mean age of 42 years were included in this study. Based on European Leukemia Net 2013, 80% of the patients achieved an optimal response 20% were in treatment failure. 38% of the patients achieved RM4 which corresponds to a bcr-abl/abl ratio <0.01%, 13% of the patients achieved RM4.5corresponding to bcr-abl/abl ratio of 0.0032%., Conclusion: CML patients had a good response to tyrosine kinase inhibitors treatment. RQ-PCR is helpful in detecting any residual disease and determining the depth of the treatment response.

The Tunisian adult's Hodgkin lymphoma (HL) Study Group was created in 1999. It aimed to improve the management of this curable hematologic malignancy by standardizing the diagnosis, assessment of disease, treatment management and therapeutic evaluation in different Tunisian centers (Hematology, oncology and radiotherapy).Since 1998, four versions of the prospective national protocol for treating adult Hodgkin lymphoma have succeeded (MDH99, MDH2002, MDH2008, MDH2015). Each version was based on the results of the previous version and analyzed according to new data from the literature. Due to this national study group, the number of patients lost to follow decreased significantly (30% before the creation of the group and only 3% for patients treated with MDH2008), the complete and uncertain response rates have improved (75% before the creation of the group and 92% in patients treated with MDH2008) with dramatically improved rates of overall survival from 57% to 90%. On the other hand there was an improvement of toxic death rate (13% of toxic deaths in MDH2002 to 4.37% in the MDH2008) with a decrease of the respective rate of primary failure and relapse by 17% and 12.5% in MDH2002 against the 11.4% and 7.8% in the MDH2008. This resulted in an improvement in overall survival (90%) and event-free survival at 5 years (75%). Now with the introduction of positron emission tomography in Tunisia, we hope yet to finalize the assessment of response and thus better adapt the treatment of this disease. Our objective remains the improvement of event-free survival rate to reach 80%.

The diagnosis of pseudotumor cerebri (PC) is based on the triad of: (1) papilledema, (2) elevated intracranial pressure with a normal cerebrospinal constituency and (3) normal central nervous system imaging studies. It is an uncommon complication of all-trans-retinoic acid (ATRA) therapy in children treated for acute promyelocytic leukaemia (APL). Its occurrence is rare among adult patients with APL and treated with ATRA . We report a case of an adult with APL who developed PC during induction therapy with ATRA-PC was managed with repeated lumbar punctures and corticotherapy.

Background: Acute promyelocytic leukaemia (APL) account for approximately 10% to 15% of all AML in most reports. Clinical features includes the presence in 80% to 90% of patients of a severe hemorrhagic syndrome, a specific balanced translocation between chromosomes 15 and 17 with a fusion of a large pert of the retinoic acid receptor a gene (RARa) on chromosome 17 to a part of the promyelocytic leukaemia (PML) gene on chromosome 15. More than 75% of patients (under 65 years of age) can be cured, with the application of a combination of anthracyclines and all-trans retinoic acid (ATRA), followed by maintenance therapy., Aim: of the study was to assess of the therapeutic management of APL 93 protocol in acute promyelocytic leukemia., Methods: We present here the results of a retrospective study concerning 34 patients with APL included between 1998 and 2004 in the APL 93 protocol : 20 in group B and 14 in group C. CR was 82 %., Results: Failure is only due to toxic death (18%) Event free survival at 4 years is 63,47% with relapse rate at 14.25%. Overall survival at 4 years is 69,72%. Our results are acceptable and can be improved with reduction of failure due to toxic death, probably with omission of cytarabine from induction and consolidation adapted by the Spanish PETHEMA Group.

The present work focuses on the therapeutic efficacy and the toxicity of alpha interferon in patients younger than age 18 years. 5 patients younger than 18 years were treated and followed up between 1990 and 1999 at the department of haematology (Aziza Othmana Hospital) Hydroxyurea was given as initial treatment to all patients. After a median period of 8 months, these patients received alpha interferon (5 millions units/m2 once). Six months after the beginning of the alpha interferon a complete hematologic response was obtained in all patients. The median overall survival was of 66 months: 3 patients are still alive (2 patients in an advanced stage and one patient in chronic phase) and 2 patients died after transformation. The most common reported side effects of alpha interferon were asthenia, weight loss, fever, myalgia, chills and headaches--these toxic manifestations were mild and were noticed in all our patients. Myelosuppression was noted in two patients. Interferon is well tolerated in patients younger than age years 18 old, with CML. It may offer an alternative to bone marrow transplantation in children in the chronic phase of CML without histocompatible donor. The role of new agents such as STI 571 needs to be evaluated as well.

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