Multiple myeloma (MM) is an incurable hematological malignancy disabling by pain. This study aims to identify the frequency of pain in patients with this disease, its characteristics, and to report the modalities of its management. Our study is retrospective about 115 newly diagnosed adult patients (< 65 years old) with multiple myeloma in the hematology department at the university hospital of Sfax, Tunisia. Nociceptive pain and neuropathic pain were recorded in 76.5% and 20% of cases respectively. Treated by thalidomide, 30 patients (16%) developed chemotherapy-induced peripheral neuropathy. Psychological pain was not estimated in our study. The management of pain differs according to the mechanism and must involve specific treatment of MM. For our patients, a global response and control of the disease was noted in 69% of cases. Pain in myeloma is often complex and multifactorial. Adequate pain management requires supporting treatment and the control of the disease, which is a predictive adverse factor for pain control. Le myélome multiple (MM) est une hémopathie maligne incurable mais aussi invalidante par les douleurs. Le but de cette étude est d’identifier la fréquence de la douleur, ses caractéristiques chez les patients atteints de MM, et de rapporter les modalités de sa prise en charge. C’est une étude rétrospective de 115 adultes jeunes âgés de moins de 65 ans atteints de MM nouvellement diagnostiqués au sein du service d’hématologie du CHU Hédi Chaker de Sfax. Les douleurs nociceptives et les douleurs neuropathiques étaient présentes chez 76,5 % et 20 % de nos malades respectivement. Sous traitement par thalidomide, 30 patients (16 %) ont développé des neuropathies toxiques. La douleur psychogène n’était pas estimée dans notre étude. La prise en charge des douleurs diffère selon le mécanisme et doit associer le traitement spécifique. Chez nos patients une réponse globale et un contrôle de la maladie ont été noté dans 69 % des cas. La douleur chez les patients ayant un myélome est souvent complexe et multifactorielle. Un traitement adéquat de la douleur nécessite des traitements de supports et un contrôle de la maladie pour un contrôle indirect de ces douleurs.

Telomeres are nucleoprotein structures that protect the chromosome ends from degradation and fusion. Telomerase is a ribonucleoprotein complex essential to maintain the length of telomeres. Germline defects that lead to short and/or dysfunctional telomeres cause telomere biology disorders (TBDs), a group of rare and heterogeneous Mendelian diseases including pulmonary fibrosis, dyskeratosis congenita, and Høyeraal-Hreidarsson syndrome. TPP1, a telomeric factor encoded by the gene ACD, recruits telomerase at telomere and stimulates its activity via its TEL-patch domain that directly interacts with TERT, the catalytic subunit of telomerase. TBDs due to TPP1 deficiency have been reported only in 11 individuals. We here report four unrelated individuals with a wide spectrum of TBD manifestations carrying either heterozygous or homozygous ACD variants consisting in the recurrent and previously described in-frame deletion of K170 (K170∆) and three novel missense mutations G179D, L184R, and E215V. Structural and functional analyses demonstrated that the four variants affect the TEL-patch domain of TPP1 and impair telomerase activity. In addition, we identified in the ACD gene several motifs associated with small deletion hotspots that could explain the recurrence of the K170∆ mutation. Finally, we detected in a subset of blood cells from one patient, a somatic TERT promoter-activating mutation that likely provides a selective advantage over non-modified cells, a phenomenon known as indirect somatic genetic rescue. Together, our results broaden the genetic and clinical spectrum of TPP1 deficiency and specify new residues in the TEL-patch domain that are crucial for length maintenance and stability of human telomeres in vivo.

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Peripheral T cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin’s lymphomas with a poor prognosis. They constitute a real problem given the absence of a well-codified therapeutic consensus. Aims: The aim of our work is to describe the prognostic and therapeutic aspects of PTCLs diagnosed and treated in south Tunisia and to compare our therapeutic results with literature data. Methods: Our study is retrospective. It concerned patients with PTCL excluding Natural Killer T cell lymphomas followed and treated in the clinical hematology department of the university hospital of Sfax during 22 years from January 2000 to June 2021. We used the International Prognostic Index (IPI) to evaluate the prognosis. Patients received anthracyclines-based therapeutic protocols, including mostly Cyclophosphamide, Adriamycin, Vincristine, Prednisone (CHOP) protocol and Cyclophosphamide, Adriamycin, Vincristine, Etoposide, Prednisone (CHOEP) protocol or other anthracycline based protocols. Autologus stem cell transplantation (ASCT) was indicated for patients aged 60 and younger with aaIPI superior to 1. Survival curves were measured using Kaplan Meier’s methods. Results: Fifty-two patients diagnosed with PTCL were registered. The most common histological type was peripheral T-cell lymphoma not otherwise specified (PTCL NOS) (27%) followed by anaplastic ALK negative T-cell lymphoma (ALCL ALK-) (23%). The median age was 49 years with a sex ratio of 2,2. A performance status equal or superior to 2 was present in 38.5% of patients. An extended stage (III-IV) was found in 85% of patients. 38.5% of patients had an IPI score superior to 1. The overall remission rate (ORR) was 44% and the complete response (CR) rate was 36,5%. The ALCL ALK positive and ALK negative had the best ORR of 66% each and the worst outcome was found in cutaneous T-cell lymphoma (ORR of 10%). The treatment response was influenced by the disease staging (p=0,011). The refractory and relapse rate was 55%, only 52% of cases received second line chemotherapy and the ORR was 20%. The 5-year overall survival (OS) and event-free survival (EFS) rates were respectively 29% and 27%. The highest 5- year OS rate was seen in ALCL ALK positive (66%). The univariate study showed that OS was influenced by the PS (p=0,0001), the IPI score (p=0,049) and the stage of the disease (p=0,002) while EFS was influenced by PS (p=0,001), disease stage (p=0,002) and response to treatment (p=0,001). Summary/Conclusion: Our results were similar to the literature data in terms of therapeutic response with an ORR of 60 to 83% and a CR of 22 to 68%. However, the survival results were inferior to reported literature (5- year OS of 34 to 70%). This, probably, can be improved with better adaptation of treatment to each entity of PTCL. Keywords: Chemotherapy, Malignant lymphoma, T cell lymphoma, Peripheral T-cell lymphoma

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.

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. This tumor has a good prognosis with cure rates of more than 80%. Therefore, epidemiological and therapeutic differences exist in terms of the phenotyping of ALL. The comparative analysis of B ALL and T ALL allowed a better differentiation of their characteristics as well as their evolution after treatment. Aims: The aim of this study is to compare the characteristics of B and T-ALL and predict the prognosis of these groups and their evolution after treatment. Methods: In this study, we enrolled retrospectively all cases of patients under 30 years old, with ALL diagnosed in the hematology department of Hedi Chaker Hospital, Sfax, Tunisia, between January 2000 and December 2021. The therapeutic protocol is EORTC 58951. We compared the epidemiological characteristics of B and T-ALL (age, sex, clinical and biological characteristics). We also compared the therapeutic outcomes of each phenotype of ALL: complete remission (CR), relapse rate, overall survival (OS), and event-free survival (EFS). Results: The comparative results of T and B-ALL were shown in the bellow table. - Characteristics TotalN= 395 LAL BN= 265 (67%) LAL TN=130 (33%) p Median age(years) 9 (1- 30) 7 (1-30) 13 (2-30) - Sex-ratio 1.58 1.38 2.1 - Tumor syndrome 297 (75%) 184 (71) 113 (88) <0.001 WBC ≥100G/L 74 (19%) 27 (10) 47 (36) <0.001 Corticoresistance 86 (22) 36 (14) 50 (38) <0.001 Complete remission 354 (90) 242 (91) 112 (86) <0.001 Failure remission 25 (6.5) 15 (6) 10 (8) - Relapse rate 116 (33) 86 (35) 30 (27) 0.084 OS at 5 years 63% 67% 54% 0.002 EFS at 5 years 58% 60% 53% 0.048 Summary/Conclusion: The frequency of T-ALL in our study (33%) is higher than those described in the literature (10 to 15%). The clinical and biological data of T-ALL in our study are characterized by more tumor syndrome and higher hyperleukocytosis than 100 G/L. The therapeutic results of T-ALL are also characterized by less frequency of corticosensitivity, complete remission, OS, and EFS. Although, there is less frequency of a relapse. Our results are compared to those in the literature. Keywords: ALL, Acute lymphoblastic leukemia, Phenotype, Children

Topic: 33. Bleeding disorders (congenital and acquired) Background: Von Willebrand disease (VWD) is defined as a defective or dysfunctional Von Willebrand Factor (VWF) that mediates platelet adhesion and aggregation at vascular damage sites. A minority of patients, particularly with type 3 VWD, develops alloantibodies to exogenous VWF whose arising complications are challenging. These antibodies make replacement VWF therapy ineffective and even dangerous by producing anaphylactic reactions. Aims: Our study aims to evaluate the clinico-biological, therapeutic and evolutionary characteristics of VWD patients with alloantibodies. Methods: Our study is retrospective, it concerned patients with VWD who developed alloantibodies. Data were recorded from VWD registry which includes patients with VWD in south of Tunisia during 23 years (from January 2000 to December 2022). Anti-VWF and anti-FVIII testing were performed in case of ineffective substitution or when an allergic reaction was occurred during substitution. The screening and the titration of inhibitors were performed by the modified Bethesda method using the coagulation analyzer Sysmex® CS-2100i in the anti-VWF testing and the STA-R® Stago automate in the anti-FVIII testing. Results: During the study period, we collected 89 cases of VWD, 44 cases had type 3. Six patients had alloimmunization: 1 had anti-VWF, 2 had non neutralisant antibodies and 3 had both anti-VWF and anti-FVIII. Thus, anti-VWF was found in 14% of patients with type 3 VWD. Median age at diagnosis of alloimmunization was 30 years [4 years - 47 years] with a female predominance (sex ratio M/F= 0.2). Circumstance of the discovery of alloimmunization were persistent hemorrhagic symptoms despite adequate substitution in 4 cases, a preoperative evaluation in 1 case and an anaphylactic reaction secondary to VWF concentrate administration in 1 case. Our patients were on replacement therapy with cryoprecipitate or VWF/FVIII plasma concentrates (Immunate®). The first patient had a hemarthrosis of the elbow resistant to substitution. Anti-VWF antibodies tested positive with a titre of 5.8 Bethesda units (BU). Recovery test of infused VWF/VLFIII plasma concentrates was carried out with a total absence of recovery for VWF. She was treated with by-passing agent combined with immunosuppressor, which allowed an inhibitor level decrease to 0 UB and a reintroduction of immunate without incident. The 2nd and 3rd patients had a non-neutralizing anti-VWF discovered during an episode of gingivorrhagia resistant to substitution for one of them and during a preoperative evaluation for the other. The anti-VWF and anti-FVIII antibodies’ screening were negative. However, an anti-VWF, considered non-neutralizing, was determined since there were a total absence of recovery for VWF. They were treated with by-passing agent (Novoseven®) combined with corticosteroid therapy with good resolution of the bleeding episode. The last 3 patients had both anti-VWF and anti-FVIII antibodies. They were revealed during an allergic reaction to the replacement therapy in 1 case and a severe bleeding syndrome resistant to substitution in 2 cases. They were treated with by-passing agent combined with immunosuppressor with good clinical resolution. Summary/Conclusion: Alloimunization in VWD is more frequently reported in our patients (14% versus 5-10% in published series). Several types of antibodies were documented. In our knowledge, the coexistence of anti-VWF and anti-FVIII is extremely rare and isn’t yet reported. In this challenging situations, by-passing agents such as Novoseven®, recombinant FVIII and immunosupressive therapy may be useful. Keywords: Bleeding disorder, von Willebrand factor (vWF), Antibody, von Willebrand’s disease

OBJECTIVEBiclonal 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.METHODSWe conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis.RESULTSA total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ± 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.CONCLUSIONBGs 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.

Topic: 10. Myelodysplastic syndromes - Clinical Background: In high-risk myelodysplastic syndromes (MDS), the goal of therapy is to prolong survival and reduce the risk of transformation into acute leukemia, but only a few drugs are currently available for treatment. Aims: We report our therapeutics results of high - risk MDS ‘patients. Methods: This is a retrospective study included patients with high risk MDS classified according to the International Prognostic Scoring System (IPSS) as intermediate-2 or high-risk groups, and treated in Hedi Chaker Hospital in south of Tunisia, between 2015 and 2021. Results: A total of 43 patients were included with a median age of 57 years (24-83), and a sex ratio of 1.1. Five patients (<45 years) underwent an allogeneic hematopoietic stem-cell transplantation (AHSCT), with unfortunately an early toxic death in 3 patients, a relapsed disease in one patient after one year, and one patient is en complete remission after 48 months. Sixteen patients were treated by Azacitidine. 93 cycles were administered with a median duration of therapy of 6 cycles (1-18 cycles). Four patients had achieving a partial response with hematologic improvement, 6 patients had a stable disease and 6 patients had a disease progression. The median of survival of this group was 15 months; overall survival (OS) at 12 and 24 months was 57% and 15 % respectively. Two patients who having a deletion of the long arm of chromosome 5 received Lenalidomide allowing to obtain in a transfusion independence in both patients, with a transient cytogenetic response and after that a progression to acute leukemia in 24 months in one patient, and persistent hematologic response after 48 months of follow up in the other patient. The remains of patients (20 patients) received best supportive care with an (OS) of 24% at 12 months and 9% at 24 months. The overall survival (OS) of the whole cohort was respectively 42% and 13% at 12 and 24 months. Summary/Conclusion: AHSCT remains the only curative treatment when, but this concerns a minority of patients. Azacitidine improve the survival of patients compared to those received supportive care. The current challenge in the management of higher risk MDS is to improve outcome by combining classical hypomethylating agents with novel drugs. Keywords: MDS

Topic: 4. Acute myeloid leukemia - Clinical Background: Acute promyelocytic leukemia (APL) in children is rare, 5-10% of peadiatric acute myeloid leukemia. Aims: In this study, we present clinical and biological characteristics and outcome of children with APL. Methods: Our study was retrospective. It concerned all children, under 20 years, with the diagnosis of APL and followed in the hematology department of Hedi Chaker Hospital Sfax, from January 2000 until December 2019. The diagnosis of APL is based on morphological, cytogenetic and molecular study. The specific treatment is similar to that of the French protocol APL93 until 2013, and then similar to that of Spanish protocol LPA2005 since January 2014. We evaluated complete remission rate, death rate and overall survival (Kaplan-Meier). Results: We collected 20 patients with APL under 20 years, among 97 children with acute myeloid leukemia (20%). It was 12 boys and 8 girls, with sex ratio 1,5. The median age was 12 years. Hemorrhage syndrome au diagnosis was present in 80% of cases. The average white blood cell count was 18360/mm3. Hyperleukocytosis (GB> 10000/ mm3) was noted in 35% of cases. Disseminated intravascular coagulation (DIC) was founded in the majority of cases (95% of cases). Fifteen patients had the t(15,17), and three patients had additional cytogenetic abnormalities. Tow patients had a normal karyotype with positif PML-RARA transcript. Tow children died before treatment with hemorrhage. Four children died during the induction course and before evaluation. Complete remission was obtained in 13 patients (73% of the evaluable patients and 93% of the treated patients) and one patient failure (7%). This child was in CR after 2nd induction course. A late bone marrow relapse was observed in 2 patients (14%), after an average period of 45 months. After a median follow-up of 49 months, overall survival and event-free survival are 70% and 60%, respectively, and relapse-free survival is 79%. Summary/Conclusion: In our series, peadiatric APL (20%) is more frequently than that reported in the literature (5-10%). Clinical and biological characteristics are similar than that noted in the literature. However, hyper-leukocyte forms and early death rate were higher. RC rate, overall survival and event free survival were lower than that reported in the literature, could be explained by the higher hyper-leukocyte forms and early death rate. Keywords: APL, Pediatric

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 12–15% of newly diagnosed ALL cases. Due to intensive therapy, outcomes in T-ALL are steadily improving with 5-year event-free survival (EFS) reaching more than 80%. Acute lymphoblastic leukemia is thought to have distinctive features in Tunisian children and young adults. The analysis of T-ALL allowed a better study of their characteristics as well as their evolution after treatment. Aims: The aim of this study was to determine the clinical and biological characteristics of T-ALL and to the analysis of T-ALL to allow a better study of their characteristics as well as their evolution after treatment. Methods: In this study, we enrolled retrospectively all cases of patients under 30 years old, with T-ALL diagnosed in the hematology department of Hedi Chaker Hospital of Sfax, Tunisia, between January 2000 and December 2021. All patients were treated with the EORTC 58951 pediatric protocol. We studied the epidemiological characteristics (age, sex, clinical and biological signs). We also studied the therapeutic outcomes: complete remission, overall survival (OS), event-free survival (EFS), and relapse rate. Results: We enrolled 130 cases of T-ALL (33%) of all ALL diagnosed during this period. Forty-six cases (36%) of these T-ALL were aged more than 15 years. The sex ratio M/F was 2.1. A tumor syndrome was noted in 113 cases (88%), of which 37 cases were young adults (29%). Hyperleukocytosis of more than 100 G/L was detected in 47 cases (36%). Cytogenetic abnormalities were found in 42 patients (31%). On the 7th day of treatment with corticosteroids, 38% of cases were corticoresistant. According to risk group stratification, 73 cases (56%) were classified into medium risk 2 (MR2) and 57 cases (45%) into high risk (HR). The rate of complete remission (CR) was 86% (112 cases). The rate of toxic death was 27%. Allogeneic bone marrow transplantation was performed in 15 of 25 patients with CR of the HR group. Relapse occurred in 30 patients (27%). With a median follow-up of 159 months (13 years), OS and EFS at 5 years were respectively 54 and 53%. Summary/Conclusion: The frequency of T-ALL in our series (32%) is higher than those described in the literature (10 to 15%). This high frequency is also found in other Tunisian series as well as in the Tunisian multicenter study of 2005 (37%). The frequency of corticoresistance in our study (38%) is comparable to the literature (38 to 40%). The CR rate in our series was 86%, comparable to the literature (80 to 90%). However, the overall survival at 5 years was 54% lower than in the literature (70-80%), which could be explained by the high rate of toxic death (27%). Our therapeutic results could be improved by using other therapeutic arms particularly immuno-therapy such Nelarabine and CART-cells. Keywords: Young adult, Acute lymphoblastic leukemia, Children

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.

Background: More than 80% of children with acute lymphoblastic leukemia (ALL) can be cured, but subsets of patients have significantly worse outcomes. Improved supportive care and intensification of chemotherapy for the high-risk group of ALL have contributed to this improvement in survival rates. Aims: In this study, we analyzed the clinical, biological features, and therapeutic results of patients treated with the high-risk group of the EORTC 58951 pediatric protocol. Methods: From January 2000 to December 2021, 395 patients with ALL aged less than 30 years were treated by the EORTC 58951 pediatric protocol in the Hematologic department of Hedi Chaker Hospital. From those 37 patients were treated by the high-risk group (VHR). The VHR group includes patients with poor prednisone response at day 8 (more than 1000 blasts/mm3 on the blood smear), those with worse cytogenetic abnormalities (t (9,22), t (4,11), 11q23 deletion...), and those with complete remission after two courses of chemotherapy. From those patients, we analyzed the clinical and biological features (Age, sex, blood count, cytogenetic abnormalities, and blasts phenotypes) and therapeutic Results: remission rate, rate relapse, overall survival (OS), event-free survival (EFS) at 10 years follow up. Results: We enrolled 109 cases (27%) of ALL classified VHR groups. The median age of patients was 12 years old. Seventy-eight cases (72%) were aged under 15 years old. The sex ratio M/F was 1,8. Fifty-seven cases (52%) had T-ALL. A tumor syndrome was noted in 87 cases (83%). Hyperleukocytosis of more than 100 G/L was detected in 38 cases (35%). Oncologic karyotype revealed t(9,22) in 6 cases (6%), 11q23 deletion in 3 cases (3%), and t(4,11) in 3 cases (3%). On the 7th day of treatment with corticosteroids, 79% of cases were corticoresistant. The complete remission (CR) rate was 87% (95 cases). The rate of toxic death was 28%. Allogeneic bone marrow transplantation was performed in 30 of 95 patients with CR. Relapse occurred in 39 patients (38%). With a median follow-up of 140 months (11 years), OS and EFS at 10 years were both 41% versus 69% for other risk groups of ALL. Summary/Conclusion: Although the CR rate was 87%, OS and EFS were only 41% lower than those reported in the literature (80%). This could be explained by the higher rate of toxic death (28%) and the higher rate of relapse (38% versus 15 to 20% in the literature). Incorporating novel therapies, particularly immunotherapy (Blinatumumab, CAR T-cells) could improve the survival rates by decreasing the intensity of conventional chemotherapy and thereby reducing associated toxicity. Keywords: Children, High risk, Young adult, Acute lymphoblastic leukemia

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous invasive non-Hodgkin’s lymphoma (NHL) originated from mature T cells. PTCL represents 10-15% of NHL patients. The clinical manifestations are variable from one entity to another within the PTCL. Aims: The aim of this study is to describe clinical characteristics and prognostic factors of a cohort of patients with nodal PTCL in south Tunisia. Methods: Our study is retrospective, it involved patients with nodal PTCL treated in the hematology department of Sfax between January 2000 and June 2021.We studied Clinical and laboratory data. The diagnosis was confirmed by histological examination according to the 2016 World Health Organization classification of hematologic malignancies. Staging was performed according to Ann Arbor system after extension assessment which includes at least a CT scan and bone marrow biopsy. Results: Thirty-eight patients diagnosed with PTCL were registered. The most common histological subtype was PTCL not otherwise specified (PTCL NOS) (n=14, 37%) followed by anaplastic ALK negative T-cell lymphoma (ALCL ALK-) (n=12, 31%), angioimmunoblastic T-cell lymphoma (AITL) (n=9, 24%) and then (ALCL ALK+) (n=3, 8%). The median age was 51 years (17- 87) among whom 12 patients (32%) were >60 years old. The sex ratio was 2.4, the male predominance was found in all histological subtypes. A history of autoimmune disease was noted in patients with AITL such as vitiligo and psoriasis in one case each. A history of skin rush was observed in one case. B symptoms were present in 76% of cases. A performance status >= 2 was present in 40% of patients. The most common discovery circumstance was the presence of peripheral adenopathy (40% of cases) with cervical adenopathy being the most common localization. Splenomegaly was present in 29% of cases mostly seen in AITL (55%) and PTCL NOS (36%). Nine patients had hepatomegaly (24%). Pleural and pericardial infiltration were noted in one patient with AITL. Testicular and breast involvement were noted in one case of PTCL NOS each. Increased LDH level was noted in 60.5% of cases. An extended stage (III-IV) was found in 82% of cases. The most frequent extra-nodal localization was bone marrow infiltration (48%). Summary/Conclusion: The clinical and prognostic data in our patients are generally similar to previous reports in the literature. However, 48 % patients in this study had bone marrow infiltration, slightly higher than that in previous studies by 20%–30%. PTCL has a poor prognosis and several studies have shown that histological subtypes, Ann Arbor stage and bone marrow involvement are related with the prognosis of PTCL patients. Keywords: T cell lymphoma, Angioimmunoblastic T-cell lymphoma, Peripheral T-cell lymphoma, Chemotherapy

Topic: 4. Acute myeloid leukemia - Clinical Background: Acute myeloid leukemia (AML) is a group of malignant hemopathies genetically and phenotypically very heterogeneous. Identification of clinical and biological prognostic factors is essential for better prognostic stratification and therefore a better adaptation of the treatment. Aims: We aim to analyze the epidemiologic characteristics and diagnostic aspects of adult AML in southern Tunisia. Methods: Our study is retrospective. We included newly adult AML patients (age: 20-60 years) diagnosed and treated in the hematology department of CHU Hedi Chaker Sfax, between January 2005 and December 2020. Diagnosis has been established according to FAB classification confirmed by flow cytometry (FC). Patients with acute promyelocytic or secondary leukemia were excluded. The classification of AML into three risk groups was based on the Medical Research Council (MRC) stratification. The molecular study is realized by the RT-PCR method in order to search for mutations with a prognostic impact (CBF-Myh11, AML-ETO, FLT3). we report the demographic and epidemiological characteristics of patients, and we analyze the clinical and biological features of AML in southern Tunisia. Results: We collected 179 cases of adult AML, including 97 boys and 82 girls (sex ratio=1.18). The median age at diagnosis was 40 years (range: 20 to 59 years). The mean time to diagnosis was 23 days (extreme: 3-65 days). Clinically, the anemic syndrome was found in 154 patients (86%), an infectious syndrome in 108 patients (60%), and a hemorrhagic syndrome in 62 patients (35%). The tumor syndrome had been noted in 88 patients (49%). The median initial white blood cell and hemoglobin level was 13.6 G/L (extreme 4 G/L- 470 G/L) and 7.2g/dL (extreme:2.1g/dL-14.2g/dL) respectively. The median count of platelet was 40 G/L (extreme: 4 G/L -697 G/L) and severe thrombopenia (platelet < 50 G/L) was noted in 102 cases (57%). The most common cytological type was AML2 (24%) followed by AML4 (21%). Cytogenetic analysis was done for 98% of patients, while it was not feasible in 4 cases because of the SARS-COV pandemic. The oncological karyotype was normal in 46% of cases. Only 32 (18%) patients had favorable abnormalities [t (8.21) in 32 cases and 16inv in 9 cases]. Karyotype was complex in 12 cases (7%). The distribution of our patients according to the cytogenetic risk group was as follows: low-risk abnormalities in 18%, intermediate-risk in 69%, and high-risk in 13% of cases. The molecular study was feasible only for 91 patients, concluding to CBF-myh11, AML-ETO, and FLT3 in 15%, 11%, and 1% respectively. Summary/Conclusion: The clinical and demographic characteristics of our patients differ from those reported in the literature only by the median age which seems younger in relation to the inclusion criteria. The cytogenetic profile of our AML is characterized by the dominance of the normal karyotype which is comparable to the literature (46% in our series vs more than 40% in the literature) making the inclusion of the majority of our patients in the risk group intermediate (69%). More investigations in terms of molecular biology (made only in half of our cases) could be beneficial to better classify our patients to further adapt the treatment of each risk group. Keywords: Acute leukemia, Acute myeloid leukemia

Topic: 4. Acute myeloid leukemia - Clinical Background: Despite the improvement treatment in acute promyelocytic leukemia (APL), early death rate, 30 days following the diagnosis, remained higher (14 à 40%). Aims: We reported in this study, clinical and biological characteristic of patients with APL, died early. Methods: Our retrospective study concerned all patients with APL with the diagnosis of APL and followed in the hematology department of Hedi Chaker Hospital Sfax, from January 2000 until December 2019. The diagnosis of APL is based on morphological, cytogenetic and molecular study. The treatment is based on all-trans retinoic acid (ATRA) and chemotherapy regimens. We included patients died early 30 days following the diagnosis. Results: Among 79 patients with APL, twenty three patients died early (30% of cases). The median age was 31 years (extreme: 2-75 years) with sex ratio 1,3. Obesity with BMI more than 25 was noted in 65% of cases. An average delay between symptoms and diagnosis was 10 days. Hyperleukocytosis more than 10000/mm3 (high risk group) was noted in 78% of cases. Thrombopenia (platelets<40000/mm3) was noted in 91% of cases, with disseminated intravascular coagulation (DIC) founded in the majority of cases (96% of cases). Nineteen patients (83%) had hemorrhage syndrome at diagnosis. Eight patients died before treatment, between one and two days of diagnosis. Fifteen patients died early during the induction course before evaluation with an average delay of 8 days (extreme: 2-28). Causes of death before treatment were haemorrhage in seven cases (87.5%). Causes of death during treatment were multiple: respiratory disease due to the differentiation syndrome, a severe haemorrhagic syndrome and or septic shock. Summary/Conclusion: Early death rate is similar to that reported in the literature. Older age, hyper-leukocyte forms, DIC and delay in diagnosis were risk factors in our study. Early diagnosis of APL is essential to reduce the mortality rate and improve overall survival, by establishing early support treatment and administration ATRA therapy as soon as the diagnosis is suspected. By the other way, the use of combined ATRA and arsenic trioxide without chemotherapy, in non-high-risk patients could be an alternative to reduce hematology toxicity and early death rate. Keywords: Hemorrhage, Mortality, Acute promyelocytic leukemia

Topic: 4. Acute myeloid leukemia - Clinical Background: Acute myeloid leukemia (AML) is a serious, but potentially curable hemopathy. Despite the progress of AML treatment in recent decades mainly due to the use of intensives therapies and the improvement of onco-hematological reanimation, this treatment remains disappointing with survivals prolonged by 30 to 40% and a significant risk of relapse in the absence of bone marrow allograft. Aims: We evaluate the therapeutic results of the national protocol inspired by the MRC-10 study in the treatment of adults AML. Methods: From January 2005 to December 2020, we retrospectively studied the outcome of adults, aged 20 to 60 years, with de novo AML treated with the national protocol of AML inspired by the MRC-10 study, in the clinical hematology department of Hedi Chaker Sfax Hospital. Secondary leukemia and FAB M3 were excluded. The classification into two therapeutic groups: favorable and unfavorable, is based on cytogenetic, molecular analysis, and chemosensitivity. Allograft is indicated for patients under the age limit defined according to the period, belonging to the unfavorable group (or favorable group with delayed molecular remission) and having an intra-family HLA-compatible donor. Allograft was performed at the national transplant center of bone marrow. We are interested in the response to treatment: complete remission rate (CRR), failure rate, toxicity-related mortality (TRM), relapse rate, and survival: overall survival (OS), and disease-free survival (DFS). The survival analysis was on the Kaplan-Meier method. Results: We collected 179 patients. The medium age was 40 years, and the M/F ratio was 1.18. The distribution of AML according to the cytogenetic risk group was as follows: 18% low-risk abnormalities, 69% intermediate-risk, and 13% high-risk. The molecular study was feasible only for 51% of cases concluding to CBF-myh11, AML-ETO, and FLT3 in 15%, 11%, and 1 % respectively. Eighty-five percent of patients received Idarubicin during induction, and the remaining received Daunorubicin. CRR after one and two courses were 65% and 68% respectively; it is only correlated with age (P=0.005) and cytogenetic risk group (P<0.0001). The failure induction rate was 16%. The mortality rate during induction therapy was 19%. Severe sepsis was the main cause of death (38%). The therapeutic group was favorable in 36 cases (32%) and unfavorable in 77 Cases (68%). Seventy percent of patients had consolidation by chemotherapy alone. Among the 113 patients in CR and treated according to the protocol, allograft was indicated for 70 patients (62%). The allograft was performed only for 35 patients: 31% (76% of patients with an HLA-compatible donor). The relapse rate was 35%. Relapse is correlated only with the feasibility or not of allograft in CR1 (P=0.03). After a mean follow-up of 100 months, 5 years OS, and DFS were 36%, and 59%respectively. OS was correlated with age at diagnosis (p=0.01), cytogenetic group (p=0.001), and allograft in CR1 (p<0.0001) while DFS was correlated only with allograft in CR1 (p<0.0001). Summary/Conclusion: The therapeutic results of our patients are similar to MRC 10 results in terms of initial failure (16% vs 10%) and survival rate (OS at 5 years was 36% vs 40%). However, our population is characterized by a very high rate of induction death (19% vs 5-10%) and a lower rate of CR after induction (68% vs >80%). Our results can be improved by reducing the death rate by developing of hematological reanimation and by adapting the consolidation treatment according to the prognostic group and the rationalization of the allograft (hoploidentical or unrelated graft). Keywords: Acute myeloid leukemia

Background Multiple myeloma (MM) is the most frequent malignant plasma cell disorder with proliferation of neoplastic plasma cells in the bone marrow or other tissue, most commonly in the upper aerodigestive tract. The invasion of the thymus is exceptional. Neurological complications are usual, but represent exceptionally the revealing symptom. Case presentation We report a case of polyneuropathy revealing a thymic plasmacytoma as a mediastinal invasion of MM in a 48-year-old woman. She was admitted after developing progressive ascending distal paresthesias and weakness in lower limbs. Examination showed symmetrical distal sensorimotor impairment with axillary and inguinal adenopathies. Electroneuromyography revealed a sensorimotor length-dependent neuropathy. Serum protein electrophoresis showed monoclonal protein peak in β-γ globulin region. Immunoelectrophoresis showed IgA lambda monoclonal gammapathy. Myelogram and bone marrow biopsy revealed plasmocytosis of 5%. Chest computed tomography showed a histologically confirmed thymic plasmacytoma associated with a lytic lesion of the 5th rib leading to the diagnosis of MM. Conclusions The association between a thymic plasmacytoma and peripheral neuropathy is rare and a workup for MM is necessary to guide therapeutic management.

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: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.