Background: Several retrospective studies have confirmed that adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric protocols have better outcomes than similarly aged patients treated with adult protocols. Aims: We reported results and feasibility of a pediatric-based protocol (EORTC 58951) in adolescents and young adults. Methods: From January 2000 to December 2020, 95 patients aged 16 to 30 years with newly diagnosed ALL were treated, in the department of hematology department of Hedi Chaker Hospital, according to the EORTC 58951 pediatric protocol. Further leukemia characteristics (Sex, White Blood cell count, Blasts phenotype, Cytogenetic results), we studied the protocol results: response to prophase), risk group stratification (average: AR1 and AR2, very high: VHR), complete remission rate (CR), death rate, relapse rate and 5 years survivals (overall OS and event free EFS). Results: Ninety-five AYA ALL were treated with the pediatric protocol. Medium age was 20 years (range: 16 to 30 years). The patients were 60 males and 35 females (SR=1.71). A WBC> 100 G/l was noted in 28%. A T blast phenotype was noted in 48% of cases. Cytogenetic abnormalities were noted in 40% of cases. Fourteen patients (14%) were treated according AR1 arm, 50 patients (53%) according AR2 arm and 31 patients (33%) according VHR arm. CR rate was 81% after one course and 89% after 2 courses. Induction death was noted in 7% and post-induction death was noted in 14%. Twenty-eight patients from VHR group with familial donor underwent allograft. Thirty-one patients treated with VHR arm protocol were eligible for allogenic stem-cell transplantation (SCT), among them 21 patients had a familial donor and 15 patients were allograft (48%). Relapse was observed in 25 patients (26%) among them 4 after allograft. Fifty-four of relapses occurred within a year of CR. The median follow up was 129 months. The five years OS and EFS were respectively 49% and 47%. Summary/Conclusion: The results of this pediatric based study show that response to therapy and prognostic in adolescent and young adults were better than those treated with adult protocols and tolerability of chemotherapy is acceptable. However, OS and EFS, better than adult ALL treated by adult protocol (OS= 14%, EFS=14% in previous local study) but less than describe in the literature.

Background: The AL amyloidosis is one of the most common types of amyloidosis that is derived from the immunoglobulin light-chain. The clinical presentation varies widely depending on which organs are involved. In this work, we report the experience of the hematology department of Sfax in the management of patients followed for AL amyloidosis. Aims: Our study aims to evaluate the clinico-biological, therapeutic and evolutionary characteristics of al amyloidosis in our patients. Methods: Our study is retrospective, it concerned AL amyloidosis patients, followed in the hematology department of Hedi Chaker Sfax hospital between January 2010 and December 2021. The treatment was based on different chemotherapy protocols: the Cybor-D protocol (Bortezomib – Cyclophosphamide – Dexamethasone), the BorTD protocol (bortezomib – thalidomide – dexamethasone) and the M-DEX regimen (melphalan – Dexamethasone). Results: Our series included 20 patients with a male predominance (sex-ratio = 1.8) and a mean age of 58 years. 85% of the patients were followed for a multiple myeloma which was then complicated by amyloidosis. The initial symptomatology was polymorphic: cutaneous-mucosal involvement, cardiac symptomatology and neurological symptomatology were noted in 50%, 30% and 25% of cases respectively. The diagnosis was made on 2 different sites in 11 patients (55% of cases). Anemia was found in 55% of cases, and renal failure was reported in 50% of thes cases. Monoclonal gammopathy was found in all patients with demonstration of the Lambda and kappa chain in 50% of cases each. Transthoracic ultrasound revealed signs of myocardial amyloid infiltration, such as wall thickening greater than 15 mm, in 11 patients. Cardiac involvement, labial amyloidosis and renal involvement were diagnosed in 60%, 55% and 25% of cases respectively. According to the classic Mayo Clinic prognostic score, 4 patients were at stage I, 4 others were at stage II and 12 patients were at stage III. Regarding the treatment, 9 patients (45% of cases) received the Cybor-D protocol, 6 patients were treated with the BorTD protocol, 4 patients received the M-Dex regimen, and 1 patient died before starting treatment. This first-line treatment resulted in objective response rate (VGPR and CR) at 42% of cases (n=8), partial response at 16% (n= 3), Progression at 16% (n=3), toxic death at 10% (n=2) and 3 patients were lost to sight before assessment. This objective response was obtained by protocols based on Bortezomib. For patients with amyloid cardiomyopathy (12 patients), 5 were progressing at the end of treatment despite the fact that 4 of them were in hematological CR, and 2 died from cardiac decompensation. A relapse occured in 6 patients out of 11(CR+VGPR+RP) after a median time of 29 months. Median overall survival was 18 months. Summary/Conclusion: Through this work, we notice the polymorphism of the amyloidosis clinico-biological presentation as well as the concept of multiorgan involvement. The light chain was Lambda in 50% of cases, whereas it is predominant (80%) in the literature (1), and cardiac involvement was the leading cause of morbidity and mortality as similar as what is reported (1). Treatment is based on Bortezomib combined with other chemotherapy molecules (2). With this protocol, we obtained an objective response rate and a median survival rate a bit lower than the rates described in literature (1).

Background: Diffuse large B cell lymphoma (DLBCL) primarily affects older patients. In fact, quarter of all DLBCL are over 75 years. The majority of these patients is unfit for aggressive treatment protocols and the lack of randomized trials in this category makes it difficult to choose the best regimen. Aims: The aim of this study is to evaluate the outcome of DLBCL in this category of patients in our center. Methods: We conducted a single-center retrospective study. Newly diagnosed DLBCL patients over 60 years in 2008-2019 treated in the hematology department of Sfax were included. The diagnosis was confirmed according to the WHO Classification of Hematological malignancies. We defined the disease stage according to Ann Arbor staging system. Patients were treated according to the last 2 versions of the national protocol (LNH2008, LNH 2013): patients aged ≤70 years and ≤75 years since 2013 were treated with 6-8 courses of CHOP+/-R and patients aged >70 years (>75 since 2013) were treated with 6 courses of miniCHOP+/-R. We evaluated the response with the International Working Group (IWG) Response Criteria for NHL 1999. We estimated overall survival (OS) and event-free survival (EFS) with Kaplan Meier. Results: A total of 66 elderly patients with DLBCL aged >60 years were identified. Mean age was 71,2 years(61-87). 59% were male. Mean time from diagnosis was 7,7 months. B symptoms were present in 71% of the cases. An altered performans status (≥2) was noted in 50% of the cases. 42 patients had a raised LDH level. The stage of the disease was advanced in 59%. aaIPI was high (≥2) in 27 cases (41%). Nine patients died before treatment (14%). 37 Patients received R+/-CHOP regimen and 20 patients received R+/-miniCHOP regimen. An overall response was noted in 34 cases (60%) with a complete remission in 70% and a partial remission in 30%. Nineteen patients did not achieve the treatment (33%) because of treatment related mortality (TRM) in 10 cases (15%). A hematological toxicity with a grade III/IV neutropenia was noted in 16 patients. Four patients were refractory (7%). Nine patients relapsed (26%). Mean delay from end of treatment was 29 months. Five patients received a platinum-based second-line chemotherapy and 4 patients were unfit for an intensive chemotherapy. Median follow-up of the study was 94 months. 3-year OS and EFS were respectively 60% and 55%. Summary/Conclusion: DLBCL is an aggressive lymphoma of the elderly. The age limit should not be an obstacle for prescribing a chemotherapy. Evaluating the elderly must be using objective tools to distinguish the category of patients unfit for an intensive treatment. In our study, CR rates were lower than the values reported in the literature (56-70%). EFS in our study was 55%, it was comparable to the literature (45-71%). TRM was slightly higher in our study (15% vs <10%). The availability of liposomal Doxorubicin, oral CHOP regimen and Dexrazoxane could change the outcome of this group of patients.

Background: Childhood acute lymphoblastic leukemia (ALL) is a hematologic malignancy with high rate of cure. Aims: We report the experience of the clinical hematology department of Sfax-Tunisia for the treatment of childhood ALL with the EORTC 58951 protocol. Methods: From January 2000 to December 2020, we retrospectively studied the outcome of childhood ALL aged less 16 years, treated with the EORTC 58951 pediatric protocol. For those patients we studied the leukemia characteristics (sex ratio, white blood cell counts WBC, blast’s phenotype, cytogenetic abnormalities) and response to treatment: response to prophase, remission rate, risk group stratification, treatment related mortality (TRM) (induction and post induction death) and survival (overall survival OS and event free survival. Results: From January 2000 to December 2020, 284 children were treated with the EORTC 58951 protocol. Medium age was 7 years (range: 1 to 15 years). Sex ratio M/F was 1.53. WBC counts more than 100 G/L were observed respectively in 41, 44 and 15% of cases. The blast’s phenotype was B in 70%. Cytogenetic abnormalities were noted in 37% of cases. A good response to prophase was noted in 80% and complete remission in 92% of cases. The EORTC risk group stratification was Low Risk (LR) in 5%, Average Risk1 (AR1) in 39%, Average Risk2 (AR2) in 25% and Very High Risk (VHR) in 31%. TRM was 10%: induction rate death was 6% and post-induction rate death was 4%. Twenty-eight patients from VHR group with sibling familial donor underwent allograft. The relapse rate was 29% of all patients in remission; 4% for LR group, 39% for AR1 group, 18% for AR2 group and 39% for VHR group. At a follow up of 126 months, OS and EFS at 10 years were respectively 61% and 56%. Summary/Conclusion: At diagnosis, childhood ALL in our study had poor characteristics particularly higher rate of T phenotype of blasts, higher rate of leukocytosis more than 100 G/L, higher rate of VHR therapeutic group and higher rate of cortico-resistant regarding occidental series. Despite the acceptable results concerning remission rate but survival rates remain lower than those observed in the literature, this is explained mainly by the high rate of relapse (29% vs ≃15%). It can be improved our results by detecting high risk patient with MRD study especially for AR1 risk group and doing allograft for VHR patients.

Background: Relapsed acute lymphoblastic leukemia (ALL) has remained challenging to treat in children, with survival rates lagging well behind those observed at initial diagnosis. Although there have been some improvements in outcomes over the past few decades, only ∼50% of children with first relapse of ALL survive long term, and outcomes are much worse with second or later relapses. Aims: In this study we describe clinical characteristics and therapeutics results of first relapse of childhood ALL. Methods: Our study included children under 16 years on first relapse of ALL treated according to the EORTC 58951 protocol between January 2000 and December 2020 in the Hematology department of Hedi Chaker Hospital of Sfax. The marrow relapse was defined as the reapparition in the peripheral smears and/or the increase of blasts (>20%) in bone marrow (BM) after a period of complete remission (CR). A combined relapse included another extra medullary location, neurological (N) or gonadal (G). Relapse treatment was based on the COOPRALL 1997 protocol and since 2008, COPRALL 2007 protocol or the VHR group of the 58951 EORTC protocol. Results: Among the 262 Childs in CR, 81 was relapsed (31%) after a medium follow-up of 127 months. There are 27 females and 54 males. Median age was 7 years and 6 months. Relapse’s frequencies in the groups low risk, average risk 1, average risk 2 and high risk were respectively 4, 39, 18 et 39% of cases. Median of relapse timing was 12 months (2 to 83). Cumulative incidence of relapse at 1, 2 et 3 years after complete remission (CR) were respectively 51, 67 et 84%. Three relapses were occurred after 5 years of CR. Timing of relapse was not correlated with treatment group (p=0.8). The relapse was only medullary in 72% of cases, only neurological in 5% of cases and combined in 19% of cases (M+N= 6%, M+G= 9% et M+N+G= 4%). Second course was delivered to 57% of these patients. Protocol followed was the COOPRALL 1997 in 12 cases (26%), COOPRALL2007 in 28 cases (61%) and EORTC VHR in 6 cases (13%). The second CR (CR2) was get in 55% (44 patients) of treated patients, among them only 6 were allograft (24%). Toxic death before CR had occurred in 19% of treated cases. Among relapsed patients without curative treatment, only one was vivant (neurological relapse). Survivors after first relapse were less than 20%. Summary/Conclusion: In our cohort, relapse’s rate was more than rates reported in other literature series (31% vs 10 to 15%). Relapse’s prognostic factors validated by the literature were the ALL’s phenotype, cytogenetic abnormalities (phi +), timing of relapse, combined relapses (medullary is more serious) and intensity of treatment. Those factors were not been find in our cohort because of the little number of cases. CR2 rates was less than literature (55 vs 80%); the revision of followed relapse’s protocol is to be discussed. As well, the survival of our patients after ALL relapse was less then reported rates (less than 20% vs 35% at three years). This is due to the abstention of treatment in patient in precocious relapse haven’t a sibling familial HLA donor.

Background: Refractory/relapsed (RR) disease is the main cause of morbidity and mortality in Diffuse Large B cell Lymphoma (DLBCL). Unfortunately, one-third of patients with diffuse large B-cell lymphoma continue on to relapsed or refractory disease despite the improvement of its management. Aims: The aim of this study is to evaluate our management of RR disease in our low-income center in the era of immunotherapy and monoclonal antibodies. Methods: This is a single-center retrospective study. We included all the cases of DLBCL diagnosed in University Hospital of Sfax between 2008-2019 that were refractory and/or relapsed. Clinical and biological characteristics at diagnosis were reported. A second biopsy was indicated in all cases when feasible. Refractory disease was defined as the absence of criteria of remission (complete or partial). Relapse was defined as the appearance of new lesions or the increase of at least 50% from nadir in the SPD from any previously involved site after a complete remission. Early relapse was defined as a relapse happening 12 months after end of treatment. The patients were treated with a second-line platinum based chemotherapy if fit. Autologous stem cell transplantation (ASCT) was indicated for patients who respond to second line treatment (partial or complete remission) and are fit for ASCT. Kaplan Meier system was used to estimate survival. Results: Among the 150 DLBCL diagnosed and treated during the study, 46 (31%) were relapsed/refractory: 13 (9%) were refractory to first line chemotherapy and 33 experienced relapse (22%). At the diagnosis, RR-patients are aged of 60 and less in 69% of the cases. A poor performans status≥2 was found in 30% of the cases. We found raised LDH levels in 53%. The disease was localized in 31%. aaIPI was at a minimum of 1 in 87% of the cases (1: 42%, 2: 24%, 3: 21%). We identified 3 predictive factors of refractory disease: Performans status (p=0,007), aaIPI (p=0,036) and raised LDH (p=0,019). For patients who relapsed, an early relapse was noted in 51,5% of the cases. Five patients relapsed after ASCT. Mean time from diagnosis was 20 months (2-72). Twenty-six patients were eligible for chemotherapy: 20 were treated with DHAP and 6 with ICE regimen. Five patients were in complete remission after salvage chemotherapy and 3 were in partial remission. Only 1 patient underwent ASCT after relapse and 3 patients after refractory disease. 1-year and 5-years Post-RR survival were respectively 24% and 14%. Summary/Conclusion: Even in the Rituximab era, patients continue to experience relapse and refractory disease. Our results are comparable to the literature where one third of DLBCL are either refractory (10-15%) or relapse (20-30%) and most relapses happen within the first 2 years after treatment. Predictive factors of RR identified in our study are the same than the factors reported in the literature in addition to age, B symptoms, advanced stage of the disease and bulk. Post-RR survival was poor in our study as well as in reports from the literature. The poor survival post-RR could be improved with new drugs regrettably not available in our country.

Background: Patients (pts) with newly diagnosed Multiple Myeloma (NDMM) face a high risk of developing a renal impairment (RI). It is one of the most feared complications in this population due to its severe immediate consequences and its poor outcome on the prognosis and the overall survival. We report our retrospective single-center study of NDMM in young pts with RI. Aims: This study aims to identify the incidence of renal failure (RF) in NDMM and analyze the renal response (RR), hematological response (HR), the overall survival (OS) and the prognostic impact after induction therapy. Methods: This retrospective single-center review over 4 years (between June 2016 and December 2020) includes young pts under the age of 65 years old with NDMM with RF eligible for autologous stem cells transplantation (ASCT). RF was defined by a serum creatinine higher than 177 μmol/L and the serum Creatinine Clearance (CC) was calculated according to the MDRD formula. All pts with RF in this study were treated with Bortezomib, Thalidomide and Dexamethasone (DT) as an induction regimen. RR and HR were defined according to the International Myeloma Working Group (IMWG14) criteria. In addition to antimyeloma treatment, pts with RI received symptomatic treatment such as intravenous hydration, corticosteroids, correction of hypercalcemia and in some cases dialysis. In this study, we identify the incidence of RF in NDMM and analyze the RR, HR, OS and the prognostic impact after induction therapy. Results: We included in our study 58 pts with NDMM. The incidence of NDMM with RF at diagnosis was 48,3% (n=28), the serum creatinine level median was 213μmol/L and the serum creatinine clearance (CC) median was 23.5 ml/min. According to the CC staging, the renal function was severely decreased in 11 cases (39%) and in the kidney failure stage in 5 cases (17%). The MM with RF immunoglobulin type was Light chain in 11 cases (39%), IgG in 12 cases (43%) and IgA in 5 cases (18%). After receiving symptomatic treatments of RF, 35% (n=10) of NDMM with RF pts had their renal function recovered whereas 64%(n=18) did not and 10% (n=3) needed dialysis. After induction therapy, the serum creatinine level median was 95μmol/L and the serum CC median was 73.5ml/min Thus, the RR was: complete in 64% (n=18), partial in 7%(n=2), minor in 18% (n=5), no response in 2 cases (7%) and one patient died before assessment. HR after induction regimen was 74% (n=20): complete response (CR) in 4 cases (14%), very good partial response (VGPR) in 8 cases (29%) and partial response (PR) in 8 cases (29%). Among the 18 pts with complete RR, 6 pts (33%) underwent ASCT. Pts with RF at diagnosis had a poorer OS median (18.5 months) comparing to those with normal renal function (OS median=21.5 months). The OS was significantly influenced by the degree of RF and the recovery of normal renal function (p<0.05). Summary/Conclusion: Our single center study showed that RI occurs in 48% of the cases in NDMM at diagnosis, which is significantly higher to what is found in the literature (5-30%). It also revealed that NDMM with RI has poorer HR and OS than pts with normal renal function when both treated by a Brotezomib induction regimen followed by ASCT. The RR after supportive care measurements and antimyeloma therapy was 74%, which is slightly lower to what is found in the literature (77%). Thus, early diagnosis and rapid initiation of a triplet Brotezomib based regimen for this high-risk group is essential and improves renal outcomes in RI pts.

The clinical features, treatments, and survivals of adult ALL patients are very different from the pediatric ALL patients. However, since the use of pediatric-like protocols for Philadephia (Ph) negative ALL (GRAALL), and treatments based on tyrosine kinase inhibitor (TKI) for Ph + ALL (GRAAPH), great improvements in adult ALL therapy have resulted. Our study aims to evaluate the characteristics, treatment patterns, as well as therapeutic results of ALL adult patients treated by GRAALL or GRAAPH protocol in a Tunisian center. Methods: Methods: Our study is retrospective about newly diagnosed ALL adult patients (>30 years old) treated between 2004 and 2020 at the hematology department of Hedi Chaker Hospital, Sfax, Tunisia, according to the GRAALL protocol for ph negative ALL, and the GRAAPH protocol (TKI containing treatment) for ph+ ALL. Imatinib was the first line TKI used. Allogenic hematopoietic stem cell transplantation (Allo-HSCT) was indicated for Phi+ and high-risk phi negative patients aged less than 50 years, and in complete remission. It was done in the national

Background: All-trans retinoic acid (ATRA) is the major advance in the treatment of acute promyelocytic leukemia (APL). Its introduction in the treatment of APL has revolutionized the outcome of this disease. Aims: The current study reports the clinical features and treatment outcome of patients with acute promyelocytic leukemia (APL) treated at the hematology department of Sfax from Tunisia. Methods: Our study was retrospective. It concerned all patients 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 evaluate the rates of remission, death and overall survival (Kaplan-Meier method). Results: We collected 79 patients. The sex ratio was 1.3 with a median age of 34 years (extreme: 2-75 years). Hyperleukocytosis (GB> 10000 / mm3) was noted in 29 patients (37%). The average white blood cell count was 21900 / mm3. The disseminated intravascular coagulation (DIC) was found in the majority of cases (72% of cases). The t(15,17) was found in 89% of cases. The PML-RARA transcript was positive in 100% of cases. Eight patients (10%) died before treatment with hemorrhage. Thirty three patients were treated by the APL 93 (group1) and thirty eight patients were treated by the protocol LPA2005 (group 2). Fifteen patients (22%) died early during the induction course before evaluation. Causes of death during treatment were multiple: respiratory disease due to the differentiation syndrome, a severe haemorrhagic syndrome and or septic shock. Complete remission was obtained in 55 patients (98% of the evaluable patients and 77% of the treated patients) and one patient failure (2%). No deaths were reported during consolidation or maintenance treatment. A late bone marrow relapse was observed in 8 patients (14,5%). At five years of follow up, overall survival and event-free survival are 66% and 64%, respectively, and relapse-free survival is 77%. Summary/Conclusion: In our series, the DIC rates are correlated with that of the literature, as well as early death rate. The complete remission and overall survival remain lower than that of the literature. This is explained by a high rate of early mortality (during induction) by hemorrhage, of the higher frequency of hyper-leukocyte forms and the delay in diagnosis and management for our patients.

Hodgkin - Clinical Background: Background: Relapsed and refractory Hodgkin lymphoma (RR-HL) challenges clinicians to devise treatment strategies that are effective and safe. Besides salvage systemic therapy, the use of consolidative stem cell transplantation, new biologics, and immunotherapeutic approaches, radiation therapy remains an integral component of treatment for many patients and must be used effectively and judiciously. The purpose of this study is to describe the indications and the modalities of radiotherapy (RT) for patients with RR-HL in our center, as well as its therapeutic results. Methods: Methods:

Background: Spinal cord compression (SCC) is the most serious complication in Multiple myeloma (MM). An emergency that must be diagnosed and treated promptly to preserve neurological functions and save the patient’s live. Aims: We studied the clinical, biological, and radiological features of patients with MM from southern Tunisia complicated by SCC and the different modalities of treatment. Methods: It is a retrospective study over 18 years (2003-2020) which included young patients (pts) (<65years old) with MM presented SCC and treated at the hematology department of Hedi Chaker Hospital Sfax, Tunisia. Here we are interested in studying the characteristics (clinical, biological, and radiological) of affected pts, the various revealing symptoms of SCC, the possible therapeutic modalities and the outcome of patients. Results: Among 173 young pts followed with MM, 18 had SCC (10%) which was inaugural in 5 pts (27% of cases). The average age was 53 years (36- 63 years) and the sex ratio M/F= 10/8. The MM immunoglobulin type was IgG in 6 cases, IgA in 7 cases, Ig D in 1 cases and light chains in 4 cases. Symptoms of SCC included pain, motor defects, sensory deficits and bowel and bladder dysfunction in respectively 72, 11,100 and 2% of cases. While in 2 cases the SCC was asymptomatic (11%). The spinal MRI showed a cervical compression in 2 cases (11%), a dorsal compression in 8 cases (44.5%) and lumbar compression in 8 cases (44.5%). In 17 cases, lesions were first treated by radiotherapy (which did not produce regression of the compression). Decompressive laminectomy was carried out one time. All patients underwent high doses of corticosteroids. Pts were subsequently treated by different regimens of systemic therapy (DT in 12 cases, MPT in 3 cases and VTD in 3 cases). In 17 cases a definite and steady regression of the neurological symptoms was achieved. Median overall survival was 34 months after identification of SCC. At the date of last news, around 66% of the pts were dead. Summary/Conclusion: The frequency of different localizations of compression in our studies are comparable to the literature, however, the SCC rate in our series is higher than those described in the other series in literature (10% vs 5%) the same for the rate of different symptoms at diagnosis (in literature more of asymptomatic form) which could be explained by the delay in the diagnosis of MM and by the neglect of minimal symptoms by patients and their consultation only after the installation of deficient signs.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, consumption thrombocytopenia, and organ injury. TTP pathophysiology is based on a severe ADAMTS13 deficiency, the specific von Willebrand factor (VWF)-cleaving protease. Aims: In this study, we aim to report our experience in patients with TTP, identify the main clinical and laboratory disease findings, treatment patterns, and evolution in these patients. Methods: This is a retrospective study of all adult patients (> 15 years) diagnosed and treated between 2000 and 2021 with TTP, at the hematology department of the university hospital of Sfax, Tunisia. Results: A total of 11 patients were enrolled in this study period. The median age was 38 years [range 22-72] and there was a female preponderance (2.6). At presentation, the majority of patients (8/11) had asthenia and neurological symptoms: confusion in 4 cases, convulsive seizure in 2 cases, and cerebrovascular accident in 2 cases. Five patients had fever, 4 had jaundice, and 3 presented with bleeding. Microangiopathic hemolytic anemia was noted in all patients with mean hemoglobin of 7.3 g/dl [5-8 g/dL], and 5% to 20% of schistocytes. Thrombocytopenia with platelets < 100x109/l occurred in 10 of 11 patients with mean platelet of 14 x109/l. Three patients had high serum creatinine levels, proteinuria and hematuria were present in 3 and 2 other cases respectively. The causal investigation showed that TTP was related to viral infection in 3 cases, newly discovered neoplasia in 2 cases, pregnancy in 3 cases, an immunologic disorder in one case, and idiopathic in 2 cases. Of the 3 pregnancy cases, 2 had a plasma activity of ADAMTS13 lower than 5%, and TTP was thus related to Upshaw-Schulman syndrome. For treatment, plasmapheresis associated with corticosteroids was promptly started in 9 patients, and 2 patients received corticosteroids alone due to hemodynamic instability. Four patients had also Rituximab as salvage therapy, and for the 2 patients with neoplasia, adequate chemotherapy was initiated. Four patients died due to shock with neurological involvement, respiratory failure, or multiple organic failure. The other 7 patients achieved remission, but two of them relapsed. Summary/Conclusion: Our study is consistent with clinical trial findings reported in the literature, showing that TTP has heterogeneous modes of presentation and not all patients have the complete typical features present. Since it has a fatal outcome, rapid diagnosis and management are recommended. Finally, the causal diagnosis should be made to initiate the appropriate curative treatment.

04. Acute myeloid leukemia - Clinical (AML A rare entity whose treatment is not established. we are studying the characteristics of a series of patients with greater than 2% noted in 3 cases (60%). Cytogenetic study the of a t (9.22) in all cases, which was isolated in 1 case. The BCR-ABL transcript was of the p190 type in 2 cases and p210 in 2 cases, while the molecular study was not done in the remaining case. Four patients were treated with tyrosine kinase inhibitor (TKI) alone with the achievement of complete remission (CR) in 3/4 of the cases while one patient was treated with the combination TKI and chemotherapy with good evolution. Allograft was not done for all patients, in 2 cases for the absence of an HLA compatible siblings donor. The median follows up was 108 months. Relapse was observed in 2 patients with CR2 in both cases. The five years OS was 80%.

Background: Hodgkin lymphoma (HL) is a hematologic malignancy with a high rate of curability. However, 5 to 20% are primary refractory to treatment or relapse after achieving a complete remission (CR) and present a therapeutic challenge. Aims: Our study aims to evaluate the clinical characteristics, treatment patterns, as well as therapeutic results in patients with refractory/ relapsed HL (R/R HL) in a Tunisian center. Methods: It is a retrospective study about adult patients (<60 years old) with R/R HL, treated between January 2008 and Mars 2020 at the hematology, oncology, and radiotherapy departments of the hospital of Sfax, Tunisia. The first-line treatment was based on ABVD in favorable early stages and BEACOPP regimens in advanced stages and localized stages with a bulky mediastinal mass. The standard of care for R/R HL was salvage chemotherapy followed by autologous stem cell transplantation (ASCT) in the national bone marrow transplant center in Tunis. The date of the point is in July 2021. Results: A total of 55 patients were enrolled, which represents 25% of our series of HL managed in this period. The median age was 30 years (range 17-59), and the sex ratio was 1.3. Twenty-five patients (45%) presented with refractory disease. Among the 30 patients (55%) who relapsed, 19 patients (63%) relapsed within 12 months after achieving CR. At relapse, advanced stage, anemia, and B-symptoms were respectively recorded in 60%, 33%, and 53% of cases. Two patients died before salvage chemotherapy (CT), so 53 patients were treated. Second-line CT regimens used were Cytarabine-based regimens (DHAC/DHAP) in 74% of cases, Gemcitabine-based regimens (IGEV) in 19%, and ICE in 7% of cases respectively. IGEV was the most effective regimen to mobilize peripheral blood stem cells (69% vs 30% with Cytarabine-based regimens). A CR was noted in 61% of cases. Radiotherapy was associated with CT in 35% of cases. Only 13 patients (42% of eligible patients) benefited from ASCT. The 5-year overall survival estimate for all patients was 46%, and 5-year PFS was 41%. Chemoresistance to salvage therapy, ≥ 2 lines of salvage therapy, non-realization of ASCT, and insufficient response after treatment were predictive adverse prognostic factors (p<0.001). Summary/Conclusion: Our study showed that CR and feasibility of ASCT were lower than that reported in international studies (61% vs 76%, and 46% vs 69 to 100% respectively), which incites us to a better involvement of ASCT. Besides, the association of new therapeutic agents such as Brentuximab Vedotin should be considered in our patients with chemoresistant HL.

Background: Plasma cell leukemia (PCL) is a rare form of leukemia and plasma cell dyscrasia defined by the presence of greater than 2×109/L peripheral blood plasma cells or plasmacytosis accounting for more than 20 % of the differential white cell count. PCL can be divided into primary PCL (PCL) and secondary PCL (sPCL) following previously diagnosed multiple myeloma (MM). It has an aggressive clinical course. Aims: In this study, we aim to identify the main clinical and laboratory disease findings, treatment patterns, and evolution in patients with PCL in a Tunisian center. Methods: Our study is a review of all cases of PCL, diagnosed and treated between 2000 and 2021 at the hematology department of the hospital of Sfax, Tunisia. Results: Nine cases of PCL were identified: 8 primary PCL cases, and only one sPCL case. The mean age was 53 years [range 31-64], and there was a female predominance (6:3). Most presenting symptoms were bone pain noted in 5/9 patients, asthenia in 3/9 patients, and bleeding was noted in only one case. Physical examination revealed extramedullary involvement in 4 patients: 2 had splenomegaly, one had hepatomegaly and one had lymphadenopathy. None of our cases showed skin infiltrates. Standard radiologic surveys showed bone osteolysis in all 9 patients, generally in the skull, and MRI showed epidural space infiltration and spinal cord compression in 2 patients. Normocytic, normochromic anemia was noted in almost all patients with mean hemoglobin of 6.9 g/dl. Rouleaux formation and a leukoerythroblastic picture were evident on almost all the peripheral blood smears. The mean leukocytosis was 15.3x109/l [range 3.4-100] and consisted of 20% to 88% of plasma cells. Thrombocytopenia with platelets < 100x109/l occurred in 50% of patients. Immunophenotyping by flow cytometry was done only in 2 cases with difficult morphology and showed expression of CD38 and CD138. Hypercalcemia was noted in almost all patients (8/9), and renal failure was present in 4 cases. Immunofixation revealed an even distribution between IgG and IgA, and light chain in 3 cases. The frequency of the Kappa chain was higher. Serum albumin levels were low in all patients. For treatment, 4 patients received VTD (Bortezomib, Thalidomide, and Dexamethasone), 2 received VAD (Vincristine, Adriamycin, and Dexamethasone), 2 were on Thalidomide Dexamethasone, and one patient received Revlemid Dexamethasone. Only one patient of these four patients who received VTD underwent autologous stem cell transplant (ASCT) after attaining CR but relapsed after 2 years into multiple myeloma and is currently in PR receiving MPT. All other patients died of progressive and refractory disease. The median survival was 9 months with a duration ranging from 2 to 63 months. Summary/Conclusion: As reported internationally, our study showed that patients with PCL were younger than myeloma patients, and presented with more aggressive clinical and laboratory features at diagnosis especially more bone lesions than classically described, and a high frequency of hypercalcemia. Besides, it indicated that even after the use of novel drugs, response to treatment is poor and PCL still has a poor prognosis.

Background: Multiple myeloma (MM) is a common hematological malignant neoplasm and it is primarily a disease of the elderly. Development of newer therapeutic agents and improving supportive care over the last decades has significantly improved outcome of MM in younger patients. However, most studies suggest that improvements are marginal in elderly patients. Aims: The aim of the study is to report the clinical, paraclinical and therapeutic features of the elderly multiple myeloma (age >65 years) in our center. Methods: We retrospectively reviewed data of patients aged over 65 years diagnosed with MM and treated at the hematology department of Hedi Chaker Hospital Sfax between January 2012 and December 2019. Response to treatment is evaluated according to the International Myeloma Working Group (IMWG). these patients are considered ineligible for autologous stem cell transplantation (ASCT). The induction regimen is based on the combination melphalan-prednisone-thalidomide (MPT) or melphalan-prednisone (MP). Clinical outcomes included: reason for treatment discontinuation, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AE). Results: A total of 40 patients (sex ratio M/F=1.35) were included in our study. Median age was 73 years [65-93 years]. 10 patients (25%) aged ≥80 years. Performance status (PS) was ≥2 in 29 patients (73%). sixty percent of the cases had at least one comorbidity. The median Charlson Comorbidity Index (CCI) was 4 [2–7]. Bone pain was the most common presenting complaint observed in 65% of the cases. Monoclonal IgG was the predominant protein M type’s (70%). According to the Durie-Salmon Staging System, IIIA was the main stage noted in 64% of the cases followed by IIIB in 23% of the cases. MPT and MP regimens were received in 57% and 17/40 respectively. ORR was 23%, including, VGPR 5 %, and PR 18%. None of the cases acheived complete remission. Stable disease occurred in 30 % and progressive disease in 7.5%. The remain cases were non evaluable (15/40). Treatment was discontinued in 14 cases (35%) after a median of 2 courses due to either progression or toxicity. Main adverse events were infectious in 25% (10 cases) and hematological in 22% (9 patients). Median Follow up was 77 months. Median survival was 24 months. OS and PFS were 47% and 44% at 2 years and 27% and 23% at 5 years respectively. Summary/Conclusion: Despite the fact that one third of our patients had no comorbidity, MPT and MP regimens in our study had insufficient results and correlated with a lower ORR and median survival comparatively to the literature (24 vs 48 months). It can be explained by the low rate of patients receiving Thalidomide. The combination of bortezomib-lenalidomide-dexamethasone for elderly patients may improve our results. In addition, structured frailty assessment is required in order to devise individualized treatment plan able to improve the clinical outcomes and the Quality of life.

Background: The core binding factor acute myeloid leukemia (CBF-AML) is characterized by t(8;21) and inv(16)(p13q22)/t(16;16)(p13;q22) cytogenetic abnormalities. It is associated with a good prognosis. Aims: In this study, we aimed to assess the treatment outcome of the pediatric CBF- AML in comparison with non CBF-AML treated in our center. Methods: We retrospectively reviewed data of patients under the age of 20 diagnosed with de novo AML in our center during january 2005 and december 2020. The treatment protocol includes: a course of induction (Cytarabine 200mg/m2/day associated with Daunorubicine (DNR) 60 mg/m2/day or Novantrone 12mg/m2/day). If a complete remission (CR) is achieved the chemotherapy is followed by: a cure of ADE (Cytarabin, DNR, Etoposide) associated with 2 cures of high dose of Cytarabine (12g/m2) before 2011 and a cure of ADE associated with 3 cures of high dose of cytarabine (18g/m2) after January 2011. Allogeneic stem cell transplantation (ASCT) from matched sibling donors was limited to patients who are in CR1, having an HLA-identical family donor before January 2011 and for patients who are in CR2 after January 2011. Endpoints were complete remission (CR), overall survival(OS), event free survival (EFS) and relapse rate. Survival statistical analysis performed with Kaplan Meyer method. Results: A total of 52 patients were included, of whom 16 (30%) presented CBF genes. The median age was 10years. The median white blood cells count at diagnostic was 28G/L. Distribution according to the FAB classification was as followed: 1(6%)M1, 8(50%) M2, 6(38%) M4 and 1(6%) M6.the most frequent subgroup was M2 (vs M1 in non CMF-AML, p=0.001). Cytogenetic analysis showed the Inv 16 (p13;q22) in 3 cases (18%) and t(8;21) (q22;q22) were observed in 11 cases (68%). Two patients had both CBFB–MYH11and AML-ETO rearrangement. Six cases (38%) had additional cytogenetic abnormalities. The correlation between cases with and without additional cytogenetic abnormalities did not conclude to any significent difference in terms of CR rate, OS and EFS. We observed a comparatively higher CR rate (87% vs 51% p=0.018) and also a better OS rate (83% vs 35%, p=0.02) at 5 years between CBF-AML and non CBF-AML. In contrast, there was no statisticly significent difference in terms of the EFS (67%vs 62%, p=0.4) and the relapse rate (31% vs 43%, p=0.3) between the 2 groups. Relapse occurred in 5 cases (31%) at a median of 13 months. A second remission was obtained in 2/5 patients. ASCT was performed in only 4 cases (3 after RC1 and 1 after relapse). Summary/Conclusion: The frequency of core binding AML in our study is higher than what has been reported in the literature (30 vs 15%) with predominance of The cytogenetic t(8,21) (68%). The additional cytogenetic abnormalities has no prognostic value. Long term survival in our series compared favorably with results reported by cooperative groups. It can be concluded that ASCT in CR1 for pediatric CBF-AML is no longer indicated.