16^th World Hematology Congress March 18-19, 2019 Rome, Italy

Shinta Oktya Wardhani is an MD Trainee in Hematology and Medical Oncology at Hasan Sadikin Hospital, Padjadjaran University and has special interest in apheresis and other hematology and oncology research with a 3rd Best Poster Presentation Award from Indonesian Society of Medical Oncology in ROICAM 6 Conference in Jakarta on 23-26 August 2018 and 2nd Best Oral Presentation in Regional Conference of Internal Medicine (Trigonum SUDEMA) in Malang on July 2018. She also become an author and co-author of some publication including “correlation between soluble urokinase plasminogen activator receptor with CD-4 T lymphocyte and WHO clinical staging of HIV infection”.

Hyperleukocytosis is defined as total leukemic blood cell count greater than 50x109 L or 100x109 L. Critical hyperleukocytosis can cause leukostasis, a poorly understood and life-threatening complication. The incidence of hyperleukocytosis and leukostasis differs among various types of leukemia. Leukapheresis is known to be a rapid and safe procedure to reduce leucocyte (leukoreduction) and early mortality in patients with hyperleukocytosis leukemia. The aim of our study is to investigate the correlation of hematologic parameter before leukapheresis to the degree of leukoreduction. We retrospectively analyzed 42 patients with hyperleukocytosis leukemia with and without clinical sign of leukostasis. Paired t-test showed that there were significant leukoreduction (p<0.001), decrease of neutrophils (<0.001) and also platelets (p<0.001) after leukapheresis. The result of bivariant analysis indicated that all haematologic parameters before leukapheresis, hemoglobin (r=0.364; p=0.009), leukocyte (r=-0.397; p=0.005), platelets (r=-0.385; p=0.006), haematocrit (r=0.512; <0.001), lymphocyte (r=0.408; p=0.004) and neutrophil (r=- 0.300; p=0.027) correlate with leukocyte reduction. This result was similar to Jin Y-study, who found that only leukocyte and haematocrit had an influence on collection efficiencies (rate of leukocyte depletion). In conclusion leukapheresis is effective in reducing leucocyte and neutrophil, but also platelets. Hematological parameters before leukapheresis significantly correlate with the degree of leukoreduction.

E Tjønnfjord took his Degree at Odense University Hospital, Denmark. He has worked in the field of hematology with a special interest in the benign hematology.He is now starting a PhD focusing on the treatment of ITP and how to improve it.

Introduction: Immune thrombocytopenia (ITP) is characterized by immune mediated destruction of platelets and suboptimal production. RITP was a randomized placebo-controlled trial in which ITP patients who failed to achieve adequate response to steroids were randomized to receive rituximab or placebo plus standards of care (Ghanima et al. Lancet 2015; 385:1653-61). Study end points were treatment failure (splenectomy or meeting criteria for splenectomy), response rates and duration of response with a follow-up of 18 months. Apart from longer duration of response in the rituximab arm, the study showed no significant differences and the other outcomes. Objective: To provide long-term rates of splenectomy, death and duration of response based on extended open follow-up after completion of the RITP study. Methods: Platelet counts, splenectomy status, ITP medication and death were retrospectively collected. Response was defined as platelet count of >30X109/L or atleast a doubling of the platelet count from baseline without administration of any platelet increasing therapy except stable or decreasing doses of prednisone or prednisolone during the past 4 weeks; or > 100X109/L for complete response (CR) after week 4 from first study drug administration. Relapse was defined as platelet count <30X109/L or reinstitution of ITP medication. The study was approved by the ethics committees in Norway and Tunisia. Results: Extended follow-up data were acquired from 90 of 109 patients participating in RITP. Median duration of follow-up from randomization to last observation was 72 months (IQR 62-82). Overall 35 patients underwent splenectomy (13 in the rituximab; 22 in the placebo arm) with a trend towards longer time to splenectomy in the rituximab arm (p=0.11) (figure 1). Eleven patients (10%) died during the extended followup: 5 in the rituximab and 6 in the placebo arms. Seventy-six of 109 patients achieved response (40 in the rituximab; 36 in the placebo arms) including complete response (28 in the rituximab; 21 in the placebo arms) during the RITP study. Figure 2 shows probability of first relapse in responding patients. Median duration of response was 8.2 (5.2-16.7) after response and 17 (8-34) months after CR, in the rituximab arm and 1.8 (1.3-3.7) and 11 (4.5- not reached) months respectively in the placebo arm. Not statistically significant (p=0.09). During the extended follow-up, 2 more patients in the rituximab arm relapsed after achieving response and 4 after achieving CR. Conclusion: To our knowledge, the data provided here represent the longest single study follow-up reported on the effect of rituximab in ITP. Although, rituximab seemed to yield longer duration of OR and CR, the effect was clearly transient and the two curves cross after 34 months. Around 20% of patients in both arms are still responders at 6 years. Interestingly a trend towards lower splenectomy rate was found in rituximab treated patients. The retrospective collection of data in the follow-up represents a limitation of this study. In the future, efforts should be made to augment the initial response to rituximab and to prolong the duration of response, as our ongoing prolong study (NCT03010202) will look at.

Shehab F Mohamed is a hematologist in National Center for Cancer Care and Research, Qatar which is a part of Hamad Medical Corporation. He has multiple publications in infections disease, hematology leukemia, MPNs

Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a subtype of extra nodal B-cell lymphoma with growth limited to the luminal of small vessels. Intramural great vessel lymphoma (IMGVL), on the contrary is extremely rare. Case report: We report a 72-year-old male, smoker (40 pack-years) with hypertension and chronic kidney disease presented with severe abdominal pain. The patient experienced decreased appetite and weight loss of around 15 kg in the past one month. The patient underwent CT abdomen with IV contrast which showed aneurysmal dilatation at the level of first lumbar vertebra (L1) with circumferential thrombus. He was diagnosed to have Type IV Thoracoabdominal Aortic Aneurysm with total occlusion of the Infrarenal aorta and severe celiac artery stenosis as well as complete occlusion of the inferior mesenteric artery, complete occlusion of the distal abdominal aorta and near total occlusion of the left renal artery. Surgical repair of thoracoabdominal aneurysm was done along with complete revascularization of the abdominal viscera including celiac artery, superior mesenteric artery, bilateral renal and aorto-bifemoral bypass. The vessels appeared completely normal without any tumor growth. However, there was a thrombus in the aorta. Macroscopic examination showed a fragmented thrombus measuring 8x8 cm in aggregate. Image 1 A surprising diagnosis of intramural great vessel lymphoma (IGVL) large B cell lymphoma was made. Patient was treated with 6 cycles of R CHOP chemotherapy with dose reduction. Discussion: Primary tumors of the aorta are extremely rare with around 100 reported cases. There are noted primarily in the abdominal aorta in association with an aneurysm or mimicking one. Intravascular large B-cell lymphoma (IVLBCL) is a distinctive subtype of extra nodal B-cell lymphoma based on intravascular growth of neoplastic B cells that is limited to the lumen of capillaries or small vessels. Primary IMGVL is exceptionally rare. To the best of our knowledge, this is the fourth reported case of intramural large B-cell lymphoma involving a large vessel which represents an entity distinct from IVLBCL clinically and histologically. Conclusion: This report debates the concept of DLBCL associated with chronic inflammation and raises the question of other pathogenetic factors involved in the pathogenesis of this rare disease.

B Yusuf Jamoh has completed his MBBS programme from Bayero University, Kano, Nigeria and had MSc Cancer Biology, with commendation, from Kingston University, London. He is a Fellow of National Postgraduate Medical College of Nigeria and was appointed as Honorary Consultant Physician, Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria. He is the Head of Clinical Haematology Unit, ABUTH. He has published 12 papers in reputed journals and he is currently acting Postgraduate Coordinator, Department of Medicine, Ahmadu Bello University, Zaria, Nigeria.

Background: Myelodysplastic syndromes (MDS) are the most common of myeloid malignancies, yet the morphological diagnosis is usually not straightforward especially in the low-grade forms. Immunophenotyping by Flow cytometry (FCM) is considered essential in the WHO’s co-criteria for diagnosis of MDS. The Existing FCM Protocol utilizes a 2-tube, 2-colour approach to identify lineage specific cluster of differentiation (CD) markers, which is labour-intensive and time-consuming. A new FCM was recently developed and validated among Japanese cohorts. It utilizes a 3-tube, 5-colour approach and generates more information in the form of ‘cardinal parameters’. The aim of this study is to determine the diagnostic utility of the new protocol by comparing it with the existing protocol, in the diagnosis of low-grade MDS in our study population. Subjects and Methods: We analyzed bone marrow samples of 40 subjects. They comprised of 27 patients who had a tentative diagnosis of MDS and 13 healthy bone marrow donors as controls. Immunophenotyping by FCM was performed using the Existing and New Protocols and the data obtained by the 2 different methods were compared.‘Cardinal parameters’ were generated in the new protocol, which are not applicable to the existing protocol. Results: There was no statistical difference between the data generated by the 2 protocols in the diagnosis of MDS. The sensitivity and specificity of the ‘cardinal parameters’ of the new protocol appeared to be outstanding Conclusion: It has been shown that the new multiplex FCM protocol for the diagnosis of MDS is relatively easy, cost effective and not inferior, compared to the Existing Protocol. However, small sample size has been identified as a limitation to the study and therefore a larger, multicenter study is recommended to assess this validation exercise. Key words: Validity, New flowcytometry protocol, diagnosis, Low grade, Myelodysplastic syndromes

Shehab F Mohamed is a Hematologist in National Center for Cancer Care and Research, Qatar which is a part of Hamad Medical Corporation. He has multiple publications in infections disease, hematology leukemia, MPNs.

Background: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder. They also have a tendency for thrombosis with predilection for unusual locations in the venous system. We report a young Filipino lady who is having two types of hemolytic anemias PNH and G6DP. We find this according to our knowledge as extremely rare. scenario: 31 Year Filipino ladies admitted in 2016 with the chief complaints of red colored urine and yellowish discoloration of eyes; she also had episodes of dizziness, generalized weakness, headache and SOB. Investigation on this admission showed anemia, peripheral smear revealed a picture of hemolysis again. Direct Antiglobulin Test (DAT) was ordered and it came out as negative and subsequently the patient received blood transfusions. She had hemolysis as evidenced by raised LDH, low haptoglobin and raised bilirubin in the absence of a positive DAT test; this made us to suspect PNH. In order to confirm the same, we did flow cytometry which showed large (PNH) clone within the red cells (69.6%), granulocytes (99%) and the monocytes (98%). The hemolysis work up at the same time showed low G6DP. Eculizumab requested for patient but meanwhile they treated with steroids and her hemoglobin improved and hemolysis stopped. Discussions PNH is classified into classic PNH (presence of hemolysis with no marrow abnormality); PNH with marrow disorders (aplastic anemia/myelodysplastic syndrome /primary myelofibrosis and subclinical PNH without clinical evidence. G6PD is needed to maintain NADPH and consequently reduced glutathione levels in red blood cells. G6PD-deficient people, mainly males can be asymptomatic but they are subjected to episodes of hemolysis, when the red blood cells are subjected to oxidative stress caused by infections, certain drugs or in the case of favism, after eating fava beans. Several polymorphic variants have been described with specific geographical distributions, though milder than other variants such as G6PD. G6PD deficiency usually only affects hemizygous males and homozygous females but heterozygous females can be affected when for example; biased X-inactivation has led to a predominance of red blood cells expressing the mutant protein. In PNH there is complement induced lysis of RBCs due to the abnormal sensitivity of RBC cell membrane. Hemolysis this causes reduction in hemoglobin and hemoglobinuria with resultant increase in LDHPNH is X linked and so do G6DP, so we suggest and hypothesis that chromosome x has role in this rare case of combined hemolytic anemia. Another interesting thing to observe or mention according to our literature review was all previous two cases in addition to our case were females. Conclusion: Association of G6DP and PNH is very rare. There is no clear evidence so far, but the hypothesis it related to chromosome X and further case reports and studies are needed to study in this association.

Shehab F Mohamed is a Hematologist in National Center for Cancer Care and Research, Qatar which is a part of Hamad Medical Corporation. He has multiple publications on infections disease, hematology leukemia, MPNs.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare life threatening blood disorder famously characterized by thrombocytopenia, micro angiopathic hemolytic anemia, fever, renal impairment and neurological abnormality. Plasmapheresis and steroids is the standard of care, however there are refractory cases of TTP which require further managements. Rituximab is used as salvage treatment for refractory TTP. We report here two difficult cases of refractory TTP responded to Rituximab twice weekly. Clinical cases: The first case is a 32 years old male patient, known case of ulcerative colitis on Mesalamine, presented because of watery diarrhea, initial investigation were suggestive of TTP (high bilirubin, low platelet, low HGB and high creatinine). He was started on plasmapheresis and prednisolone. During his stay he devolved status epileptics for which he was intubated, started on levetiracetam and transferred to the Intensive care unit (ICU) He started to show improvement in terms of increase in platelets count after plasmapheresis and steroids, then he deteriorated and so he was started on Rituximab twice per week in addition to the steroids and plasmapheresis. He was extubated later after improvement and sent to the medical word for further rehabilitation and medication adjustment. The second case is a 26 years old male patient, presented complaining of anorexia, nausea and yellowish discoloration of the sclera and a few episodes of vomiting for 3 days before admission. Patient was initially doing well then he started to develop neurologic symptoms in the form of dysphasia, confusion and eventually he became obtunded and nonresponsive requiring intubation and MICU admission, those neurological finding in addition to his lab picture of microangiopathic hemolysis and very low platelets, warranted the diagnosis of TTP. Patient received plasmapheresis daily, rituximab twice weekly and steroids, started to improve gradually after that eventually patient’s neurological status improved and completely recovered. Discussion: Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening blood disorder. The pathophysiology is lack of protease which cleavage von Willebrand large multimeric. The protease called ADAMTS13 and it could be absent congenitally or acquired Idiopathic TTP. The established management is plasma exchange (PE) along with steroids 80% of patients to survive, however, the result is still there are refractory and relapse cases. Refractory cases have higher morbidity and mortality. There is increase in usage of Rituximab as salvage therapy in cases of TTP. The two cases were of young males. The patients were not responding and developing neurological symptoms, while on steroids and PEX that means refractory. According to our knowledge rituximab twice weekly along with other chemotherapy agents was never used before. Our two patients were refectory to PE although, it was going on daily for more than 2-3 weeks along with steroids. Conclusion: Rituximab addition to PE and steroids is good strategy. Rituximab could be savage and lifesaving. We suggest it can be used twice weekly safely, although further studies needed to proof efficacy