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Subsequent neoplasms (SNs) compromise long-term survivors after hematopoietic cell transplantion. We performed a retrospective analysis of SNs in a cohort of 10358 recipients of umbilical cord blood transplantation (UCBT) reported to Eurocord/EBMT registries from 1988 to 2018. A total of 233 patients developed SNs. Median age at UCBT was 31 years (y) (0.3-69), and 84 were pediatric patients. Indications for UCBT were malignant hematological diseases in 199 patients (85%). Three groups of SNs were observed. Post-transplant lymphoproliferative disorders (PTLD) were reported in 145 patients in a median of 4 months after UCBT. Of these, 9/145 patients died from relapse, 83/145 from PTLD, and 24/145 from transplant-related causes. At last follow-up, 29/145 were alive; 5y-overall survival (OS) after PTLD diagnosis was 21±3%. Acute leukemia / myelodysplasia (AL/MDS) was diagnosed in 23 patients in a median of 28 months after UCBT and included 3 donor-cell AL. Four of 23 patients died from relapse of primary disease, 8/23 from progression of SNs, and 4/23 from TRM. Seven patients were alive at last follow-up; 5y-OS after AL/MDS diagnosis was 36±10%. Solid tumors (ST) were reported in 65 patients in a median of 54 months after UCBT. Most common tumor sites were lung, thyroid, bone and soft tissue. A total of 33/65 patients died (26 due to ST, 6 to relapse of primary disease, 1 cause missing). At last follow-up, 32/65 patients were alive; 5y-OS after the diagnosis of ST was 51±6%. In conclusion, despite their poor outcomes, SNs that occur after UCBT are extremely rare. Identification of associated risk factors and early detection may help to improve OS.

Four decades ago, Broxmeyer et al. demonstrated that umbilical cord blood (CB) contained hematopoietic stem cells (HSC) and hypothesized that CB could be used as a source of donor HSC for rescue of myeloablated bone marrow. In 1988, Gluckman et al. reported the first successful matched sibling cord blood transplant (CBT) in a child with Fanconi Anemia. In 1991, Rubinstein et al. established an unrelated donor CB bank, and in 1993, the first unrelated CBT used a unit from this bank. Since that time, >40 000 CBTs have been performed worldwide. Early outcomes of CBT were mixed and demonstrated the importance of cell dose from the CB donor. We hypothesized that improvements in CB banking and transplantation favorably impacted outcomes of CBT today and performed a retrospective study combining data from Eurocord and Duke University in 4834 children transplanted with a single unrelated CB unit (CBU) from 1993 to 2019. Changes in standard transplant outcomes (overall survival [OS], disease free survival [DFS], acute and chronic graft-versus-host disease [GvHD], treatment related mortality [TRM], and relapse) over 3 time periods (1: 2010 to 2019) were studied. Increased cell dose and degree of HLA matching were observed over time. OS, times to engraftment, and DFS improved over time. The incidence of TRM and GvHD decreased while the incidence of relapse remained unchanged. Relative contributions of cell dose and HLA matching to transplant outcomes were also assessed and showed that HLA matching was more important than cell dose in this pediatric cohort.

In single unrelated cord blood transplantation (UCBT), an increasing number of HLA allele mismatches (MM) has been associated with inferior overall survival (OS) attributed to higher transplant-related mortali-ty (TRM). Previous studies on the role of allele-level HLA matching following double UCBT (dUCBT) showed conflicting results. Herein we report the impact of allele-level HLA matching on outcomes of a large dUCBT cohort . We included 963 adults with hematologic malignancies, with available allele-level HLA matching at HLA-A, -B, -C and -DRB1, receiving dUCBT between 2006-2019. Assignment of donor-recipient HLA match was performed considering the unit with the highest disparity with the recipient. 392 patients received dUCBT with 0-3 and 571 with ≥4 allele MM. Day-100 and 4-year TRM were 10% and 23%, for recipients of dUCBT with 0-3 MM compared to 16% and 36% for those with ≥4 MM (HR 1.58, p=.002; and HR 1.54, p=.002), respectively. Higher degree of allele MM was also associated with worse neutrophil recovery and lower incidence of relapse; no significant effect on graft-versus-host disease was observed. Patients receiving units with 0-3 MM had a 4-year OS of 54% versus 43% for those with ≥4 MM (HR 1.40, p=.005). The inferior OS associated with higher HLA disparity was only partially mitigated by increased total nucleated cell doses. Our results confirm that allele-level HLA typing is a significant factor for OS following dUCBT and units with ≥4 MM (≤4/8 HLA-matched) should be avoided if possible.

The association between acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) and the human leukocyte antigens (HLA) has rarely been studied in terms of diversity of peptide-binding pockets. The objective of this study was to analyse whether motifs of HLA class I and class II peptide-binding pockets and/or their amino acid positions were differentially associated with ALL and AML. We included 849 patients from the Eurocord/European Blood and Marrow Transplant registry. The HLA peptide-binding pockets whose amino acid variability was analysed were B and F for HLA class I, P4, P6, and P9 for HLA-DRB1, and P4 and P9 for HLA-DQB1. The motif RFDRAY in P4 of HLA-DRB1*16:01/02/03/05 alleles and the motif YYVSY in P9 of HLA-DQB1*05:02/04/05 alleles, were statistically associated with ALL (corrected p value [p

Treatment of Venous thromboembolism (VTE) in cancer patients is challenging due to higher risk of VTE recurrence or bleeding under anticoagulants. We assessed the effectiveness of a dedicated “Allo-Thrombosis Cancer” multidisciplinary care program (AlloTC-MCP) that incorporated individualized care, regular follow-ups, telephone counselling, and a patient education program. From September 2017 to October 2019, 100 consecutive cancer patients with new VTE onset were enrolled in this observational single-center prospective pilot study and received standard (control group, n = first 50 patients enrolled) or AlloTC-MCP care (n = next 50 patients enrolled) over a 6-month VTE treatment follow-up period. Primary end-point was the percentage of adherence to the International Clinical Practice Guidelines (ITAC-CPGs) at 6 (M6) month follow-up. Among the 100 patients with different cancer types (22% genitourinary, 19% breast, 16% gastrointestinal, 15% lymphoma, 11% lung and 17% others), 51 patients (61%) had metastatic disease and 31 (31%) received chemotherapy alone. Main baseline cancer and VTE clinical characteristics did not differ between the 2 groups. Adherence rates to ITAC-CPGs was significantly higher in the AlloTC-MCP group (100% (M0), 72% (M3) and 68% (M6)) compared with the control group (84% (M0), 8% (M3) and 16% (M6)). Quality of Life (QoL) was significantly improved in the AlloTC-MCP group 6 months after inclusion. The “AlloTC-MCP” was associated with improved adherence to ITAC-CPGs and merits further expansion.

The public French Cord Blood Banks Network was established in 1999 with the objective of standardizing the practices governing umbilical cord blood (UCB) banking in France. The Network adopted a strategy to optimize its inventory and improve the quality of its banked units based on a quality improvement process using outcome data regularly provided by Eurocord. This study aimed to describe the results, over 10 years, of UCBT facilitated by a national network that used the same criteria of UCB collection and banking and to assess how modifications of banking criteria and unit selection might influence transplant outcomes. Nine hundred and ninety-nine units (593 single-unit and 203 double-unit grafts) were released by the Network to transplant 796 patients with malignant (83%) and non-malignant (17%) diseases. Median cell dose exceeded 3.5 × 107 TNC/kg in 86%. There was a trend to select units more recently collected and with higher cell dose. Neutrophil engraftment was 88.2% (85.7–90.7) and 79.3% (72.6–86.5) respectively for malignant and non-malignant diseases with a trend to faster recovery with higher cell doses. The respective 3-year transplant-related mortality were 31.1% (27.5–35.1) and 34.3% (27.0–43.5). OS was 49% ± 4 in malignant and 62% ± 4 in non-malignant disorders. In multivariate analysis, cell dose was the only unit-related factor associated with outcomes. Our results reflect the benefit on clinical outcomes of the strategy adopted by the Network to bank units with higher cell counts.

Bone marrow transplant, more recently called hematopoietic stem cell transplant (HSC), is a complex medical procedure in which a patient with or without malignant hematologic disease receives a combination of chemoradiation followed by an injection of HSC, either from the same patient (autologous transplant) or from a healthy donor (allogeneic transplant).

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

Unmanipulated haploidentical hematopoietic stem cell transplantation (HCT) with post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis (haplo-PTCY) and unrelated double-unit umbilical cord blood transplantation (dUCBT) are feasible options for treating patients with high-risk acute myelogenous leukemia (AML). This study compared outcomes after dUCBT and haplo-HCT using peripheral blood stem cells (PBSCs) in adult patients with AML in complete remission (CR) who underwent transplantation in European Society for Blood and Marrow Transplantation (EBMT)-affiliated centers. In a population of adults with de novo AML in first or second CR, we compared outcomes after dUCBT (n = 165) and after haplo-PTCY PBSC (n = 544) performed between January 2013 and December 2018. Patients receiving in vivo antithymocyte globulin, Campath, or ex vivo T cell depletion were excluded. The median follow-up was 33 months for the haplo-PTCY arm and 52 months for the dUCBT arm. No statistically significant differences were observed between the 2 arms in the rates of grade II-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 1.31; P =. 18), grade III-IV acute GVHD (HR, 1.17; P =. 56), chronic GVHD (HR,. 86; P =. 48), relapse (HR, 1.07; P =. 77), nonrelapse mortality (NRM) (HR,. 94; P =. 77), leukemia-free survival (LFS) (HR,. 99; P =. 95), or overall survival (OS) (HR,. 99; P =. 97). Favorable cytogenetic risk was the sole factor predictive of lower relapse incidence (RI). Younger age at transplantation was associated with lower NRM and higher LFS and OS. Both dUCBT and haplo-PTCY with PBSCs can be considered valid approaches for adult AML patients in CR. New strategies should be investigated in both settings to define the most appropriate conditioning regimen and potentially decrease RI and NRM through better immune reconstitution and optimal supportive care.

Background : Graft failure (GF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HCT). In the absence of autologous recovery, a second HCT is necessary to attempt preventing death due to prolonged pancytopenia. Previous studies describing outcomes of second HCT performed after a GF with different types of donor sources report a wide range of overall survival (OS) and transplant related mortality (TRM), however studies including a large number of patients receiving a second transplant with umbilical cord blood as the graft source are scarce. Objective : To describe umbilical cord blood transplants (UCBT) performed after GF following a previous HCT. Study Design : Retrospective registry-based study, using data extracted from Eurocord and the European Society for Blood and Marrow Transplantation (EBMT) databases. The study reports outcomes of 247 umbilical cord blood transplants (UCBT), performed in EBMT transplant centers, after GF following a previous HCT. Data were analyzed separately for patients with malignant (n=141) and non-malignant diseases (n=106). Results : The most frequent HCT that resulted in GF was also UCBT (65.0% and 68.9%), and most GF occurred within 100 days after transplantation (92.3% and 85.9%), for malignant and non-malignant diseases, correspondingly. Median follow-up was 47 for surviving patients with malignant and 38 months for those with non-malignant diseases. We observed a similar cumulative incidence of neutrophil engraftment of 59.1% (95% CI 51.4- 67.9%) and 60.4% (95% CI 51.7- 70.6%), in a median time of 23 and 24 days for malignant and non-malignant diseases, respectively. The 3-year OS was 28.9% (95% CI 21.8- 37.3%) in the malignant disease group and 49.1% (95% CI 39.5- 58.8%) in the non-malignant. In patients with malignancies, TRM was 39.9% (95%CI 32.5 - 49.1%) at 100 days and malignant 57.5% (95%CI 49.4 - 66.8%) at 3 years. In multivariate analyses, none of the characteristics studied were statistically significantly associated with engraftment or overall survival. Conclusion : Although survival for patients requiring a second transplant is not optimal, UCB remains a valid life-saving option for patients with GF.

Treatment of Venous thromboembolism (VTE) in cancer patients is challenging due to higher risk of VTE recurrence or bleeding under anticoagulants. We assessed the effectiveness of a dedicated "Allo-Thrombosis Cancer" multidisciplinary care program (AlloTC-MCP) that incorporated individualized care, regular follow-ups, telephone counselling, and a patient education program.From September 2017 to October 2019, 100 consecutive cancer patients with new VTE onset were enrolled in this observational single-center prospective pilot study and received standard (control group, n = first 50 patients enrolled) or AlloTC-MCP care (n = next 50 patients enrolled) over a 6-month VTE treatment follow-up period. Primary end-point was the percentage of adherence to the International Clinical Practice Guidelines (ITAC-CPGs) at 6 (M6) month follow-up.Among the 100 patients with different cancer types (22% genitourinary, 19% breast, 16% gastrointestinal, 15% lymphoma, 11% lung and 17% others), 51 patients (61%) had metastatic disease and 31 (31%) received chemotherapy alone. Main baseline cancer and VTE clinical characteristics did not differ between the 2 groups. Adherence rates to ITAC-CPGs was significantly higher in the AlloTC-MCP group (100% (M0), 72% (M3) and 68% (M6)) compared with the control group (84% (M0), 8% (M3) and 16% (M6)). Quality of Life (QoL) was significantly improved in the AlloTC-MCP group 6 months after inclusion.The "AlloTC-MCP" was associated with improved adherence to ITAC-CPGs and merits further expansion.

Bone marrow transplant, more recently called hematopoietic stem cell transplant (HSC), is a complex medical procedure in which a patient with or without malignant hematologic disease receives a combination of chemoradiation followed by an injection of HSC, either from the same patient (autologous transplant) or from a healthy donor (allogeneic transplant).

International audience

Background: Circulating endothelial cells (CECs), originated form endothelial progenitors (EPCs) are mature cells not associated with vessel walls and detached from the endothelium. Normally, they are present in insignificant amounts in the peripheral blood of healthy individuals. On the other hand, elevated CECs and EPCs levels have been reported in the peripheral blood of patients with different types of cancers and other diseases. Objective: This review aims to provide an overview on the characterization of CECs and EPCs, to describe isolation methods and to identify the potential role of these cells in hematological diseases and hematopoietic stem cell transplantation. Methods: We performed a detailed search of peer-reviewed literature using keywords related to CECs, EPCs, allogeneic hematopoietic stem cell transplantation, and hematological diseases (hemoglobinopathies, hodgkin and non-hodgkin lymphoma, acute leukemia, myeloproliferative syndromes, chronic lymphocytic leukemia). Results: CECs and EPCs are potential biomarkers for several clinical conditions involving endothelial turnover and remodeling, such as in hematological diseases. These cells may be involved in disease progression and in the neoplastic process. Moreover, CECs and EPCs are probably involved in endothelial damage which is a marker of several complications following allogeneic hematopoietic stem cell transplantation. Conclusion: This review provides information about the role of CECs and EPCs in hematological malignancies and shows their implication in predicting disease activity as well as improving HSCT outcomes.

International audience; Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

Four decades ago, Hal Broxmeyer demonstrated that umbilical cord blood (CB) contained hematopoietic stem cells (HSC) and hypothesized that CB could be used as a source of donor HSC for rescue of myeloablated bone marrow. In 1988, Gluckman et al reported the first successful cord blood transplant (CBT) of a child with Fanconi Anemia using matched sibling CB. This patient survives and 35 years later still has durable hematopoiesis from the CB donor graft. In 1991, Rubinstein et al established an unrelated donor (UD) CB bank and in 1993 the first UD CBT was using a unit from this bank. Since that time, >40,000 CBTs have been performed worldwide. We hypothesized that changes in cord blood banking (increased size, diversity, and quality of banked units enabling selection of units with higher cell doses and closer HLA matching) and in transplantation (less use of steroids, availability of newer therapies for prophylaxis and treatment of graft versus host disease [GVHD], improved antifungal and antiviral detection and therapeutics) have improved outcomes of CBT today. To address this hypothesis, we performed a retrospective study combining data from Eurocord and Duke University in a large cohort of children transplanted with a single UD CB unit (CBU) from 1993-2019. Standard transplant outcomes (overall survival [OS], disease free survival [DFS], acute and chronic GVHD, treatment related mortality [TRM], and relapse) and changes in outcomes over 3 time periods (1:2010, n=1802) were studied. Relative contributions of cell dose and HLA matching to transplant outcomes over time were assessed. A total of 4834 patients (4015 from Eurocord and 819 from Duke) were analyzed. The majority of patients, (59%, n=2839) had malignant diagnoses including 1422 with ALL, 887 with AML and 167 with MDS. Of the 1995 with non-malignant diagnoses, 761 had inborn errors of metabolism, 644 had primary immunodeficiency, 325 had a bone marrow failure syndrome and 206 had a histiocytic disorder. Half of the patients had positive serologies for CMV prior to transplant. The median age of the cohort fell from 5.2 to 3.25 years over time. In patients with malignancies, use of total body irradiation decreased over time. The median total nucleated cell (TNC) and CD34+ cell doses administered were 8.07x10e7 and 6.17x10e5 cells/kg and increased over time. HLA matching and transplantation of patients in earlier disease states also increased over time, p In conclusion, we analyzed the largest cohort of pediatric patients undergoing CBT over the past 3 decades. OS, DFS and engraftment have improved over time accompanied by decreases in TRM and acute GVHD. Relapse and chronic GVHD were stable and remain low. These improvements are explained by the increased availability of high quality banked CBUs enabling selection of closer HLA matching and units with higher cell doses. The numbers of CBTs have decreased in the past decade, but these results support the ongoing use of CBT in children lacking matched related or unrelated donors. Figure 1 Figure 1. Disclosures Kurtzberg: Neurogene: Consultancy; CryoCell: Patents & Royalties: Duke licensed IP, and data and regulatory packages for manufacturing and use of cord blood and cord tissue MSCs in the treatment of patients with hypoxic ischemic encephalopathy, cerebral palsy, autism, acute ischemic stroke, COVID-ARDS, and COVID-MIS-C. ; Sinocell: Patents & Royalties: Duke licensed IP, data, and regulatory packages for use of autologous and sibling cord blood to treat children with cerebral palsy.; Celularity: Current holder of stock options in a privately-held company. Troy: SinoCell: Patents & Royalties; CryoCell: Patents & Royalties; Bristol Myers Squibb: Research Funding; Synthetic Biologics: Honoraria; Gamida Cell: Consultancy; The EMMES Corporation: Consultancy; The Community Data Roundtable: Consultancy; AegisCN: Consultancy.

Graft failure (GF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HCT). The incidence of GF after HCT using human leukocyte antigen (HLA) matched donors is lower than 5%; however, a higher incidence is observed when considering HLA mismatched donors or alternative donor sources and the use of reduced intensity conditioning (RIC) regimens. In the absence of autologous recovery, a second HCT is necessary to attempt preventing death due to prolonged pancytopenia. Previous studies describing outcomes of second HCT performed after a GF with different types of donor sources report a wide range of overall survival (OS) and transplant related mortality (TRM), however studies including a large number of patients receiving a second transplant with umbilical cord blood (UCB) are scarce. In this retrospective study, using registry data from Eurocord and the European Society for Blood and Marrow Transplantation (EBMT), we report the outcomes of 247 umbilical cord blood transplants (UCBT) performed after GF following a previous HCT. Data were analyzed separately for patients with malignant (n=141) and non-malignant diseases (n=106). UCB was the most frequent stem cell source that resulted in GF (65.0% and 68.9%, for malignant and non-malignant diseases, respectively), and most of the reported GF occurred within 100 days after HCT (92.3% and 85.9%). The most frequent diagnosis in malignant diseases was acute leukemia (64.5%), mainly acute myeloid leukemia (AML). In non-malignant diseases, the diagnoses most often reported were inborn error of metabolism (IEM) (37.7%), followed by bone marrow failure syndrome (BMF) (34.0%) and primary immune deficiency (PID) (21.7%). In malignant and non-malignant diseases, we observed a similar cumulative incidence of neutrophil engraftment of 59.1% (95% CI 51.4- 67.9%) and 60.4% (95% CI 51.7- 70.6%), in a median time of 23 and 24 days, and a 3-year OS of 28.9% (95% CI 21.8- 37.3%) and 49.1% (95% CI 39.5- 58.8%). TRM at 100 days and at 3 years for malignant diseases was 39.9% (95%CI 32.5 - 49.1%), and 57.5% (95%CI 49.4 - 66.8%). In multivariate analyses, none of the characteristics were statistically significantly associated with engraftment or overall survival. Although survival for patients requiring a second transplant is not optimal, UCB remains a valid life-saving option for some patients with GF as it is an immediately available source of stem cells in severely ill patients. The most appropriate stem cell source for salvage transplants remains controversial, as it depends on multiple factors including center choice, donor availability, underlying disease and existing comorbidities. Disclosures Peffault De Latour: Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Other, Research Funding; Jazz Pharmaceuticals: Honoraria; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding.

Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23–230) and 8.6×108 (range 0.7–75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units.

// Dominique Farge 1 , Francis Cajfinger 2 , Nicolas Falvo 3 , Toufek Berremili 4 , Francis Couturaud 5 , Okba Bensaoula 6 , Lionel Vedrine 7 , Hocine Bensalha 1 , Isabelle Bonnet 8 , Denis Pere-Verge 9 , Marie Coudurier 10 , Veronique Li 11 , Hanadi Rafii 1 , Ilham Benzidia 1 , Jean M. Connors 12, * and Matthieu Resche-Rigon 13, * 1 Assistance Publique-Hopitaux de Paris, Saint-Louis Hospital, Internal Medicine, Autoimmune and Vascular Disease Unit, UF 04, Diderot University, Paris, France 2 Medical Oncology, Hopital Pitie-Salpetriere, Paris, France 3 Departement de Pathologie Vasculaire, CHU Dijon, Dijon Cedex, France 4 Department of Cardiology, Annecy Hospital, Annecy, France 5 Brest University Hospital, CHU de Brest, Brest, France 6 Department of Oncology, CLCC Curie Institute, Centre Rene Huguenin, Saint Cloud, France 7 Hopital d'Instruction des Armees du Val-de-Grâce, Paris, France 8 Department of Oncology, Hospital of Valenciennes, Valenciennes, France 9 CH Saint Joseph Saint Luc, Lyon, France 10 Chambery CH, Chambery, France 11 CH Thonon-Les-Bains, Thonon-les-Bains, France 12 Hematology Division, Harvard Medical School, Boston, MA, USA 13 Service de Biostatistique et Information Medicale, AP-HP Hopital Saint-Louis, Paris, France * These authors contributed equally to this work Correspondence to: Dominique Farge, email: dominique.farge-bancel@aphp.fr Keywords: cancer thrombosis; venous thromboembolism; anticoagulation therapy; quality of life; LMWH Received: March 30, 2018 Accepted: May 02, 2018 Published: June 05, 2018 ABSTRACT Background: Clinical guidelines recommend at least 3-months low molecular weight heparin (LMWH) treatment for established venous thromboembolism (VTE) in cancer patients. However, no study has analyzed the impact of 3–6 months of LMWH therapy on quality-of-life (QoL) in cancer patients. Results: Among 400 cancer patients included at M0, 88.8% received long-term LMWH. Using a random-effects linear regression model with time as covariate, QoL scores in the MOS SF-36 (Global HRQoL, 1.3-fold per month [95% confidence interval (CI) 0.81–1.79], p < 0.0001) and EORTC QLQ-C30 (global health status/qol, 2.25-fold per month [95% CI 1.63–2.88]; p < 0.0001) questionnaires significantly improved over the 6-month study period in patients treated with LMWH, while VEINES-QOL scores did not change. In the MOS SF-36 and EORTC QLQ-C30, the following factors were associated with change in QoL: symptomatic VTE, cancer dissemination and histological type. Factors pertaining to reduced mobility were also identified as significant predictors of QoL outcomes, including being bedridden in the MOS SF-36 and ECOG score ≥ 2 in the EORTC QLQ-C30. Presence of acute infection and not undergoing anti-angiogenic therapy were additional factors associated with QoL improvement in the EORTC QLQ-C30. Methods: QUAVITEC, a prospective, longitudinal, multicenter study, recruited all consecutive eligible adult cancer patients with objectively confirmed VTE between February 2011 and 2012. Patients were asked to answer three QoL questionnaires at anticoagulant treatment initiation (M0) and at 3 (M3) and 6 (M6)-month follow-ups. Conclusion: QUAVITEC is the first study to show that QoL was improved in cancer patients receiving long-term LMWH treatment for established VTE.

• Similar patterns in the use of umbilical cord blood transplantation have been observed in Europe and North America

Strongyloides stercoralis (S.S.) is a human intestinal parasite, which may lead to complicated strongyloidiasis. We report a case of disseminated strongyloidiasis following the treatment of myeloma. The patient developed skin lesions, respiratory distress, aseptic meningitis and bacterial and fungal sepsis. The diagnosis of strongyloidiasis was established through endotracheal tube secretions. Despite the treatment with Ivermectin and Albendazole, the outcome was fatal. The value of screening for strongyloidiasis is unclear but may be of benefit in patients with hematological malignancies from high endemic areas. Keywords: acute respiratory failure, disseminated strongyloidiasis, myeloma, steroids

This retrospective study aimed to analyse the impact on overall survival (OS) and event-free survival (EFS) of chimaerism status and kinetics following allogeneic conventional and reduced-intensity conditioning haematopoietic stem cell transplantation, and to compare this with the impact of other well-known factors. We investigated the chimaerism status of 187 patients [84 females, 103 males; median age 39.5 years (range, 17-62 years)]. After transplantation, 121 patients (65%) presented full donor chimaerism (FDC) and 63 (34%) mixed chimaerism (MC). For MC, we divided the population into patients who presented regressive mixed chimaerism (RMC) (21 patients: 11%), stable mixed chimaerism (SMC) (20 patients: 11%) and progressive mixed chimaerism (PMC) (22 patients: 12%). At last follow-up, 71 patients were alive and 116 had died (48% from disease progression and 52% from transplant-related causes). With a mean follow-up of 39.4 and 34.8 months, the 5-year probabilities of OS and EFS for the total group were, respectively, 55% and 43%: 69.5% and 61% for FDC, 35.4% and 25% for RMC, 42.6% and 28.6% for SMC, and 21% and 10.4% for PMC (P < 0.0001 and P < 0.0001). Multivariate analysis only showed a significant impact of chimaerism status on OS, as well as acute and chronic graft-versus-host disease on EFS, with a trend for conditioning regimen.

Most cases of chronic myeloid leukemia (CML) are associated with the presence of BCR-ABL1 fusion gene; a molecular anomaly that introduced targeting therapy to CML. This study was setup primarily to optimize the real-time quantification detection of BCR-ABL1 transcripts, in order to pave the way for using this method as a diagnostic tool to support the clinical management of CML patients in Qatar. A secondary objective was to evaluate the response of CML patients to Imatinib (IM) and exploit adaption of this technique as an indicator of emerging drug resistance reported in Qatar. Peripheral blood (PB) samples from 26 CML patients receiving Imatinib, were analysed via serial Real-time quantitative polymerase chain reaction (RT-qPCR) to monitor the ratio of BCR-ABL1 to normal ABL1 transcripts. EuropeanLeukemia Net (ELN) 2006 and 2009 guidelines were employed to assess the molecular response to Imatinib. For patients to be classified as optimal responders, major molecular response (MMR) had to be achieved by 18 months of treatment. 1 Patients responding to Imatinib achieved major molecular response (MMR) during the 1st year of treatment; while patients who resisted Imatinib treatment did not achieve any molecular response within this time frame. This was the first molecular study to evaluate the molecular response of CML patients (citizens and residents) to IM in Qatar.

Background: Imatinib is failing as a first line treatment in more than 40% of chronic myeloid leukemia (CML) patients in Qatar. We thus investigated ABL1 kinase domain mutations and additional chromosomal abnormalities (ACAs) as underlying mechanisms to explain this high rate of treatment failure. Methods: Between November 2006 and December 2011, all CML patients in Qatar were studied for BCR-ABL1 kinase domain mutations and ACAs. Total RNA was extracted and cDNA was produced via reverse transcriptase polymerase chain reaction (RT-PCR). PCR was used with special precautions to avoid amplification of wild type ABL1; the ABL1 kinase domain was then screened for mutations by direct DNA sequencing technology to detect the emergence of mutant clone. Cytogenetic analysis of bone marrow (BM) metaphases and fluorescence in situ hybridization (FISH) of peripheral blood (PB) and BM interphases were performed according to standard protocols. European Leukemia Net (ELN) response criteria were employed to identify the...

Chronic Graft-versus-Host Disease (cGVHD) has a negative impact on transplant related death and quality of life after hematopoietic stem cell transplantation. In an attempt to thoroughly assess cGVHD after double umbilical cord blood transplantation (dUCBT), we used the major revised consensus criteria (NCC 2005) proposed by the National Institutes of Health (NIH) in 2005. Material and methods: This is a retrospective study using Eurocord-EBMT database. A specific questionnaire including the NCC 2005 characteristics and features was sent to each transplant centers for collecting data. Eligible pts were adults >18years, who received dUCBT for hematological malignancy in an EBMT center between 2006 and 2014, achieved neutrophil engraftment, survived ≥100 days and developed cGVHD. Results: A total of 154 pts were included. Median age at dUCBT was 43 years (18-70). The primary diagnosis was acute myeloid leukemia in 40%, acute lymphoblastic leukemia in 21%, myelodysplastic/myeloproliferative disease in 19%, and other hematological disorders in 20%. The majority of pts was transplanted in CR, including 51% in CR1, 37% in CR2. Reduced intensity conditioning regimen (mainly with low dose total body irradiation) was used in 60% of cases. 24% pts received anti-thymocyte globulin before transplant. Cyclosporine and mycophenolate mofetil (MMF) was the most common (79%) combination for GVHD prophylaxis. 70% (n=107) of pts received gender mismatched grafts, and 59% had 1-2 major ABO incompatibility. Most (>80%) grafts had 2 HLA mismatches with the recipients. Median number of total nucleated cells at cryopreservation was 5.1(2.3-13.3) ×107/Kg. All pts achieved neutrophil engraftment in a median of 25 days and 89% had full donor chimerism at day 100. Median follow-up was 27.5 (3-103) months, 45 pts relapsed and 60 pts died (28 of relapse, 12 of GVHD and 20 of other TRM). Grade II-IV acute GVHD occurred in 88 pts in a median time of 24 (6-106) days. Grade III-IV aGVHD was reported in 43 pts, mainly with skin and gastrointestinal (GI) tract involvement. Median time for cGVHD onset was 219 (47-2056) days, and most of these were reported within the first 1.5-2 years. Based on Seattle criteria, cGVHD was limited in 73 (47%) pts and extensive in 81 (53%) pts. According to NIH criteria (NCC2005), global cGVHD severity was scored as mild in 67 (44%), moderate in 53 (35%) and severe in 33 pts (21%). cGVHD presented mainly as one or two organs involvement, with skin being the most common site. 56% pts (n=86) had a single organ involvement (mainly skin n=60; 38%). Skin, GI tract, and oral mucosa were the top three affected sites (93%; n=143), both in solo and multiple involvements. 23 patients had > 3 affected organs, skin being most common (n=20; 87%). No joint or fascia involvement was reported as a single organ involvement in any grade. Mild and moderate cGVHD presented as one or two organs involvement, mainly affecting skin, GI and oral mucosa. Severe cGVHD often involved skin, GI, lung and liver. Severe GI tract cGVHD was mostly reported as a single organ involvement. Severe lung involvement was reported in 12 pts (8%). Major functional impact by scoring grade 3 was observed in skin (n=7), GI (n=8), liver (n=5), eye (n=3), oral mucosa (n=2), and lung (n=5). Twenty %pts (n=31) received only topical or no treatment, for 1 or 2 organs involvement and mild to moderate grade cGVHD. The first line treatment of cGVHD included systemic steroids +/- calcineurin inhibitors (CNI) or MMF based regimen, and was used in 72% pts (n=111). cGVHD resolved in 94 pts (61%), and remained clinically significant in 57 pts (mild, n=14; moderate, n=20 and severe, n=23). Among the 12 pts who died of cGVHD, there was multiple organs involvement in most cases; and 6 pts had severe lung cGVHD. Conclusion: According to NCC 2005 criteria, we report that, after dUCBT, cGVH was usually mild with skin being the most common site resulting, in this small group of patients, in a relatively low incidence of severe cGVH with as a consequence a better survival and quality of life. Disclosures Michallet: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria.

Objective: To evaluate semen parameters and measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) concentrations before and 7 days after packed red cell transfusion (PCTx) in adults with sickle cell disease (SCD). Methods: This prospective study investigated 18 young adults with transfusion-dependent SCD, aged 20.7 +/- 2.88 years, with full pubertal development (Tanner's stage 5) (euogonadal), and capacity to ejaculate. Their serum ferritin levels were 1488 +/- 557ng/ml. Basal serum concentrations of FSH, LH, T and IGF-I were evaluated before and 7 days after packed red cell transfusion (PCTx). We studied the effect of PCTx on semen parameters and the endocrine functions in these 18 patients with SCD. Results: Following PCTx, a significant increase of Hb from 8.5 +/- 1.17 g/dl to 10.5 +/- 0.4 g/dl was associated with increased testosterone (12.3 +/- 1.24 nmol/L to 14.23 +/- 1.22nmol/L and gonadotropin concentrations. Total sperm count increased significantly from 87.4 +/- 24.6 million/ml to 146.2 +/- 51.25 million/ml total progressive sperm motility (TPM) from 40.8 +/- 11.1 million/ml to 93.4 +/- 38.3 million/ml, and rapid progressive sperm motility progressive motility (RPM) increased from 29.26 +/- 8.75 million/ml to 67.4 +/- 29 million/ml. After PCTx the total sperm count, TPM and RPM were significantly higher in the ETx group versus the TTx group. Before and after PCTx, testosterone concentrations were correlated significantly with sperm total count, volume, TPM and RPM (r= 0.53, 0.55, 0.42 and 0.38 respectively, p= 0.01). Before and after PCTx, hemoglobin concentrations were correlated significantly with sperm count, TPM, RPM and percentage of sperms with normal morphology (r= 0.60, 0.69, 0.66 and 0.86 respectively, p

Background: Myeloproliferative neoplasms (MPNs), that is, essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are a group of MPNs that can lead to significant rates of morbidity and mortality among affected patients. Symptomatic burden in MPNs is present in most of MPN patients. We sought to use the broadly applicable instrument MPN symptom assessment form (MPN-SAF) to assess symptoms in MF, ET and PV among populations of Qatar. Methods: Using the MF-SAF as a base instrument, we added several key additional symptoms previously identified as present in all subtypes of MPNs including headaches, concentration, dizziness, insomnia, sexual problems and mood changes on a 0 (absent) to 10 (worst-imaginable) scale. The MPN-SAF was administered jointly with the EORTC-QLQ-C30 as the co-validation instrument using prospective cohorts in Qatar. Results: MPN-SAF patient data: 123 MPN-SAF surveys were administered (English (45%), Arabic (55%) in 45 ET patients (36.5%); 35 PV patients (28.5%); 15 MF patients (12.2%); 28 MPN unclassified (22.7%); an average of 7.8 years (range 0 - 43 years)) from their MPN diagnosis. Participants were of age range (26 - 58 years) and gender (52% female) characteristic of disease. Prior hemorrhage (10%) and thrombosis (25%) were frequent. 78% of the patients currently receive cytoreductive therapy and 87% received cytoreductive therapy in the past. Patients and Symptomatic Burden: 19 items assessed in the MPN-SAF demonstrated consistently that the most common symptoms were decreased quality of life (93%), fatigue (84%) and insomnia (65%). The least common symptoms (

Introduction: Hematopoietic stem cell transplantation (HSCT) is, to date, the only curative therapy for sickle cell disease (SCD). However, HSCT is offered to relatively few patients with SCD for a number of reasons including lack of a suitable HLA-matched donor, lack of consensus on indications for HSCT, the potential for trading one chronic condition (i.e., SCD) for another, such as chronic graft-versus-host disease (GVHD), and the mortality associated with the procedure. To-date, most HSCTs for SCD have utilized matched siblings as donors and are performed in children and adolescents. We report outcomes after HLA-matched sibling HSCT of patients reported to the Eurocord-Monacord/European Group for Blood and Marrow Transplantation (EBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR). Material and methods: One thousandpatients with SCD received HLA identical sibling HSCT between 1991 and 2013; n=439 from CIBMTR and n=561 from EBMT centers. HSCTs were performed in 90 centers in 23 countries. Results: Median age at HSCT was 9 years (range 1-54y); 85% of patients were aged The cumulative incidence (CI) of neutrophil engraftment at day+60 was 98% (96.6% for CB, 98.3% for BM and 95.2% for PB) with a median time to recovery of 19 days, while that for platelet engraftment was 98 % (96±2% for CB, 99±1% for BM and 98±9% for PBSC) with a median time to recovery of 25 days. Twenty-six patients experienced primary and 47 patients secondary graft failure; 67 patients died mainly due to GVH or infection. The 3-year probabilities of overall (OS) and event-free survival (EFS, alive with engraftment) were 94% (95% CI 92-95) and 90% (95% CI 68-82), respectively. According to stem cell source, 3-year OS was 99% after CB, 94% after BM and 80% after PBS (p Conclusion: This large registry based international study shows that HLA identical sibling transplant is successful more than 90% of the patients with severe SCD with limited transplant related complications (rejection, GVHD). Strategies aimed at lowering graft failure and GVHD are desirable to further optimize the observed 3-year event-free survival. Importantly, these data should increase awareness to early referral to HSCT of patients with severe SCD. Disclosures Walters: ViaCord and AllCells, Inc: Other: Medical director. Bertrand:ERYTECH Pharma: Consultancy. Peters:Medac: Research Funding; Fresenius: Research Funding; Amgen: Research Funding; Jazz: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Sanovi: Research Funding; Pierre-Fabre: Research Funding.

In the Middle East and North Africa (MENA) region, cancer has many epidemiologic and clinical features that are different from those in the rest of the world. Additionally, the region has a relatively young population and large disparities in the availability of resources at diagnostic and treatment levels. A critical need exists for regional guidelines on cancer care, including those for lymphoid malignancies. A panel of lymphoma experts from MENA reviewed the 2009 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Non-Hodgkin’s Lymphoma and Hodgkin Lymphoma and suggested modifications for the region that were discussed with the United States NCCN Lymphoma Panels. This article presents the consensus recommendations. (JNCCN 2010;8[Suppl 3]:S29–S35)

Essential thrombocythemia(ET) is a chronic myeloproliferative neoplasm characterized by sustained thrombocytosis, bone marrow megakaryocytic hyperplasia and an increased risk of thrombosis and hemorrhage. The goal of treatment is to prevent the development of vascular complications without increasing the risk of transformation. Patients aged>60 years or a history of thrombosis have a high risk of thrombosis while those with a platelet count>1,500x109/l have a higher risk of hemorrhage.Patients with low-risk ET can be managed with low-dose of acetylsalicylic acid or even observation only, while patients with a high-risk disease are candidates to cytoreductive treatment, hydroxyurea being the first choice therapy. Anagrelide is the most suitable option for patients with resistance or intolerance to hydroxyurea. All patients must be submitted to a rigorous control of cardiovascular risk factors. Interferon alfa2a (pegasis) is a nonleukemogenic drug that can induce cytogenetic remissions or reversion from monoclonal to polyclonal patterns of hematopoiesis in some cases, this study addressing the safety efficacy and toxicity of pegasis( once weekly versus once monthly ) in ET Methods Inclusion criteria were: Patients with ET diagnosed as per WHO classification 2008, age 18 to 45 years, and either no previous treatment or Hydroxyurea or anagralide for less than 1 years. ET diagnosis workup included ferritin, exclusion of secondary causes like infections and not meeting WHO criteria for PV, MDS and CML Pretreatment evaluation also included patient history, physical examination, complete blood count (CBC) and serum chemistries (UE), including liver and renal function studies, thyroid function tests (TFT), and molecular study for JAK2V617F mutation. Exclusion criteria included (significant hepatic and renal dysfunction, history of psychiatric disorder, in particular depression, autoimmune hepatitis, severe cardiac dysfunction, known hypersensitivity to IFN. The primary end point was hematological response to pegasis at 12 months. Complete hematological response (CR) as per ELN guidelines' and Molecular response (MR) was defined as “complete” when JAK2V617F became undetectable with the technique used (ie, %V617F< 1%), “partial” when > 50% decrease of baseline %V617F was obtained, and “minor” when %V617F decrease was between 20% and 49%. Follow-up evaluations included adverse event (AE) assessment monthly for 3 months, then every third month until the 12th month with CBC, UE weekly during the first month and monthly thereafter. TFT, CBC, JAK2 mutation studies were taken every 6 months. After inclusion, HU was stopped 2 weeks before Pegasis initiation. Pegasis was started subcutaneously at 50 microgram weekly for 4 weeks then 135 mcg/wk from week 5.all patients achieved complete hematological remission from week 10 were randomized into two arms arm(A)135 mcg/wk and arm(B) 135 mcg/month Baseline characteristics of the patients are. Median age was 31.5 year vs 30 year, and 20 patients in each arm 18 patients were males 22 were females three patients had a history of major thrombotic events. Treatment before inclusion included HU in 18 patients, and no treatment in the remaining 22 patients,JAK2 mutation was found in all patients All the patients responded to Pegasis at the 12-month evaluation including 40 hematological CRs (100%)No patient experienced signs or symptoms of thrombosis or hemorrhage during the whole study period. Median relative decrease of %V617F during the first year was 52% decreased in arm A versus 50 % in arm B,. Hematological response was achieved in all of the patients within 2 months and were sustained beyond the first year. Most common toxicities during the first month included musculoskeletal pain in 6 patients versus 2, skin toxicity in 4 versus 0, and GI symptoms in 2 versus 0 , none of the toxicity exceeds WHO Grade 2 with no stsatistical differences between the two groups. Conclusion 135 mcg Pegasis once monthly is as effective as once weekly dose with reduced toxicity Reducing the vascular risk and preventing evolution to MF, MDS, Percentage of V617F appears to be a good tool to monitor minimal residual disease and to evaluate treatment efficacy however further studies are needed to confirm these results and to look for the efficacy of more reduced doses. Disclosures: Yassin: qatar national research fund: Patents & Royalties, Research Funding. Al-Dewik:qatar national research fund: Patents & Royalties, Research Funding. Cassinat:qatar national research fund: Patents & Royalties, Research Funding.

Essential thrombocythaemia (ET) is a chronic myeloproliferative syndrome due to sustained proliferation of megakaryocytes,which results in elevated numbers of circulating platelets, thrombotic or haemorrhagic episodes and occasional leukaemic transformation.Familial essential thrombocythemia,also called hereditary or inherited thrombocythemia or thrombocytosis, is a rare disorder transmitted in an autosomal dominant with clinical presentation and complications resembling sporadic essential thrombocythaemia (ET).Mutations in the thrombopoietin (TPO) gene causing overproduction of TPO and elevated TPO serum levels familial essential thrombocythemia is a heterogeneous disorder as families have been described with an activating mutation in the gene for the TPO receptor (c-MPL), the thrombopoietin gene, a germline mutation in JAK2 V617I or without a mutation in any of these genes Occurrence of Essential thrombocythemia among arab population never been reported before. In this study, essential thrombocythemia is documented in 25 families from 5 major tribes in Qatar Familial cases were defined when two or more individuals within the same pedigree were affected with MPNs. Clinical records of affected relatives were reviewed systematically to confirm MPNs diagnosis. Patients without family history of were defined as having sporadic. MPNs Diagnosis of MPNs was made in accordance with the WHO criteria 2008 Ninety eight members of both sexes from 18 to 62 years of age in three successive generations. The propositus had a persistent elevation of the platelet count, splenomegaly, a normal hemoglobin level, a normal white blood cell count, and abnormal platelet aggregation. Platelet arachidonic acid metabolites assayed by high-performance liquid chromatography and serum thrombopoietin levels were normal. Megakaryocytes were increased in number and size. Both mature and early immature megakaryocytes, but no atypical megakaryocytes, were identified by surface immunofluorescence. Bone marrow cultures showed normal myeloid and erythroid colony formation, and chromosome studies revealed a normal The analysis of mutations of JAK2 and MPL may improve our ability to identify these conditions. In a consecutive series of patients observed in our Institution from January 2011 to June 2013 total No of 300 MPNs patients were diagnosed, out of 300 patient, 119 had PV, 160 had ET, 15 had PMF and six patient had unclassified atypical MPN case. Out of 119 PV pts, 116 (97.4%) were positive for the JAK2 V617F mutation and 3 cases met the WHO criteria for PV but were negative for JAK2 V617F and JAK2 exon 12 mutations. Out of 160 ET pts, 80 (50%) were positive for JAK2 V617F, one had MPL S505N mutation and 79 cases met the WHO criteria for ET but were negative for both JAK2 617F and MPL mutations. Out of 15 PMF pts 5 (33.3%) were positive for JAK2 V617F and the unclassified case which was characterized by Deep Vein Thrombosis had JAK2 exon 13 mutation (R564L). 25 Arab families were described as having familial ET (5 major tribes were screened )20 were having JAK2V617F positive in three consequetive generations ,4 families were having Familial ET in three generations but both Jak2v617F and MPL were negative MPL S505N mutation was found in one family( Father and daughter).there was no difference in clinical presentation and response to therapy in sporadic versus familial cases. Conclusion In our series of familial cases clinical presentation, therapeutic approach type and severity of complications were comparable to that of sporadic cases. Furthermore, the present study indicates the relevant possibility of familial MPNs, thus suggesting the opportunity of a detailed family history as part of the initial work-up of patients with MPNs; in addition it also suggests the usefulness of an accurate biological studies Disclosures: Yassin: qatar national research fund: Patents & Royalties, Research Funding. Al-Dewik:qatar national research fund: Patents & Royalties, Research Funding. Cassinat:qatar national research fund: Patents & Royalties, Research Funding.

Abstract 3209 Objective: To evaluate semen parameters and measure serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) concentrations before and 7 days after packed red cell transfusion (PCTx) in young adults with sickle cell disease (SCD). Design: Prospective study. Setting, Patients: This study investigated 18 young adults with transfusion – dependent SCD, aged 20.7 +/− 2.88 years, with full pubertal development (Tanner's stage 5) (euogonadal), and capacity to ejaculate. They were regularly transfused since early childhood and underwent chelation therapy using desferrioxamine which was replaced by deferasirox for the last 4–5 years. Ten were on top-up transfusion (TTx) and 8 were on exchange transfusion (ETx) regimen. At the time of the study their serum ferritin levels were 1488 +/− 557ng/ml. Basal serum concentrations of FSH, LH, T and IGF-I were evaluated before and 7 days after packed red cell transfusion (PCTx). Interventions: We studied the effect of PCTx on semen parameters and the endocrine functions in these 18 patients with SCD. Main Outcome Measures and Results: After Packed RBCs Transfusion(PCTx) significant increase of Hb from 8.5 +/− 1.17 g/dl to 10.5 +/− 0.4 g/dl was associated with increased testosterone (12.3 +/− 1.24 nmol/L to 14.23 +/− 1.22nmol/L and gonadotropins' concentrations. Total sperm count increased significantly from 87.4 +/− 24.6 million/ml to 146.2 +/− 51.25 million/ml and total progressive sperm motility (TPM) from 40.8 +/− 11.1 million/ml to 93.4 +/− 38.3 million/ml, and rapid progressive sperm motility progressive motility (RPM) increased from 29.26 +/− 8.75 million/ml to 67.4 +/− 29 million/ml. After PCTx the total sperm count, TPM and RPM were significantly higher in the ETx group versus the TTx group. Before and after PCTx, Testosterone (T) concentrations were correlated significantly with sperm total count, volume, TPM and RPM (r = 0.53, 0.55, 0.42 and 0.38 respectively, p: 0.01). Before and after PCTx, hemoglobin (Hb) concentrations were correlated significantly with Sperm count, TPM, RPM and % of sperms with normal morphology (r= 0.60, 0.69, 0.66 and 0.86 respectively, p < 0.001). Conclusion: Our study suggests that in males with SCD blood transfusion is associated with significant acute enhancement of sperm parameters and with an increased concentration of serum testosterone, LH and FSH. Improvements of sperm parameters were significantly higher in the Exchange Transfusion group vs. the Top up Transfusion group. These “acute” effects on spermatogenesis are reached with an unknown mechanism/s and suggest a number of pathways that need further human and/or experimental studies. Disclosures: Yassin: Hamad medical corporation MRC: Employment, Research Funding. Soliman:Hamad medical corporation MRC: Employment, Research Funding. Elawwa:Hamad medical corporation MRC: Consultancy, Research Funding.