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Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment for myelofibrosis (MF). Relapse occurs in 10–30% and remains a major factor for dismal outcomes. Previous work suggested that graft-versus-host disease (GVHD) might be associated with risk of relapse. This study included 341 patients undergoing their first (n= 308) or second (n= 33) alloHSCT. Anti-T-lymphocyte or antithymocyte globulin was used for GVHD prophylaxis in almost all patients. Median time to neutrophile and platelet engraftment was 13 days and 19 days, respectively. The cumulative incidence of acute GVHD grade II-IV was 41% (median, 31 days; range, 7–112). Grade III-IV acute GVHD was observed in 22%. The cumulative incidence of chronic GVHD was 61%. Liver was affected in 23% of acute GVHD cases and 46% of chronic GVHD cases. Severe acute GVHD was associated with high non-relapse mortality. The development of acute GVHD grade II and moderate GVHD was an independent factor for reduced risk for relapse after transplantation without increased risk for non-relapse mortality, while especially acute GVHD grade IV was associated with high non-relapse mortality. Last, we identified that ongoing response to ruxolitinib, accelerated-phase MF at time of transplantation and splenectomy prior to transplantation were independent predictors for relapse.

We retrospectively analyzed high-risk ALL patients in CR1 receiving total body irradiation based conditioning regimen with ATLG (n= 74) or PTCy (n= 73) for GVHD prophylaxis. The 3-year OS and LFS were similar in both groups: 65 and 60% in the ATLG group and 64 and 67% in the PTCy group (p= 0.9 and 0.5, respectively). CIR and NRM rate at three years was 12 and 21% after PTCy and 19 and 20% after ATLG (p= 0.4 and p= 0.9, respectively). Acute GvHD grades II-IV and grades III/IV at 100 days was 46 and 19% after PTCy and 33 and 10% after ATLG (p= 0.08 and p= 0.9, respectively). Chronic GvHD of all grade at two years was higher after PTCy: 55% versus 26% (p< 0.001). Based on the propensity score matching (PSM) analysis, aGvHD grades II-IV was trending higher in the PTCy group compared to the ATLG group (p= 0.07). In contrast to the PSM analysis, on multivariate analysis the receipt of PTCy compared with ATLG was associated with a reduced CIR (p= 0.026). Our retrospective single-center analysis shows a lower incidence of acute and chronic GvHD while displaying similar LFS and OS after ATLG compared to PTCy in TBI based allogeneic stem cell transplantation for high-risk ALL.

Splenomegaly is a hallmark of myelofibrosis (MF), and reports on the impact of spleen size on the outcome of allo-HSCT have been conflicting, possibly due to differences in methods of assessment. We retrospectively analysed the impact of spleen volume and length measured by computed tomography on allo-HSCT outcome in 93 patients, 74% of whom had prior ruxolitinib treatment. Median spleen volume and length were 1.58 dm3and 20 cm, respectively. We found a strong correlation between spleen volume and length (Pearson’s r= 0.95, p< 0.001), Spearman (rho = 0.96, p< 0.001). After a median follow-up of 41.7 months, 5-year overall and disease-free survival were 66% and 59%, respectively. Spleen size did not impact overall survival or non-relapse mortality. Larger spleen volume and length as continuous variables were associated with slower platelet and leucocyte engraftment and a higher risk of disease relapse in univariate and multivariate analyses. Spleen length measured precisely by imaging is a good surrogate for spleen volume. In the era of JAK inhibitors, larger spleen size reflects advanced disease in MF and is associated with an increased risk of relapse but has no impact on non-relapse mortality and overall survival after allo-HSCT.

Data on the influence of different Anti-lymphocyte globulin (ATLG) doses on graft versus host disease (GVHD) incidence and immune reconstitution in matched unrelated (MUD) allogeneic Stem cell transplantation (allo-SCT) is limited. This retrospective study conducted at the University Medical-Center Hamburg compares GVHD and Immune reconstitution after myeloablative MUD (HLA 10/10) PBSC allogeneic stem cell transplant between 30 mg/Kg (n= 73) and 60 mg/Kg (n= 216) ATLG. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100, and 180 posttransplant. Neutrophil and platelet engraftments were significantly delayed in the 60 mg/kg group with a higher Cumulative incidence of Infections (67% vs 75% p= 0.049) and EBV (21% vs 41% p= 0.049) reactivation at day 100 in this group. In the 30 mg/kg group, we observed a faster reconstitution of naïve-B cells (p< 0.0001) and γδ T cells (p= 0.045) at day+30 and a faster naïve helper T-cell (p= 0.046), NK-cells (p= 0.035), and naïve B-cell reconstitution (p= 0.009) at day+180. There were no significant differences in aGVHD, cGVHD, NRM, RI, PFS, and OS between the groups. The choice of ATLG dose has significant impact on IR but not on GVHD after MUD-allo-SCT. Higher doses are associated with delayed engraftment and increased infections.

Patients with relapsed/refractory acute myeloid leukemia (AML) have a dismal prognosis. Allogeneic stem cell transplantation (allo-SCT) provides a curative approach; however, the overall survival (OS) remains low (20% to 40%). In this setting, although some effective approaches have been evaluated in recent years, the management of such patients still remains challenging. In this study we evaluated the predictive role of post-transplant day 100 minimal residual disease (MRD) detection for post-transplantation outcomes for patients with refractory AML. Fifty-six adult patients with refractory AML (median age 58, range 20-76; male, 61%) who underwent allo-SCT were included in this retrospective monocentric study. Twenty-nine patients (52%) received fludarabine, amsacrine, and cytarabine (FLAMSA)–based conditioning. MRD was assessed using multicolored flow cytometry (MFC) according to European Leukemia Net guidelines (“different from normal” and leukemia-associated phenotype). The sensitivity of the method was 10−4to 10−5. The median marrow blast count at allo-SCT was 25% (range 6% to 91%). At day 100 after transplantation, 40 patients (71%) experienced MFC-MRD negativity, and 16 patients (29%) were MRD positive. All included patients survived at least 100 days after transplantation without relapse. Univariate and multivariate analysis based on Kaplan-Meier and Cox proportional hazards method were performed. The median follow-up was 16 months (range 3 to 66). The post-transplantation day 100 MRD-negative patients instead received 2 allografts (27% versus 6%, P = .08). In multivariate analysis, day 100 MRD status (negative versus positive) (OS: 0.23 [0.1 to 0.54], P=0.001; relapses: 0.20 [0.1 to 0.49], P = .0005) and FLAMSA versus other regimens (0.34 [0.1 to 0.83], P = .018; relapses: 0.43 [0.17 to 1.1], P = .07) independently impacted post-transplantation survival. We suggest that post-transplantation day 100 MFC-MRD detection plays predictive role in refractory AML patients and may help to define possible candidates for early post-transplantation interventions aiming to decrease the relapse risk and improve survival.

•γδ T cell reconstitution in minimal/measurable residual disease-positive patients with acute myelogenous leukemia is associated with a lower rate of relapse and a higher rate of survival.•Post-transplantation cyclophosphamide is associated with lower post-transplantation levels of γδ T cells compared with antithymocyte globulin.•γδ T cells are not associated with development of acute graft-versus-host disease.

Hematopoietic stem cell transplantation (HSCT) has been accessible to the population residing in Lebanon and surrounding countries since 1997. HSCT programs were developed in two major hospitals in Beirut: American University of Beirut Medical Center (AUBMC) and Makassed General Hospital. Mount Lebanon Hospital initiated an autologous HSCT activity later. Between 2012 and 2016, the HSCT activity in Lebanon reached a total of 897 transplants, among which 303 (33.8%) were allogeneic HSCT and 594 (66.2%) were autologous HSCT. Overall, autologous HSCT activity has remained stable over the past 5years, whereas allogeneic HSCT activity has seen a steep increase between 2012 and 2013 followed by a modest increase later. Haploidentical transplantation has mushroomed and represented almost half of allogeneic HSCT activity in 2016. AUBMC and Makassed General Hospital are members of the European Blood and Marrow Transplantation (EBMT) and East Mediterranean Blood and Marrow Transplantation groups, and AUBMC has been accredited by JACIE (Joint Accreditation Committee – ISCT & EBMT) since 2016. The past 5years have seen an increase in HSCT-related research and publications, mainly from AUBMC. These research activities were predominantly focused on personalized conditioning for allogeneic HSCT and post-transplant maintenance therapy.

Introduction:

Myelofibrosis is one of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) characterized by clonal myeloproliferation. Allogeneic hematopoietic stem-cell transplantation is the only potentially curative treatment for patients with myelofibrosis. With that, it can resolve fibrosis and lead to complete loss of the clonal burden. More than 90% of myelofibrosis patients harbor driver mutations in one of the 3 genes JAK2, CALR, and MPL, with JAK2mutations being associated with worse outcomes.

Background:

Background:Several studies have shown that the leukemic stem cells (LSCs: CD34 +CD38 -CD45RA +/Combi-6 +) play a crucial role in the development of relapses in AML patients (pts). LSCs are less sensitive to conventional therapy; moreover, their phenotypical characteristics may allow immune evasion promoting relapses after allo-SCT. Although ELN guidelines recommend including LSCs into MRD assessment, this approach has not yet been studied extensively in the allogeneic setting. Here we suggested that peri-transplant LSCs detection may provide additional prognostic information to conventional (c)MRD in AML pts allografted in CR.

•full donor chimerism can mitigate negative impact of pre-transplant MRD positivity•qPCR-MRD is more predictive for post-transplant relapse than MFC-MRD•mixed chimerism has limited predictive value for post-transplant relapses•mixed chimerism without post-transplant MRD is not associated with worse outcomes

Introduction:

Introduction

No relevant conflicts of interest to declare.

Ayuk: Celgene/BMS: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Mallinckrodt/Therakos: Honoraria, Research Funding; Miltenyi Biomedicine: Honoraria; Novartis: Honoraria; Takeda: Honoraria.

No relevant conflicts of interest to declare.

In this “real-life” retrospective study, we assessed outcome after a “personalized” treatment strategy for patients with acute myeloid leukemia (AML) in a tertiary care center. Our strategy consisted of induction therapy adjusted to age, comorbidities and molecular abnormalities, as well as allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1), whenever possible, for patients with European Leukemia Net 2017 (ELN) intermediate or high-risk patients. Allo-SCT was followed by post-transplant maintenance consisting of 5-azacytidine (AZA) for most patients, or sorafenib for patients with FLT-3 ITD. We included 99 consecutive patients (65% male). The median age at diagnosis was 49 years (range, 18-88) with 28 patients older than 60. Karyotype was normal in 59 patients. Molecular analysis revealed core binding factor (CBF) mutation in 13 patients (13%), NPM1 mutation in 26 patients (26%), FLT3-ITD and FLT3-TKD mutation in 15 (15%) and 1 (1%) patient, respectively. According to the ELN 2017 classification, 24, 48 and 27 patients belonged to the low, intermediate and high-risk groups, respectively.

No relevant conflicts of interest to declare.

Background:Achieving complete cytogenetic response (CCyR) at 12 months for patients with chronic phase chronic myeloid leukemia (CML) treated with imatinib as first line, is associated with significantly improved progression-free survival. Nilotinib has shown a faster and higher rate of CCyR and molecular response as compared to imatinib. However, nilotinib use is associated with diet restriction, higher financial costs, and its long-term use is incriminated in cardiovascular and metabolic complications.

Introduction:Interim disease evaluation and its timing during induction chemotherapy (day 14 or day 21) for patients with acute myeloid leukemia (AML) remains controversial. It has been suggested that failure to achieve complete remission (CR) at day 21 is associated with a poor prognosis. Nonetheless, the significance of persistent disease and the need for an early double induction is questionable.

Introduction:Allogeneic hematopoietic stem cell transplantation (allo-SCT) offers the only chance of long-term remission and possibly cure for almost all hematologic malignancies. The conditioning regimen plays an important role and its choice is influenced by various factors, such as, age of patient, performance status, disease risk, and remission status at the time of transplantation.

Introduction: Autologous stem cells transplantation (ASCT) is a treatment option used in various hematological malignancies. ASCT can prolong disease free survival, improve survival, and may be curative. We investigated the variables affecting engraftment among patients treated with high dose-chemotherapy and ASCT.

INTRODUCTION:Relapsed / Refractory leukemia and lymphoma (R/R, L/L) patients have a very poor prognosis despite all the well-known therapeutic strategies. Sequential conditioning followed by allogeneic stem cell transplantation (allo-SCT) provides an efficient disease control in those high risk patients.

Introduction :High-dose therapy (HDT) combined with autologous stem cell transplantation (ASCT) is a standard front-line treatment strategy for patients with newly diagnosed multiple myeloma (MM). Unfortunately, almost all the patients will eventually relapse, emphasizing the need for new treatment options or strategies to improve outcomes in these patients. A recent meta-analysis clearly demonstrated that post-transplant lenalidomide maintenance improves overall survival (OS), conflicting results were reported on the benefit of early post-transplant consolidation with bortezomib, lenalidomide, and dexamethasone (VRD). The aim of this study was to assess the effect of VRD consolidation on complete remission (CR) rate at Day100 post ASCT, a surrogate marker for progression free survival (PFS) and OS.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Kharfan-Dabaja: Incyte: Speakers Bureau; Seattle Genetics: Speakers Bureau.

Purpose:Relapse after allogeneic hematopoietic SCT (allo-SCT) for AML or myelodysplastic syndrome (MDS) remains the main cause of treatment failure and is associated with a very poor prognosis and a short survival despite the type of the salvage therapy. Options include reductions of immunosuppressive therapy, chemotherapy with or without infusion of donor lymphocytes (DLI) or second allo-SCT, but results remain disappointing. Other studies (C Jabbour et al, and Craddock Charlie et al) demonstrated the efficacy and safety of 5-azacytidine (Vidaza) maintenance post Allo-SCT.

Introduction:Despite allogeneic hematopoietic stem cell transplantation (HSCT), prognosis of fms-like tyrosine kinase 3 (FLT3) mutated acute myeloid leukemia (AML) remains poor due to the high risk of relapse. Sorafenib, a multikinase inhibitor active on FLT3, has shown encouraging results in these patients.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

CONTEXT:Cytomegalovirus reactivation (R-CMV) is often diagnosed in allogeneic hematopoietic cell transplant recipients and could determine a CMV-related disease in these immunocompromised patients, involving any organ. R-CMV and end-organ disease after ASCT has not been studied thoroughly. Autograft recipients are generally considered to have low risk of R-CMV or end-organ disease.

BACKGROUND:

POST TRANSPLANT BRENTUXIMAB MAINTENANCE APPEARS MORE EFFECTIVE THAN POST TRANSPLANT SALVAGE BRENTUXIMAB FOR RELAPSED /REFRACTORY HODGKIN LYMPHOMA

BACKGROUND:Concomitant NPM1 and FLT3 mutation occurs in 20% of AML patients. Molecular response and achievement of negative minimal residual disease (MRD) are strong predictors of long-term outcome. However, little is known about the dynamics of molecular response in NPM-1 and FLT-3 double positive mutations.