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Introduction: Immunotherapy with Chimeric Antigen Receptor T cells (CAR-Τ) is a promising innovative treatment for refractory B cell malignancies offering a considerable chance for long-term survival in patients (pts) with an otherwise dismal prognosis. Since January 2020, two anti-CD19 CAR T cell products have been introduced into clinical practice in Greece: a) tisagenlecleucel (Kymriah) for adults with relapsed/refractory diffuse large B-cell Lymphoma (r/r DLBCL) including transformed follicular lymphoma (TFL), as well as for children or young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL), and b) axicabtagene ciloleucel (Yescarta) for adults with r/r DLBCL including TFL and primary mediastinal B-cell lymphoma (PMBCL). The aim of this study was to present the real-world experience of the initial application of CAR T cell therapy in adult pts in Greece, with special focus on early toxicity and disease outcomes. Methods: Data from all consecutive pts were collected from the two transplant centers which were initially accredited for CAR T cell therapies in adult pts: Evangelismos Hospital, Athens and George Papanicolaou Hospital, Thessaloniki. Between November 2019 and July 2021, 51 pts were referred for CAR T cell treatment. In 41 pts lymphocyte collection was performed and product manufacturing was successfully completed in 35; in 2 pts insufficient cell expansion was noted and in 4 manufacturing was terminated due to disease progression and patient death. Results: From January 2020 until July 2021, CAR T cells were infused in 27 pts; 3 pts could not receive the product due to clinical deterioration/death and 5 pts are presently being scheduled for infusion. Of the 27 treated pts, 16 received tisagenlecleucel and 11 axicabtagene ciloleucel. The median age of infused pts was 49 (18-69) years. Diagnosis was DLBCL (n=16), PMBCL (n=3), TFL (n=2), B-ALL (n=6), and the median number of previous lines of treatment was 4 (2-5). Five pts with lymphoma had undergone autologous, and 4 pts with B-ALL allogeneic stem cell transplantation. In total 18/27 pts received bridging therapy, including radiotherapy (n=5), chemoimmunotherapy (n=9), steroids (n=3), and inotuzumab ozogamicin (n=1). The median time from leukapheresis to product delivery and infusion was 35 (15-81) and 59 (35-152) days, respectively. All pts received lymphodepleting therapy before CAR T cell infusion with combination of cyclophosphamide and fludarabine. For patient monitoring, prophylactic therapy and management of toxicity, the EBMT (Yakoub-Agha I, et al. Haematologica 2020) and MD Anderson (Neelapu S, et al. Nat Rev Clin Oncol 2018) guidelines were adopted. Twenty-six pts developed neutropenia (grade II: 2, grade IV: 24) and 20 thrombocytopenia (grade I: 7, grade II: 3, grade III: 1, grade IV: 9), with a median duration of 11 (4-132) and 20 (3-150) days, respectively. Cytokine release syndrome (CRS) and neurotoxicity (ICANS) were noted in 21 (grade I: 8, grade II: 7, grade III: 6) and 5 (grade I: 3, grade III: 2) pts, respectively. Tocilizumab was administered for CRS according to guidelines, and steroids were additionally required for CRS and/or ICANS in 12 pts. In 2 pts, persistent ICANS necessitated further treatment with anakinra (n=2), siltuximab (n=1), and cyclophosphamide (n=1). Hypogammaglobulinemia was encountered in 14/27 pts. With a median follow-up of 7.3 (1-17) months, overall response rate was 48% with 12 (45%) pts being currently in complete remission (CR). No treatment related mortality was observed. Disease-free (DFS) and overall survival (OS) were 52% and 85.3% at 1-year, respectively. DFS and OS were significantly associated with baseline LDH levels (p=0.017 and 0.050, respectively) and grade II/III CRS (p=0.041 and 0.015, respectively, Figure). Conclusions: Despite the limited experience in the real-world setting, CAR T cell therapy can be administered safely and may successfully rescue patients with DLBCL or B-ALL who lack alternative treatment options. Close monitoring of patients and prompt recognition and management of side effects are mandatory for achieving the benefits of therapy. Figure 1 Figure 1. Disclosures Baltadakis: WinMedica: Other: Travel Grants; Gilead: Other: Travel Grants; Genesis Pharma: Other: Travel Grants; Abbvie: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Pfizer: Honoraria, Other: Travel Grants; Astellas: Honoraria; Alexion: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Baxalta Hellas: Other: Travel Grants. Gavriilaki: Pfizer Corporation: Research Funding; Gilead Corporation: Honoraria; Alexion, Omeros, Sanofi Corporation: Consultancy. Tzannou: Allovir: Current equity holder in publicly-traded company; Gileas: Honoraria. Anagnostopoulos: Abbvie: Other: clinical trials; Sanofi: Other: clinical trials ; Ocopeptides: Other: clinical trials ; GSK: Other: clinical trials; Incyte: Other: clinical trials ; Takeda: Other: clinical trials ; Amgen: Other: clinical trials ; Janssen: Other: clinical trials; novartis: Other: clinical trials; Celgene: Other: clinical trials; Roche: Other: clinical trials; Astellas: Other: clinical trials .

Feasibility of haploidentical stem cell transplantation (haploSCT) is enhanced by use of post-transplant cyclophosphamide (PTCY). Despite preservation of non-alloreactive T cells, delayed reconstitution of cellular immunity and viral reactivation may compromise the outcome of T cell replete haploSCT. The study included 47 patients, aged 19-70 (median, 53) years, who underwent haploSCT with PTCY for myeloid (n=35) or lymphoid (n=12) malignancies. Myeloablative conditioning was mainly utilized (n=36). Graft source was peripheral blood (n=29) or bone marrow (n=18). Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood in cases with hemorrhagic cystitis (HC). Preemptive therapy was the principal modality for CMV infection in all but 1 patient who received letermovir prophylaxis. Reconstitution of cellular immunity was assessed by flow cytometry. With a median follow-up of 30 months, cumulative incidences (CIN) of relapse and non-relapse mortality were 13.4% (95% CI, 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free and overall survival were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34/45 patients at risk. Recurrent CMV infection occurred in 17/34 with median 1.5 (range, 1-6) episodes per patient. Median duration of anti-CMV therapy was 27 (range, 14-199) days. CMV disease was documented in 2 patients. CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 1 year, and preemptive therapy with rituximab was required in 2 patients. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%). CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy was required in 5/13 and nephrostomy in 1/13 patients. Reconstitution of T cell immunity was considerably delayed, with median CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was associated with the recovery of CD4+ cells at 3 months (Figure, median CD4+ count of 191/uL versus 62/uL in patients with 1 or ³2 episodes of CMV reactivation, respectively; p=0.009). Haplo-SCT with PTCY is associated with substantial rates of viral reactivation resulting in the need for prolonged antiviral therapy and considerable morbidity as well. Strategies to prevent viral infection are strongly warranted. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution.

Newer cytogenetic scoring systems for myelodysplastic syndromes (MDSs), like cytogenetic stratification of the revised international prognostic scoring system (IPSS-R) or monosomal karyotype, may also improve outcome prediction after hematopoietic SCT (HCT). We compared the prognostic value of specific cytogenetic abnormalities, IPSS-R karyotype and monosomal karyotype for HCT outcome in 98 patients with MDS and AML post MDS. Higher-risk IPSS-R karyotype, 3q21q26 and transformation to AML before HCT were associated with increased cumulative incidence of relapse (CIR), whereas OS was adversely influenced by del 5q/-5, abnormalities of chromosomes 11 and 17 and cytogenetic IPSS-R very poor category. Karyotype with ⩽2 abnormalities and no abnormalities of chromosomes 3, 5, 7, 11 and 17 was an independent prognostic factor of lower CIR (hazard ratio (HR)=0.2, P=0.01) and longer OS (HR=0.5, P=0.03). In conclusion, some specific cytogenetic abnormalities and high cytogenetic complexity, as reflected by IPSS-R very poor karyotype, rather than monosomal karyotype, were associated with higher CIR and shorter OS after HCT. Conversely, results were encouraging in patients lacking those abnormalities, who may be very good candidates for HCT.

Introduction: The preferred method for haploidentical stem cell transplantation (haploSCT) is currently the use of post-transplantation cyclophosphamide (PTCY) since it obviates the need for depletion of T lymphocytes, which is associated with profound immunosuppression. Despite preservation of non-alloreactive donor T cells, reconstitution of pathogen-specific immunity may be delayed even after T cell replete haploSCT. The incidence and clinical sequelae of viral reactivation may thus compromise the outcomes of the procedure. Patients and Methods: The study included 47 patients, who underwent haploSCT with PTCY from 12/2013 until 05/2019 and achieved stable donor engraftment. Median age at transplant was 53 years (range, 19-70). The indications for transplant were acute myeloid (n=19) or lymphoblastic (n=10) leukemia, myelodysplastic syndrome (n=10), myelofibrosis (n=4), chronic myeloid (n=2) or lymphocytic (n=1) leukemia, and T-prolymphocytic leukemia (n=1). Myeloablative conditioning was mainly utilized (n=36), with the exception of certain patients who received reduced-intensity (n=10) or non-myeloablative (n=1) regimens. The graft source was peripheral blood in 29 and bone marrow in 18 cases. Tacrolimus in combination with mycophenolate mofetil was administered for prevention of graft-versus-host disease. Recipient/donor cytomegalovirus (CMV) serostatus was -/- (n=2), -/+ (n= 5), +/- (n=11), or +/+ (n=29). CMV, Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months post haploSCT. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood specimens in cases with symptoms suggestive of hemorrhagic cystitis (HC). Prophylaxis with letermovir was available in 1 patient only, and preemptive antiviral therapy was the principal modality for the management of CMV infection. Cellular immunity reconstitution was assessed by flow cytometry at 3, 6, and 12 months after transplant. Results: With a median follow-up time of 30 months (range, 2-64), the cumulative incidences (CIN) of relapse and non-relapse mortality (NRM) were 13.4% (95% confidence interval [CI], 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free (DFS) and overall survival (OS) were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. The CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34 out of 45 patients who were at risk, whereas recurrent CMV reactivation was observed in 17 patients with a median number of 1.5 episodes (range, 1-6) per patient. The median total duration of antiviral therapy for CMV infection was 27 days (range, 14-199). CMV disease (pneumonia) was documented in 2 patients. The CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 12 months. No case of EBV-related post-transplant lymphoproliferative disorder was observed, however preemptive therapy with rituximab was required in 2 patients with rapidly increasing EBV viral load. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%), but only one required therapy with foscarnet due to high viral load (>10,000 copies/ml). The CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy for bladder hemostasis was required in 5/13 and nephrostomy in 1/11 patients with HC. Reconstitution of helper T cell immunity was considerably delayed, with median absolute CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was significantly associated with the recovery of CD4+ cells at 3 months (Figure; median CD4+ count of 191/uL versus 62/uL in patients with 1 and 2 or more episodes of CMV reactivation, respectively; p=0.009). Conclusions: HaploSCT with PTCY is associated with substantial rates of viral reactivation (especially CMV and BKV) resulting in the need for prolonged antiviral therapy and considerable morbidity. Strategies to prevent viral infection are strongly warranted in haploidentical stem cell transplantation. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution following haploSCT. Figure Disclosures Tsonis: Gilead: Other: Travel Grant; Astellas: Other: Travel Grants; Gilead: Other: Travel Grant; Aenorasis: Other: Travel Grant; Takeda: Other: Travel Grant; Pfizer: Other: Travel Grant; Innovis: Other: Travel Grant.

Introduction Lower respiratory tract infections (LRTI) due to parainfluenza (PIF) or respiratory syncytial virus (RSV) represent a major challenge for immunocompromised patients especially those after allogeneic stem cell transplantation (allo-SCT). Evidence-based guidelines for the management of respiratory virus infections in allo-SCT recipients are limited due to the paucity of effective antivirals and the lack of prospective randomized trials. In this study, we report our experience with the use of oral ribavirin with or without the addition of IVIgG in allo-SCT recipients with LTRI due to RSV and PIF. Patients and methods This is a retrospective study performed in 3 BMT centers in Athens, Greece (2 adult and 1 pediatric center). Review of medical records was performed with the aim to identify patients with RTIs who received treatment with oral ribavirin. LRTI was defined according to the European Conference on Infections in Leukaemia (ECIL-4) (Ref 1). Presence of RSV or PIF in specimens from nasopharyngeal wash and/or BAL was documented with the use of a PCR assay. Ribavirin was administered at a dose of 20-30mg/kg divided into 4 daily doses, with appropriate dose adjustment according to creatinine clearance. Treatment with ribavirin was continued until significant symptomatic and radiological improvement. Co-administration of IVIgG was at the discretion of the treating physician and was mostly based on the availability of IVIgG and on the severity of underlying illness. IVIgG was administered at a daily dose of 400mg/kg for a total dose of 2 g/kg. Informed consent was given by patients or their parents. Results Forty-nine episodes of LRTI due to RSV or PIF were reported during a nine-year period in 7 children and 37 adult patients after allo-SCT. Three children and 2 adult patients had a second LRTI due to RSV, 6, 8, 8, 10 and 12 months after the first episode. Patient's characteristics are shown in Table 1. All patients presented with fever and cough. In almost all of the patients auscultation revealed a prolonged expiratory phase, diffuse wheezing, while the presence of crackles was more prominent finding in patients presenting with pneumonia. Arterial blood gas analysis showed moderate to severe hypoxemia. In 32 out of 49 episodes oxygen supplementation was required while 7 patients required mechanical ventilation. All 49 episodes treated with oral ribavirin while in 37 cases ribavirin was administered in combination with IVIgG. High resolution CT-scan was performed in 41 episodes and revealed bilateral abnormalities in all patients examined. Small centrilobular nodules, bronchial wall thickening (32 out of 41 episodes) and ground-glass opacities (21 out of 41 episodes) were common findings, while a pattern of diffuse air-space consolidation was observed in 11 cases. In 43 LRTI episodes a rapid response to treatment in a median of 3 days (range, 2 - 5) was observed. Complete resolution of all symptoms and signs of disease occurred after a median of 9 days (7 - 20) of treatment. One patient with pneumonia due to PIF3 who needed mechanical ventilation had a complete resolution of all symptoms of disease. Six deaths attributable to LRTI were observed among a total of 49 episodes (all 6 patients were in need for mechanical ventilation). Disease relapse confirmed microbiologically occurred in only 1 patient with LRTI due to RSV 10 days after the end of treatment with ribavirin. One children developed bronchiolitis obliterans syndrome (BOS) 9 months after the resolution of RSV infection. Cryptogenic organizing pneumonia (COP) was observed in two patients 1 and 2 months after the complete resolution of LRTI due to PIF. Both patients had an excellent response to treatment with steroids. Conclusions Oral Ribavirin has an excellent efficacy and safety profile. Complete and fast resolution of infection occurred in 88% of cases. From the present study it is not clear if the addition of IVIgG offers any therapeutic benefit. References Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for Diagnosis and Treatment of Human Respiratory Syncytial Virus, Parainfluenza Virus, Metapneumovirus, Rhinovirus, and Coronavirus. Clin Infect Dis 2013;56(2):258-66 Disclosures Tsonis: Gilead: Other: Travel Grant; Astellas: Other: Travel Grants; Innovis: Other: Travel Grant; Pfizer: Other: Travel Grant; Takeda: Other: Travel Grant; Aenorasis: Other: Travel Grant. OffLabel Disclosure: Tabl Ribavirin. Current indication: Treatment of active hepatitis C in combination with interferon-a.

Allogeneic stem cell transplantation (allo-SCT) remains the main therapeutic option for patients with high-risk hematologic malignancies, albeit with the requirement of a properly matched and timely available donor. Dual-unit umbilical cord blood transplantation (dUCBT) has become an alternative modality, which offers immediate access to allo-SCT for most adult patients who lack an appropriate volunteer donor. We retrospectively analyzed the outcomes of consecutive dUCBT procedures that were undertaken by our center over a seven-year period, with focus on factors affecting engraftment and survival. Between 2006 and 2013, 40 patients underwent dUCBT at a median age of 37 years (range, 16-60) for various hematologic malignancies (acute myeloid leukemia: 22, myelodysplastic syndrome: 5, chronic myelogenous leukemia: 2, acute lymphoblastic leukemia: 6, mixed-phenotype acute leukemia: 2, plasmacytoid dendritic cell neoplasm: 1, hepatosplenic T cell lymphoma: 1, chronic lymphocytic leukemia: 1). The majority of patients (73.7%) had advanced or intermediate-phase disease at the time of transplantation, with a median time from diagnosis to transplant of 17.7 months (range:3.1-92.3). Recipient body weight ranged from 48 to 110 kg (median, 73). The conditioning regimen was myeloablative in 33 (82.5%) patients (busulfan-based in 22, and total body irradiation-based in 11 cases). Antithymocyte globulin was not administered during conditioning, with the exception of one case. Most units (55/80, 68.75%) were 4/6 antigen matched to recipient at HLA-A, -B, and -DRB1 loci, and the remaining were 5/6 matched. By retrospective high-resolution typing for class I HLA alleles, histocompatibility was demoted in 62.3% of units. By additional allele-level typing at HLA-C and -DQB1 loci, the degree of compatibility varied from 8/10 to 3/10, with 80.5% of the units being ≤6/10 matched to the patient. The median dose of cryopreserved total nucleated cells (TNC) per unit was 2.53 x 107/kg (range, 1.09-5.66). At infusion, patients received in total a median of 4.55 x 107 TNC/kg (range, 2.65-9.3) and 1.7 x 105 CD34+ cells/kg (range, 0.54-5.14) from both units. The cumulative incidence (CI) of neutrophil engraftment was 92.5% (37/40 patients), with achievement of an absolute neutrophil count (ANC) greater than 500/uL at a median of 20 days (range, 12-52) (Figure 1). Platelet recovery (>50x109/L) occurred at a CI of 63.2%, and a median time of 84 days (range, 32-363). No influence of cell dose (TNC or CD34+) or of the degree of HLA match on the incidence and kinetics of engraftment could be detected. Acute graft-versus-host disease (aGVHD) of grades II-IV and III-IV developed in 85% and 12.65% of patients, respectively. The CI of chronic GVHD was 31% (extensive in 54.5% of cases). There was a statistical trend for increased incidence of cGVHD with 500/uL) engraftment.Figure 1. Cumulative Incidence curve of neutrophil (ANC>500/uL) engraftment.Figure 2Cumulative Incidence curve of non-relapse mortality.Figure 2. Cumulative Incidence curve of non-relapse mortality.Figure 3Overall Survival (Kaplan-Meier curve).Figure 3. Overall Survival (Kaplan-Meier curve). In conclusion, dUCBT can lead to stable donor engraftment even across multiple HLA disparities and can overcome the barrier of cell dose. Despite considerable early mortality, dUCBT offers the possibility of long-term survival in about one third of adult patients with poor-prognosis hematologic malignancies, for whom allo-SCT would not be otherwise feasible. Disclosures: No relevant conflicts of interest to declare.

Abstract 4116 The main prognostic determinant of the outcome of allogeneic stem cell transplantation (allo-SCT) for acute myeloid leukemia (AML) is disease phase at transplant while the relevance of the assessment of minimal residual disease (MRD) at transplant has not been elucidated. Although molecular markers are highly sensitive for the detection of MRD, they are available in only half of AML cases to date. On the other hand, multiparametric flow cytometry (MFC) offers the feasibility of MRD assessment in virtually all patients. We retrospectively studied the influence of pre-transplant MRD status by MFC on the outcomes of patients with AML in relation to other known prognostic factors. From 01/2003 to 12/2010, 102 AML patients (male/female; 58/44), aged 15–64 (median; 42) years, received allo-SCT in our center at first (CR1, N=69) or subsequent (CR≥2, N=33) morphologic complete remission. Donors were HLA-compatible siblings (N=45), matched unrelated (N=34) or alternative (haploidentical relatives or unrelated cord blood; N=6 and 17, respectively). The conditioning regimen was myeloablative in 85 (83.33%), and reduced-intensity in 17 (16.67%) cases. Data on MRD assessment by four- or five-color MFC before transplant were available in 92 patients. MRD was defined as any percentage of cells with an aberrant antigen expression pattern compared to normal or regenerating marrow. Transplant outcomes associated with MRD in univariate and multivariate analysis were overall (OS) and disease-free (DFS) survival, relapse incidence, and non-relapse-related mortality (NRM). Prognostic parameters included in the statistical model were the following: age and gender of recipient or donor, interval from diagnosis to transplant, de novo versus secondary AML, CR1 versus CR≥2 at transplant, cytogenetic risk group (according to Intergroup ECOG/SWOG definition), recipient and donor cytomegalovirus (CMV) serostatus, donor type, conditioning regimen (myeloablative versus reduced-intensity), degree of HLA match, method of graft-versus-host disease (GVHD) prophylaxis, and the modified European Blood and Marrow Transplantation Group (EBMT) risk score (Hemmati et al, 2011). With a median follow-up of 47 (range, 6–98) months, OS and DFS were 54.2% and 51.72%, respectively. The cumulative incidence of relapse was 24.45%, and of NRM 23.82%. Eighteen out of 92 (19.57%) patients had MRD by MFC before allo-SCT. According to univariate analysis, the presence of MRD showed a negative association with OS (29.63% versus 63.17% at 4 years in patients with or without MRD, respectively, P=0.053) and DFS (28.52% in MRD-positive versus 59.74% in MRD-negative cases at 4 years, P=0.025, Figure 1). Presence of MRD correlated with higher incidence of relapse compared to MRD negativity (52.7% versus 15.8%, respectively, P=0.001) (Figure 2), but did not influence NRM. In multivariate analysis (Cox proportional hazards, backward stepwise selection), the parameters that remained independent adverse risk factors in terms of specific outcomes were: a) For OS: age and male gender of patient, alternative donor, unfavorable karyotype, CR≥2, and secondary AML, b) For DFS: presence of MRD (HR=3.2, P=0.009), CR≥2 (ÇR=3.1, P=0.005), reduced-intensity conditioning (HR=2.6, P=0.034), and unfavorable karyotype (HR=2.06, P=0.074), c) For relapse: presence of MRD (ÇR=3.83, P=0.003), and unfavorable karyotype (HR=3.55, P=0.007), and d) For NRM: age of recipient, CR≥2, and alternative donor. In conclusion, the presence of MRD by MFC before allo-SCT for AML is associated with a significantly higher risk of relapse and an inferior DFS, despite morphologic complete remission at transplant. Moreover, pre-transplantation MRD status has independent prognostic significance in addition to the disease phase, cytogenetic risk group, and intensity of the conditioning regimen. Prospective studies are warranted to examine if the adverse impact of MRD on the outcomes of allo-SCT can be reversed by immunologic manipulations aiming at augmenting graft-versus-leukemia (GVL) effect. Disclosures: No relevant conflicts of interest to declare.

Introduction. Primary Bone Lymphomas [PBL] are rare extranodal non Hodgkin’s Lymphomas [NHL] constituting about 5% of all extranodal NHL. In this study we present our experience from a retrospective analysis of patients with PBL; we have assessed the patient characteristics, response to therapy and outcome. Patients - Methods. From a population of 600 newly diagnosed patients with NHL who have been registered to our Unit between 1990 and 2004, 18 [ 3% ] have been classified as PBL. Apart from patient characteristics and clinical course, 12 cases were studied with immunohistochemistry for expression of antigens associated with different stages of B-cell differentiation. The median age of the patients [12 men, 6 women, M/F ratio 2/1] was 54 years (range 32 – 83). The stage of the disease was evaluated as I in 12 patients (66 %), II in one (6%), and IV in five patients (28%). The histology was that of a diffuse large -B-cell lymphoma in 17 cases [94%] while one patient [6%] had lymphoplasmacytoid lymphoma. The most common site of involvement was the axial skeleton (13/18, 72%), followed by the long bones of the extremities (5/18, 27%). All studied tumors revealed a germinal center [ G-C] immunophenotype signature [bcl−6 +], but only 4 of 12 [33%] confirmed their G-C origin [bcl-6+CD10+]. Results: Sixteen patients were treated with an anthracycline based chemotherapy regimen with [14] or without [2] radiotherapy [RT]. Only one patient was treated with RT alone, while one patient denied treatment. Fifteen patients (88%) achieved complete remission, one (6%) partial remission, and one patient (6%) had progressive disease to first line therapy with a CHOP-like regimen. Five patients (30%) experienced relapse; in three cases the relapses involved the CNS. Finally, 16 patients remain alive: 14 in CR [10 (60%) in 1st, 4 (23%) in 2nd CR], and one (6%) with active disease. Two patients (11%) have died, both with CNS disease. One patient survives without recieving treatment. With a median follow-up time of 47 months (range 8– 150), the 6 year actuarial overall and disease free survival was 72% and 52% respectively. Conclusions: PBL are rare extranodal NHL. They mostly involve the bones of the axial skeleton. The vast majority of them present with a germinal center immunophenotypic profile. The response rate is high (88%). However, the disease recurs in one third of the cases, most often in the CNS.