ALBERT

Description: Abstract 4537 Most of lymphoma patients are chemo- and radiosensitive. Using a conventional therapy we can cure about 50% of patients (pts). Unfortunately the rests achieved only partial remission or have a rapid relapse after treatment. These pts are a real challenge for nowadays hematology. Till now there is not a recommended scheme of therapy. Using high dose chemotherapy with autologous hematopoietic cell transplantation (AHCT) is the most popular one. During the last year in our Department we have been started using BeEAM as the conditioning treatment, and the results of a single centre observation are presented now. Material and Methods Actually: between April, 2011 and February, 2012 we conducted AHCT using BeEAM as conditioning treatment in 23 pts with lymphoma (18 pts with Hodgkin Lymphoma (HLy), 2pts with diffuse large B cell lymphoma (DLBCL), 2 pts with T cell lymphoma (TCL), 1 with follicular lymphoma (FL). There were 14 male and 9 female, with a median age of 37,6 (range 21–62 yrs). Ann Arbor staging at diagnosis was as follows: II-33%, III-50%, IV-17%; 83% of patients manifested B-symptoms. Clinical manifestation at diagnosis included: enlargement of the lymph nodes (n=18), bone marrow infiltration (n=2), lung infiltrates (n=3). Initially, all patients received at least 2 cycles of chemotherapy; in HLy all pts received ABVD, in non HLy- RCHOP. None of them achieved complete remission (CR). Partial response (PR), defined as the reduction of measurable disease by ≥50% without the appearance of any new lesions, achieved 11pts. The rests underwent high dose chemotherapy (HDT) followed by AHCT without remission (NR). Stem cells were collected from peripheral blood after IVE chemotherapy (Ifosfamide 3g/m2 iv in 1–3d, Etoposide200mg/m2 iv in 1–3d, Epirubicine 50mg iv in1d) and subsequent administration of G-CSF at a dose of 10ug/kg/d, starting from +5 day after chemotherapy till the last day of collection. Collections were performed using Optia Spectra. All pts collected the sufficient number of CD34+ cells for AHCT procedure. Conditioning regimens before AHCT consisted of BeEAM (Bendamustine 200mg/m2 in -8-7d, Etoposide 200mg/m2 in -6-3d, Ara-C 400mg/m2 in -6-3d, Melphalan 140mg/m2 in -2d). A median number of transplanted CD34+ cells was 5,58 (2,05–17,8×10∧6/kg). All except one pt successfully engrafted. 1 pt with Hly died within 8 day after transplantation due to infection. Hematopoietic recovery was as following: WBC count 〉 1,0×10∧9/L after median of 12 days (range 9–15 days),ANC〉 0,5×10∧9/L after median of 13 days (range 9–16 days) and platelet count 〉20×10∧9/L after median of 13days (range 7–20 days). Results 3 pts died after AHCT. Two of them due to progression of the disease within 5 and 16 months after AHCT. Both were without remission before AHSCT. 1 pt died due to heart insufficient after 3 months after AHCT. The complications after transplantation procedure were rare and included mainly: bacterial infection in the upper respiratory tract (n=3), viral skin infection (n=1), oral mucositis (n=2). At the last contact, 19 pts are alive and 9 of them achieved CR, and 3 – stable disease. One pt underwent sibling alloHCT and 2 others will undergo alloHCT within 2 months. 4 pts with Hly were treated with anty CD 30+. Conclusion Autologous hematopoietic cell transplantation using IVE for mobilization and BeEAM as conditioning is effective treatment for lymphoma patients with refractory disease. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Autologous hematopoietic stem cell transplantation (AHSCT) remains the treatment of choice in multiple myeloma (MM) patients (pts). In earlier research it has been suggested that the expression of dipeptidyl peptidase-4 (DPP4, CD26) influences both the homing and lymphocyte reconstitution after AHSCT in pts with lymphoproliferative neoplasms. The aim of the study is to investigate the effect of transplanted CD26 positive cells of the hematopoietic recovery and lymphocyte reconstitution in MM pts after AHSCT. Patients and methods Forty eight pts with MM with median age 56 (range 21-76) were undergoing AHSCT in our center in years 2011-2013. Conditioning regimen was Melphalan 200. Number of all CD26+ cells, CD26+ lymphocytes, CD26+ monocytes and CD26+ and CD34+ cells were measured in harvested material. Number of lymphocyte's subpopulations (all lymphocytes CD3+, helpers CD3+CD4+, suppressors CD3+CD8+, natural killer (NK) CD3-CD16+CD56+, cytotoxic NK CD3+CD16+CD56+, lymphocytes B CD3-CD19+) were measured in peripheral blood during regeneration period after AHSCT. In both flow cytometry was used. The hematopoietic regeneration was measured as following: the day of white blood cells' regeneration when WBC count reached 〉1,0x109/L, the day of granulocytes' regeneration when ANC 〉0,5x109/L and the day of platelets' regeneration when PLT 〉20x109/L. Results All pts successfully engrafted. The results of AHSCT are shown in table nr 1. Table 1. The number of transplanted cells and regeneration during the procedure AHSCT in pts with MM. Parameter Median Range Mean Standard deviation Number of transplanted WBCx108/kg b.w. 4,26 0,73-18,8 5,43 4,36 Number of transplanted CD34+cells x106/kg b.w. 3,36 2,2-8,2 3,52 1,28 Number of transplanted CD26+ lymphocytes [109/L] 46,5 9-148 53,6 30,8 Number of transplanted CD26+ monocytes [109/L] 3,65 0-82 8,03 13,05 Number of all transplanted CD26+ cells [109/L] 50,42 9,6-213 62,5 23,2 Regeneration WBC 〉1x109/L (day) 13 10-20 13 2,64 ANC 〉0.5x109/L (day) 13 9-20 13,3 2,16 PLT 〉20x109/L (day) 14 11-20 14,1 2,18 As regards regeneration of hematopoietic cells after AHSCT it was shown that a higher number of transplanted CD26+ monocytes improves the reconstitution of suppressor (p=0,019) and NK lymphocytes (p=0,0237). A higher number of all transplanted CD26+ lymphocytes has a positive impact of the reconstitution of suppressor lymphocytes (p=0,0054), whereas a higher number of all transplanted the CD26+ cells improves the regeneration of cytotoxic NK (p=0,0126) and helper lymphocytes (p=0,0261). There were no confirmed adverse effects of the number of CD26+ cells on the hematopoietic regeneration0 and lymphocytes B reconstitution after AHSCT. Discussion Our research shows that the number of transplanted CD26-positive cells may improve immune reconstitution after AHSCT in patients with multiple myeloma, which was not clearly demonstrated before. As is well known faster lymphocyte reconstitution after AHSCT is associated with improved patient survival. Therefore, the greater the number of transplanted autologous CD26-positive cells may be associated with improved survival, which, however, needs further investigation. Disclosures No relevant conflicts of interest to declare.

Description: Dipeptidyl peptidase IV(DDP IV) known as CD26 can play a role in the process of mobilization as well as in regeneration during hematopoietic cells transplantation. As we know from the studies conducted in vitro and in animals models DDP IV inactivates chemokine CXCL12 (stroma direct factor 1) causing interruption the connection between marrow stoma and hematopoietic cells through CXCR4 receptor.In physiological conditions on the surface of hematopoietic cells concentration of CD26 is low.The purpose of this study was to examine a correlation between the number of CD26+ and CD34+ cells collected during mobilization in multiple myeloma (MM)patients (pts) and investigate the expression of CD26+ on monoclonal cells’. The second purpose was to examine whether CD34 cells have expression of CD26 parallel.30MM pts were mobilized in our department between 2011-2013. For harvest intermediate dose of cyclophosphamid and G-CSF were administered. The number of CD26+ cells and CD34+ cells were measured using immunophenotyping method before starting the procedure in peripheral blood and in collected materialResults All pts collected sufficient for AutoHCTnumber of CD34+ cells,the medianwas 3,8 (2,05-11,1x10^6/kgb.w.).Before mobilization 49,65% of blood nucleated cells showed CD26 expression while in collected material -79,95%. The CD34+ cells in peripheral blood showed low expression of CD26 – median 4,5%. In thecollected material the expression of CD26in CD34+ cells did not increase –median 2,5%, but the number of CD34+ cells (p=0,0003)increased. On mononuclear cells (monocytes and lymphocytes) there were demonstrated also the increase ofCD26 expression after mobilization chemotherapy and G-CSF (p=0,0002).Conclusion In MM patients after mobilization chemotherapy (cyclophosphamide+G-CSF) statistically significant increase ofnumber of CD26+ cellswere observed. It will be interesting to investigate the role of CD26+ cells during autotransplantation. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4519 Diffuse large B-cell lymphoma (DLBCL) remains one of the most frequently seen non-Hodgkin lymphoma (NHL) with an aggressive disease course. It estimates that only 40–50% of patients (pts) may be cured with chemo - and radiotherapy; the remaining pts subset remains partially chemosensitive or resistant. High dose chemotherapy (HDT) followed by autologous haematopoietic stem cell transplantation (AHSCT) is a method of choice for the pts who didn’t achieve complete remission (CR) after R-CHOP or CHOP treatment. We present 80 pts with DLBCL (47 male and 33 female, with a median age of 52. (range 18–68 yrs) who were underwent AHSCT between January 1999 and April 2011 in our Department. Ann Arbor staging at diagnosis was as follows: II- (n=11), III- (n=17), IV- (n=32); 48 of pts manifested B-symptoms. 50 of pts had an aged-adjusted IPI 2 or 3, 8 pts - IPI 4. Clinical manifestation at diagnosis included: hepatomegaly (n=16), splenomegaly (n=19), enlargement of the lymph nodes (n=39), bone marrow infiltration (n=7), lung infiltrates (n=5), digestive system involvement (n=9), CNS (n=4), tonsils (n=3). Initially, all were treated CHOP but 65 of them received chemotherapy with rituximab and achieved partial response (PR) which was defined as the reduction of measurable disease by ≥50% without the appearance of any new lesions. Patients with PR proceeded to high dose chemotherapy (HDT) followed by AHSCT. Stem cells were collected from peripheral blood after IVE chemotherapy (IVE – ifosfamide 3g/m2 iv in 1–3d, etoposide, epirubicine 50mg iv in1d) in 67 patients, in 9 with other treatment and subsequent administration of granulocyte-colony stimulating factor (G-CSF) at a dose of 10ug/kg/d, starting from +5 day of chemotherapy till the last day of collection. G-CSF alone (10ug/kg/d) was used in 4 remaining patients. Collections were performed using Optia Spectra. All patients collected the sufficient number of CD34+ cells for AHSCT procedure. Conditioning regimens preceeding AHSCT consisted of CBV in 73 cases, BEAM in 6 and LACE in one. A median number of transplanted CD34+ cells was 3,97 (1.25 – 35.76×10^6/kg). All patient successfully engrafted. Hematopoietic recovery was as following: WBC count 〉 1,0×10^9/L after median of 12 days (range 8–16 days),ANC〉 0,5×10^9/L after median of 14 days (range 8–17 days) and platelet count 〉20×10^9/L after median of 14 days (range 7–21 days). None of pts die due to AHSCT (TRM 0%). The major complications after AHSCT were rare and included: bacterial infections of the respiratory tract (n=15), viral infections (n=10), oral mucositis (n=9). 145 months’ disease free survival (DSF) was estimated to be 88% with a 145 months’ overall survival of 86%. 69 patients achieved CR after AHSCT (86,3%). Six pts underwent second AHSCT and 4 of them achieved CR. At the last contact, 75 pts are alive with a median follow-up period of 56 months (range 3–145). 5 patients died due to disease progression. HDT followed by AHSCT seems to be highly effective and safe procedure for DLBCL patients. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Azacitidine is the current standard of care for higher risk MDS patients (HR MDS) changing the natural course of diseases. Early drug discontinuation (receiving less than 4 azacitidine cycles - early failure - EF) is a poor prognostic marker, while factors affecting early failure are largely unknown. Objectives: To identify predictive factors for early azacitidine failure in MDS/CMML/low blast percentage AML patients Methods: The study included retrospectively MDS/CMML and 20-30% bone marrow blasts AML patients treated from 2008 to 2019 in 12 Polish hematologic centers cooperating within Polish Adult Leukemia Group (PALG). Baseline demographic, laboratory, clinical and treatment characteristics were obtained and were evaluated as potential EF predictors. Cox proportional hazard models were used to define statistical significance of variables using the R statistical platform. Results: We collected data on 315 patients with MDS (67%), CMML (12%) and with AML (21%). Median age was 69 years and 61% were male. Median number of azacitidine cycles was 7 (1-69) and 84 patients (29%) received maximum 3 cycles. Patients achieved more than 3 cycles showed better OS compared to those ≤ 3 cycles (20 months vs 4 months)(p

Description: Abstract 4515 Chronic lymphocytic leukemia (CLL) is an incurable disease when treated with standard chemotherapy. The only possibility to provide cure is allogeneic stem cell transplantation (allo-SCT). CLL patients aged less than 55 account for about 15% of patients and these cases allo-SCT should be taken into consideration. The indications for allo-SCT are as follows: del17p, resistance to chemoimmunotherapy, Richter’s syndrome or recurrent disease. A retrospective analysis of allo-SCT in 18 patients (10 males, 8 females) with CLL transplanted in years 2000–2010 was performed. The aim of the study was to assess of long term follow-up outcome of allo-SCT in CLL patients. The median age at diagnosis was 41ys (range: 35–51). The sibling donor was available in 16 cases (2 pts were mismatched), unrelated donors were in 2 cases (1 mismatched). Most of the pts (16 out of 18) were MRD positive when allotransplanted. Median lymphocytosis preceeding allo-SCT was 5.9G/l. Peripheral blood was the source of stem cells in 9 cases (50%), and bone marrow in the remaining 9 cases, 2 pts were transplanted with stem cells from bone marrow and peripheral blood. 4 pts (22%) underwent the allograft procedure twice or more. Reduced intensity conditioning with alemtuzumab was performed in 9 pts (50%), myeloablative regimen in 4 cases and RIC with rituximab in one case.The median number of CD34+cellsx10^6/kg was 4.1 (range: 0.86–9.64). All but one patient engrafted (this pt was transplanted again successfully in one year time). Acute graft-versus host disease (GvHD) was noted in 46% of pts (only in 2 pts grade IV). Extensive GvHD was observed only in 2 pts. Donor lymphocyte infusion (DLI) was performed in 8 pts (44%). With a median follow-up of 73 months (range: 9–89) for surviving patients, the five-year Kaplan-Meier of overall survival (OS) and progression free survival (PFS) was 55,5% and 34%, respectively. At five years, the cumulative probability of non-relapse mortality was 15%. Allogeneic stem cell transplantation remains the effective treatment in CLL for selected group of patients. Disclosures: No relevant conflicts of interest to declare.

Description: Background: AML is the most common acute leukemia in adults. While most adults 〈 60 years achieve complete remission (CR) with intensive induction chemotherapy, approximately one third have primary refractory disease and, overall, the majority of AML patients still relapse despite having attained initial remission (Dohner et al, Blood 2017). The combination of an anthracycline and cytarabine has been the mainstay of intensive AML induction for more than 50 years. Combined with cytarabine (AraC), high-dose daunorubicin (90 mg/m2) in induction (DA-90) resulted in a higher rate of CR (70.6% vs. 57.3%, P

Description: Background Although the introduction of novel agents improved the survival outcomes in patients with multiple myeloma (MM), some patients died within one year (early mortality, EM) following diagnosis. In this study, we evaluated the EM rate, and investigated the risk factors associated with EM in MM patients. Aims In this study we investigated risk factors associated with EM in MM patients initially treated with novel-agent containing regimen. Methods We conducted a multicenter (15 Polish sites) retrospective study a cohort of symptomatic MM pts diagnosed between October 2006 and November 2019 and living 〈 365 days (d) after diagnosis. All pts were dead at the time of the analysis. Data were collected from medical registries and databases. Mortality rate and cause at 2, 6, and 12 months following diagnosis was evaluated. Clinical staging was performed using the International Staging System (ISS). Response to treatment was evaluated according to the International Myeloma Working Group (IMWG) consensus criteria (2016). Statistical analysis was performed using R-studio v.1.3.959. and significant levels were set at p2 comorbidities at diagnosis. Heart disease was presented at diagnosis in 57% pts and diabetes in 22% pts. First-line treatment (1stL), 41% of the pts patients were bortezomib-based (Bor) regimens, 25% Bor with thalidomide (VT)-based, 22% IMiD-based and 13% others. Response evaluation showed an overall response rate (ORR) of 44% (3% CR; 14% VGPR; 27% PR). 46% pts survived 〈 2 months, 29%; 2-6 months and 25%: 6-12 month. Median time until death was 2.5 month; 31% of pts died directly from progression disease (PD), and 69% from other causes [infection in 66%, cardiovascular complications in 27%, RI in 8%]. In our study, age 〉 65 y (HR 1.67; 95% CI 1.24-2.26; p=0.0007), and 〉75 y (HR 1.5; 95% CI 1.10-2.03; p=0.0087), 〉2 comorbidities (p=0.002), heart disease (HR 2.12; 95% CI 1.57-2.85; p 〈 0.0001), RI (HR 0.7; 95% CI 0.53-0.95; p=0.029), dependence of dialysis (HR 1.50; 95% CI 1.05-2.14; p=0.029) were associated with increased risk of death. Mortality predictive value showed HRC (p=0.05), lactate dehydrogenase levels (HR 0.65; 95% CI 0.38-1.1; p=0.002), and 〉PR (HR 0.30; 95% CI 0.21-0.43; p