ALBERT

Description: Impact of complete response on outcome is a subject of ongoing debate. Aim: In this retrospective analysis of all myeloma-ASCT patients transplanted between 1999– 2007 (n: 116) in our center with a minimum 3 mo followup (n: 91) and a disease status available at the time of M (n:66) were analyzed for evaluation of the impact of response at M, preASCT, postASCT; the preASCT use of novel agents ; timing of M (〉,〈 6 mo) and ASCT (〉,〈 12 mo) on response and survival. 91 patients aged 33–66(med: 52) were included. Induction (VAD/T D/MP: 72/8/10) was given for a median of 8.3 mo pre M. 45 patients received additional chemo (n:3), (V :1, T :17, both:10) or none(n:41) untill ASCT with Melphalan (200 mg/sq.m) within 12 months (54%). For 〈 90% response, V/T alone or in combination was given during the postASCT period and/or received a second ASCT/NMA. SPSS version 11.0 was used for Kaplan Meier survival and Chi Square analysis. Results: Patient characteristics between early vs late M or ASCT, novel agent (+) vs (−) were similar .〉90% response rates at different time points (M/preASCT/postASCT) were: 54.5%, 59.7% and 61.3%. One third of patients could be mobilized early. Response rates of early and late M were: 73.6% vs 46.6% (p=0.04). Novel agents were used less frequently in early M patients (22% vs 40%). Among all analyzed, only response during M, timing of M and use of V/T were found to be influential on PFS and/or OS. Evaluation of factors (b2mg,ISS,age,chemo line)on response during M revealed only late M to be associated with less response (p=0.05). Among early M patients, amplitude of response (〉90% vs others) did not prolong PFS or OS. However, among patients who were mobilized later, achievement of 〉90% response prolonged PFS at 3 yr (100% vs 85%,p=0.03) at 5 yr (100% vs 44%,p=0.03) (Fig.1). The impact of response to induction, on OS was also observed in all patients irrespective of M time (3 yr: 93% vs 83%, 5 yr: 80% vs 55%, p=0.02). Comparison of patients who had received at least one novel agent during the preASCT, compared to those not, revealed an OS prolongation (3yr:100% vs 81%; 5yr: 81% vs 56%, p=0.03). (Fig. 2). Patients who had received a novel agent were mobilized at similar times but were transplanted later (9/27 vs 28/42, p= 0.01). Although there was a trend, novel agents did not influence PFS or response rate significantly at any time point. Conclusions: In this retrospective analysis, we were able to demonstrate a benefical effect of response amplitude, earlier (

Description: Factors that predict response to treatment in CML has been defined for busulphan and Interferon. Search for prognostic parameters in the imatinib era are still continuing. Very recently a new prognostic scoring of CML patients has been defined by Kantarjian et al (Blood, 2004; 10: 1182).The value of these scoring systems in prediction of molecular response to first line use of IM has not been published yet. With this aim, we have evaluated the hematological and molecular response of all CML patients chronic (n: 74)/accelerated (n: 9) treated with IM in this prospective study. Since IM has been approved for secondary ( May 2001)and primary (May 2003) treatment in Turkey, we have evaluated 22 patients- first line use (Group 1) and 61 Interferon failures (Group 2) following a median follow-up of 9–35 months. Hasford prognostic score was available and calculated in 67 of these patients online at www.pharmacoepi.de/cmlscore.html. Scores were: Group 1 low:8 /medium:5 /high:2; Group 2:low:16 /medium:29 /high:7. In group 2, time from diagnosis to IM treatment was 29 m(3–144). Method: RNA was isolated from blood or marrow (High Pure RNA isolation kit, Roche) and used for quantitative detection of bcr-abl transcripts with “LightCycler t(9;22) Quantification Kit”. Results were expressed as ratio to G6PD standarts. Results: Age and Hasford distribution were comparable in group 1 and 2. The tumor burden (median)according to scoring was Group1: low: 0.014 /high: 0.0453 and Group 2: low: 0.0035 /high: 0.012. Level of bcr-abl transcripts were higher in group1 vs 2(0.03 vs 0.009) and Hasford-high vs low, regardless of previous treatment. We could not show any correlation between Hasford score and transcript level at diagnosis (Pearson, r=.314, p=0.255). 20% of the Group 1-high and 60% of Group 1-low patients achieved major and complete CR at 6m and 12m. Similar evaluation revealed a weaker response rate in Group-2: 21–30% depending on risk score and time (6–12m). Time to mol CR (less than 10e5) occurred at a median of 6 (6–12) months in 26.7% (6m) of Group1 and 9m (3–12) in 7.7% (6m) of Group 2. Resistance developed both in Group 1(2/22) and Group 2 (7/61). Among scored patients, mol CR was achievable in Group-1(only low risk). However in Group 2, molCR could be obtained both in low (n:17) and high (n:17) risk patients. The median levels of bcr,abl transcript were: Group1:0.029 (molCR+) vs 0.059(molCR-) and Group 2: 0.0498 (molCR+) vs 0.0988(molCR−). Conclusion: In accordance with previous reports both molecular and cytogenetic remissions were observed earlier and more frequently among patients who received IM as a first line agent compared to second line use. Among patients being treated after Interferon, Hasford scoring at diagnosis did not have an impact on the prediction of response to IM. This finding is in paralel to Kantarjian’s results. However, in our study de novo CML patients’ bcr,abl transcript levels and the Hasford score showed an association with response. The shorter median follow-up in Group 1 may also have an impact on these results and updates are warranted. Like ours, the recent publications (Brummendorf 2003 and Drummond, 2004) on the correlation of telomere length with Hasford score and the response to treatment with IM support the value of this score in previously untreated patients with CML.

Description: Recently, in an effort to reduce the transplant related mortality, AHCT with reduced intensity conditioning (RIC) have been developed. It has been reported that patients receiving RIC from an ABO-mismatched donor had more transplant-associated complications compared to ablative AHCT (BMT2001;28: 315, Transfusion2002; 42:1293, Transfusion2003; 43: 1153). In this single center, retrospective, historical case-matched study, we aimed to analyze the influence of ABO-incompatibility on transplant-related morbidity and mortality between ablative and RIC. Between 1988 and 2003, 39 patients underwent AHCT with RIC and only 14 were ABO-incompatible. Ten patients with ABO-incompatibility and having a regular follow-up for blood group typing were evaluated for immuno-hematological complications, such as acute or delayed-type hemolysis (DTH), pure red cell aplasia (PRCA), thrombotic thrombocytopenic purpura (TTP) and early transplant-related complications, were compared to 20 case control recipients having matched pretransplant characteristics and similar follow up, but myeloablative regimen, either bone marrow (BM) or peripheral blood (PB) stem cells infused. Patients’ characteristics are shown in table below. All the recipients and donors underwent a detailed pretransplant work up and all the recipients were followed twice a week post transplant by a transfusion specialist according to guidelines (BMT, 2001;28:315). Median follow-up was 195 days (range, 51–538d). We did not observe any acute hemolysis, but 11 experienced DTH. No significant differences were encountered among the three groups in terms of DTH (p=0.356). In all recipients having a major ABO incompatibility, the blood group switched to donor type, but 50% of the patients with minor ABO-incompatibility still had either their antigen persistency or the appearance of donor-derived isoagglutinins. We observed mild (n=1, BM group) and severe pure red cell aplasia (n=1, RIC group) in two patients having a major ABO-incompatibility. TTP was developed in one patient with major ABO-incompatibility. In conclusion, we did not observe any difference between ablative AHCT and RIST in ABO incompatible patients in terms of immuno hematological complications in contrast to published case series. In addition, we could not show any negative impact of ABO-incompatibility on the severity of acute GVHD and the rate of early transplant related mortality. Table Conditioning Ablative Reduced Intensity Source (patients) PB (n=10) BM (n=10) PB (n=10) Gender (M/F) 2/8 6/4 5/5 Median age (range) 34 (16–45) 31 (17–46) 33 (21–47) Diagnosis CML (2), AML (7), other (1) CML (2), AML (6), other (2) CML (4), AML (1), other (5) ABO-incompatibility Major 5 6 5 Minor 5 4 5 Delayed type hemolysis 5 (50%) (22,23,55,90,120) 2 (20%) (18,27) 4 (40%)(20,130,165,188) RBC transfusion (100 days) 3 (0–15) 4 (0–10) 5 (0–10) Median days of the independence from pRBC 7 (0–31) 18 (0–41) 7 (0–28) Median follow-up (days) 195 (90–538) 194 (63–467) 200 (51–511) Acute GVHD (grade II–IV) n (%) 3 (30%) 4 (40%) 4 (40%) TRM 100, n (%) 1 (%10) 1 (%10) 1 (%10)

Description: The number of centers choosing peripheral blood stem cell (PBSC) source for allogeneic transplants is rapidly growing. To evaluate the current practice of PBSC collection and apheresis technology, we analyzed the efficiency of four different cell separators. Forty procedures, (10 for each separator) performed on various cell separators (Baxter-Amicus, Fenwal CS3000+, COBE-Spectra and Fresenius AS204), were analyzed retrospectively. All the donors were HLA identical siblings of the patients (M/F: 16/14) with a median age of 33 years (range, 16–62). There was no statistical difference between donor’s body weight (mean 35.7±15.8) and age between four groups. They received 5mcg/kg rhG-CSF (Amgen-Roche) sc. twice daily for 4 days and the stem cell collection was performed on the subsequent dose of G-CSF on day 5. Two to three times the total blood volume (total processed volume

Description: Allogeneic hematopoetic cell transplantation (allo-HCT) is currently the only curative treatment option for non-M3 AML in first or second remission (CR1, CR2). Cytogenetic risk factors, pretransplant disease status and factors apart from leukemia could affect the success of allo-SCT. It is still uncertain that allo-SCT in CR1 has superior efficacy especially for those patients who have cytogenetically standard risk. The optimization of supportive care in last 2 decades decreased early transplant related mortality substantially. In this intent-to treat, single center, retrospective study we analyzed 40 consecutive AML patients who underwent allo-SCT between January 2011 and November 2013 at our centre to determine the role of allo-SCT in CR1 or beyond. Patients were evaluated for overall survival (OS), disease free survival (DFS), early (30 - 100 day) and late (101-365 day) transplant related mortality (TRM). Survival was estimated using the Kaplan–Meier method, and the log-rank test was used to compare survival curves among variables. Median age was 48 years (19-64 y). Among those patients who had cytogenetic data (28 patient, 70%), 12 (30%) were in high-risk category. Median time from diagnosis to allo-HCT was 6.5 months (2-54 months). Median follow-up period for living patients was 419 days (105-857). Pretransplant disease status was as follows; 24 patients (60%) in CR1, 12 patients (30%) in CR2 and 4 patients (10%) had active disease. The conditioning regimens for allo-SCT consisted of myeloablative (Bu16-CY120) (n=32, 80%) or reduced-intensity regimens (Flu150-Bu8)(n=8, 20%). Donors were HLA-matched siblings for 32 patients (80%), unrelated for 7 patients (17.5%) and haploidentical for 1 patient (2.5%). All but 2 patients (95%) received peripheral blood stem cells. All patients received primary antifungal prophylaxis. Overall, TRM at day 30 and 100 were 7.5% (n=3) and 10% (n=4), respectively. Late death (〉100 days) was observed in 7 patients (17.5%) and 3 of them were related to allo-SCT. Grade 2-4 aGVHD was seen in 20 (50%) patients and chronic extensive GVHD in 8 patients (20%). Of those 24 patients who underwent allo-HCT in CR1, 18 patients (75%) were still in remission without any sign of disease. Nine of 16 patients (56.3%) who underwent allo-SCT beyond CR1 lost due to relapsed leukemia. Survival analysis revealed superior OS between patients in CR1 (median 901 days) and beyond CR1 (median 202 days) (log-rank, OS p=0.003). For disease free survival we have seen the same profile (p=0.007) (Fig 1 and 2). In CR1 patients (n=24) univariate analysis revealed no impact of standard-risk cytogenetics, high HCT-CI (³2), high WBC at dx (〉30k), sex (F to M), ABO mismatch and double induction for CR achievement. The only adverse factor for short OS in CR1 was past history of invasive fungal infection pre allo-SCT (p=0.038, 901d vs 553d)(Fig 1). Allogeneic HCT in AML patients should be undertaken in CR1 with matched sibling donor. Pre-tx invasive fungal infection was the only worst predictive factor for OS in CR1 AML patients cohort. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Aim and Scope: Substantial morbidity and mortality is caused by respiratory complications in 40–60% of patients after HSCT. Bronchiolitis obliterans syndrome (BOS) is reported in 2–13% of patients, occurring within 6–12 months post transplant. The LEWP launched a retrospective survey in 2003 to document the incidence, current practice for the diagnosis, clinical work-up and treatment of BOS after allogeneic HSCT. Patients&Method: Between 2003 – 2005, 31 centers reported 226 patients with BOS. Adjusted BOS criteria were accepted (normal spirometry pretransplant, respiratory symptoms in the absence of an infection and combination of 3/4 items at onset: FEV1

Description: High dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (HSCT) rescue is a potentially curative&consolidative therapy for advanced hematological malignancies, and it also permits the administration of higher doses of chemotherapy to overcome tumor cell resistance. In this study, our aim is to evaluate 167 consecutive myeloma (MM) and lymphoma (ML) patients referred to our center between August 2010 and May 2013. Patients data are analyzed in intent to successful hematopoietic stem cell (HSC) mobilization and collection. In our country we have limited access to plerixafor, as salvage HSC mobilizing agent, permitted only after a failed mobilization&collection trial of chemotherapy and G-CSF. Our center's policy is to collect HSC with G-CSF in all MM (exception of prolonged revlimide use and prior autologous HSCT), and non-heavily pretreated ML patients. Candidates for poor mobilization underwent first CT and G-CSF, and second line receive plerixafor. Under these circumstances 86 lymphoma patients (31 Hodgkin and 55 NHL) and 81 MM patients (F/M: 57/110, med. age 52, range 18-72) were included in this study. Nearly 〉15% of the patients received more than 2 cycles of chemotherapy before HSC collection. Mobilization with G-CSF as a single agent resulted in optimal CD34+ cell yield for 121 (72%) patients. In myeloma G-CSF as first line resulted with 92.7% successful HSC mobilization and collection. Overall 17 patients received plerixafor as 2nd or 3rd line, and resulted with sufficient HSC collection in 57.3%. In three cases (MM:1, ML:2) additional support with autologous bone marrow collection necessary. Only in 9 (5.3%) patients all attempts for mobilization failed including plerixafor. After any type of mobilization regimen median count for pCD34+ cells obtained was 18/mcl. Median yield of 3.3 x 106/kg CD34+ cells/kg was collected with range of 0.2-33.9x106/kg in total apheresis sessions. MM patients have significant high levels of preapheresis circulating CD34+ count in comparison to ML patients (29 vs 15, p=0.001). pCD34+ cell did not correlate with body mass index, age, underlying disease and previous treatment cycles. There is a close correlation between pCD34+ cell count and collected CD34+ cells in all types of mobilization regimens as G-CSF, chemotherapy and plerixafor (relatively; p

Description: Minority of patients with Hodgkin’s lymphoma (HL) are primary refractory or relapse very early after first-line chemotherapy or even after high-dose chemotherapy (HDCT) and autologous HSCT. The dismal outcome of these patients was shown by many previous studies. We evaluated the role of allogeneic stem cell transplantation in this setting. We retrospectively analysed 6 consecutive patients (med age 45) with primary refractory advanced stage Hodgkin’s lymphoma transplanted between 2011-2013. The median time from initial diagnosis and from autologous HSCT to allogeneic transplantation was 44.1 mo.s and 12.4 mo.s, respectively. The donor sources were sibling in 4, unrelated in one and haploidentical in 1. The conditioning regimen was myeloablative (BU-CY) in 3 and reduced intensity (Flu-Mel±ATG) in 3 adjusted according to their age and comorbid conditions. All of them received peripheral blood stem cells. Engraftment failure was not observed. None of them were complicated with VOD or other early complications of HSCT. Day 100 transplantation related mortality was 16.7% (1 patient). The patient succumbed to carbapenemase+ klebsiella pneumonia sepsis on day +11. Median follow up of the surviving patients was 14.65 months (range, 6-26). At the last follow up 3 of them were in CR, one patient had progression after HSCT and achieved stable disease with brentuximab and DLI. One patient died from acute abdominal infection on +187 while in CR. Only one patient was complicated with both acute and chronic GVHD (unrelated HSCT). The myeloablative regimen was tolerated well and the patients achieved durable remission. The expired patients were both in RIC arm. Although the number of transplanted patients is low we can conclude that allogeneic HSCT using myeloablative regimen is safe and effective in short term. Primary refractory HL patients should be evaluated for allogeneic HSCT, as upfront or following failure of autologous HSCT and HDCT. Ablative regimen is tolerated as well as RIC, and more effective than allo RIC for disease control in the light of our current limited cohort. Disclosures: No relevant conflicts of interest to declare.

Description: Aim: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (AHCT). As GVHD prophylaxis regimen, post-transplant cyclophosphamide (Post-Cy) has been associated with less acute and chronic GVHD. Anti-Thymocyte Globulin (ATG), which is another GVHD prophylaxis regimen, could reduce the risk of chronic but not acute GVHD. Anti-thymocyte globulin (ATG) in association with a calcineurin inhibitor (CNI) and methotrexate or mycophenolate mofetil (MMF) is widely used in the setting of unrelated donor transplantation (UDT). Recent studies proned non-inferior results of haplotype matched donor transplantation (HMDT) using Post-Cy in comparison with UDT. However, there is no consensus about the optimal GVHD prophylaxis regimen or choosingwisely. Aim of this study was to compare the outcome of two GVHD prophylaxis regimens; Post-Cy used in HIDT or UDT and ATG used for unrelated donors in a single-cohort of consecutive transplant recipients. Material and Methods: Two hundred adult (17-72 years) patients who underwent HIDT and UDT with a minimum 100 days follow-up at Florence Nightingale Hospital Hematopoietic Stem Cell Transplantation Center between 2011 and 2017 were included in this study. Medical records of patients were reviewed retrospectively. Transplantation was performed in cases with high or very high DRI. HIDT was performed in 73 cases and UDT in 127 cases. One hundred eighty five out of 200 cases with a complete follow-up were included in the statistical analysis. Sixty-seven patients underwent HIDT with Post-Cy (Group 1), 97 patients with UDT receiving ATG (Group 2) and 21 with UDT receiving Post-Cy (Group 3). Patients who completed minimum 100 days post-transplantation follow-up were identified as eligible for survival analysis. Results: Median age of patients was 42.8±14.9 years. Percentage of male patients was 65.6%, 68% and 38% for HIDT with Post-Cy (Group 1), UDT with ATG (Group 2) and UDT with Post-Cy groups (Group 3), respectively, which is significantly different (p=0.03). Bone marrow was used in 58.2% patients as stem cell source in HIDT, contrary to UDT, which is below 1% (p