ALBERT

Description: Double umbilical cord blood (dUCB) allogeneic transplantation following low dose TBI, cyclophosphamide and Fludarabine (TCF regimen)-based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there is little data regarding the impact on long-term outcome of CD3+ T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases and who receieved dUCB conditioned with TCF were included in this retrospective study. Peripheral blood CD3+ TCC was considered until day +100 post-tranplant in order to determine the impact of full versus mixed chimerism on long-term outcomes. Twenty-nine and 7 patients were documented with full and mixed CD3+ TCC, respectively, within the first 100 days post-transplant. With a median follow-up of 36 months, 3 year-OS, DFS, and relapse incidence were 61%, (95% CI 43-75); 50% (95% CI 32.5-66) and 28% (95% CI 16-44), respectively. In univariate analysis, a full CD3+ TCC was associated with a better 3-year DFS : 59% (95% CI 39-75.5) versus 14% (95% CI 7-46), (HR=0.24 [0.09-0.65], p=0.005) and a lower cumulative incidence of relapse : 24% (95% CI 21.5-57) versus 78% (95% CI 52-99), (HR=0.18 [0.05-0.5], p=0.004). In multivariate analysis, a full CD3+ TCC remained associated with a lower incidence or relapse (HR=0.17, 95% CI 0.028-0.99, p=0.049). CD3+ TCC has no impact on GVHD and NRM in this study. In conclusion, in our study, full CD3+ TCC was independently associated with a lower risk of relapse after dUCB TCF RIC allogeneic transplant in adults, highlighting the need to develop immunotherapy approaches allowing for early conversion to full chimerism after dUCB. Abstract 2479. Table 1 Patients, sustained cord blood and transplantation characteristics. Patients, sustained cord blood and transplantation characteristics Full TCC (n=29) Mixed TCC (n=7) p No.of patients % No.of patients % Patients characteristic Age at transplant, years, median (range) 57 (22-69) 47 (17-64) NS Sex female 14 48 3 43 NS Hematological malignancy : Lymphoid / myeloid 14 / 15 48 / 52 3 / 4 43 / 57 NS Statut at transplant : RC / RP 23 / 6 79 / 21 6 / 1 86 / 14 NS Time to transplant, days, median (range) 395 (137-5645) 216 (92-604) NS Cord blood characteristics Age of cord blood, months, median (range) 31 (9-165) 116 (23-140) NS Matching cordon with patient NS 4/6 10 35 3 43 5/6 19 65 3 43 6/6 0 0 1 14 Number of total nucleated cell 10^8/kg before and after thawing, respectively, median (range) 0,28 (0,16-0,455) ; 0,248 (0,157-0,406) 0,222 (0,135-0,492) ; 0,22 (0,11-0,392) NS Number of CD34+ cell 10^6/kg before and after thawing, respectively, median (range) 0,066 (0,022-0,215) ; 0,043 (0,02-0,2) 0,078 (0,031-0,427) ; 0,041 (0,019-0,259) NS Mismatch between cord blood and patient Sex 14 48 3 43 NS Serology CMV 13 45 3 43 NS ABO 16 55 2 28 NS Rhesus 22 76 6 86 NS Graft Neutrophil count recovery 〉0.5 G/L, days, median (range) 17 (6-32) 11 (7-20) NS Platellet recovery 〉20G/L, days, median (range) 41 (0-164) 31 (0-67) NS Acute GVHD (grade II-IV / grade III-IV) 19 (12 / 6) 65 (41 / 21) 4 (3 / 1) 57 (43 / 14) NS Chronic GVHD (Limited / Extensive) 11 (8 / 3) 38 (28 / 10) 3 (2 / 1) 43 (28 / 14) NS Chimerism Rate, %, median (range) 100 (96-100) 82 (14-94)

Description: Abstract 3472 Allo-SCT procedures are currently undergoing a profound evolution. The spectra of patients and diseases for which this approach is now considered have increased considerably over the past years. This is mainly due to the introduction in routine practice of the so-called nonmyeloablative or RIC regimens. While it is well established that fludarabine is the backbone drug to secure engraftment, there is a wide variability in the degree of myeloablation between the different RIC protocols, and the toxicity profile might vary significantly from one protocol to another. The combination of fludarabine and Busulfan (usually 8 mg/Kg total dose) with or without ATG, is among the most widely used RIC protocols worldwide. In an attempt to further decrease the toxicity of the transplant procedure, we hypothesized that further reduction (50%) of the Busulfan dose can allow improving transplant outcome for lymphoid neoplasms. With this background, this retrospective analysis was performed to assess whether a RIC regimen including fludarabine (120 mg/m2), low dose busulfan (4 mg/Kg total dose administered orally over a single day) and ATG (Thymoglobuline®, 2.5 mg/Kg/d for 2 days; FB1A protocol, n=44), is a valid alternative to the classical RIC regimen including fludarabine (90 mg/m2) and TBI (2 Gy.) (FTBI, n=27) prior to allo-SCT. The cohort included 37 males (52%) and 34 females (48%) treated consecutively in a single centre, with a median age at time of allo-SCT of 53 (range, 15–66) y. Diagnoses included 39 NHL (55%), 17 Hodgkin lymphomas (24%), 12 CLL (17%) and 3 myeloma (4%). PBSCs were used as stem cell source in 42 patients (91%), while 4 patients (9%) received classical bone marrow. A matched-related donor was used in 18 cases (39%) and an unrelated donor in 28 cases (61%). With a median follow-up of 43 (range, 3.7–85) months after allo-SCT, all patients, but one (from the FTBI group) engrafted. In the FB1A group, the acute grade 3–4 GVHD rate was 20.5% (n=9), the chronic GVHD rate was 32% (n=14), the relapse rate was 23% (n=10) and the TRM rate was 25% (n=11). In the FTBI group, the rate of grade 3–4 acute GVHD rate was 44% (n=12; P=0.03 in comparison to the FB1A group), the chronic GVHD rate was 52% (n=14; P=0.09), the relapse rate was 15% (n=4; P=NS) and the TRM rate was 37.0% (n=10; P=NS). At 2 years, overall survival was 66% (95%CI, 51–78%) in the FB1A group versus 55% (95%CI, 36–73%) in the FTBI group (P=NS). Disease-free survival (DFS) was also comparable between both groups (at 2 years, 59% in the FB1A group, vs. 48% in the FTBI group, P=NS). In a Cox multivariate analysis for OS or DFS, the type of RIC regimen was not significantly associated with outcome. In all, these results suggest that in patients with lymphoid malignancies, a RIC regimen including Fludarabine, ATG and low dose busulfan (4 mg/Kg total dose) is a valid alternative to the classical Fludarabine and low dose TBI-based RIC regimen with a favorable toxicity profile and efficient disease control. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Achieving a PET-negative metabolic (m)CR with salvage chemotherapy prior to autologous stem cell transplantation (ASCT) in relapsed/refractory Hodgkin lymphoma (R/R HL) is a strong predictive factor for long-term progression-free survival (PFS). In a phase I dose-escalation trial we have shown a favorable toxicity profile of 3 cycles of DHAP in combination with brentuximab vedotin (BV) with a high mCR rate (12/12 patients). A subsequent phase II study in 55 patients has been performed; the 6 patients treated at full dose of BV-DHAP in the phase I part were added to the current analysis. Methods BV was given at a fixed dose of 1.8 mg/kg on day (d) 1 of 3 cycles of DHAP q 3 weeks (dexamethasone 40 mg iv d 1-4, cisplatin 100 mg/m² iv d1 and cytarabine 2x2 g/m² iv d2). Cycle 2 was used for stem cell mobilization; after the 1st and 3rd cycle patients received pegylated G-CSF to prevent prolonged neutropenia and dose delays. The primary endpoint of the study was the mCR rate after 3 cycles of BV-DHAP based on central PET-review. Patients with a partial or complete response proceeded to high dose chemotherapy (BEAM) and ASCT. Results Twenty-three of the 61 patients (29 males; median age 29 yrs, range 19-71) had not achieved a CR to 1st line treatment (37%), which consisted of ABVD (n=45), (escalated) BEACOPP (n=11) or other regimens (n=5). The median time from response to 1st line treatment to relapse was 6 months (range 0-160 months); 38 patients (62%) had either primary refractory disease or early relapse (

Description: Background: The course of follicular lymphoma (FL) is characterized by iterative relapses. Several reports have demonstrated that intensive chemotherapy followed by autologous stem cell transplantation (auto-SCT) is an attractive treatment. Because a subgroup of patients obtains prolonged complete remission after auto-SCT, some authors have postulated that auto-SCT may cure FL patients. In order to address this issue and to characterize long-term responders, we retrospectively studied the outcome of 80 FL patients who underwent auto-SCT in our institution. Patients characteristics: Between 1989 and 2004, 80 FL patients underwent auto-SCT in the Haematology Department of Nantes Medical University, France. All patients had a FL according to the WHO classification. Median age at diagnosis was 45.7 (range 27–62) and median age at the time of transplantation was 48.1 (range 27–69). Auto-SCT was performed upfront in 36 cases, at first relapse in 36 cases and at a subsequent relapse in 8 cases. Median time from diagnosis to auto-SCT was 53 months. At diagnosis, 25 patients presented with a FLIPI

Description: Positron emission tomography using fluorine 18-fluorodeoxyglucose (FDG-PET) is required in the assessment of therapeutic response in diffuse large B-cell lymphoma. Limited studies addressed the interest of FDG-PET prior autologous stem cells transplantation (auto-SCT) in High-grade non Hodgkin’s lymphoma (HG-NHL). Between April 2002 and December 2005, 42 HG-NHL (DLBCL in 35 cases and aggressive transformation in 7 cases) patients underwent auto-SCT in our institution and were systematicaly explored prior and after auto-SCT using computed tomography (CT) and FDG-PET. The therapeutic strategy included R-CHOP or R-DHAP as induction chemotherapy followed by auto-SCT. In note, auto-SCT was always included in the initial strategy and scheduled after completion of induction chemotherapy for patients at least in partial response (PR) according CT assessment. Pre-auto-SCT FDG-PET results did not influence the scheduled strategy. Auto-SCT was performed as part of the first-line therapy in 35 cases (83 %) or at the time of relapse in 10 cases. Prior auto-SCT, 14 patients were in PR and 24 in CR/Cru. Conditioning regimen consisted of BEAM in all cases (except one patient). The median follow-up (calculated from the time of auto-SCT) for living patients was 34,5 months [19–74 months]. The 2-years EFS and OS estimates were 79,6 % [63,2%; 89,3%] and 90,5 % [76,6%; 96,3%], respectively. According to pre and post auto- SCT FDG-PET results, patients were classified into 3 groups: NEG/NEG (n=25) POS/ POS (n=8) and POS/NEG (n=9). The 2-years EFS and OS estimates for NEG/NEG, POS/ POS and POS/NEG patients were 88 % versus 19 % versus 100 % (p= 0,0001) and 92 % versus 75 % versus 100 % (p = 0,19), respectively. According to FDG-PET response after auto-SCT, the 2-years EFS estimates for NEG versus POS patients were 90, 9 % versus 19 % (p

Description: Abstract 2875 Background: Radioimmunotherapy (RIT) is under study as a consolidation treatment after chemotherapy induction in follicular lymphoma patients. This approach also appears interesting in diffuse large B-cell lymphoma (DLBCL) patients 〉60 years, who are not candidates for bone marrow transplantation. 90Y-epratuzumab tetraxetan (Immunomedics, Inc.) is a radiolabeled humanized anti-CD22 antibody that has been used for a fractionated RIT, showing high rates of durable complete responses with manageable hematologic toxicity in previously-treated indolent and aggressive non-Hodgkin lymphoma (NHL) patients (Morschhauser et al., J Clin Oncol. 2010;28(23);3709-16). A French phase II trial sponsored by the GOELAMS group is ongoing, assessing fractionated RIT using 90Y-epratuzumab tetraxetan as a consolidation therapy after first-line chemotherapy in disseminated DLBCL patients 〉60 years. The protocol has been designed to include 75 patients; 64 patients have been already enrolled. We report the initial results, in particular safety data, on the first 29 available patients. Design and Method: From October 2008 to November 2009, 29 untreated DLCBL patients 〉60 years were studied in several French institutions with an initial course of six cycles of R-CHOP14 followed 8 weeks later by two weekly infusions of 90Y-epratuzumab tetraxetan (15 mCi/m2 [555 MBq/m2]) 7 days apart. Hematologic and non-hematologic toxicities were evaluated using NCI-CTC v.3.0. Treatment responses were classified according to the 1999 International Workshop for Response Criteria for NHL. Results: Twenty-six patients underwent the entire course of R-CHOP and 23 received the 2 weekly RIT injections. Following R-CHOP, grade 3–4 neutropenia was observed in 20 patients (68.9%) and grade 3–4 thrombocytopenia in 4 (13.7%). During RIT infusions, 4 patients showed transient change of pulse or blood pressure, with 2 attributed to vasovagal reactions. RIT toxicity included grade 3–4 hematologic toxicity in 18 of 23 patients (78.3%); the most common grade 〉 3 toxicities were neutropenia (N=18, 78.3%) and thrombocytopenia (N=17, 73.9%). Serious febrile neutropenia was observed in 4 cases (13.8%) after R-CHOP and in 2 patients (8.7%) following RIT. Compared to R-CHOP, RIT non-hematologic toxicity was uncommon; moderate or severe gastrointestinal toxicity was observed in 10 patients (34.5%) after R-CHOP and in 2 (8.7%) following RIT; moderate or severe infection in 9 patients (31.0%) after R-CHOP and in 1 (4.3%) after RIT; and moderate or severe mucositis in 10 (34.4%) patients following R-CHOP, while no patient had mucositis after RIT. Following RIT, red cells and/or platelets transfusions were given to 12 patients (52,2%). Following R-CHOP, 10 of the 25 patients (40.0%) achieved a complete response (CR) or unconfirmed CR (CRu), 13 patients (52.0%) had a partial response (PR) and 2 patients (8.0%) had a stable disease. Six weeks after RIT, 13 patients (56.5%) achieved a CR or CRu, 9 patients (39.1%) had PRs, and 1 patient (4.3%) had progressive disease. Four of 13 patients (30.7%) who achieved less than a CR or CRu with R-CHOP improved their remission status 6 weeks after RIT. Conclusion: These preliminary results indicate the feasibility and safety of fractionated RIT with 90Y-epratuzumab as a consolidation therapy for elderly DLBCL patients. Additional data will be presented at the time of the communication. Disclosures: Off Label Use: monoclonal antibody epratuzumab labeled with yttrium 90 in phase II clinical trial. Wegener:Immunomedics, Inc.: Employment, shareholders. Goldenberg:Immunomedics, Inc.: Employment, shareholders.

Description: Introduction: Allogeneic stem cell transplantations (allo-SCT) using alternative donors are increasingly used in patients lacking suitable matched sibling or unrelated donor. Recently, the use of post-transplant cyclophosphamide (CY) has allowed to re-consider first-generation relatives (brother, sister, father, mother, son or daughter) as haplo-identical donors for allo-SCT. Indeed, the incidence of severe acute GVHD is lowered by post-transplant administration of CY, due to the early destruction of putative alloreactive T cells. Still, some patients may not have a suitable relative donor for various reasons such as older age of the parents, no siblings nor children, no cord blood available, or because use of a graft from a first-generation haplo-identical relatives is contra-indicated. The probability of having a haplo-identical donor among siblings is 50% while it is almost 100% when considering both biological parents and offspring. When considering as a potential donor the child of a matched or haplo-identical sibling, the probabilities for the donor to be haplo-identical with the recipient remain 50% and 25%, respectively. Thus, second-generation relative donor (i.e. nephew or niece) may be finally considered as a source of stem cell graft. Methods: Here we report the case of a 61-year old man who received a T-replete haplo-identical allo-SCT with high-dose post-transplant CY from his second-generation relative nephew. In 2010, the patient was diagnosed with ALK- CD30+ anaplastic T-cell lymphoma and received 8 cycles of CHOD allowing to obtain morphologic and metabolic partial response. The patient received an allo-SCT from a sibling matched donor (brother) on November 2010 after an FB2A2 reduced-intensity conditioning regimen but secondary graft failure was rapidly documented in spite of donor lymphocyte infusions. Relapse occurred in September 2014 and brentuximab vedotin was administered each 21 days for seven cycles allowing to obtain a complete morphologic and metabolic response. It was decided to perform a second allograft using a different donor. The patient was childless and no unrelated donor or cord blood units were available. It was thus chosen to ask for donor the son of the matched brother, who was haplo-identical and had no antibodies directed against the patient's HLA specificities. This nephew had a O- blood group and negative CMV serology while the recipient was O+ and CMV+. Results: The second allograft was performed on April 2nd 2015 using the Baltimore (Luznik, BBMT 2008) conditioning regimen with 2 days of post-transplant CY. A megadose of peripheral blood stem cell was administered (14.16x106 CD34+ cells/Kg) at day 0. Neutrophils and platelets recovery (〉50 Giga/L) were achieved as early as days +18 and +33, respectively, with full donor whole blood chimerism (99.8%) at day +30, persisting on day +60 and +100 (both whole blood 99.9%, CD3+ T cells: 99.9%).Grade 2 acute cutaneous GVHD occurred at day +21. The evolution was favorable after initiating corticosteroids at 2 mg/kg/day with tapering thereafter. Not surprisingly, CMV reactivation was documented at day+22, controlled by ganciclovir treatment. Immune reconstitution evaluated at days +30, +60 and +100 showed normal monocyte counts while B lymphocytes were undetectable. NK cells increased from 42/mm3 at day+30 to 453/mm3 at day +60 and 665/mm3 at day +100. Interestingly, after profound lymphopenia within the first 100 days post-transplant, CD8+ T large granular lymphocytes expansion was documented at day + 110. At four months post-transplant, the patient is alive in persistent metabolic remission with no active acute or chronic GVHD nor active infection. His outcomes will be updated for the meeting. Conclusion: T-replete haplo-identical allo-SCT with high-dose post-transplant CY using a second-generation relative donor was feasible allowing for full engraftment and moderate acute GVHD in our patient. This result expands the possibility to find a donor for a selected patient, meanwhile paving the way for using unrelated haplo-identical donor, which could be of interest when considering solid transplantation. Indeed, combining solid organ transplantation and allo-SCT from the same haplo-identical donor may open the door to withdraw immunosuppression in this particular setting, because stable tolerance may be induced, as it has been already reported for kidney transplant (Kawai, NEJM 2013). Disclosures Moreau: Celgene: Honoraria, Other: Adboard; Amgen: Other: Adboard; Takeda: Other: Adboard; Janssen: Other: Adboard; Novartis: Other: Adboard.

Description: Abstract 3889 During the last decade, the role of Interim 2-[18F]fluoro-2-deoxy-D-glucose emission positron tomography (FDG PET-CT) has increased for Hodgkin's lymphoma (HL) evaluation and it is strongly recommended for both staging and post treatment evaluation. Early treatment response assessment is a challenge for risk-adapted therapy and interim PET-CT has emerged as a powerful prognostic tool to predict treatment outcome, a negative exam predicting a favorable disease-free survival while a positive study a worse prognosis. However, FDG PET response criteria are a matter of ongoing debate. So, the aim of our study was to confirm the prognostic value of interim FDG PET-CT performed after 4 courses of chemotherapy (ABVD) but also to compare the respective performances of the different published criteria: International Harmonization Project (IHP), Gallamini criteria, 5-point scale (Gallamini A et al. Haematologica 2006; 91: 475–481; Juweid ME et al. J Clin Oncol 25:571-578, 2007; Barrington SF et al. Eur J Nucl Med Mol Imaging 2009;36(Suppl. 2):S252; Meignan M et al. Leukemia & Lymphoma, August 2009; 50(8): 1257–1260; Gallamini A, et al. Leuk Lymphoma. 2009 Nov;50(11):1761-4.) Design and methods: From 2002 to 2006, newly diagnosed patients with HL who underwent interim PET-CT after 4 courses of ABVD were eligible for the purpose of the present study. Treatment strategy after 4 courses of ABVD was then adapted according to prognostic factors at diagnosis and interim PET-CT result. PET images were interpreted prospectively visually by at least two nuclear medicine physicians with expertise in lymphoma imaging with the criteria used before 2005: negative result was defined as no residual uptake above local background. All other findings were considered as positive. Using these evaluation criteria, interim PET positive patients who were not in CR on CT underwent autologous stem cell transplantation. Interim PET positive patients who reached CR on CT and interim PET negative patients received additional courses of ABVD (patients with advanced HD or bulky disease at diagnosis) or radiotherapy alone (stage I or II without bulky disease). Retrospectively and for the purpose of the present study, interim PET results were interpreted using the more recent criteria (Gallamini criteria, IHP criteria and 5-point scale method) Results: 90 patients were included. Median age at diagnosis was 34.4 (16-71). 49% of the patients presented with B-symptoms and 50% had stage III-IV disease. According to initial criteria, 31 patients had a positive interim PET result. Among these patients, 28 underwent ASCT. Fifty-nine patients had a negative interim PET-CT. Six of 31 patients with positive interim PET-CT and 7 of 59 patients with negative interim result presented treatment failure. Thus, the negative predictive value (NPV) and positive predictive value (PPV) for predicting 2 years progression free survival (PFS) was 95% and 16%, respectively. Retrospectively, interim PET-CT was analyzed according to different recent published criteria using mediastinum and liver background as threshold for positivity. With these criteria, NPV remained very high (from 95% to 96%). However, the PPV increased from 25% to 55% according to the threshold used. Taken together, the statistical analysis revealed that Interim PET-CT was significantly correlated with PFS only for two methods: the Gallamini criteria and the 5-point scale method. Conclusion: The first part of our study using the criteria used before 2005 shows the high NPV of interim PET-CT for predicting treatment outcome in HL. However, better prognostic values are obtained by using higher threshold for positivity such as liver background even after 4 cycles of ABVD. Indeed, our analysis underscores the better results reached by the Gallamini criteria and 5-point scale methods. The better method to predict PFS was obtained by the 5-point scale (scores 1, 2, 3 and 4 were classified as negative while only score 5 was classified as positive) showing a PPV and NPV of 55% and 96%, respectively. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Recently, theuse of high-dose post-transplant cyclophosphamide (PTCY) has contributed to reconsider T-replete haplo-identical allo-SCT because of the lower incidence of severe graft-versus-host disease (GVHD) observed in patients. However, the influence of PTCY on early outcomes has been poorly studied so far, especially in comparison to the standard use of anti-thymoglobulin (ATG) as GVHD prophylaxis. Patients and Methods: This retrospective study was conducted at the University Hospital of Nantes with the aim to compare the incidence of early outcomes (engraftment, neutrophils and platelets recovery, viral infections (HHV-6, CMV, EBV, BKv, ADV), acute GVHD, relapse or deaths and day+100 non-relapse mortality (NRM)) between patients receiving either PTCY (n=30) or ATG (n=46) as part of GVHD prophylaxis for a RIC allo-SCT. In the PTCY group, RIC was the Baltimore regimen (Luznic, BBMT 2008) in 17 patients while 9 patients received clofarabine instead of fludarabine because of a myeloid malignancy and 4 patients a sequential approach. In this group, 6 and 24 patients received 1 or 2 days of PTCY, respectively, while donors were matched (sibling n=2, unrelated n=5) in 7 cases and haplo-identical in 23, respectively. All patients received cyclosporine + MMF with PTCY as GVHD prophylaxis. In the ATG group (2 days of ATG for siblings and 10/10, 3 days for 9/10), 13, 11 and 22 patients received respectively a FB2, FB3 or CloB2 RIC regimen (Chevallier, Haematologica, 2014). Donors were siblings in 18, matched unrelated in 23 and mismatched unrelated (9/10) in 5. GVHD prophylaxis was cyclosporine alone in case of sibling donors and cyclosporine +MMF for all other cases. The characteristics of both groups (PTCY vs ATG) were similar in terms of gender (male: 63% vs 54%), type of disease (myeloid: 67% vs 63%) and disease status at transplant (complete remission: 43% vs 67%). PTCY patients were significantly younger (median age: 55.5 vs 63 years, p=0.01) and had been previously allografted in a significantly higher proportion (40% vs 4%, p=0.003). Patients were transplanted between March 2012 and April 2015 and were considered up to day+100 post-transplant. All patients received peripheral blood stem cells as stem cell source except one patient in the PTCY group who received bone marrow. Results: All patients engrafted except one in the ATG group. The median time of neutrophils recovery was similar between both groups (PTCY 18 days vs ATG 19 days, p=0.9). Conversely, median time of platelets recovery was significant higher for the PTCY group (27 vs 13 days, p