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  • 1
    Publication Date: 2016-12-02
    Description: Introduction: Allogeneic stem cell transplantation is a potentially curative treatment for patients with high-risk non-Hodgkin lymphoma (NHL). Fludarabine/busulfan based conditioning regimens are widely used in Europe for this purpose. Busulfan dose intensity discriminates between reduced intensity (FB2, 2 days of busulfan at 4 mg/Kg/d per os or 3.2 mg/kg/d iv) and reduced-toxicity myeloablative (FB3/FB4, 3 or 4 days of busulfan at 4 mg/Kg/d per os or 3.2 mg/kg/d iv) conditioning regimens (Bacigalupo, 2009). While some data have been recently published showing some advantages of higher busulfan dose intensity for myeloid malignancies, there is no such data available in the lymphoid setting. Methods: This was a large retrospective study conducted on behalf of the SFGM-TC including all adults allografted in France between January 2004 and December 2014 for NHL (n=378). Clinical data were obtained through ProMISe (Project Manager Internet Server), an internet-based system shared by all French transplantation centers. We aim to compare various outcomes (overall (OS) and lymphoma free (LFS) survivals, relapse incidence (RI), non-relapse mortality (NRM), acute and chronic GVHD) between those who received FB2 (n=277) or FB3/FB4 (n=101) as conditioning regimens. GVHD free relapse free survival (GRFS) was also studied (defined as alive with no previous grade III-IV aGvHD, no moderate or severe chronic GvHD (cGvHD) and no relapse). Results: Both groups were comparable for the following variables: median follow-up (FB2: 24.9 vs FB3/4: 23 months), gender (male 61% vs 53%), disease type (low-grade lymphoma 25% vs 21%, mantle-cell lymphoma 17% vs 13%, high-grade lymphoma 25% vs 21%, T cell lymphoma 32% vs 45%), disease status at transplant (complete remission/very good partial response 64% vs 62%, partial response 28% vs 31%, active disease 8% vs 7%), donor type (sibling 43% vs 49.5%, matched unrelated 56% vs 47), median number of previous courses of treatment (2 vs 2, p=0.44), stem cell source (peripheral blood 96% vs 95%). FB2 patients were significantly older (median 57.3 vs 53.1 years, p=0.07), have been transplanted more recently (median year of transplant: 2011 vs 2010, p=0.001) and have been more previously autografted (69% vs 50.5%, p=0.001). FB3/4 patients have been allotransplanted earlier during the evolution of their disease (median time between diagnosis and allograft 18.2 vs 33.8 months, p=30 months), there were also no significant differences between both groups in terms of OS, LFS, RI or NRM. In multivariate analysis there was a trend for worse outcome using FB3/FB4 regimens (OS: HR 1.46, 95%CI: 0.96-2.23, p=0.07; LFS: HR: 1.43, 95%CI: 0.99-2.06, p=0.05; RI: HR 1.54; 95%CI: 0.95-2.48, p=0.07). These results were also confirmed using a propensity score-matching strategy including 184 FB2 and 98 FB3/4 patients. Conclusion: This large retrospective study showed that reduced toxicity myeloablative fludarabine/busulfan regimens did not improve outcomes of adults allografted for NHL. FB2 conditioning regimen still should be considered as the standard of care conditioning regimen in this setting. To validate these results, prospective studies are needed, like the French prospective trial currently ongoing for myeloid diseases (NCT01985061). Also, new conditioning regimens and post-allograft strategies should be tested to improve outcomes of patients. Disclosures Peffault De Latour: NOVARTIS: Consultancy, Honoraria, Research Funding; PFIZER: Consultancy, Honoraria, Research Funding; ALEXION: Consultancy, Honoraria, Research Funding.
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  • 2
    Publication Date: 2019-11-13
    Description: Introduction: Corticosteroid-refractory graft-versus-host disease (GVHD) remains a serious complication of hematopoietic stem cell transplantation (HSCT) with high morbidity and mortality rates. Unfortunately, no standard therapy exists for this setting. Ruxolitinib (ruxo), an oral selective Janus-associated kinase (JAK) inhibitor, achieved good results for corticoresistant acute and chronic GVHD in preclinical and clinical studies, with 80% overall response rates. Recent studies showed an increased risk of infections in patients treated with ruxo, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivations. Patients and methods: In order to assess the efficacy and the safety of ruxo, we reviewed here the outcome of 57 patients who received ruxo for corticosteroid-refractory GVHD (in case of digestive tract involvement or in the absence of available ongoing clinical trials) or as a steroids-sparing medication. EBV and CMV reactivation risks were also assessed in the 137 consecutive patients received HSCT between January 1, 2012 and December 31, 2017 and who presented acute or chonic GVHD (57 of whom received ruxo). For this purpose, each reactivation were analyzed separately as a competing risk with death in a cause specific Cox model of survival after the first GVHD occurrence and the onset of ruxo therapy was coded as time dependent covariate. Results: The median age of 57 patients with ruxo was 55 years (range, 49 to 61). Indication for HSCT was acute myeloid leukemia for 25% patients, lymphoma for 30%, acute lymphoblastic leukemia for 11%, myeloproliferative neoplasm for 14% and myelodysplastic syndrome for 7%. Only 9% of this patients received ruxo before HSCT. Unrelated donor was used for 60% patients and main source of hematopoietic stem cells was peripheral stem cells (93%). T cell depletion with polyclonal anti-thymocyte globulin was performed for 89% of patients. Conditioning with high doses cyclophosphamide was used for 21% patients. A lymphopenia 4 log or increasing viral charge of 0.5 log) occurred in 19 patients after ruxo with a 6-weeks cumulative incidence (6WCuI) of 22% (95CI [95% confidence interval]: 15-34). It was the first reactivation in 13 patients. CMV reactivation (〉 3 log) occurred in 8 patients after ruxo with a 6WCuI of 4% (95CI: 7-25). It was the first reactivation in 3 patients (Figure 1). The distribution of first reactivation before ruxo and in the remaining 80 patients is shown in Table 1. Thus, 6WCuI of first EBV and CMV reactivation after the first episode of GVHD was 24% (95CI: 19-31) and 20% (95CI: 15-25) respectively. Finally, onset of ruxo coded as time dependent covariates retained a significant adverse prognostic value for the competing risks of death and first episode of EBV reactivation (HR [Hazard Ratio]: 2,657, p
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  • 3
    Publication Date: 2013-11-15
    Description: Background Follicular lymphoma is the second most common non-Hodgkin lymphoma subtype. PET-CT is a useful tool to evaluate staging and monitoring of follicular lymphoma. Calculation of maximal standardized uptake value (SUV max) is variable and related to the aggressiveness of lymphoma. In tumor cells, there is an increase in uptake and consumption of glucose. Therefore GLUT-1, a membranous glucose transporter, may have an impact on the SUV max. To our knowledge, data regarding eventual correlation between GLUT-1 and SUV in different subtypes of lymphoma is sparse (Hye Kyung Shim et al, Nuclear Medicine and Biology 2009; S. Hartmann et al, BMC Cancer 2012), especially in follicular lymphoma. In addition, Ki67, a marker of cell proliferation is also linked to the metabolism of tumors cells. Only few studies have shown a correlation between SUV max and Ki-67 in follicular lymphoma (Tomas Papjik et al, European Journal of Haematology 2010; Yi shou et al, Journal of Cancer Research and Therapeutics 2012). Elsewhere, it was demonstrated that microenvironment composed of dendritic cells, macrophages, T cells and vascular endothelium play a key role in the prognosis of follicular lymphoma (Pedro Farinha et al, Blood 2005), it could have also an impact on SUV max. The aim of our study was to identify histological markers involved in glucose metabolism, cell proliferation and microenvironment, influencing SUV max in follicular lymphoma. Materials and Methods Lymph node biopsies of 21 patients treated in our hematologic department at diagnosis and/ or relapse were retrospectively included. Patients underwent PET-CT and node biopsy simultaneously. Five histological markers (Ki67, GLUT 1, CD20 for B lymphocytes, CD3 for T lymphocytes, and CD68 for macrophages) were analyzed. Pathologists perform visually the immunostaining analysis without knowledge of the PET-CT results. Percentage of expression of immunological markers was compared with SUV max from the biopsy site. The correlation was analyzed using Spearman’s method to calculate the coefficient of correlation r. Results Ki-67 (median 40, range [3; 80]) and GLUT1 (median 53, range [0; 100]) were not related to the level of expression of the SUV max (respectively r = 0.3603 and p = 0.1086, r = 0.0215 and p = 0.9283). Concerning the microenvironment, CD68 (median 6, range [0; 18]) and CD3 (median 22, range [7; 60]) did not show any correlation (respectively r = 0.1370 and p = 0.5536, r = -0.2115 and p = 0.3708). Interestingly, percentage of CD20 expression (median 79, range [51; 99]) appears to be correlated significantly with the SUV max (r = 0.4924, p = 0.0274). Discussion and Conclusion In this study, it was not possible to identify a specific histological marker influencing the SUV max. Otherwise, interest in glucose metabolism and particularly other isoforms of GLUT receptor or enzymes involved in the metabolism, like hexokinase, appears to be a promising track. Considering that CD20 stains B tumor cell and normal B lymphocyte in the tumor, it could be interesting to analyze the ratio of CD20/CD10, assuming that all tumor cells express CD10. Disclosures: No relevant conflicts of interest to declare.
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  • 4
    Publication Date: 2019-11-13
    Description: Patients with t-MN have a poor prognosis with median overall survival 〈 1 year due to high risk features of the disease and refractoriness to chemotherapy. HSCT represents the only curative treatment. Outcome after HSCT has progressively improved over time with a last EBMT study showing a 2-year OS at 44% in patients with secondary leukemia (79% post MPN or MDS) (BBMT 2018: 1406). Previous large studies showed survival 〈 30% in patients transplanted for t-MN (Blood. 2010:1850; Haematologica 2009:542). We recently reported in patients transplanted for a leukemia arising from MDS, MPN and CMML that the primary disease impacts the outcome, particularly patients with a previous MPN had the worst outcome (BJH, 2019: 725). We report here outcome of patients who received HSCT for a t-MN (excluding post MDS, MPN and CMML) with the hypothesis that the primary cancer impacts the outcome. From EBMT registry, patients with MDS or AML occurring after a primary cancer who received a HSCT between 01/06 and 12/16 were included. OS and RFS were analyzed using Kaplan Meier curves and log-rank test, relapse and NRM were analyzed as competing risks with cumulative incidence curves and Gray's test. 2334 patients were identified. Primary cancers were CLL in 102, non-Hodgkin lymphoma (NHL) in 668, Hodgkin lymphoma (HL) in 235, plasma cell disease (PCD) in 111, breast cancer in 643 and other solid tumor (ST) in 575. 981 patients had MDS and 1353 had AML at time of transplantation. Performance status by Karnofsky score was 90 or higher in 1376 (59%) patients. 722 (31%) patients were transplanted from HLA matched sibling donor (SIB) and 843 (36%) received a myelo-ablative conditioning regimen (MAC). 1307 patients were in remission at time of transplantation: 29% of MDS and 76% of AML patients. Three-year OS and RFS were 34 and 32% respectively. OS was significantly better in patients with AML in CR (43%) than not in CR (21%). OS and DFS were impacted by the primary cancer: post NHL (30 and 27%), post HL (29 and 28%), post ST (34% for both), post breast cancer (41 and 37%), post CLL (34 and 31%) and post PCD (32 and 25%) (p
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  • 5
    Publication Date: 2012-11-16
    Description: Abstract 4332 Background: Azacitidine (Aza), inhibitor of DNA methyltransferases, plays an important role in epigenetic regulation of gene expression and tumorogenesis, and is active in myeloid neoplasia such as myelodysplasia (MDS) and de novo acute myeloid leukemia (AML). Efficacy of Aza for relapsed and refractory AML has not been so far reported. Methods: We report in 2 french centers (Amiens, Rouen) retrospective study, the results of Aza for relapsed or refractory patients. All patients received Aza (75 mg/m2 per day over 7 days for 4 weeks cycles), until progression, and at least one cycle. Leukocyte blood count was 〈 10109/l. The primary endpoint was overall response rate (ORR), according to IWG 2006: complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), hematological improvement (HI). Secondary endpoints were duration of response and overall survival (OS). Results: 41 patients (26 males and 15 females) with a median age of 59 years (range 28–78) were studied from August, 2007 and November, 2011 (Table): 15 had refractory and 26 relapsed AML. At relapse 11/26 had MDS, defined by blast count
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  • 6
    Publication Date: 2018-11-29
    Description: Prognosis of graft failure patients is dismal, and another transplant is the sole option for long-term survival. Currently, there is no consensus concerning the best option for treating patients undergoing primary graft failure and finding a new donor within an acceptable delay is challenging. In the last years, haploidentical transplants with post-transplant cyclophosphamide (PT-Cy) have shown acceptable results in the treatment of many hematological diseases, including some cases of graft failure. To address the interest of haploidentical transplants as a salvage option in this context, we retrospectively collected and analyzed data from 26 primary graft failure (PGF) patients transplanted between 2011 and 2017 in 15 centers belonging to the Francophone Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Inclusion criteria were the occurrence of PGF defined as non-achievement of a minimum absolute neutrophil count of 500/μL without evidence of disease relapse at D+28 after transplantation and the use of a haploidentical transplantation with PT-Cy as graft-versus-host-disease (GvHD) prophylaxis. Continuous variables are presented as medians and inter-quartile range. They were compared between groups using the Wilcoxon rank sum. Categorical variables are presented with counts and percentages and were compared using the Fisher exact test. All tests were 2-sided, and a p-value below 0.05 was considered to be significant. Analyses were performed using the R statistical platform (version 3.4.1). This study was performed according to the Declaration of Helsinki and was approved by the SFGM-TC scientific council. Nineteen patients had a diagnosis of myeloid malignancy (8 acute myeloid leukemias, 4 myelodysplastic syndromes, 4 myeloproliferative neoplasms, 1 unclassified myeloid disorder), 3 had a lymphoid neoplasm, and 4 had a bone marrow failure syndrome (2 acquired and 2 congenital). Twenty-four patients had previously received an allogeneic transplantation, and 2 had already failed two previous allogeneic transplants. Male/female ratio was 2.25. Median age at haploidentical transplant was 42 years (2-58). Fifteen patients received peripheral blood as stem cell source, and 11 received bone marrow. Eleven transplants were female to male. Twelve patients received an ABO-matched graft, 6 had a major ABO-incompatibility, 7 a minor incompatibility and one missing data. The median number of infused CD34+ cells was 5.2 x106/kg (1.2 - 12.5). There was no ex-vivomanipulation of cells. CMV matching was available for 22 transplantations, of which 6 were high-risk (seropositive recipient with a seronegative donor). Fludarabine-based reduced intensity conditioning was used in all but one patient who received clofarabine + 4Gy TBI. Twenty patients received TBI 2Gy. Three patients received ATG. Fourteen patients received the Baltimore regimen (53%). The median delay between the previous and the salvage transplantation was 77 days (39-1161). All patients received PT-Cy associated with cyclosporine, and 24 patients also received MMF for GvHD prophylaxis. Median follow up was 487 (16-2010) days. The cumulative incidence (CI) of neutrophil recovery at day 30 was 81%, and the median time to neutrophil engraftment was 19 (13-34) days. Four patients (15%) presented primary graft failure and died within a median time of 5 (3-8) weeks after transplantation of infectious complications. Cumulative incidence of grade II-IV aGvHD at day-100 was 13%, and 1-year CI of cGvHD was 32%. One-year CI of relapse was 16%. Overall survival was 58% at 1 year (Figure 1; confidence interval: 39-85). Among the 22 patients who engrafted, 6 patients died. HSCT complications accounted for 80% of the causes of deaths (4 multiorgan failure, 1 GvHD, 1 interstitial pneumonitis, 1 bacterial infection, 1 post-transplant lymphoproliferative disorder). To the best of our knowledge, this is the first cohort describing the outcomes of haploidentical transplants with PT-Cy rescuing patients with primary graft failure. Our cohort presents promising outcomes in a particularly challenging situation, suggesting that haploidentical transplants with PT-Cy might appear as a valid salvage strategy for patients with PGF. Prospective well-designed trials are urgently needed before the inclusion of Haplo-PT-Cy in the treatment strategy of patients with PGF. Figure 1. Figure 1. Disclosures Mohty: MaaT Pharma: Consultancy, Honoraria. Peffault De Latour:Pfizer Inc.: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding.
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  • 7
    Publication Date: 2012-11-16
    Description: Abstract 4854 The incidence of B cell Non Hodgkin Lymphoma (NHL) is steadily increasing with age and about 40% of cases occur in patients aged over 70 years. Some series have reported that low grade NHL lymphomas represent about 35% of all B NHL in elderly patients. However few data are available on the outcome of patients aged over 75 years. Methods We report in a retrospective study the outcome and management of 62 patients aged over 75 years and followed between Jan, 2006, and Jan, 2012 from 2 french centers (Amiens, Abbeville). The primary endpoint was overall survival (OS); secondary endpoints were response rates, progression free survival (PFS), and toxicity. Results 62 patients were registered with median age of 80,4 years (75–92): 31 patients with follicular lymphomas (FL) and 31 other low grade LNH: 15 Marginal Zone Lymphomas (MZL) of witch 11/31 splenic MZL, 1 gastric MALT, 5 lymphoplasmocytic and 10 lymphocytic lymphomas. At diagnostic, evaluation included: computed tomography scan for 46/62 patients (76%), bone marrow biopsy: 17/62 (27%), abdominal echography for 13/62 (24%) patients, echocardiography 24/62 (39%) and positron emission tomography for 11/62 (17%) patients. Charlson score (0–27) was evaluable for all of them with a median score of 2(0–4). At analysis, the median follow up was 23 months (range 0–79). Median FLIPI was 3 (0–5) for FL and median IPI 3(0–5) for other NHL. 21/31 (68%) FL patients and 27/31 (87%) other NHL had stage III or IV in the Ann Arbor classification. 47/62 (76%) patients received chemotherapy: 27/31 (89%) FL patients and 20/31 (65%) with other NHL. 12/62 (19%) patients were undergoing watchfull waiting (11 patients with other NHL, 1 FL); 1 patient refused chemotherapy; 1 FL patient died before any treatment. 29/47 (61%) treated patients received Rituximab (R). In the FL group, 12/31 (39%) received RCVP (C=Cyclophosphamide, V=Etoposide, P=Prednisone), 12/31 (39%) RCHOP-like regimen, 2/31 (6%) chlorambucil, 1/31 (3%) corticotherapy alone, 1/31 (3%) radiotherapy alone and 2/31 (6%) chemotherapy plus radiotherapy. For other low grade NHL, 2/31 (6%) received RCVP, 3/31 (9%) RCHOP-like regimen, 10/31 (32%) Chlorambucil, 1/31(1%) Fludarabine, 4/31(13%) orally cyclophosphamide and corticosteroid. 17 on 47 treated patients (36%) were in complete remission: 10/27 (37%) FL and 7/20 (35%) other NHL. The 2-years OS was 67%: 61% in the FL group and 74% other NHL (difference not significative); the 2-years PFS was 68%: 60% for FL and 77% for other low grade NHL. In univariate analysis, OS was affected by IPI (p=0,02) and FLIPI (p=0,008) (figure), but not by serum albumin concentration ≤ 35g/L, lymphopenia ≤1G/L, or Charlson score. 25 deaths were reported (14 FL and 11 other NHL): 9 lymphoma progressions, 6 sepsis, 3 attributed to cardiac failure and 1 to pulmonary embolism. The most frequent side-effects were hematological: febrile neutropenia (15 patients) and cardiac: acute failure (4 patients). Conclusion Our results in older patients with low grade lymphoma compare favorably with results in younger population. IPI and FLIPI only affect OS whereas geriatric evaluation with Charlson score is not relevant, possibly due to the small number of patients and short follow-up. These results prompt us to realize prospective studies in this population, reducing toxicity and improving efficacy with novel approach. Disclosures: No relevant conflicts of interest to declare.
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  • 8
    Publication Date: 2013-11-15
    Description: Up to now allo-HSCT is the only curative treatment for patients with myelofibrosis (MF) (Ballen, et al, Guardiola, et al 1999, Kroger, et al 2007, Robin, et al 2011). The engraftment rate ranges from 70% to 95% and is influenced by spleen size (delayed in patients with splenomegaly and faster in patients splenectomized prior to allo-HSCT). JAK1/JAK2 inhibitor Ruxolitinib is reported to decrease spleen size and constitutional symptoms. These effects could also be benefit for patients eligible for transplantation, by reducing their splenomegaly and improving their performance status, factors known to impact the results of allo-HSCT. The present study analyzes outcome of patients with MF who have been reported to the SFGM-TC registry. From 2008 to 2013, 11 patients with primary MF (n=7), MF secondary to PV or ET (n=3) or acute myeloid leukemia secondary to MF (n=1) were treated with Ruxolitinib before allo-HSCT. Median age at allo-HSCT was 54 years (range: 44-66); there were 9 men and 2 women. Nine patients had the JAK2V617F mutation. At Ruxolitinib initiation, median white blood cells were 4.4G/L (3.5–13.7), hemoglobin was 10g/dL (7.5-13.3) and platelets were 99G/L (41-290); all patients had palpable splenomegaly and 8 had constitutional symptoms. Lille score was low in 4, intermediate in 2 and high in 4 patients, respectively. Cytogenetics were favorable in 2, unfavorable in 3 (complex karyotype) and not done or failure in 6 patients, respectively. The median time between diagnosis and treatment with Ruxolitinib was 353 days (16-2687) and median time from diagnosis to allo-HSCT was 433 days (199–2793). Ruxolitinib was progressively tapered in 3 patients (with steroids for 2 of them) and discontinued without tapering in 4 (missing data for 3). Median time between Ruxolitinib withdrawal and allo-HSCT was 10.5 days (4-66). All patients received reduced intensity conditioning regimen based on Fludarabine and a graft-versus-host disease (GVHD) prophylaxis including ciclosporine. Donors were: HLA matched sibling in 4, matched unrelated donor in 3 and mismatched unrelated donor in 4 patients. All but one patients received peripheral stem cell transplantation (one patients received bone marrow). Before allo-HSCT, 7 patients were in partial response and 4 were stable. After Ruxolitinib treatment, 8 patients had an estimated reduction of spleen size 〉 25% and 2 underwent splenectomy. There was no progressive disease on therapy and only one patient experienced a grade III-IV hematological toxicity. All patients had neutrophil engraftment (〉0.5G/L) in median on day +17 and 10/11 patients had platelet engraftment (〉 20G/L) in median on day +21. Chimerism was full donor in 8, mixed in 1 (who relapsed at day 178), and not available in 2 patients, respectively. One patient who was 100% donor chimerism remains pancytopenic and transfused 90 days after allo-HSCT. Three patients experienced grade II and 2 grade IV acute GVHD after a median time of 18 days after allo-HSCT. Acute GVHD was refractory to corticosteroids in 2 patients and was the cause of death in 1 patient. Only 2 patients had chronic GVHD. Median time from Ruxolitinib initiation to last follow-up was 339 days (166 – 1928), 6 (54%) patients were assumed in complete remission (blood cell count normal and 100% donor chimerism) and 9 (80%) were alive. Two patients relapsed on days 77 and 148 and one of them received a second allo-HSCT. In this retrospective study, Ruxolitinib before allo-HSCT seems to be well tolerated with excellent engraftment rate. A prospective study (JAK-ALLO) is ongoing in France on behalf of SFGM-TC to precisely analyze the role of Ruxolitinib before allo-HSCT. Disclosures: Kiladjian: Novartis, Celgene, AOP Orphan: Research Funding; Novartis, Sanofi, AOP Orphan: Honoraria; Novartis, Sanofi, AOP Orphan: Membership on an entity’s Board of Directors or advisory committees. Mohty:Novartis: Honoraria, Research Support Other. Robin:Novartis: Research Funding.
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  • 9
    Publication Date: 2015-12-03
    Description: Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, has demonstrated efficacy alone or in combination with chemotherapy in CD30 refractory Non-Hodgkin Lymphoma (NHL). It has been approved in anaplastic large cell lymphoma (ALCL) and promising results have also been published in other CD30 positive T-cell lymphomas such as cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL). In patients with relapsing or refractory NHL, BV has mainly been proposed as a bridge for autologous or allogeneic transplantation (Allo-HSCT). Very few data are available about patients with T-cell NHL receiving Allo-HSCT after BV. The aim of our study was to study safety and efficacy of this procedure in a retrospective series of patients treated on behalf of SFGM-TC. Inclusion criteria were: - CD30 positive T cell NHL including ALCL, CTCL and PTCL, - Partial or Complete response after BV treatment, - Allogeneic HSCT performed after BV as last salvage treatment. BV was administered at 1,8mg/kg dose every 3 weeks in outpatient department. Allo-HSCT was performed according to institutional guidelines. Twenty-six patients receiving Allo-HSCT in France after salvage therapy including BV were identified. Patients characteristic are summarized in Table 1. With a median follow-up of 13 months (1.5-40), 8 patients relapsed and 7 patients died. Two-year OS and PFS were respectively 76% and 47%. Among patients with ALCL (n=15) 2 patients relapsed and 2 patients died. Whereas in the CTCL group (n=5), 5 patients relapsed and 1 patient died and in the PTCL group (n=6), 1 patient relapsed and 4 patients died. Two-year OS were 93%, 80% and 21% (p
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  • 10
    Publication Date: 2018-11-29
    Description: Introduction: Primary cutaneous T cell lymphomas (PCTCL) including Mycosis fungoides (MF) and Sézary syndrome (SS) account for 75% of primary cutaneous lymphomas. The 5-year survival is 18-40% in patients with advanced-stage PCTCL. Management strategies and prognosis of PCTCL depend on the disease stage (affected body surface area, blood, visceral and nodal involvement). Allogeneic hematopoietic cell transplantation (allo-HCT) can be used to treat advanced stages in young adults who are otherwise in good health. However, post-transplant relapse is still an issue with no clear guidelines regarding its management. Here we describe the largest study investigating donor lymphocyte infusions (DLI) in patients who relapsed after allo-HCT for PCTCL. Patients and methods: We conducted an observational, retrospective, French multicenter study. Between January the 1st 2000 and December the 31st 2017, all patients who underwent an allo-HCT for PCTCL regardless of the subtype and who received DLI for a post-transplant relapse were included. Data were collected using the ProMISE database. As needed, centers were asked to provide additional data. Statistical analyses were carried out by the Lille University Hospital (CHRU Lille) Biostatistics Methodology Unit and were performed using SAS software (SAS Institute version 9.4). Results: All 13 patients who received DLI after allo-HCT for a PCTCL in France were enrolled in the study (Figure 1). Mean duration of follow-up was 718 days. See table 1 for study population characteristics. Four patients (30%) presented acute graft versus host disease (GVHD) following allo-HCT, of which no incidences were superior to grade 2. Those four patients relapsed at day 342, 463, 499 and 659 after allo-HCT. Five patients (38%) presented chronic GVHD of which three had an extensive presentation. Those three patients relapsed at day 1082, 1568 and 1861. Table 2 details relapses and relapse management in our cohort. Table 3 shows parameters relative to allo-HCT, post-therapeutic management, and follow-up. Objective response rates to DLI was 62% (n=8). Five patients (38%) showed complete response and three patients exhibited partial response (32%). Five patients (38%) did not respond to DLI. The median best response duration to DLI was 181 days. Six out of the eight patients who responded to DLI relapsed (75%); the median time before the relapse after DLI was of 405 days. The two patients who have received DLI and did not relapse on January the 1st 2018 had 321 and 1350 days follow-up. Progression-free survival (PFS) was 46% at 1 year and 19% at 5 years (Figure 2). Overall survival rates were 100% at 1 year and 59% at 5 years (Figure 3). Six patients (46%) presented GVHD after DLI of which three cases were chronic GVHD. Two of them was an extensive presentation. One patient had received an allo-HCT from a female donor. One patient received bone marrow transplant carrying a 9/10 mismatch. All other patients received peripheral blood stem cell (PBSC) transplantation; two of them received a geno-identical stem cell transplantation from sibling donors and three patients received non-sibling donor HSCT with a 10/10 mismatch. Only three patients received DLI following SFGM-TC guidelines. Four patients died before January the 1st 2018 in our cohort. One patient died because of direct complications of the HSCT and related treatments. Two patients died because of a disease relapse. One patient died from unrelated cause (severe pulmonary). Conclusion: With a 5-year survival rate of 59% from the date of post-transplant relapse, DLI appears to be an effective treatment in cases of patient relapse after allo-HCT for PCTCL. DLI should be considered in the management of post-transplant relapse whenever possible. To our best knowledge, this is the largest study cohort investigating DLI in the post-transplant setting Disclosures Bagot: Takeda: Membership on an entity's Board of Directors or advisory committees; Actelion: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Peffault De Latour:Amgen Inc.: Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer Inc.: Consultancy, Honoraria, Research Funding.
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    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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