A phase II trial 90y-ibritumomab tiuxetan in combination with reduced intensity regimen of fludarabine (flu) and melphalan (mel) followed by allo-HCT in patients with refractory B-cell lymphoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6545-6545 ◽  
Author(s):  
Auayporn Nademanee ◽  
Andrew Antony Raubitschek ◽  
Ni-Chun Tsai ◽  
Jennifer Simpson ◽  
Neil Martin Kogut ◽  
...  
Keyword(s):  
Disease Control ◽  
B Cell ◽  
Median Time ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Disease Status ◽  
Gvhd Prophylaxis ◽  
Transformed Lymphoma ◽  
Grade Ii

6545 Background: RIC allo-HCT has reduced transplant-related mortality (TRM) in patients with relapsed NHL. However, relapses do occur despite potential graft vs. lymphoma (GVL) effect. We hypothesized that adding Zevalin to Flu/Mel may improve disease control and reduce relapse post allo-HCT. Methods: Patients received In- Zevalin on day -21 followed by 90Y- Zevalin 0.4mCi/kg on day -14, flu 25 mg/m2 daily on days -9 to -5 and mel 140 mg/m2 on day -4. Rituximab (R) level was measured on Day -22 and -15 and if the level was ≥ 10 μg/ml, R was not given prior to In-Zevalin or 90Y- Zevalin to enhance biodistribution. Tacrolimus and sirolimus was used for GVHD prophylaxis. Between 10/2007 and 11/2011, 31 were treated. Median age 55 (range 27-67), median regimen =3 (range 2-8). Median time from diagnosis to HCT was 20 mo (range 5-105). Histology: DLBCL (including transformed lymphoma)=14 (45%), MCL=7 (23%), FL=5 (16%) and SLL/CLL=5 (16%). Disease status at HCT: 1CR=7, Relapse=9, ≥2CR=5, primary refractory =10. Fifteen had chemoresistant and 19 had FDG PET+ at HCT. Donors: sib=13, URD=18. Results: All patients engrafted with the median time to ANC ≥500 and platelet ≥ 20,000 was 14 (range 10-28) and 13.5 days (range 11-28), respectively. There were 10 deaths from disease progression (2) infection (5) GVHD (1) and multi-organ failure (2). TRM at day +100 and at 1 yr was 6.5% and 17%, Five with DLBCL relapsed between 3-7 mos. Grade II-IV acute GVHD was 65%, Grade III-IV was 16%, chronic GVHD was 65%. Fifteen became PET- at day +100 while 4 remained PET+ and relapsed. Twenty-one are alive at a median followup of 24 mos (range 2-46). The 2 yrs OS and PFS was 65% (95% CI, 51-75%) and 57% (95% CI, 46-67%), respectively. Univariate analysis identified disease status predict for OS and PFS while histology predict for PFS. Conclusions: This study demonstrates the feasibility of adding Zevalin to flu/mel in the allo-HCT setting for B-cell NHL and suggest that this approach could be used to provide early disease control before GVL effect takes place. Innovative approaches should be explored in DLBCL.

Comparison Between Related T-Cell Depleted HLA-Haploidentical Stem Cell Transplantation (TCD-Haplo) and Umbilical Cord Blood Transplantation (UCBT) in Pediatric Patients with Acute Leukemia, a Eurocord, PDWP-EBMT Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1215-1215
Author(s):  
Franco Locatelli ◽  
Myriam Labopin ◽  
Gerard Michel ◽  
Rupert Handgretinger ◽  
Cristina Diaz de Heredia ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Acute Leukemia ◽  
Advanced Disease ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Gvhd Prophylaxis ◽  
Risk Of Relapse

Abstract Both TCD-Haplo and UCBT are used for treating children with either acute lymphoblastic (ALL) or myeloid (AML) leukemia in need of an allograft and lacking a suitable donor. Although both these types of HSCT have been shown to be effective in curing children with acute leukemia, to date, no study has compared the outcomes of these two types of transplant. We performed a retrospective registry-based study on children (less than 18 years) with either ALL or AML, receiving, after a myeloablative conditioning regimen, a TCD-Haplo (CD34+ cell positive selection, CD3+ negative or TCR alpha/beta+ cell depletion) or single unit UCBT. Patients given pharmacological graft-versus-host disease (GVHD) prophylaxis after graft infusion in haplo HSCT were excluded. Transplants were performed from 2001 to 2012 in EBMT centers; 1067 patients received single UCBT and 266 TCD-Haplo for AML (n=478) or ALL (n=855). Median follow up was 28 (range 1-150) and 20 (range 1-152) months for UCBT and TCD-Haplo, respectively. Compared to TCD-Haplo, UCBT recipients were younger (median age 5.96 years vs 9.6 years, p=<0.0001), were transplanted more frequently in CR1 (42% vs 24%, p=<0.001), less frequently in advanced disease (10% vs 21%, p=<0.001) and had more often negative cytomegalovirus (CMV) serology (45% vs 31%, p=<0.001). Conditioning regimen was mainly total body irradiation (TBI)-based, 56% versus 50% for TCD-Haplo and UCBT, respectively. For UCBT, patients CSA+steroids was the most commonly used (72%) GVHD prophylaxis. A higher proportion of patients transplanted with TCD-Haplo received ATG in the conditioning regimen (90% vs 74%, p=<0.001). Acute GVHD (grade II-IV) incidence was 16% and 28% (p<0.001) while that of chronic GVHD was 14% and 16%, (p=0.40) for TCD-Haplo and UCBT respectively. Since diagnosis was the most important factor influencing outcome, the analysis was performed separately for patients with ALL and AML. For ALL (n=855) in univariate analysis, the 2-year probability of leukemia-free survival (LFS) was 35% and 43% (p=0.08), for TCD-Haplo and UCBT, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) was 28% and 29% (p=0.57), and relapse incidence (RI) was 36% and 28% (p=0.01) for TCD-Haplo and UCBT, respectively. According to disease status, for patients in CR1 (n=300), 2-year RI was 21% versus 20%, p=0.75; NRM 30% versus 24%, p=0.59; and 2- year LFS 49% versus 56%, p=0.87; for TCD-Haplo and UCBT, respectively. For patients in CR2 (n=478), 2-year RI was 34% versus 29%, p=0.75; NRM 28% versus 32%, p=0.29; and 2- year LFS 38% versus 39%, p=0.63, for TCD-Haplo and UCBT, respectively. For patients in advanced disease (n=77), 2-year LFS was 5% versus 8%, p=0.08 for TCD-Haplo and UCBT, respectively. For patients with AML (n=478), 2-year probability of LFS was 21% and 58% (p=<0.0001), for TCD-Haplo and UCBT, respectively. CI of NRM was 43% and 19% (p=<0.001), and RI was 36% and 23% (p=0.01) for TCD-Haplo and UCBT, respectively. According to disease status, for patients in CR1 (n=207), 2-year RI was 31% versus 14%, p=0.06; NRM 45% versus 16%, p=0.002; and 2-year LFS 24% versus 69%, p=<0.001; for TCD-Haplo and UCBT, respectively. For patients in CR2 (n=180), 2-year RI was 28% versus 24%, p=0.49; NRM 44% versus 21%, p=0.004; and 2- year LFS 28% versus 55%, p=0.0005, for TCD-Haplo and UCBT, respectively. For patients in advanced disease status (n=91), 2-year LFS was 10% versus 22%, p=0.44 for TCD-Haplo and UCBT, respectively. In multivariate analysis adjusted for differences between the 2 groups, for patients with ALL, no statistically significant differences were observed according to the graft source. Disease status was the only factor associated with better LFS (HR 4.84, p<0.0001). TCD-Haplo was associated with greater risk of RI (HR 1.58, p=0.01). For AML, in multivariate analysis, TCD-Haplo was associated with greater risk of relapse (HR 1.67, p=0.05) and of NRM (HR= 1.94; p=<0.001), and worse LFS (HR 1.94, p=<0.001) when compared to UCBT. Advanced disease at transplantation (HR 2.89, p=<0.001) was the other factor associated with LFS and RI. This retrospective analysis demonstrates that children with ALL have comparable probability of LFS after either UCBT or TCD-Haplo. By contrast, in children with AML, UCBT is associated with lower risk of relapse and NRM than TCD-Haplo, this translating into better LFS. These results may help guide physician choices for transplanting children with acute leukemia. Disclosures No relevant conflicts of interest to declare.

Outcomes after Double Umbilical Cord Blood Transplantation in Children: A Survey on Behalf of Eurocord and PDWP-EBMT

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2570-2570
Author(s):  
Federica Giannotti ◽  
Annalisa Ruggeri ◽  
Gerard Michel ◽  
Jean-Hugues Dalle ◽  
Tracey O'Brien ◽  
...  
Keyword(s):  
Single Unit ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Median Number ◽  
Cell Dose ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Grade Iii

Abstract Double UCBT (dUCBT) has been used in adults to reach an acceptable cell dose. For most children a single unit with a total nucleated cell (TNC) dose >3x107/Kg can be easily identified, but that is not always the case for heavier patients (pts). Use of dUCBT might decrease relapse and increase graft-versus-host-disease (GvHD). Data on dUCBT in children are scarce in the literature. A recent randomized study in children has described similar outcomes after double compared to single UCBT. Our study provides an overview of the use of dUCBT in the pediatric population reported to Eurocord. We retrospectively analyzed the outcomes of unrelated dUCBT in 177 children transplanted between 2002 and 2012 in 61 EBMT centres. Analysis was performed separately for pts with malignant (n=139) and non-malignant (NM, n=38) diseases. Among pts with malignancies, 76 had ALL, 40 AML, 6 MDS, 2 CML, 11 NHL, 3 Hodgkin Lymphoma and 1 Multiple Myeloma. Median age at dUCBT was 15 years (1.3-17.9) and median weight was 55 kg (13-97). Disease status at dUCBT was 1st complete remission (CR) (36%), ≥2nd CR (34%) or advanced (25%), and missing in 5% of the pts. In this group, 117pts received a myeloablative conditioning (MAC) and 22 a reduced intensity regimen (RIC). Cyclophosphamide+fludarabine+TBI was administered to 41% of the pts; 55% received ATG in the conditioning. Median number of collected TNC was 5.7x107/kg (3,6-12,8). Considering the unit with the higher number of HLA incompatibilities with the recipient, 56% had 2 mismatches. GvHD prophylaxis was cyclosporine-A (CSA) based in 93% of the pts (58% received CSA + mycofenolate mofetil). Median follow-up was 31 months. Cumulative incidence (CI) of neutrophil (PMN) and platelet (PLT) engraftment was 88% at 60 days and 64% at 180 days after dUCBT, and it was achieved with a median time of 24 and 45 days, respectively. Among the 122 pts with PMN engraftment, 85/94 with available data on chimerism were full donor and, of these, 20% had dual chimerism. CI of acute GvHD grade II-IV and grade III-IV at 100 days was 51% and 26%, respectively; it was significantly higher in pts who did not receive ATG (grade II-IV: 35% vs 67%, p=0.004; grade III-IV: 12% vs 37%, p=0.0075). Chronic GvHD was observed in 24/104 pts at risk (60% extensive; 2-year (yr) CI: 18%). The 2-yr CI of relapse was 31%. In univariate analysis, RIC, advanced stage at transplantation and a collected TNC dose lower than the median, were significantly associated with higher rates of relapse.The 2-yr CI of transplant related mortality (TRM) was 27%. Overall, 73 pts died: 35 of relapse, 15 of infections, 9 of GvHD and 14 of other causes. The 2-yr disease free survival (DFS) and overall survival (OS) were 42% and 45%, respectively. Among pts with NM disorders, 24 had bone marrow failure syndrome (BMFS) (10 Fanconi Anemia, 13 Acquired Aplastic Anemia and 1 other inherited BMFS), 2 hemoglobinopathies, 7 immune deficiencies and 5 metabolic disorders. Median age at dUCBT was 11 years (0.7-17.9) and the median weight was 40 kg (13-70). In this group, 27 pts received a RIC (40% TBI based), 10 a MAC (90% busulfan based), and 1 no conditioning regimen. ATG was administered to 82% of the pts and GvHD prophylaxis was CSA-based in 77%. The median number of collected TNC was 8.4x107/kg (1,2-11,2) and 60% of the grafts had ≥2 HLA mismatches with the recipient. Median follow-up was 39 months. Overall, 28 pts achieved PMN engraftment and 16 PLT engraftment, with a median time of 23 and 61 days, respectively. In univariate analysis, pts with BMFS compared to others had a significantly lower CI of PMN engraftment (58% vs 100%, p=0.002). Among the 10 pts who did not engraft, 3 had autologous reconstitution and 3 had a subsequent allogeneic HSCT. Forteen pts developed acute GvHD grade II-IV and 10/25 pts at risk had chronic GvHD (3 extensive). Overall 21 pts died (17 with BMFS): 9 of infections, 5 of GvHD and 7 of other causes. The 2-yr OS was 42% and it was significantly lower in pts with BMFS compared to those affected by other NM disorders (28% vs 70%, p=0.03). In pts with malignancies, despite a higher incidence of acute GvHD, DFS and OS seem to be comparable to those reported in the literature for single UCBT or HSCT from other alternative stem cell sources. In the NM disorders group, despite the high cell dose, dUCBT did not seem to improve results in pts with BMFS. This survey suggests that dUCBT is feasible in children and should be considered when a single unit with an adequate cell dose is not available. Disclosures No relevant conflicts of interest to declare.

scholarly journals From Ex-Vivo T-Cell Depletion to Post-Transplant Cyclophosphamide: Improved GvHD-Free & Relapse-Free Survival but Comparable Chronic GvHD Incidence in Haploidentical Transplantation. A 15 Years EBMT Registry Analysis on Behalf of the TCWP-EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 876-876
Author(s):  
Maria Teresa Lupo-Stanghellini ◽  
Christophe Peczynski ◽  
Hildegard T. Greinix ◽  
Emmanuelle Polge ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Research Funding ◽  
Ex Vivo ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Disease Status ◽  
Free Survival ◽  
Patient Gender ◽  
Gvhd Prophylaxis ◽  
Grade 3

Background: Haploidentical stem cell transplantation (Haplo HSCT) has emerged in the past three decades as an alternative curative option when an HLA match donor is not available. Over time, the use of Haplo has increased dramatically, reaching superimposable results when compared to unrelated and related HSCT strategies, confirming its validity. The widespread use of Haplo mainly relies upon technical advances, control of alloreactivity through graft-versus-host disease (GvHD) prophylaxis combined with a rapid and almost universal probability to find an Haplo donor for any candidate patient. The aim of our study was to provide a picture of acute (aGvHD) and chronic GvHD (cGvHD) incidence in Haplo HSCT across different platform in the past 15 years, where Haplo moved from ex-vivo T-cell depleted (TCD) platform to in-vivo TCD platform to the post-transplantation cyclophosphamide (PTCy). Methods: We compared the outcomes of adult patients receiving a 1st Haplo HSCT for any hematological malignancy according to GvHD prophylaxis - ex-vivo + in-vivo TCD (n=160), in-vivo only TCD (n=507) or PTCy (n=2593) - and reported to the EBMT registry in 2004-2016. Patients with missing data on disease status at last follow-up and GvHD information were excluded. Primary endpoint was GvHD-free & Relapse-free survival (GRFS) with events defined by death or relapse or grade ≥3 aGvHD or extensive (ext) cGvHD. Secondary endpoints were progression-free survival (PFS), overall survival (OS), aGvHD and cGvHD, incidence of relapse (IR) and non-relapse-mortality (NRM). Due to sample size in the first cohort of ex-vivo TCD, multivariate analysis compared only in-vivo TCD vs PTCy cohorts. Table 1 illustrates patients' characteristics. Results: Univariate analysis for 3-year outcomes are reported on table 2. PTCy provides better GRFS, OS, PFS, NRM versus ex-vivo or in-vivo. IR was not significantly different. Likewise, the 3-year CI of cGvHD and ext cGvHD were similar between PTCy, in vivo TCD and ex-vivo TCD (cGvHD 27% [25-29%], 25% [21-29%], 18% [12-25%], p 0.03; ext cGvHD 11% [10-12%], 10% [8-13%], 8% [4-13%], p 0.45). On the contrary the 100-day CI of grade ≥2 aGvHD were lower in the ex-vivo TCD vs PTCy and in-vivo TCD (19% [14-26%], 28% [26-30%], 32% [28-36%], p 0.002) while grade ≥3 aGvHD were lower in the PTCy group vs ex-vivo and in-vivo TCD (9% [8-10%], 11% [7-17%], 14% [11-18%], p &lt;0.001). After adjustment for diagnosis, patient age, disease status, Karnofsky PS, donor/patient gender and CMV, cell source, conditioning intensity, previous auto and year of transplant, the multivariable model comparing in-vivo TCD and PTCy showed better outcome for PTCy. Compared to in-vivo TCD, the hazards for GRFS was 0.76 for PTCy (p 0.004), the HR for PFS was 0.71 (p 0.001) and the HR for OS was 0.7 (p 0.0008), the HR for NRM was 0.63 (p 0.001). Moreover, compared to in-vivo TCD, PTCy yielded similar hazards for grade≥2 aGvHD (HR: 1.02, p 0.89), grade≥3 aGvHD (HR 0.79, p 0.27), cGvHD (HR 1.17, p 0.37), ext cGvHD (HR 1.18, p 0.52) and relapse (HR 0.8, p 0.1). Variables associated with GRFS were active disease, Karnofsky PS ≥90%, diagnosis, donor/patient gender and CMV. An ancillary analysis evaluating the stem cell source effect in the PTCy cohort only, demonstrates comparable outcome endpoints (OS, PFS, NRM, IR) at 2-year between bone marrow (BM) and peripheral blood (PB) PTCy. In univariate analysis GRFS and the 2-year CI of cGvHD were not different between BM and PB (GRFS 47% [45-50%], 46% [44-49%], p 0.085; 2-year CI of cGvHD 25% [23-28%], 27% [25-30%], p 0.2) while ext cGvHD, 100-day CI of grade ≥2 aGvHD and grade ≥3 aGvHD were lower in BM PTCy vs PB PTCy (ext cGvHD 8% [7-10%], 12% [10-14%], p &lt;0.001; grade ≥2 aGvHD 20% [18-22%], 36% [33-38%], p &lt;0.001; grade ≥3 aGvHD 6% [5-7%], 12% [10-14%], p &lt;0.001). Compared to BM PTCy, the HR for cGvHD was 1.55 for PB PTCy (p 0.001), the HR for ext cGvHD was 2.04 (p 0.0003), the HR for grade ≥2 aGvHD was 1,94 (p &lt;0.0001), the HR for grade ≥3 aGvHD was 2.01 (p 0.0001). Conclusions: In the present EBMT registry study on more than 3000 patients transplanted from an Haplo donor, we report improved outcome (better GRFS - in spite of comparable chronic GvHD - OS and PFS, lower NRM) and widespread use in different diagnosis setting other than acute leukemia in PTCy platform. PTCy strategy provides a concrete progress into the field: even if cGvHD still represent a major issue, exploitation of BM PTCy seems to protect against most severe GvHD manifestation. Disclosures Mohty: Jazz Pharmaceuticals: Honoraria, Research Funding. Kröger:Sanofi-Aventis: Honoraria; Riemser: Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Medac: Honoraria; JAZZ: Honoraria; DKMS: Research Funding; Celgene: Honoraria, Research Funding. Basak:Celgene: Honoraria; Teva: Honoraria.

HLA-DP Mismatches Increase the Risk of Acute GVHD after Unrelated Donor Hematopoietic Transplantation (UDT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3125-3125 ◽  
Author(s):  
Marcos de Lima ◽  
Simrit Parmar ◽  
Ping Liu ◽  
Poliana A. Patah ◽  
Pedro Cano ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Unrelated Donor ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Reduced Intensity ◽  
Grade Iii

Abstract The HLA class II DP locus encode for both subunits of DPB1 heterodimers, which have low levels of expression on the cell surface of antigen presenting cells. We hypothesized that donor-recipient HLA-DP mismatch would lead to an increased incidence of acute (a) graft-versus-host disease (GVHD), and that 2 mismatches would likely be even more significant. Methods: We studied 84 consecutive patients (pts) with myeloid leukemias in complete remission (CR) transplanted from 01/02 to 02/06. Preparative regimens were ablative IV Busulfan-based (n=58) or Cy/TBI (n=2), and reduced intensity (Fludarabine (Flu)/Bu 130 mg/m2/2 doses plus Gleevec (n=8), and Flu/Melphalan 140 mg/m2 (n=16). Stem cell (SC) source was bone marrow (n=70) or peripheral blood (n=14). ATG was given in 78 cases. GVHD prophylaxis was tacrolimus and mini-methotrexate in all cases, with additional pentostatin in 31 pts. High-resolution typing was sequence-based for HLA-A, B, DRB1; SSP was used for DRB3/4/5, DQB1 and DPB1, and SBT/SSOP for HLA-C. A Cox proportional hazards regression model was used to study aGVHD-free and relapse-free (RFS) survival. Variables with a p-value <0.25 by univariate analysis were included in the multiple regression analysis (MV). Variables were age, gender, weight, conditioning regimen, GVHD prophylaxis, diagnosis, cytogenetics, SC source, ABO group, infused CD34 and CD3 cell dose, and HLA matching. AGVHD-free survival was calculated from transplant date to date of development of grade II–IV GVHD or completion of 100 days of follow-up. Results: Median age was 48 yrs (range, 14–72). Diagnoses were MDS (n=5), AML (n=58), and CML (n=21). 54 pts (64%) were beyond 1st CR; all CML pts were in >1st chronic phase (CP). Sixty-one pts were 10/10 HLA match (A, B, C, DRB1, DQB1), and 23 had one or more mismatches. All but one pt engrafted neutrophils at a median of 13 days. 33 pts (39%) and 13 pts (15%) developed grade II–IV and III–IV aGVHD, respectively. Chronic GVHD incidence was 51%. With a median follow-up of 18 mo. (range,1.3–52) 60 pts are alive; 40 pts have relapsed or died. Median survival has not been reached. Number of DP mismatches and incidence of aGVHD is shown in the table. The following covariates influenced aGVHD-free survival by MV analysis: Flu-based regimen (P=0.005; HR 0.25 (95%CI 0.1–0.66), reduced intensity regimens (p=0.02; HR 0.35 (95%CI 0.15–0.83) and presence of 2 DPB1 mismatches (p=0.02; HR 3.07 (95%CI 1.19–7.95). Presence of 1 DPB1 mismatch was not significantly associated with aGVHD. There was no statistically significant correlation between presence of 2 DP mismatches and RFS (P=0.17;HR 0.3 (95%CI 0.06–1.65);HR 0.75 for 1 mismatch) or with cGVHD. Actuarial 2-yr survival for 10/10 matched pts without DP mismatches (12/12) versus those with DP mismatches is 82% versus 71%(P=0.6). In the 10/10 matched group, GVHD was the cause of death only among recipients of 2 DP mismatches transplants (n=4). Conclusion: Mismatching at HLA-DPB1 may increase the risk of aGVHD following UDT. The role of DP in the development of GVHD and GVL effects merits future study. Incidence of acute GVHD 10 of 10 matches number of DP mismatches grade II–IV grade III–IV 0 8% 0% 1 23% 8% 2 45% 18% < 10 of 10 matches number of DP mismatches grade II–IV grade III–IV 0 45% 15% 1 82% 36% 2 80% 40%

Age and Disease Status Are Important Risk Factors for Outcome after Reduced Intensity Conditioning (RIC) Umbilical Cord Blood Transplantation (UCBT) in Adults

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4412-4412
Author(s):  
Sabine Fürst ◽  
Catherine Faucher ◽  
Jean El Cheikh ◽  
Jean Marie Boher ◽  
Patrick Ladaique ◽  
...  
Keyword(s):  
High Risk ◽  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Disease Status ◽  
Significant Difference ◽  
Grade Ii ◽  
Grade Iii

Abstract UCBT in adult patients with hematological malignancies has significantly increased over the last 5 years. In addition, the introduction of RIC regimens can allow a decreased incidence of TRM. Thus, the use of UCBT after a RIC regimen can represent an attractive treatment modality for those high risk patients who lack a suitable HLA-matched donor. The aim of this analysis was to assess the outcome of 35 patients who received RIC UCBT in a single centre between 2005 and 2008. All 35 patients had high risk hematological malignancies (AML, n=19; ALL, n=9; NHL, n=5; CML, n=1; and Hodgkin disease, n=1). 27 patients (77%) were in CR (CR1, n=18; CR2, n=8; CR3, n=1), whereas 8 had a more advanced disease (PR, n=2; refractory, n=6) at time of UCBT. Of note, 12 patients (34%) have already received and failed prior autologous transplantation. The median age and weight was 44 (range, 17–62) years and 63 (range, 44–125) kg with 13 patients (37%) older than 50 years (range 51–62). The RIC regimen included Fludarabine 200 mg/m2, Cyclophosphamide 50 mg/kg and low dose TBI (2 Gy). All patients received CSA and MMF for GVHD prophylaxis. 13 patients (37%) received a single CB unit, whereas 22 (63%) received 2 CB units in order to achieve a minimum required cryopreserved cell dose of 3.0×10e7 TNC/kg. For the entire group, the median cryopreserved and infused cell doses were 4.8×10e7 TNC/Kg (range, 3.3–7.0) and 3.7×10e7/Kg (range, 1.9–5.5) respectively. 94% of the patients received 1–2 HLA mismatched grafts. Neutrophil engraftment (ANC&gt;500/μL) occurred in 33 patients (94%) at a median of 20 (range, 6–45) days and a sustained platelets recovery (&gt;50000/μL) was observed in 25 patients (71%) at a median of 36 (range, 23–136) days after UCBT. Hematological recovery was comparable between single and double CB unit recipients. Primary and secondary graft failure occurred in 4 and 1 patients respectively (AML, n=2; ALL, n=1; CML, n=1; NHL, n=1). Two out of these 5 patients underwent and failed a second UCBT. The overall incidence of grade II–IV acute GVHD was 54% (95%CI, 41–77%; 7 grade II, 10 grade III and 2 grade IV). 19 patients were evaluable for chronic GVHD for an overall incidence of 37% (8 limited and 5 extensive cases). 20 patients (57%; 95%CI, 42–76 %) with experienced at least one episode of a “serious” or “life-threatening” infectious complication (virus other than CMV reactivation, n=11; bacteria, n=10; fungal, n=4) at a median time of 74 (range, 0–595) days after UBCT, requiring long-term hospitalization, and of whom 8 patients were in grade III–IV acute GVHD. 7 patients (20%) experienced severe interstitial pneumonia, with 4 patients (11%) developing ARDS. Most importantly, 5 patients (14%) also required transfer to ICU. With a median follow-up of 468 (range, 105–1170) days, 10 patients (28%) had relapsed or progessed with this being significantly lower in those patients transplanted in CR (P=0.01), but without a significant difference between single and double CB recipients. 14 patients have died (infection, n=5; GVHD, n=3; relapse, n=6; TRM=23%). The KM estimate of OS and DFS was 61% (95%CI, 42–75%) and 52% (95%CI, 34–67%) at 2 years respectively for the entire population. On univariate analysis younger age at transplant and disease status in CR were the only factors associated with significantly better outcome. Although our patients population is small, we conclude that RIC UCBT is an efficient therapy for high risk hematological malignancies. Age and the disease status at transplant are crucial for patients outcome and further efforts are needed to define risk factor specific transplant procedures. Infectious complications and GVHD are still a matter of concern warranting better strategies to provide optimal prophylactic approaches.

A Phase II Study Using Post-Transplant Cyclophosphamide (PTC) As Graft Versus Host Disease (GVHD) Prophylaxis in Patients Undergoing HLA Matched Sibling Donor Stem Cell Transplant (SCT) for Severe Aplastic Anemia (SAA)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4199-4199
Author(s):  
Biju George ◽  
Vikram Mathews ◽  
Kavitha M Lakshmi ◽  
Rayaz Ahmed ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Median Time ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Post Transplant ◽  
Sibling Donor ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Grade Ii

Abstract Abstract 4199 Between September 2010 and June 2012, 15 patients with SAA underwent HLA identical sibling donor SCT using post transplant cyclophosphamide for GVHD prophylaxis. The conditioning regimen consisted of Inj Fludarabine 30 mg/m2/day from day -7 to -2 and Inj Cyclophosphamide 50 mg/kg IV on days -3 and -2. Total Body irradiation (TBI) 200 cGy as single fraction was added on day -1 from December 2011 because of concern regarding graft failure. GVHD prophylaxis consisted of Inj Cyclophosphamide administered at 50 mg/kg/day IV on day +3 and +4 post SCT. G-CSF mobilized peripheral blood stem cells (PBSC) was the graft source. There were 10 males and 5 females with a median age of 25.9 years (range: 8 – 42). The median time from diagnosis to SCT was 7.5 months (range: 2 – 36). All had 6/6 HLA matched sibling donors except 1 who had a 9/10 matched family donor. The median PBSC cell dose infused was 5.4 × 108 MNC/Kg (range: 2.4 – 8.5) and 9.58 × 106CD34/Kg (range: 5.4 – 17.2). Thirteen patients engrafted (86.6%) with a median time to ANC >0.5 × 109/L of 15.4 days (range: 15–17) and Platelet count >20 × 109 of 16.6 days (range: 12–32). Grade II –IV acute GVHD occurred in 3 patients (23%) at 42, 49 and 68 days post SCT. GVHD was grade II in 2 patients and grade IV in 1 patient. Two responded to a combination of cyclosporine and prednisolone while one patient with grade IV GVHD expired with refractory GVHD at median time of 64 days post SCT. Of the 11 evaluable patients, 4 (36.3%) developed chronic GVHD which was limited in all. Two patients who developed de novo chronic GVHD were managed with prednisolone alone. Overall 7 patients (46.6%) have not required any immunosuppression after SCT while 3 have required immunosuppressive therapy for 114, 127 and 225 days respectively At a median follow up of 11 months (range: 1 – 22), 11 (73.3%) are alive and well including 7 patients who did not require any immunosuppressive therapy following SCT. In conclusion, the use of post transplant cyclophosphamide as GVHD prophylaxis following sibling donor transplant for SAA is associated with low rates of GVHD. What makes it more attractive is the fact that 46% did not require any immunosuppression post SCT. Larger studies are required to understand the utility of this prophylaxis in sibling donor transplants for aplastic anemia. This trial is registered in the Clinical Trials Registry India - CTRI/2010/091/001480. Disclosures: No relevant conflicts of interest to declare.

Long-Term Follow-Up Of Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation For High Risk Follicular Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5519-5519
Author(s):  
Silvana Novelli ◽  
Albert Esquirol ◽  
Javier Briones ◽  
Pilar Leoz ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
High Risk ◽  
Median Time ◽  
Risk Score ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Related Donor

Abstract Introduction Follicular lymphoma (FL) is the most frequent indolent lymphoma. Autologous hematopoietic stem cell transplantation (ASCT) allows durable progression-free survival in selected relapsed patients. Recently, the EBMT lymphoma working party has published the recommendations for ASCT and allogeneic hematopoietic transplantation (alloTPH) in FL. For those high-risk young patients relapsing after ASCT, alloTPH is a valid therapeutic option; the majority being done with reduced intensity conditioning (alloRIC). Aims Our aim is to describe the outcome of patients with FL who underwent an alloTPH in our cente. Factors potentially influencing outcome such us age, sex, FLIPI at diagnosis, disease status prior alloTPH, EBMT risk score, type of donor, graft vs host disease (GVHD) prophylaxis and development of GVHD were also analized. Methods Actuarial estimates of OS and PFS rates were calculated using the Kaplan-Meier method. OS was estimated from the date of transplantation to the date of death or last follow-up. PFS was defined as the time from transplantation until progression or death from any cause. Patients We retrospectively found 26 alloTPH in the period 1999 - 2013. Two alloTPH were conditioned with a myeloablative regimen. Patients who underwent an alloRIC (n=24) were all conditioned with Fludarabine 30 mg/m2/5 days and Melphalan 70 mg/m2/1 day. Results AlloTPH was from a matched related donor in 70.8% of cases, from a mismatched related donor in 4.2%, matched unrelated donor in 8.3% and from a mismatched unrelated donor in 16.7%. The median age was 49.5 years (range 35-61). The median time from diagnosis to alloTPH was 48 months (range 9 – 190), male: female ratio was 2:1. FLIPI at diagnosis was 0 in 16.7%, FLIPI 1 in 25%, FLIPI 2 in 33.3%, FLIPI 3 in 8.3% and FLIPI 4 in 16.7. Mean number of treatment pre alloTPH was 4.5 (range 2-6). Ten patients (41.7%) had previously received an ASTC. Response before alloTPH was complete response in 54.2%, partial response in 37.5% and stable disease in 8.4%. The majority of patients (95.8%) had an EBMT risk score higher than 3. Graft vs host disease prophylaxis consisted on cyclosporine + short course of methotrexate in 54.2%, cyclosporine + micophenolate in 41.7% and sirolimus + tacrolimus in 4.2%. In vivo T-cell depletion was done in 4 patients receiving grafts from a mismatched unrelated donor (ATG or alemtuzumab, 2 patients each). Mean CD34 cells/Kg infused was 6.45 x106/kg (range 1.92 – 15.6). The median time to granulocyte recovery (>0.5x109/L) was 15 days (range 11-19) and the median time to platelets recovery (>50x109/L) was 14 days (range 6-56). Acute GVHD was developed in 45.8% of patients; it was global grade 1-2 in 36.4% ,and grade 3-4 in 63.6%. Chronic GVHD was present in 58.3% of patients. The median time of chronic GVHD presentation was 196 days after alloTPH (range 101 – 569 days). Regarding opportunistic infections, 20.8% of patients reactivated CMV with no disease, 16.7% had intestinal disease due to CMV. Thirteen per cent of patients developed pulmonary fungal infection (i.e Aspergillus sp). With a median follow up of 48.50 months (range 0-161), the 5 years OS was 66.1% (CI 95% 43.76 - 88.44) and the 5 years PFS was 63.8% (CI 95% 43.22 - 84.4). Overall morbidity at 3, 6 and 12 months after alloTPH was 5%, 5% and 10.3% respectively. Only 1 patient relapsed at 38 months after alloTPH but is still alive. Causes of death were refractory GVHD (n=5), sepsis (n=3) and acute renal failure due to microangiopathy (n=1). Survival was influenced by GVHD prophylaxis. At the median time of follow up (48.50 months) patients receiving cyclosporine-methotrexate had an OS of 82.5% vs 30% for patients receiving cyclosporine-MMF (p<0.01). Other variables (FLIPI at diagnosis, sex, age older than 60 years, the EBMT risk score pre alloTPH and disease status) had no influence on survival. Conclusions AlloTPH for high risk FL patients seems to overcome the negative effect of FL prognostic factors at diagnosis. This strategy shows an excellent disease control with a low transplant-related mortality. Disclosures: No relevant conflicts of interest to declare.

Single-institution experience of allogeneic stem cell transplantation for diffuse large B-cell lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19524-e19524
Author(s):  
Benjamin Puliafito ◽  
Solmaz F. Afshar ◽  
Zachary Galitzeck ◽  
Amir S. Steinberg
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Median Time ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Disease Status ◽  
Novel Therapies ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e19524 Background: Given the promising results of novel therapies such as CAR-T, there is heightened scrutiny on the long-term outcomes of allogeneic stem cell transplant (alloHCT) in diffuse large B cell lymphoma (DLBCL). We present the characteristics and long-term follow-up of DLBCL patients (pts) who underwent alloHCT at our institution over the past 10 years. Methods: Adult pts who underwent an initial alloHCT for DLBCL at our institution from 2008 to 2018 (n = 18) were included. Pt, disease, transplant (tx), and GVHD history were retrospectively collected from reports to CIBMTR and chart review. Outcomes of progression-free survival (PFS) and overall survival (OS) were analyzed in February 2020. Results: Eighteen pts underwent an alloHCT for DLBCL at a median of 19.5 months post-diagnosis (range, 6 – 83 mo). The median age at the time of tx was 53 years old (range, 30 – 67 yrs). The median Karnofsky score was 70 (range, 30 – 100). The majority of the pts (78%) had stage IV disease. The median number of prior chemotherapy regimens was 3 (range, 1 – 6). Disease was chemosensitive in 11 pts (61%), chemoresistant in 4 pts (22%), and undetermined in 3 pts (16%). Eleven pts (61%) had a previous autoHCT with a median time between txs of 8 months (range, 4 – 28 mo). The disease status at time of tx included CR1 (n = 2), CR3+ (n = 2), PR (n = 4), PIF-resistant (n = 3), PIF-sensitive (n = 1), REL1-resistant (n = 1), and REL3+-sensitive (n = 3). Fifteen patients received PBSC and 3 patients received cord blood. Donors were HLA-identical siblings (n = 5), monozygotic twins (n = 1), and unrelated (n = 12). Conditioning regimens were Flu/Mel (n = 10), Flu/Mel/ATG (n = 2), Flu/TBI (n = 2), Flu/Cy/TBI (n = 1), Cy/TBI (n = 2), and BEAM (n = 1). Acute GVHD developed in 16 pts (89%) with max grades of III or IV in 10 pts despite 94% of pts receiving GVHD prophylaxis. Chronic GVHD developed in 5 pts (28%; 3 pts with limited disease and 2 pts with extensive disease). PFS rates were 56% at 6 months, 33% at 1 year, and 24% at 3 years. OS rates were 72% at 6 months, 39% at 1 year, and 24% at 3 years. The median time to death was 7.5 months (range, 1 – 74; mean 12.9 mo) with primary disease as the most common cause of death (5/18 pts; 28%). At the time of analysis, 4 pts (22%) were alive with a maximum survival of 58 months (range, 28 – 58 mo). Conclusions: A significant portion of DLBCL patients had durable responses after alloHCT with 24% of patients alive at 3 years, despite high rates of GVHD and a broad range of disease status. As novel therapies continue to emerge, alloHCT should still be considered in specific populations of relapsed and refractory DLBCL.

scholarly journals A Calcineurin Inhibitor Free Graft Versus Host Disease (GVHD) Prophylaxis for Patients Undergoing Matched Related (MRD) and Matched Unrelated Donor (MUD) Allogeneic Hematopoietic Cell Transplant (Allo-HCT)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3893-3893
Author(s):  
Madiha Iqbal ◽  
Felipe Andres Mendieta Nieto ◽  
Kaitlyn M Brannick ◽  
Zhuo Li ◽  
Hemant S. Murthy ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Calcineurin Inhibitor ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Matched Donor

Abstract Introduction Post-transplantation cyclophosphamide (PTCy) and calcineurin inhibitor (CNI) based GVHD prophylaxis has shown lower rates of acute and chronic GVHD when compared with the traditional prophylaxis of calcineurin inhibitor (CNI) and methotrexate (MTX) in matched donor (related and unrelated) allo-HCT. The combination of PTCy with sirolimus as a calcineurin inhibitor-free GVHD prophylaxis has shown promising results with cumulative rates of grade II-IV acute and chronic GVHD in the range of 15-27% and 20-27% respectively in patients undergoing matched and haploidentical allo-HCT. We report a single center, nonrandomized comparison of patients undergoing matched donor allo-HCT receiving PTCy in combination with sirolimus (PTCy/Siro) with those receiving the standard GVHD prophylaxis of tacrolimus and MTX (Tac/MTX). Methods One hundred and sixteen consecutive patients who had undergone a MRD or MUD allo-HCT between January 2018 to January 2021 and received either PTCy with sirolimus or tacrolimus with methotrexate as GVHD prophylaxis regimens were eligible for inclusion. The selection of PTCy with sirolimus or tacrolimus with methotrexate as GVHD prophylaxis regimen was based on physician choice. Primary endpoints were cumulative incidence of acute (grade II to IV) and chronic GVHD. Secondary endpoints were a) neutrophil and platelet engraftment; b) overall survival (OS); c) non-relapse mortality (NRM); d) relapse; e) clinical infections and f) time to immunosuppression (IS) withdrawal. Kaplan-Meier method was used to estimate 1-year and 2-year freedom from long term adverse events, including chronic GVHD, relapse, NRM and OS. All tests were two-sided with alpha level set at 0.05 for statistical significance. Results Out of a total of 116 patients undergoing MRD and MUD allo-HCT, 29 received PTCy/Siro and 87 Tac/MTX. Baseline characteristics were similar between the two arms except patients in PTCy/Siro were younger with median of 48 (range: 24-69) years vs. 61 (range: 20-73) years (p=0.004) in Tac/MTX. There was difference in primary indication for allo-HCT between the two arms with non-hodgkin lymphoma (NHL) being the most common in PTCy/Siro and acute myeloid leukemia (AML) in the Tac/MTX group. Patients receiving PTCy/Siro had a significantly higher median CD3 day 100 chimerism at 100 (90-100) vs. 90 (40-100) % (&lt;0.001) and a significantly shorter median time to IS withdrawal at 138 (37-312) vs 232(66-1120) days for patients receiving Tac/MTX. There was no difference between the two arms for length of hospital stay and time to neutrophil engraftment, but PTCy/Siro had a significantly longer median time for platelet engraftment at 17.5 (12-74) vs.14 (11-38) days (p= 0.001). No significant difference was observed between the two arms for incidence of grade II to IV acute GVHD, grade III to IV acute GVHD, steroid refractory acute GVHD or clinical infections (Table 1). After a median follow up of 1.1 (range: 0-1.8) years, patients receiving PTCy/Siro were significantly less likely to have chronic GVHD with 2-year freedom from GVHD of 75% (95%CI: 58-98%) vs 20% (95%CI 10-40%), p=0.005 (Figure 1). There was no difference between the two arms for OS, disease relapse or non-relapse mortality (Table 2). Conclusion In this study, the combination of PTCy/Siro is associated with a significantly lower risk of chronic GVHD when compared against the traditional GVHD prophylaxis of CNI and methotrexate, despite significantly earlier IS withdrawal. Other long-term outcomes of interest remained comparable between the two arms. Chronic GVHD contributes to significant morbidity and mortality in patients undergoing allo-HCT. Newer strategies to limit the impact of chronic GVHD are needed. The results of our study warrant validation in a large, multicenter, randomized prospective trial. Figure 1 Figure 1. Disclosures Murthy: CRISPR Therapeutics: Research Funding. Foran: gamida: Honoraria; takeda: Research Funding; novartis: Honoraria; trillium: Research Funding; boehringer ingelheim: Research Funding; OncLive: Honoraria; abbvie: Research Funding; certara: Honoraria; sanofi aventis: Honoraria; syros: Honoraria; taiho: Honoraria; revolution medicine: Honoraria; bms: Honoraria; servier: Honoraria; pfizer: Honoraria; actinium: Research Funding; aptose: Research Funding; kura: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding.

scholarly journals Non-Myeloablative Conditioning Regimen before T-Cell Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Advanced Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4614-4614
Author(s):  
Catalina Montes De Oca ◽  
Thomas Pagliardini ◽  
Stefania Bramanti ◽  
Sabine Furst ◽  
Jean Marc Schiano de Collela ◽  
...  
Keyword(s):  
Research Funding ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Research Support ◽  
Myeloablative Conditioning ◽  
Term Survival ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Low Incidence

Introduction: allogeneic transplantation (allo-HSCT) is a curative treatment for patients with advanced lymphoma. Haploidentical (haplo-SCT) transplantation extended the accessibility to allo-HSCT, overcoming the issue of donor availability. However, alternative donor allo-HSCT is still considered at higher risk of non-relapse mortality due to the HLA disparity and thus an anticipated higher incidence of GVHD. In this context, the use of a non myeloablative conditioning (NMAC) regimen combined with post transplantation cyclophosphamide (PT-Cy) based GVHD prophylaxis may reduce procedure related toxicity. The aim was to evaluate the toxicity and efficacy of haplo-SCT using NMAC with PT-Cy in advanced lymphoma patients. Methods: We here report the retrospective experience of a bicentric transplantation program. We analyzed a cohort of lymphoma patients undergoing Haplo-SCT and homogeneously receiving NMAC and PT-Cy. Inclusion criteria were: 1) first allo-HSCT for advanced lymphoma between 2009 and 2018; 2) haploidentical donor; 3) NMAC (fludarabine cyclophosphamide and 2 gray TBI GVHD prophylaxis consisted of PT-Cy day+3 and +4 , cyclosporine A and MMF starting from day +5. Multivariate analyses included age, disease type (NHL vs HL), HCT-CI (< vs ≥ 3), graft source (PBSC vs BM), disease status at haplo-SCT (CR vs other). Results: One hundred forty seven patients (73 NHL; 74 HL) with a median age of 46 years (range: 19-71) were included. PBSC (peripheral blood stem cell) was used as graft source in 96 patients (65%). Patients received a median number of 3 conventional chemotherapy lines before haplo-SCT (1-8). Sixty-five (44%) had relapse after Auto-HCT. At the time of haplo-SCT, 96 patients (66%) were in complete remission. The cumulative incidences of day+100 grade 2-4 and 3-4 acute GVHD were 30% and 3%, respectively. The cumulative incidences of 2-year chronic and moderate or severe chronic GVHD were 13% and 8%, respectively. With a median follow up of 39 months (6-114), 2-year NRM was 14%, with a trend for higher risk in patients with HCT-CI ≥ 3 (HR 0.39, 95CI [0.15-1.04] p = 0.061) while age was not associated with an increased risk of NRM (HR 1.01, 95CI [0.98-1.05], p = 0.450). Two-year cumulative incidence of relapse (CIR) was 21% and 18% in HL and NHL patients, respectively. Disease status at the time of haplo-SCT was strongly associated with relapse (HR 2.99, 95CI [1.41-6.35], p = 0.004) In HL patients, 2-year PFS, OS and GRFS were 65%, 77% and 57%, respectively, while corresponding values in NHL patients were 65%, 69% and 55%, respectively. Two-year PFS and GRFS were significantly higher in patients who underwent haplo-SCT in CR (PFS: CR vs. no CR: 72% vs. 55%, p=0.045; GRFS: CR vs. no CR: 63% vs. 42%, p=0.010). There was a trend for better 2-year OS in CR (OS: CR vs. no CR: 78% vs. 63%, p=0.063. Conclusion: We confirm the feasibility of haplo-SCT using NMAC and PT-Cy with low incidence of GVHD (notably severe forms) and NRM. In addition, we observed a relatively low incidence of relapse (19%) in this cohort of heavily pretreated patients, underlining a potent graft-versus-lymphoma effect after haplo-SCT, leading to promising survivals, including high rate of GRFS (>50%), suggesting a preserved long term quality of life in survivors. We conclude that NMAC haplo-SCT with PT-Cy should be considered as a valuable curative option for advanced lymphoma patients, with a favorable toxicity profile and promising long term survival. Figure Disclosures Stoppa: celgene: Other: travel fees, lecture fees; takeda: Other: travel fees. Carlo-Stella:MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Boehringer Ingelheim: Consultancy; Genenta Science sr: Consultancy; Sanofi: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; Servier: Consultancy, Honoraria, Other: Travel, accommodations; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Other: Travel, accommodations; Janssen Oncology: Honoraria; AstraZeneca: Honoraria. Chabannon:EBMT: Other: Working Party Chair, Board member; Fresenius Kabi: Other: research support; Miltenyi Biotech: Other: research support; Terumo BCT: Other: speaker's fees; Celgene: Other: speaker's fees; Novartis: Other: speaker's fees; Gilead: Other: speaker's fees, hospitalities; Sanofi SA: Other: research support, speaker's fees, hospitalities. Santoro:Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; BMS: Consultancy. Blaise:Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria; Molmed: Consultancy, Honoraria; Pierre Fabre medicaments: Honoraria.

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