scholarly journals Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Adult Patients with t(4;11)(q21;q23) KMT2A/AFF1 (MLL/AF4) B-Acute Lymphoblastic Leukemia in First Complete Remission (CR1): Favorable Outcome of Patients with Negative Minimal Residual Disease (MRD) Status at Transplant. a Report from the Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation (ALWP-EBMT)

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 669-669
Author(s):  
Jordi Esteve ◽  
Myriam Labopin ◽  
Tomasz Czerw ◽  
Depei Wu ◽  
Liisa Volin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Board Of Directors ◽  
Research Funding ◽  
Prognostic Value ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Adult Patients ◽  
Unrelated Donor ◽  
Strong Impact ◽  
Advisory Committees

Abstract Introduction: B-ALL with t(4;11)(q21;q23) (t(4;11) B-ALL) is a well characterized adult B-ALL subtype associated with an unfavorable prognosis, mainly due to a high relapse risk, which is followed by a poor outcome. In order to prevent relapse during frontline treatment, alloHCT in CR1 is recommended by many cooperative groups, although the specific outcome and prognostic factors related to this procedure have been scarcely analyzed. Patients and Methods: We searched in the ALWP-EBMT database all adult patients (pts) (i.e., ≥18 year-old) with B-ALL reported to harbor a t(4;11) translocation who underwent an alloHCT in CR1 from a matched related or unrelated (10/10 or 9/10) donor during the 2000-2016 period, and analyzed their outcome. The prognostic value of the MRD status at the time of transplant, as reported by centers, was specifically addressed. In addition, a comparative analysis with analogous pts with normal karyotype B-ALL (NK B-ALL) was performed, adjusting for main significant variables including the pre-transplant MRD status. Results: Overall, we identified 151 pts with t(4;11) B-ALL and 567 with NK B-ALL. Compared to NK B-ALL, pts with t(4;11) B-ALL were older (median age, 38.1 vs. 33.8, p=0.028), presented with a higher WBC count (114 vs. 7.9x109/L¸ p<.001), and were allografted within a shorter period from diagnosis (5.3 vs. 5.8 months, p=0.001). In the t(4;11) B-ALL cohort, 103 transplants were performed from an unrelated donor (68%), conditioning was myeloablative (MAC) in most cases (86%), and in 114 of them (88%) included TBI. Eighty pts (53%) received in vivo T-cell depletion (TCD) (Table 1). With a median follow-up of 62 months, in pts with t(4;11) B-ALL, the 2-year relapse incidence (RI), NRM, LFS, OS, and graft- and relapse-free survival (GRFS) were 29.8% (22-38), 19.5% (14-27), 50.7% (42-59), 59.8% (52-68), and 34.6% (27-43), respectively. Acute grade II-IV GvHD and 2-year chronic GvHD were 34.7% (27-42) and 38.5% (30-47), respectively. Outcome after relapse was poor, with a 2-year OS of only 14.9% (4-26). MRD at the time of alloHCT was undetectable in 62 (69%) of the 90 pts with available information, and showed a strong favorable impact on outcome, with a lower RI (21 vs. 45% at 2 years, p=0.003) and higher LFS (67 vs. 27%, p=0.00004), OS (81 vs. 26%, p=0.000005)and GRFS (47 vs. 24%, p=0.01) compared to pts with detectable MRD at transplant. The prognostic value of the pre-transplant MRD status was confirmed in a multivariate analysis (performed among patients with known MRD status), in terms of RI (HR=0.23, CI: 0.09-0.55; p=0.0011), NRM (HR=0.16, 0.05-0.52; p=0.0023), LFS (HR=0.20, 0.10-0.40; p=10-5), OS (HR=0.14, 0.07-0.30; p<10-5), and GRFS (HR=0.38,0.2-0.69; p=0.001). Patient age and year of transplant also showed independent prognostic value for NRM, LFS, OS, and GRFS. Comparison between t(4;11) B-ALL and NK B-ALL showed a strong impact of the MRD status. In univariate analysis, outcome after alloHCT in both t(4;11) B-ALL and NK B-ALL groups was similar in pts without detectable MRD at transplant, with comparable RI (21 vs. 26%, p=0.35), NRM (12 vs. 18.5%, p=0.37), LFS (67 vs. 56%, p=0.14), and OS (81.4 vs. 69%, p=0.069). In contrast, among pts with detectable MRD at alloHCT, LFS and OS were superior in NK B-ALL compared to t(4;11) B-ALL pts (50 vs. 27%, p=0.02; and 62 vs.26%, p=0.01, respectively). In multivariate analysis, and considering MRD-negative NK B-ALL as the reference category, t(4;11) B-ALL pts allografted without detectable MRD showed a better LFS (HR=0.624,0.335-0.978; p=0.04) and OS (HR=0.523,0.296-0.925; p=0.02). On the contrary, MRD-positive t(4;11) pts showed a worse outcome compared to the remaining MRD-stratified subgroups, with higher RI (HR=3.28,1.63-6.60; p=.0009), and shorter LFS (HR=2.42,1.65-4.93; p=0.00017) and OS (HR=3.51,2-6.18; p=1x10-5) (Figure 1). Conclusions: Outcome of adult pts with t(4;11) B-ALL who received an alloHCT in CR1 is favorable, especially in those with a negative MRD status pre-alloHCT. These results, when compared to previously reported results in non-allografted pts, strongly suggest a neat beneficial effect of alloHCT for this adult B-ALL subset. Nonetheless, further studies should evaluate the magnitude of this benefit in comparison with contemporary non-allograft post-CR strategies, as well as the optimal management for pts failing to achieve a MRD-negative status. Disclosures Socié: Alexion Pharmaceuticals, Inc.: Consultancy. Schmid: Celgene: Research Funding, Speakers Bureau; MoilMed: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding, Speakers Bureau. Mohty: Sanofi: Honoraria, Speakers Bureau.

Analysis of Transfusion Dependency Development and Disease Evolution in Patients with MDS with 5q- and without Transfusion Needs at Diagnosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3180-3180
Author(s):  
Felix Lopez-Cadenas ◽  
Blanca Xicoy ◽  
Silvia Rojas P ◽  
Kaivers Jennifer ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Board Of Directors ◽  
Research Funding ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Rank Test ◽  
Advisory Committees ◽  
Disease Evolution ◽  
Free Survival

Abstract Introduction: Myelodysplastic syndrome with del5q (MDSdel5q) is the only cytogenetically defined MDS category recognized by WHO in 2001, 2008 and 2016 and is defined as a MDS with deletion on the long arm of chromosome 5 and less than 5% of blast cells in bone marrow. It is known that for patients with MDSdel5q and transfusion dependence (TD), Len (LEN) is the first choice of treatment. However, data regarding factors that may impact on the development of TD or disease evolution in patients diagnosed without TD are scanty. In our study a retrospective multicenter analysis on patients with low-int 1 MDSdel5q without TD at diagnosis has been performed in order to answer these questions. Patients and methods: We performed a multicenter collaborative research from the Spanish (RESMD) and German MDS registries. Data from 153 low risk MDSdel5q without TD at diagnosis were retrospectively analyzed. Statistical analysis: Data were summarized using median, range, and percentage. The event of TD was defined as the development of TD according to the IWG criteria (2006) and/or the beginning of a treatment which could modify disease course (LEN or ESA). Transfusion or treatment free survival (TFS), overall survival (OS) and leukemia free survival (LFS) were measured from diagnosis to TD or treatment, the first occurred (or to last follow up if none), last follow up or death from any cause and evolution to AML, respectively. TFS, OS and LFS were analyzed using the Kaplan Ð Meier method. The Log-rank test was used to compare variables and their impact on survival for univariate analysis.Multivariate analysis was performed using Cox's proportional hazards regression model. For comparison of Kaplan Meier curves the long rank test was used, with statistical significance with p<0.05. Statistical analysis was performed using SPSS 20.0. Results: Main clinical and biological characteristics were summarizing in table 1. From the total of 153 patients, finally 121 were evaluable. During the study 56 patients (46.2%) became in TD and 47 (38.8%) did not develop TD but received a modified disease course treatment. In this sense, most of the patients developed relevant anemia regarding those data (103 out of 121 patients, 85%). Median time to TD or treatment (TFS) was 20 months (1-132) from diagnosis. Secondary MDS (p=0.02), thrombocytosis (>350 109/L) (p=0.007), and neutropenia (<1.5 x 109/L) (p=0.02) were associated with poorer TFS. Thrombocytosis and neutropenia retained statistical significance in the multivariate analysis (Table 2). Among the TD patients (N=56), 42 (75%) received treatment: 28 LEN, 7 ESA and 7 other treatments. Among patients that did not develop TD (N=65), 47 (72.3%) received treatment before TD development: 16 LEN, 28 ESA and 3 other treatments. In order to know the evolution of these patients, survival analysis was performed. Median follow up was 58.9 months among alive patients and 57% of them were alive at the time of the last follow up. Estimated OS at 2 and 5 years was 94% and 64%. Regarding Univariate analysis, platelet <100 x 109/L (p=0.03), patients older than 71 years (p=0.001), and progression into AML (p=0.02) were associated with poorer OS. On the contrary, patients who had received treatment showed better OS (p<0.0001). This benefit is more evident among patients receiving LEN, median OS for patients receiving LEN, ESA/other treatments and not treated group was 137 months (CI 95%: 59,4 -215,5), 99,3 months (CI 95%: 46,6 -152) and 57,9 months (CI 95%: 38,2 -77,6), respectively, p<0.0001 (Figure 1). In the multivariate analysis, patients older than 71 years and LEN treatment retained the statistical significant impact on OS (Table 2). Twenty-eight patients (23%) progressed into AML, median time to AML was 35 months (5-122). When univariate analysis was performed, variables with adverse impact on LFS were platelets <100 x 109/L(p=0.019), neutropenia < 0.8 x 109/L (p=0.026), an additional cytogenetic abnormality (p=0.013) while treatment with LEN had a favorable impact (p=0.035). In the multivariate analysis only the presence of additional cytogenetic abnormalities retained statistical significance (Table 2). CONCLUSIONS: Most of the patients with low risk del(5q) MDS and no TD at diagnosis developed symptomatic anemia very early after diagnosis (20 months). Carefully monitoring should be stablished in order to detect this time point. Outcome of this subset of patients could improve after target therapy. Figure 1 Figure 1. Disclosures Del Cañizo: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; janssen: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees. Díez Campelo:celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Risk Factors for Severe Form of COVID-19 after Allogeneic Hematopoietic Stem Cell Transplantation: A SFGM-TC Multicentre Cohort Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-34
Author(s):  
Alienor Xhaard ◽  
Constance Xhaard ◽  
Maud D'Aveni ◽  
Hélène Salvator ◽  
Marie-Laure Chabi-Charvillat ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Intensive Care ◽  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Univariate Analysis ◽  
Immunosuppressive Treatment ◽  
Severe Form ◽  
Advisory Committees

COVID-19 greatly affected Europe between March and May 2020. Initial reports suggest cancer and haematological malignancies as risk factors for severity and mortality, but the role of allogeneic stem cell transplantation (alloHSCT) remains unclear. The Société Francophone de Greffe de Moelle et Thérapie Cellulaire conducted a multicentre retrospective study of alloHSCT recipients diagnosed with COVID-19. We described the COVID-19 disease characteristics in this population and examined risk factors for severity and mortality. Data were collected retrospectively from the patients' charts and the ProMISe database. Diagnosis was retained only if a reverse transcription polymerase chain reaction assay test from a nose swab was positive for SARS-CoV-2. Patients were classified as severe if they were transferred to an intensive care unit (ICU) due to COVID-19 or died of COVID-19, and non-severe in other cases. Comparisons of characteristics were performed using student's t-tests and Mann-Whitney U tests for normally and abnormally distributed data, respectively, for continuous variables and χ2 or Fisher's exact tests, when appropriate for categorical variables. Risk factors associated with a severe form of COVID-19 were assessed using both univariate and multivariate logistic regressions. All analyses were performed using SAS version 9.4.6 (SAS Institute Inc., Cary, NC, USA. A two-tailed significance level p&lt;0.05 was used. Fifty-four patients were diagnosed, including 21 with severe forms (intensive care transfer and/or death). Haematological characteristics did not vary between patients with severe or non-severe forms of COVID-19. Patients with a severe form of COVID-19 were more likely to be diagnosed earlier after alloHSCT (0.78 vs. 2.1 years, p=0.01), to have comorbidities (80.9% vs. 54.5%, p=0.05) and to receive immunosuppressive treatment (81% vs. 51.5%, p=0.03). Severe COVID-19 patients were more likely to have symptoms at COVID-19 diagnosis (100% vs. 81.8%, p=0.04), especially pneumonia and symptoms other than respiratory or digestive (asthenia, neurological symptoms, myalgia, dysgeusia, skin lesions and arthralgia), and to experience co-infection during the course of the disease (52.4% vs. 21.2%, p= 0.001). At COVID-19 diagnosis, patients with a non-severe form were more likely to have a higher platelet count (226 G/L vs. 98 G/L, p= 0.01), while other biological characteristics did not vary between the two cohorts. In univariate analysis, shorter time from transplant to COVID-19 (before 211 days, p=0.01), pneumonia (OR 12.21 [95% CI 2.43 - 61.46], p=0.002), symptoms other than pulmonary or digestive (OR 1.21 [95% CI 1.02 - 11.16], p=0.04), immunosuppressive treatment (OR 5.97 [95% CI 0.75 - 47.42], p=0.03) , co-infection (OR 5.84 [95% CI 1.65-20.63], p=0.006) and comorbidity (OR 3.54 [95% CI 0.98-12.83], p=0.05) were associated with severe COVID-19. The only biological parameter associated with severity was a lower platelet count &lt;71G/L (OR 28.00 [95% CI 2.07-379.25]), p=0.008. In multivariate analysis, pneumonia and other symptoms retained a significant association with severe COVID-19. Thirteen patients died of COVID-19: in univariate analysis, risk factors for death from COVID-19 were similar to the risk factors for severe COVID-19 (i.e. shorter time from alloHSCT, p=0.03; pneumonia, p=0.01; co-infection during the course of COVID-19, p&lt;0.01, and lower platelet count, p&lt;0.01). In multivariate analysis, none of the above mentioned factors remained significantly associated with death from COVID-19. As SARS-CoV-2 continues to spread internationally, given the lack of vaccine or treatment, alloHSCT recipients should maintain a high level of awareness to avoid contamination. Figure Disclosures Dalle: Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Bellicum: Consultancy, Honoraria; AbbVie Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Orchard: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Medac: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Rubio:MSD: Honoraria; Novartis: Honoraria; Neovii: Research Funding; Medac: Consultancy; Gilead: Honoraria.

scholarly journals Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Flurabine Improves Transplant Outcomes in Older MDS Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 253-253
Author(s):  
Betul Oran ◽  
Kwang Woo Ahn ◽  
Caitrin Fretham ◽  
Mithun Vinod Shah ◽  
Ryotaro Nakamura ◽  
...  
Keyword(s):  
Total Dose ◽  
Board Of Directors ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Sensitivity Analyses ◽  
Unrelated Donor ◽  
Advisory Committees ◽  
Hematopoietic Stem

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only potentially curative therapy in eligible patients with myelodysplastic syndromes (MDS). Reduced-intensity conditioning (RIC) regimens that have been developed to extend HSCT to older patients resulted in encouraging outcomes. However, several retrospective studies have raised concerns about disease control when RIC is used in MDS and the ideal conditioning regimen has not yet been found. In this study, we aimed to compare two most commonly used RIC regimens; intravenous use of fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel). Study population: Through the CIBMTR, after excluding patients with ex-vivo T cell depletion, we identified 1045 MDS patients aged ≥ 60 years and underwent first HSCT with matched related or matched (8/8) unrelated donor (MRD and MUD) using RIC between 2007-2016. RIC was defined via CIBMTR criteria as a regimen that incorporated an IV busulfan (BU) total dose ≤ 7.2 mg/kg or low-dose melphalan (MEL) total dose ≤ 150 mg/m2. By that, we identified 697 MDS patients who received FluBu (BU 6.4 mg/kg: 87%, BU 3.2 mg/kg: 13%) and 448 receiving FluMel (MEL 140 mg/m2: 80%, MEL 100 mg/m2: 20%). Results: The two groups, FluBu and FluMel, were comparable for disease and transplant related characteristics except the more frequent use of ATG or Campath in FluBu group (39% vs. 31%). The median age was 67 in both groups, and 26% and 19% of FluBu and FluMel groups were aged ³70, respectively. Hematopoietic comorbidity index (HCT-CI) was ³3 in 61% and 59% of FluBu and FluMel groups and MDS risk score by CIBMTR at HCT was high/very high in 34% in both groups. FluMel was associated with a reduced relapse incidence (RI) after HSCT compared with FluBu as presented in Table 1 and Table 2. Adjusted RI at 1-year was 43% with FluBu and 25% with FluMel (p=&lt;0.0001). On the other hand, transplant related mortality (TRM) was higher with FluMel compared with FluBu (27% vs. 15%, p=&lt;0.0001). The difference persisted at 2- and 3-years after HSCT as presented in the figure. Since the magnitude of improvement in RI was greater with FluMel than the improvement in TRM with FluBu, disease-free survival (DFS) was improved at 1-year and beyond with FluMel compared with FluBu (48% vs. 41% at 1-year, p=0.030, and 38% vs 28% at 3-years, p=0.0030). These outcome differences remained significant when sensitivity analyses were performed excluding patients who received RIC with either BU 3.2 mg/kg or Mel 100 mg/m2. FluMel, did not lead to higher incidence of severe grade 3-4 aGvHD (HR=1.2, 95%CI, 0.9-1.6, p=0.3) or chronic GvHD (HR=0.9, 95%CI=0.7-1.06, p=0.2). However, grade 2-4 aGVHD was observed more often with FluMel than FluBu (HR=1.3, 95%CI, 1.1-1.6, p=0.006). This led to inferior outcomes of GRFS within the first 2 months with FluMel (HR=1.9, HR=1.4-2.6, p&lt;0.001) but superior outcomes of GRFS beyond 2 months with FluMel compared with FluBu (HR=0.7, 95%CI=0.6-0.8, p&lt;0.001). Conclusion: Our results suggest that between the two most commonly used RIC regimens in older MDS patients, FluMel was associated with superior DFS and overall survival compared with FluBu due to reduced RI despite higher TRM. Disclosures Oran: AROG pharmaceuticals: Research Funding; Astex pharmaceuticals: Research Funding. Nakamura:Kirin Kyowa: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Celgene: Other: support for an academic seminar in a university in Japan; Merck: Membership on an entity's Board of Directors or advisory committees. Scott:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Speakers Bureau. Popat:Jazz: Consultancy; Incyte: Research Funding; Bayer: Research Funding.

scholarly journals Post-Transplant Cyclophosphamide (PT-Cy) Based Haploidentical Cell Transplantation (Haplo) Versus Rabbit Anti-Thymocyte Globulin (r-ATG) Based HLA Matched Unrelated Donor (MUD) Transplantation in Patients (pts) with Relapsed/Refractory Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4530-4530
Author(s):  
Akash Mukherjee ◽  
Denái R. Milton ◽  
Alison Gulbis ◽  
Celina Ledesma ◽  
Elias Jabbour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Research Funding ◽  
Hemorrhagic Cystitis ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Advisory Committees ◽  
Gvhd Prophylaxis ◽  
Comorbidity Index ◽  
Similar Survival

Background PT-Cy has emerged as an effective strategy for graft-versus-host disease (GVHD) prophylaxis in Haplo. The reported risk of GVHD with non-PT-Cy in pts receiving MUDs varies between centers. In this report, we compared the engraftment rates, survival, risk of GVHD and comorbidities between PT-Cy Haplo and r-ATG-based MUDs approach in pts with relapse/refractory lymphoma receiving an allogeneic transplantation. Method We retrospectively evaluated 160 adult pts with lymphoma who received Haplo (n=35) or r-ATG-MUDs (n=125) at our center between 2012 and 2018. Pts received GVHD prophylaxis of r-ATG (2-4 mg/kg total on days -3 to -1), tacrolimus and methotrexate if MUD, and tacrolimus and mycophenolate mofetil in addition to PT-Cy (50 mg/kg on days+3, +4) if Haplo. Tacrolimus taper was initiated at 6 months after transplantation in pts with no active GVHD. The study was IRB-approved. Results Haplo pts were more likely to be younger (median age 47 vs 55 yrs; P=0.032), have a lower HCT-Comorbidity Index (median 2 vs 3; P=0.048), and to include more diffuse large b-cell lymphoma (31% vs 22%, and Hodgkins disease (29% vs 16%) (P=0.015). Significant differences were also observed in the conditioning intensity and cell source of transplants between the 2 groups. The majority of Haplo pts (80%) received a reduced intensity-conditioning (RIC) of melphalan/fludarabine +/- 2Gy TBI; the remaining received a myeloablative (MA) busulfan-based regimen (9%) or nonmyeloablative (NMA) (11%) conditioning. In comparison, the percentage of MUDs pts receiving RIC, MA and NMA [bendamustine, fludarabine, rituximab or fludarabine, cyclophophamide, rituximab were 31%, 22% and 46%, respectively (P<0.001). The percentage of pts receiving bone marrow as a source of cells in the Haplo and MUDs groups were 74% vs 14%, respectively (P<0.001). There was no difference in the # of prior therapies received (median = 3, in both), the # of pts who failed a prior autologous (37% vs 26%; P=0.21), disease status (CR vs PR vs refractory; P=0.3), IPI >2 (25% vs 19%, P=0.73) or PET-positive status (55% vs 44%, P=0.33) at study entry between the 2 groups. PT-Cy Halplo group had a significantly higher incidence of symptomatic BK- induced hemorrhagic cystitis compared to r-ATG MUD group (49% vs 10%, P< 0.001). Delayed engraftment was noted in PT-Cy Haplo group compared to r-ATG MUD group with median time to achieve ANC > 500 (18 days vs 10 days; P<0.001), and platelets > 20k were 25.5 days vs 10 days (P<0.001), respectively. The median follow-up time for pts treated with PT-Cy Haplo and r-ATG MUD pts was 12.1 and 20.8 months, respectively. Similar survival and non-relapse mortality (NRM) rates were observed between the 2 groups. The 1-year OS rates were 64% vs 67% (P=0.76) and the 1-year PFS rates were 52% vs 58% (P=0.67). The cumulative incidence (CI) of 1-year NRM was 30% vs 26%, respectively (P=0.66). Chemo-sensitivity (Figure 1), NMA conditioning (Figure 2), and HCT-Comorbidity Index of < 4 were associated with a better OS and PFS in univariate and multivariable analyses. Among histologies, pts with follicular lymphomas had the best OS and PFS. T-cell lymphoma had the worse outcomes. In addition, cystitis was associated with a lower survival rate by univariate analysis (P=0.036). The CI of acute 2-4 GVHD (26% vs 33%, P=0.43), acute 3-4 GVHD (14% vs 12%, P=0.66), and 1-year CI of chronic GVHD (6% vs 15%, P=0.19) were not statistically different between PT-Cy Haplo and r-ATG MUD. By univariate analysis, bone marrow source of graft was the only factor that was found to be significantly associated with a lower risk of chronic GVHD (HR 0.34; P=0.041) (Figure 3). Conclusion Our data show similar survival rates and risk of acute and chronic GVHD in pts with lymphoma who received PT-Cy Haplo and r-ATG MUD. The use of bone marrow graft was the only predictor of a lower incidence of chronic GVHD. Considering the statistically significant delayed time to engraftment and the higher risk of hemorrhagic cystitis, a MUD remains the donor of choice in lymphoma pts who have this option. Disclosures Jabbour: Takeda: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Cyclacel LTD: Research Funding; AbbVie: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Oran:Astex pharmaceuticals: Research Funding; AROG pharmaceuticals: Research Funding. Kebriaei:Kite: Honoraria; Amgen: Research Funding; Jazz: Consultancy; Pfizer: Honoraria. Popat:Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Champlin:Johnson and Johnson: Consultancy; Sanofi-Genzyme: Research Funding; Actinium: Consultancy.

COMPARISON Among Citology, Histology, and FLOW Cytometry IN Evaluating Blast VALUES IN Myelodysplatic Syndromes (MDS). Survey FROM the Italian “PIEMONTE MDS REGISTRY”

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4028-4028
Author(s):  
Alessandro Levis ◽  
Daniela Maria Gioia ◽  
Laura Godio ◽  
Mauro Girotto ◽  
Bernardino Allione ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Board Of Directors ◽  
Research Funding ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Laboratory Data ◽  
Prognostic Impact ◽  
Advisory Committees ◽  
Blast Count

Abstract Abstract 4028 BACKGROUND. The corner stone of the WHO classification and prognostic scores of myelodysplastic syndromes (MDS) is the blast count in bone marrow. The standard cytology evaluation of at least 500 bone marrow cells is easy to perform, but some concerns arise about reproducibility of this method. Nowadays bone marrow trephine biopsy and flow cytometry are frequently considered for the diagnosis of MDS. However there is so far paucity of data comparing cytology, histology and flow cytometry in quantifying bone marrow blasts in order to differentiate non RAEB from BAEB-I and RAEB-II cases. AIM OF THE WORK. The Aim of the work was to analyse the differences and the prognostic impact of cytology, histology and flow cytometry in differentiating non RAEB from BAEB-I and RAEB-II. PATIENTS AND METHODS. Since 1999, clinical and laboratory data from 1256 new cases of MDS were prospectively recorded into the Piemonte MDS Registry. Blast count could be performed with the three different methods: BMC (bone marrow cytology) has been performed in 844 cases, BMH (bone marrow histology) in 874 cases, and BMF (bone marrow flow cytometry) in 636. In order to quantify blasts, immune-histochemistry evaluation of CD34+ cells was used in BMH, while both CD34+ and CD117+ cells were considered in BMF. Out of the total of the 636 patients analysed by BMF only 420 had an accurate and complete registration of CD34 and CD117 positivity and were considered for the present analysis. In two hundred and thirty six cases all three evaluations were contemporary available. The concordance of each diagnostic method with the others and their prognostic value were evaluated in both univariate and multivariate analyses. A comparison between BMC and BMH was available in 571 cases, between BMC and BMF in 228 cases, and between BMH and BMF in 279 cases. RESULTS. The disagreement in classifying patients as non-RAEB or RAEB-I or RAEB-II between BMC and BMH was 156/571 (27%), with BMH over-evaluating blasts in 114/571 cases (20%) and under-evaluating blasts in 42/571 cases (7%). The disagreement between BMC and BMF was 80/228 (35%), with BMF over-evaluating and under-evaluating blast percentage in comparison to BMC in 53/228 (23%) and in 27/228 (12%) cases respectively. The disagreement between BMH and BMF was present in 113/279 (41%), with BMF over-evaluating and under-evaluating blast percentage in comparison to BMH in 44/279 (16%) and in 69/279 (25%) cases respectively. In univariate analysis all three methods of quantifing blasts and differentiating non-RAEB from RAEB-I and RAEB-II retained an important prognostic value for both leukemic evolution and survival. However when the three models were tested in multivariate analysis in order to define the best predictor of leukemic evolution, BMC retained the best predictive value. CONCLUSIONS. When BMH or BMF are used instead of BMC in order differentiate non-RAEB from RAEB-I and RAEB-II, the shift to a different WHO category is evident in at least 30% of patients and BMH and BMF do not play the same role as BMC. BMC still remain the standard method to quantify blasts for classification and prognostic evaluation of MDS. Disclosures: Off Label Use: Lenalidomide in Mantle Cell Lymphoma. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Saglio:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Outcomes of Total Body Irradiation- Versus Chemotherapy-Based Myeloablative Conditioning Regimen in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide for Acute Lymphoblastic Leukemia: ALWP of the EBMT Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 320-320 ◽  
Author(s):  
Bhagirathbhai Dholaria ◽  
Myriam Labopin ◽  
Emanuele Angelucci ◽  
Johanna Tischer ◽  
Mutlu Arat ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Disease Status ◽  
Advisory Board ◽  
Hematopoietic Cell ◽  
Advisory Committees

Background The intensity of a conditioning regimen has significant impact on outcomes of allogeneic hematopoietic cell transplantation in acute leukemia. In acute lymphoblastic leukemia (ALL) patients undergoing matched donor transplant, total body irradiation (TBI)- based myeloablative conditioning (MAC) regimen was associated with improved leukemia free survival (LFS) compared to chemotherapy (CT)-based MAC (Eder S. et al. 2017). Haploidentical hematopoietic cell transplantation(haplo-HCT) with post-transplant cyclophosphamide (PTCy) has emerged as a safe alternative in absence of a matched donor. The optimal MAC in haplo-HCT setting is yet to be defined. We studied the outcomes of TBI- vs. CT-based MAC in ALL patients undergoing haplo-HCT and reported to the Acute Leukemia Working Party of the EBMT. Methods The study included 427 ALL (B-ALL-75%) patients, that underwent haplo-HCT with PTCy during the years 2010-2018, following TBI- (n=188, 44%) or CT- (n=239, 56%) based MAC. Regimen intensity was defined by EBMT criteria and cases with busulfan dose &lt;9 mg/kg or TBI dose ≤6 Gy were excluded. All disease status were included (CR1=208, CR2+=135; advanced=84). Ninety-one (27%) patients had Philadelphia+ disease. Graft source was bone marrow in 229 (54%) patients. Fludarabine-TBI (72%) and thiotepa-busulfan-fludarabine (65%) were the most common TBI and CT-based regimens, respectively. Cyclosporin with mycophenolate was used as GVHD prophylaxis in 64% of patients. The patients, disease, and transplant related characteristics were similar in both cohorts. Median patient age was 32 yrs and the median follow ups for TBI and CT cohort were 20.7 (IQR-11.7-35.3) and 26.2 (IQR-10.2-41) months, respectively. Results In univariate analysis, day 100 incidences of acute GVHD II-IV and III-VI were 38% vs. 30% (p-0.07) and 19% vs. 13% (p-0.14) for TBI and CT cohort, respectively. Two-year overall and severe chronic GVHD incidences were 34% vs. 30% (p-0.51) and 17% vs. 12% (p-0.18) for TBI and CT cohort, respectively. Graft failure was reported in 6 (3%) and 19 (8%)(p-0.09) patients who received TBI and CT-based MAC, respectively. Death from veno-occlusive disease was reported in 4 (5%) TBI patients and 8 (7%) CT patients. There was no difference in reported deaths due to infection (28%) or interstitial pneumonitis (4%) among study cohorts. In multivariate analysis, TBI was associated with significant improvement in nonrelapse mortality (NRM) [HR=0.51, 95% CI:0.32-0.83, p&lt;0.01] and LFS [HR=0.71, 95% CI:0.52-0.97, p-0.03] and higher incidence of aGVHD II-IV [HR=1.5, 95% CI:1.02-2.19, p-0.04]. Finally, relapse incidence (RI), acute GVHD (aGVHD) III-IV, OS and GVHD free relapse free survival (GRFS) did not differ between the groups. Two-year NRM, LFS and OS of TBI and CT cohort were 21% vs. 31% (p&lt;0.01); 45% vs. 37% (p-0.05) and 51% vs. 47% (p-0.18), respectively (Figure 1). Other factors negatively impacting OS were disease status (CR2, HR=1.69, p-0.01 or advance, HR=2.62, p&lt;0.01) and use of peripheral blood as graft source (HR=1.49, p-0.02). Interestingly, peripheral blood graft source also negatively impacted LFS (HR=1.44, p-0.02), aGVHD II-IV (HR=1.58, p-0.02 and GRFS (HR=1.54, p&lt;0.01). Philadelphia+ disease was associated with reduced RI (HR=0.39, p-0.01) but had no impact on LFS (HR=0.80, p-0.29) or OS (HR=0.81, p-0.34)(Table 1). In a subgroup univariate analysis of patients &lt;40 yrs old, TBI was associated with reduced 2-year NRM (19% vs. 28%, p-0.04) without impacting other outcome measures. In patients with pre-HCT disease status CR2 or advance disease, improvement in 2-year NRM (22% vs. 36%, p-0.02) was observed with TBI but no interaction was seen with other endpoints. Conclusions TBI based MAC resulted in significant reduction of NRM, translating into a better LFS without impacting aGVHD III-IV, chronic GVHD, RI or OS when compared to CT based MAC. Non-significant difference in OS between TBI and CT cohorts might be related to lower number of events, short follow-up and/or salvage therapies after relapse. These novel findings based on a large cohort of ALL patients, support the use of TBI based MAC and bone marrow graft in haplo-HCT with PTCy. Disclosures Dholaria: Celgene: Honoraria. Labopin:Jazz Pharmaceuticals: Honoraria. Angelucci:Novatis: Honoraria, Other: Chair Steering Committee TELESTO protocol; Celgene: Honoraria, Other: Participation in DMC; BlueBirdBio: Other: Local advisory board; Jazz Pharmaceuticals: Other: Local advisory board; Roche: Other: Local advisory board; Vertex Pharmaceuticals Incorp., and CRISPR Therapeutics: Other: Participation in DMC. Apperley:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Socie:Alexion: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplant Versus No Transplant in Adult Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in First Complete Remission and Complete Molecular Remission

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 46-48 ◽  
Author(s):  
Armin Ghobadi ◽  
Kahee A Mohammed ◽  
Rawan Faramand ◽  
Hagop M. Kantarjian ◽  
Elias Jabbour ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Philadelphia Chromosome ◽  
Advisory Board ◽  
Adult Patients ◽  
Advisory Committees ◽  
Free Survival ◽  
Advisory Role

Introduction: Allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR1) is the standard of care for adult patients with Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL). The addition of tyrosine kinase inhibitors (TKI) to therapy have resulted in significantly higher rates of complete molecular remissions (CMR) and better overall outcomes. Given the increased toxicity associated with HCT, we aimed to study the benefit of HCT in adult patients with Ph+ ALL in CR1 in CMR. Methods: We performed a multi-institutional, retrospective analysis of 186 patients ≥18 years of age who received induction therapy including TKI for Ph+ ALL from January 2001 through December 2018 and achieved a CMR CR1. Patients achieving CMR within 3 months of diagnosis were included. Sixty-six patients underwent HCT consolidation (HCT group) and 120 patients did not receive HCT in CR1 (no HCT group). Primary outcomes of interest were overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and GVHD free relapse free survival (GRFS). GRFS was defined as being alive without grade III-IV acute GVHD, extensive or systemic chronic GVHD requiring therapy, or relapse. Although GRFS in no HCT group should be exactly as RFS, GRFS comparison was done to compare the composite outcome of quality of life in addition to survival in two groups. Landmark analysis was performed at 3 months to ensure CMR in all subjects at time 0. Survival end points were estimated using Kaplan-Meier method and analyzed with the log-rank test and Cox proportional hazard regression models. Gray's test was used for the comparison of cumulative incidence between cohorts. Results: Patient characteristics at diagnosis are summarized in Table 1. Compared to the non-transplanted patients, HCT patients were younger (median age 45 years vs. 56 years, p &lt;0.001) and had better performance status at diagnosis (Karnofsky score &gt; 90% in 90% of patients vs. 60%, p&lt;0.001). Among patients in the no HCT group, 92.5% were treated with TKI as maintenance therapy with 43% receiving the treatment for more than 3 years. In the HCT group, 86.4% underwent myeloablative conditioning, 81.8 % had a matched related or unrelated transplant, and 47% had TKI as maintenance therapy after transplantation. The rates of patients with transplantation-comorbidity index (HCT-CI) of 0, 1-2, and 3 or more at transplant were 26.7%, 33.3% and 40% respectively. Median follow-up for survivors was 73.2 months (range, 4.3-206 months). Among transplant patients, 65.2% developed acute GVHD with 48.8% of them having a maximum grade of 2. Additionally, 51.6% developed chronic GVHD. In both univariate and multivariate analysis, there was no statistically significant difference in OS or RFS between the two treatment groups (Figure 1A and 1B). Compared to the non-transplanted patients, HCT patients had higher rates of NRM (HR: 3.57; 95% CI: 1.62-7.85), lower rates of CIR (Figure 1C), and a trend toward lower GRFS (Figure 1D). Five-year estimates of the probabilities of OS, RFS, CIR, and GRFS were 65%, 59%, 21%, and 38% for allo-HCT group and 58%, 54%, 28%, and 54% for no allo-HCT group, respectively. Conclusions: Comparing transplant versus chemotherapy only consolidation in CR1, this multicenter retrospective study shows that adult patients with Ph+ ALL in CMR have similar estimates of OS and RFS. Lower CIR in the HCT group was offset by higher NRM, resulting in similar RFS. Results of this study need to be confirmed in a prospective randomized trial. Disclosures Ghobadi: Kite: Consultancy, Research Funding; BMS: Consultancy; Amgen: Consultancy, Research Funding; EUSA: Consultancy; WUGEN: Consultancy. Kantarjian:Janssen: Honoraria; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz: Research Funding; Immunogen: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Honoraria, Research Funding; Sanofi: Research Funding; Oxford Biomedical: Honoraria; BMS: Research Funding; Amgen: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Ascentage: Research Funding; BioAscend: Honoraria; Aptitute Health: Honoraria; Adaptive biotechnologies: Honoraria; Delta Fly: Honoraria. Jabbour:AbbVie: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding. Short:Astellas: Research Funding; Amgen: Honoraria; AstraZeneca: Consultancy; Takeda Oncology: Consultancy, Honoraria, Research Funding. Uy:Daiichi Sankyo: Consultancy; Astellas Pharma: Honoraria; Agios: Consultancy; Pfizer: Consultancy; Jazz Pharmaceuticals: Consultancy; Genentech: Consultancy. DiPersio:Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Champlin:Actinium: Consultancy; Johnson and Johnson: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Takeda: Patents & Royalties; Cytonus: Consultancy; Omeros: Consultancy. Ravandi:Macrogenics: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Orsenix: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding. Kebriaei:Amgen: Other: Research Support; Jazz: Consultancy; Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Novartis: Other: Served on advisory board; Ziopharm: Other: Research Support.

scholarly journals Impact of Chronic Graft-Versus-Host Disease on Long-Term Outcomes of Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Adults with High-Risk Acute Lymphoblastic Leukemia in First Remission

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3980-3980
Author(s):  
Jae-Ho Yoon ◽  
Sung-Soo Park ◽  
Young-Woo Jeon ◽  
Sung-Eun Lee ◽  
Byung-Sik Cho ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Median Time ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Advisory Committees

Abstract Background : The role of reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC-HCT) in adult acute lymphoblastic leukemia (ALL) remains unclear because the interpretation of transplantation outcome is mainly limited by the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of the criteria used to select patients for RIC-HCT. Previously, we conducted a phase 2 trial of RIC-HCT in adults with high-risk ALL who were ineligible for myeloablative conditioning and showed the potential role of this strategy, especially in patients in first complete remission (CR1). Here, we report the long-term outcomes of RIC-HCT by analyzing 122 consecutive adults with high-risk ALL in CR1, particularly focusing on the prognostic relevance of chronic GVHD. Methods: During the period between 2000 and 2014, 122 patients in CR1 (median age, 52 years [range, 15-65 years]; 54 Ph-negative ALL and 68 Ph-positive ALL) were given an identical RIC regimen consisting of fludarabine (150 mg/m2 in total) and melphalan (140 mg/m2in total). The indications for RIC-HCT were advanced age (≥50 years; n=79; 64.8%) and comorbid conditions (n=43; 35.2%). Graft sources were peripheral blood stem cells (n=118; 66 matched sibling donor, 23 matched unrelated donor, 29 mismatched unrelated donor) and bone marrow (n=4; 1 matched sibling donor, 1 matched unrelated donor, 2 mismatched unrelated donor). The median time to transplantation was 155.5 days (range, 103-291 days). GVHD prophylaxis was attempted by administering calcineurin inhibitors (cyclosporine for sibling donor transplants, tacrolimus for unrelated donor transplants) plus methotrexate. Antithymocyte globulin was administered to the patients who received mismatched unrelated donor grafts. If residual leukemia was detected in the absence of GVHD at 3 months after transplantation, calcineurin inhibitors were rapidly discontinued. Results: The median time for neutrophil and platelet recovery was 12 days (range, 8-30 days) and 13 days (range, 5-60 days) after RIC-HCT. Sixty-two patients developed acute GVHD (53 grade II, 5 grade III, 4 grade IV). The cumulative incidence of acute GVHD at 1 year was 50.8% (42.6% for Ph-negative and 57.4% for Ph-positive, P=0.152). Except for 11 patients with early deaths within 100 days, 77 developed chronic GVHD (30 mild, 29 moderate, 18 severe), resulting in a 5-year cumulative incidence of 63.6% (69.1% for Ph-negative ALL and 58.8% for Ph-positive ALL, P=0.319). The median time to onset of chronic GVHD was 140 days (range, 37-843 days) after transplantation. Cytomegalovirus reactivation >10,000 copies/mL was observed in 40.2% (44.4% for Ph-negative ALL and 36.8% for Ph-positive ALL, P=0.447). After a median follow-up duration of 57.9 months (range, 17.7-206.8 months), the 5-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 27.5% (23.9% for Ph-negative ALL and 30.2% for Ph-positive ALL) and 19.0% (17.4% for Ph-negative ALL and 20.3% for Ph-positive ALL), respectively, and the 5-year disease-free survival (DFS) and overall survival (OS) rates were 53.5% (58.4% for Ph-negative ALL and 49.7% for Ph-positive ALL) and 59.8% (60.2% for Ph-negative ALL and 59.3% for Ph-positive ALL). In multivariate analysis, the presence of chronic GVHD lowered CIR (HR, 0.23; 95% CI, 0.10-0.48; P<0.001), but severe chronic GVHD increased NRM (HR, 8.76; 95% CI, 3.39-22.6; P<0.001). Thus, the presence of mild to moderate chronic GVHD was closely related to better outcomes in terms of DFS (HR, 0.45; 95% CI, 0.32-0.64; P<0.001) and OS (HR, 0.44; 95% CI, 0.30-0.64; P<0.001) in all patients as well as in both subgroups of patients. In Ph-positive ALL subgroup of patients, patients without achievement of major molecular response until the time of transplantation had also significantly higher CIR (HR, 7.42; 95% CI, 3.04-18.10; P<0.001) and poorer DFS (HR, 3.47; 95% CI, 1.48-8.14; P=0.004) and OS (HR, 2.58; 95% CI, 1.03-6.47; P=0.043). Conclusion: Our long-term follow-up data with a uniform treatment strategy suggest that RIC-HCT is a valid alternative choice for providing a long-term disease control for adult high-risk ALL patients in CR1. Minimal residual disease-based treatment strategies to reduce leukemia cell burden before HCT and to enhance the graft-versus-leukemia effect are needed in the future. Disclosures Kim: ILYANG: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lee:Alexion Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Haplo-Cord Transplantation Vs Unrelated Donor Stem Cell Transplantation in Patients with AML/MDS Older Than 50

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1235-1235 ◽  
Author(s):  
Joanna Rhodes ◽  
Koen van Besien ◽  
Hongtao Liu ◽  
Usama Gergis ◽  
Stephanie B. Tsai ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Post Transplant

Abstract Haplo-cord Transplantation Vs Unrelated Donor Stem Cell Transplantation In Patients with AML/MDS older than 50 Between 2007 and 2013, 109 patients with AML/MDS who were 50 years and older and had no HLA- matched related donor underwent allogeneic hematopoietic stem cell transplant. 64 had an HLA identical unrelated donor and received fludarabine/melphalan/alemtuzumab conditioning and post transplant tacrolimus for graft vs host disease (GVHD) prophylaxis. 45 underwent haplo-cord (HC) SCT with fludarabine/melphalan/ thymoglobulin; post-transplant tacrolimus and MMF. We compared patient characteristics and transplant outcomes between both groups. (Table 1) Age distribution and ASBMT risk category were similar. There were more patient's with AML in the HC group. (P=0.01) Time to neutrophil recovery, treatment related mortality (TRM), relapse rate, progression free survival (PFS) and overall survival (OS) were nearly identical between the two groups. Time to platelet recovery was on average 5 days longer after HC (p=0.05) The incidences of acute and chronic GVHD were very low in both groups, in part due to the use of in-vivo T cell depletion. HC transplant with reduced intensity conditioning is a curative treatment for older patients with AML/MDS who lack HLA identical unrelated donors. Despite inclusion of many patients with high risk features, nearly two thirds were estimated to be alive one year after transplant and very few had chronic GVHD. Haplo-cord grafts are more readily available, a potential advantage over MUD grafts in situations where transplant is needed urgently. TableMatched Unrelated DonorHaplo Cord PN6445Age (range)62 (50-73)62 (50-74)AML/MDS45/2041/5 0.01ASBMTLow/Int /High21/6/3015/10/200.7KPS 9090Time to ANC >50010110.1Time to Plt >2018230.05PFS@ 1 Y (95% CI)46 (34-58)41 (26-56)0.6OS@ 1 Y (95% CI)57 (44-70)64 (49-79)0.8Cum Inc TRM @100 d (95% CI)9 (2-16)9 (0-18)0.2Cum Inc TRM @ 1 Y(95% CI)25 (14-36)29 (15-44)0.2Cum Inc Relapse @ 1Y (95% CI)30 (18-42)26 (12-40)0.5Cum Inc AGVHD @ 100 D (95% CI)25 (14-36)29 (13-43)0.7Cum Inc CGVHD @ 1 Y (95% CI)6 (0-12)7 (0-15)0.9 Disclosures van Besien: Miltenyi: Research Funding. Mark:Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Artz:Miltenyi: Research Funding.

scholarly journals A Phase 3 Trial of Thymoglobuline for Prevention of Chronic Gvhd in Transplantation from an HLA-Matched Sibling

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Gi June Min ◽  
Byung Sik Cho ◽  
Sung-Soo Park ◽  
Silvia Park ◽  
Seung-Ah Yahng ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Acute Leukemia ◽  
Randomized Trial ◽  
Board Of Directors ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Phase 3 ◽  
Advisory Committees ◽  
Free Survival ◽  
Matched Sibling

Antihuman T-lymphocyte immune globulin (ATG) was shown to lower the incidence of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor. The type, dose, and duration of ATG treatment is a matter of ongoing controversy in allo-HSCT. Furthermore, there has been no phase 3 study to explore the role of ATG-thymoglobulin for the prevention of cGVHD in allo-HSCT from matched siblings, whereas results from a recent randomized trial of ATG-Fresenius was reported (NEJM 2016). We performed a prospective, single-center, open-label, randomized trial of ATG-thymoglobulin as a part of the conditioning regimen. The primary endpoint was the cumulative incidence (CI) of cGVHD at a 2-year evaluation. A total of 126 patients with acute leukemia were planned to be enrolled and assigned randomly at a 1:1 ratio to receive ATG-thymoglobulin (1.25 mg/kg at three and two days before allo-HSCT) or receive no ATG-thymoglobulin stratified according to the refined Disease Risk Index and conditioning intensity. Both groups were well balanced for NCCN risk, disease type, disease status, and MRD status at HSCT. The current study finally enrolled 120 patients with a median of 560 days of follow-up (range 52 - 1257). The CI of cGVHD in the ATG group (n=60) and non-ATG (n=60) group at 2 years after allo-HSCT was 37.2% and 82.7%, respectively (p&lt;0.001). Moderate-to-severe cGVHD occurred in 11.7% of the ATG group and 47.2% of the non-ATG group (p&lt;0.001). In multivariate analysis, non-AGT group, NCCN favorable to intermediate risk, and reduced intensity conditioning remained significant risk factors for the CI of chronic GVHD. There were no significant between-group differences in the CI of infectious complications, acute GVHD, or other allo-HSCT-related adverse events. In contrast, the ATG group had a significantly increased CI of relapse (CIR) compared with the non-ATG-group (28.8% vs 11.7%, p=0.010), which remained significant in the multivariate analysis. Disease-free survival, overall survival, and GVHD and relapse free survival were similar between the ATG and non-ATG groups. In conclusion, the current study revealed that the use of ATG-thymoglobulin, even at a relatively low dose (2.5 mg/kg), decreases the occurrence of cGVHD at a cost of an increased risk for relapse in the setting of allo-HSCT from matched sibling donors for acute leukemia. The optimal dose, timing, and duration of ATG-thymoglobulin should be investigated further. Disclosures Kim: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sun Pharma.: Research Funding; ILYANG: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Research Funding. Lee:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kim:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AML Global Portal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Hanmi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL&H: Research Funding; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy, Honoraria; Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Yuhan: Consultancy, Honoraria; SL VaxiGen: Consultancy, Honoraria; AbbVie: Honoraria; Sanofi-Genzyme: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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