scholarly journals Reduced Intensity Vs. Standard Conditioning Followed By Allogeneic Stem Cell Transplantation for Patients with MDS or Secondary AML: A Prospective, Randomized Phase III Study of the Chronic Malignancies Working Party of the EBMT (RICMAC-Trial)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 320-320 ◽  
Author(s):  
Nicolaus Kröger ◽  
Ronald Brand ◽  
Dietger Niederwieser ◽  
Uwe Platzbecker ◽  
Kai Hübel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Randomized Trial ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Working Party ◽  
Unrelated Donor ◽  
Reduced Intensity

Abstract Introduction Retrospective studies in MDS/sAML suggest that reducing the intensity of the conditioning regimen prior to allogeneic stem cell transplantation reduces the risk of non-relapse mortality but is associated with a higher risk of relapse, but prospective randomized studies for MDS are lacking so far. Patients and Methods Within the Chronic Malignancies Working Party (CMWP) of EBMT, we performed a prospective randomized trial comparing a busulfan based (Busulfan 8mg/kg orally or equivalent dosis intravenously (iv) plus fludarabin 180mg/m²) reduced intensity conditioning regimen (RIC) and a standard myeloablative busulfan (Busulfan 16mg/kg orally or equivalent dosis iv plus cyclophosphamide 120mg/kg) based regimen (MAC) in patients with MDS or sAML (<20 % blasts). Between May 2004 and December 2012, 129 patients were included from 18 centers and 7 nations and 127 could be analysed. Major inclusion criteria were: MDS (according to FAB: RA, RARS, RAEB, RAEB-t), CMML, and sAML, blasts less than 20 %, matched related or unrelated donor (HLA 8/8, 1 mismatch was allowed), age 18 - 60 years (for unrelated) and 18 - 65 years (for HLA-identical sibling). Included patients were stratified according related vs unrelated donor and blast count < or > than 5%. The primary endpoint of the study was 1 year non-relapse mortality.The median age of the patients was 51.4 years (r.19-64y). Donors were HLA-identical sibling (n=34), matched unrelated (n=59) and mismatched related or unrelated (n=30). The patients were well distributed in both arms regarding age, gender, IPSS risk profile, number of blasts at transplantation, donor source and mismatch donor. Results Leukocyte count more than 1.0 x 10e9/L and platelet count more than 50x10e9/L at day 28 was reached in 90 % and 70% after RIC and in 92% and 77% after MAC, respectively Acute GvHD II-IV was noted in 29% after RIC and 32% after MAC. Chronic GvHD was seen in 61% after RIC and 64% after MAC. The cumulative incidence (CI) of non-relapse mortality (NRM) after 1 year was 17% (95% CI 8-26%) after RIC and 28% (95% CI 16-39%) after MAC (p=0.18). The CI of NRM at 1 year after HLA-identical sibling transplantation was lower than after unrelated transplantation after RIC (0% vs 23%, p=0.06) as well after MAC (17% vs 32%; p=0.18) The CI of relapse at 2 years was 18% (95% CI 8-27%) after RIC and 15% (95% CI 5-24%) after MAC (p=0.5), resulting in a 2 year relapse-free and overall survival of 61% (95% CI 48-73%) and 74% (95% CI 63-86%) after RIC and 56% (95% CI 43-69%) and 61% (95% CI 48-73%) after MAC (p=0.50 and p= 0.07, respectively). Conclusion This prospective randomized trial of EBMT provide evidence that RIC resulted in at least similar 2 year relapse-free and overall survival as in MAC for patients with MDS and sAML and less than 20% blasts. Disclosures Kobbe: Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Medac: Other; Astellas: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Other.

Long-Term Follow-Up of Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3032-3032
Author(s):  
John Kuruvilla ◽  
Qikun Bao ◽  
Mira Goldberg ◽  
Vikas Gupta ◽  
Thomas L. Kiss ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Small Sample ◽  
Unrelated Donor

Abstract Introduction Allogeneic stem cell transplantation (Allo-SCT) remains an option for patients with chronic lymphocytic lymphoma (CLL). Our program employs a strategy using allo-SCT for patients (pts) with high risk disease based on clinical characteristics and prior therapy. We performed a retrospective analysis to examine long-term disease control and treatment toxicity. Methods A total of 52 patients (pts) are included who underwent allo-SCT at our institution between Aug 1989 and Dec 2005. Patients were in a chemosensitive remission at the time of SCT. The conditioning regimen consisted of busulfan (1 mg/kg PO q6h X4 days between 1989–200 and 3.2 mg/kg IV daily X 4days subsequently) and cyclophosphamide 60 mg/kg X 2 days. Cyclophosphamide 60 mg/kg X 2 days and TBI 12 Gy was used for unrelated donor SCT. Reduced intensity conditioning (RIC) SCT were typically performed with Fludarabine 50 mg/m2 for 4 days and 2 Gy TBI. GVHD prophylaxis was with cyclosporine A and methotrexate. Results There were 34 males and 18 females. The median age at the time of transplant was 51 years (range 26 to 65). Histologic subtype was: CLL and/or small lymphocytic lymphoma (SLL); 48 and T-prolymphocytic leukemia (PLL): 4. The median number of prior chemotherapy regimens was 3 (range 1 – 10) and was unavailable in 16. Prior chemotherapies included: anthracycline-based: 24, prior purine analog: 32, prior platinum-based: 8, prior auto-SCT: 1, prior rituximab: 5. The median time from diagnosis to allo-SCT was 58 months (range 5 – 260). 10 pts underwent RIC SCT. Graft source was: matched sibling (MSD) bone marrow (BM): 18, MSD peripheral blood stem cells (PBSC): 20, Mismatch related (MMRD) bone marrow (BM): 1, MRD PBSC: 4, matched unrelated donor (MUD) BM: 8, MUD PBSC: 1. At 5 years, the overall survival of the entire cohort is 51% (95% confidence intervals: 34 – 68%) with two long-term survivors of 14 and 17 years. Treatment-related mortality (TRM) was 20 of 52 pts (38%). 4 pts have relapsed ((8% of total cohort) and non-relapse mortality was 1 pt (2%). Overall survival by intensity of SCT conditioning regimen was not significant (p=0.3). TRM was similar in pts who received fully myeloablative SCT (40% vs. 20% in RICSCT group, p=0.29). Conclusions Acceptable survival post-SCT is possible using an allo-SCT strategy in CLL. However, TRM remains high in this group of heavily pre-treated patients with a median age of over 50 that predominantly received fully myeloablative allo-SCT. Due to small sample size, the potential benefit of reduced TRM with RICSCT cannot be demonstrated. Ideally, allo-SCT should be considered earlier in the course of the disease based on risk stratification utilizing traditional risk factors and modern prognostic factors such as FISH studies and novel markers.

scholarly journals Comparison of Allogeneic Stem Cell Transplantation for Transformed Acute Myeloid Leukemia Derived from MDS, CMML or MPN. a Report of the Chronic Malignancies Working Party of EBMT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3499-3499 ◽  
Author(s):  
Nicolaus Kröger ◽  
Diderik-Jan Eikema ◽  
Liesbeth De Wreede ◽  
Anja van Biezen ◽  
Dietrich W. Beelen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Acute Myeloid

Abstract Introduction Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukemia (CMML) can progress to acute myeloid leukemia (transformed AML). The aim of this EBMT registry study was to compare 3 year outcome in patients with transformed AMLwho received allogeneic stem cell transplantation according to the primary disease. Patients and Methods Within the European Society of Blood and Marrow Transplantation (EBMT) registry, we found 4214 patients (female: 39%, male: 61%) with transformed acute myeloid leukemia, who received allogeneic stem cell transplantation between 2000 and 2014. The primary disease was MDS (n=3541), CMML (n=251) or MPN (n=422). The median age at transplantation was 58 years (range, 18-79) and 59% received a reduced intensity (RIC) conditioning regimen. The majority of the patients received stem cells from an unrelated donor (62%) and 50% were in complete remission at time of transplantation. Within the different groups of primary diseases, MDS patients were more often in CR (53%) than patients with CMML (47%) or MPN (43%). RIC was also more frequently used in MDS patients (65%), than in CMML (64%) and MPN patients (58%). Results After a median follow up of 46.5 months , the estimated 3 year relapse-free (RFS) and overall survival (OS) for the entire group was 36% (95%CI: 34-38%) and 40% (95% CI: 33-42%), respectively.The cumulative incidence of relapse and non-relapse mortality (NRM) was 37% (95% CI: 35-39%) and 27% (95% CI: 26-29%), respectively. In a univariate analysis, patients with primary disease MDS had a significant better 3 year OS and RFS (41% and 37%) than patients with CMML (36% and 30) and MPN (32% and 25%) (p<0.001), due to a significant lower incidence of relapse at 3 years (35% vs 43% vs 50%, p<0.001). Other risk factors for worse OS were higher patient's age (>60 years), unrelated donor, not being in complete remission and low Karnofsky index (< 80%), while T-cell depletion, intensity of the conditioning regimen and TBI as conditioning regimen did not influence survival significantly. In a multivariate analysis for OS beside age >60 years (HR 1.31; 95% CI: 1.13-1.52, p<0.001), unrelated donor (HR 1.12; 95% CI: 1.04-1.23, p=0.005), CMV +/- constellation (HR 1.13; 95%CI: 0.99-1.28, p=0.05), Karnofsky index > 80 (HR 0.66; 95% CI: 0.58-0.74, p< 0.001), non CR (HR 1.50; 95% CI: 1.38-1.63, p<0.001) PBSC as stem cell source (HR 0.86; 95% CI:0.75-0.97, p=0.02) and transformed AML from MPN (HR 1.24; 95% CI: 1.085-1.41, p=0.002) remained a significant factor in comparison to transformed AML from MDS, while outcome of transformed AML from CMML did not reach statistical significance in comparison to MDS (HR 1.10; 95% CI: 0.933-1.30, p=0.25) Conclusion This large EBMT registry study demonstrates that the primary underlying disease influence outcome of transformed acute myeloid leukemia in addition to other risk factors. Disclosures Kröger: Novartis: Honoraria, Research Funding. Maertens:Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Amgen: Consultancy. Kobbe:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation in Older Patients with Acute Myeloid Leukemia: Analysis of the Francophone Society for Stem Cell Transplantation and Cell Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3447-3447
Author(s):  
Regis Peffault De Latour ◽  
Matthieu Resche-Rigon ◽  
Didier Blaise ◽  
Johan Maertens ◽  
Patrice Ceballos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Sibling Donor

Abstract Background: Nowadays acute myeloid leukemia (AML) patients above the age of 60 years are often candidates for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT). However, little is known about the outcomes of HSCT in this particular population, due to the low number of HSCT with robust follow-up, the heterogeneity between centers, as well as reports usually mixing AML and other diseases such as myelodysplastic syndrome. We used the database of the Francophone society for stem cell transplantation and cellular therapy to address this question in a large cohort of patients in a recent time period. Patients and methods: 1167 consecutive patients aged ≥60 years with AML in complete remission (CR), transplanted between January 1st 2006 and January 1st 2016, reported to ProMISe (Project Manager Internet Server), an internet-based system shared by 36 Francophone transplantation centers, were reviewed. Classical post-HSCT endpoints were studied such as engraftment, acute and chronic graft-versus-host disease (GvHD), non-relapse mortality (NRM), relapse rate, leukemia free survival (LFS) as well as overall survival (OS). Cytogenetic risk was assessed according to the European Leukemia Network 2017 for patients in first complete remission. Data were analyzed using proportional hazards models and proportional sub-distribution hazards models in presence of competing risks. Results: Patients' Characteristics are detailed in Table 1. The median age at HSCT was 62.9 years (Interquartile range -IQR 61.9-66.1). Patients aged ≥60 years but less of 65 represented 63.8% of the population with 68.2% of patients transplanted in the recent period (2011-2016). Most patient had de novo AML (91.6%), in first CR (76.9%) with intermediate risk (83.8%) according to ELN-2017 classification. A matched unrelated donor (MUD) was used in 45 % of transplants and the majority of patients received peripheral blood stem cells (83.7%). Half of the patients received fludarabine and 2 days busulfan as conditioning regimen. The majority of patients (70.9%) received anti-thymocyte globuline (ATG). Engraftment occurred in 1089 patients (93.3%; 95%CI, 91.9-94.8). Day 100 cumulative incidence of grade II-IV acute GVHD was 24.6% (15.7% grade II; 5.8% grade III; 3% grade IV). At last follow up, 378 patients had developed chronic GVHD (severe in 37.2% of them; 95%CI, 34.0-40.3). With a median follow-up of 3.5 years (95%CI, 3.1-3.7 years), overall survival (OS) and LFS probabilities at 3 years were 50.7% (95%CI, 47.7-54.0) and 44.8% (95%CI, 41.8-48.1), respectively. In multivariable analysis, the only factor associated with worse OS was the use of a mismatched unrelated donor compare to MUD [Hazard Ratio (HR): 1.35 (95% CI, 1.01 to 1.80), p=0.04]. At 3 years, relapse incidence was 34.4% (95% CI, 31.5-37.4). The use of a sibling donor compared to MUD [Sub-distribution Hazard Ratio (SHR): : 1.49 (95% CI, 1.19 to 1.87), p<0.001], poor risk AML in CR1 according to ELN classification [SHR: 1.49 (95% CI, 1.10 to 2.02), p=0.01], as well as the use of ATG in the conditioning regimen [SHR: 1.57 (95% CI, 1.21 to 2.05), p<0.001] were associated with a higher risk of relapse. During the study, 534 patients died (main causes of death was relapse, 53%); leading to a CI of NRM of 20.7% at 3 years (95%CI, 18.2-23.2). A karnofsky score above 90% [SHR: 0.74 (95% CI, 0.56 to 0.98), p=0.04] and the use of a sibling donor compare to MUD [SHR : 0.43(95% CI, 0.30 to 0.63), p<0.001] were associated with reduced NRM. Conclusion: With more than 3 years follow-up, which is long enough for our results to be considered to be robust, the use of a mismatched unrelated donor was the only factor associated with worse overall survival in this population of AML patients aged of 60 years or more. Relapse appeared as the first cause of death, independently related to AML ELN poor risk classification, but also to the use of a sibling donor and of ATG in the conditioning regimen. This study highlights the major role of alloreactivity in this particular population, where modulation of T-cell alloreactivity as well as donor choice should be urgently addressed in well-designed prospective trials. Disclosures Peffault De Latour: Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer Inc.: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

Allogeneic Stem Cell Transplantation from Unrelated Donors after Reduced Intensity Conditioning in Patients with MDS/sAML. A Report from the Chronic Leukemia Working Party (CLWP) of the EBMT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5176-5176 ◽  
Author(s):  
Nicolaus Kroeger ◽  
Ronald Brand ◽  
Rodrigo Martino ◽  
Philippe Guardiola ◽  
Anja van Biezen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Working Party ◽  
Stem Cell Source ◽  
Unrelated Donors

Abstract We analysed the results of 67 patients with MDS/sAML who were transplanted with allogeneic stem cell transplantation from unrelated donors after a reduced intenisity conditioning and reported to the EBMT. The median age was 52 years (range 17–70 years) and stem cell source was bone marrow (n = 30) or peripheral blood progenitor cells (n = 33).. The graft was HLA matched in 57 patients while 8 patients received SCT from HLA-mismatched donor. The MDS classification was as follows: RA/RARS: n=8, RAEB/CMML: n = 14, RAEB-t/sAML: n = 22. The conditioning regimen consisted of fludarabine/busulfan (n=15), fludarabine/melphalan (n=6), fludarabine and TBI (n=8) or fludarabine and others (n=36)At time of transplantation only 12 (18%) were in first complete remission. The Kaplan-Meier estimates of the probability of 2 years overall and disease free survival were 33 % (95% CI: 21–45 %) and 24 % (95% CI: 12–36 %), respectively. The probability of relapse at two years was 58 % (95% CI: 40–76 %) and of one year treatment-related mortality 37 % (95% CI %: 23–51 %). In an univariate analysis assessing source of stem cells, age, disease type, T-cell depletion, and HLA-matching no factor was significant for OS, EFS, TRM and Relapse. Allogeneic stem cell transplantation after a reduced intensified conditioning followed by unrelated SCT seems to be a feasible approach in those patients who were no candidates for a standard conditioning but is associated with a considerable number of relapses.

Impact of Dendritic Cell CD16+ Recovery on Outcome after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1409-1409
Author(s):  
Carme Talarn ◽  
Alvaro Urbano-Ispizua ◽  
Rodrigo Martino ◽  
Montse Batlle ◽  
Concha Herrera ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Critical Role ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Poor Prognostic Factor ◽  
Reduced Intensity

Abstract Dendritic cells (DCs) play a critical role in the regulation of alloimmune responses. Therefore, the number and function of these cells after allogeneic stem cell transplantation (allo-SCT) might influence patients’ outcome, an aspect scarcely investigated, particularly in the setting of reduced-intensity conditioning transplants (allo-RIC). Against this background, we studied DCs recovery in 92 patients (median age 50, range 17–67; male 57%), undergoing allo-RIC from HLA identical donors in five Spanish institutions between October 2002 and December 2004. Median follow up was 250 days (range, 25–708). Conditioning regimen consisted on fludarabine 150 mg/m2 + melphalan 140 mg/m2 for lymphoid malignancies (n=54), and fludarabine 150 mg/m2 + busulphan 10 mg/kg for myeloid malignancies (n=38); 71 (90%) patients had advanced disease. Peripheral blood samples were obtained at 1, 3, 6 and 12 months after transplant. DCs were identified as positive for HLA-DR and negative for lineage markers (CD3, CD14, CD19, and CD56). The expression of CD33, CD123 and CD16 was used to identify DC1, DC2 and DC CD16+ subsets, respectively; the immunophenotypic analysis being centralized at a single institution. The most significant association with clinical outcome was found with DC CD16+ levels at three months after transplantantation. Thus, at that time point, patients with a DC CD16+ count lower than the median (&lt;1.5×104/mL) had a significantly higher incidence of relapse (59% vs. 45%; p=0.04), more transplant related mortality (30% vs. 0%; p=0.01), worse event free survival (EFS) (24% vs. 51%; p=0.002) and overall survival (0% vs. 55%; p=0.002). Only two factors were associated with worse EFS in the multivariate analysis: autologous transplantation before allo-RIC (RR 6.5, 95%CI 1.6–26.2; p=0.008), and DC CD16+ count lower than the median at +3m (RR 13.1; 95% CI 1.7–100.5; p=0.01). In conclusion, this study shows that besides a well-known poor prognostic factor (i.e., prior autologous transplantation) a low DC CD16+ count at three months after allo-RIC is associated with a poorer outcome, this probably reflecting impaired immunosurveillance mechanisms.

Results of a Two-Arm Phase II Clinical Trial Using Post-Transplantation Cyclophosphamide for Prevention of Graft-Versus-Host Disease in Haploidentical and Mismatched Unrelated Donors Hematopoietic Stem-Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 152-152 ◽  
Author(s):  
Sameh Gaballa ◽  
Isabell Ge ◽  
Riad O. El Fakih ◽  
Jonathan E. Brammer ◽  
Sa A. Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Disease Risk ◽  
Risk Index ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Equity Ownership ◽  
Reduced Intensity

Abstract Allogeneic stem cell transplantation offers curative therapy for many patients (pts) with high-risk hematologic malignancies. Donor availability remains a major limitation for many pts. The introduction of high-dose post-transplant cyclophosphamide (PTCy) has significantly improved the outcomes of pts undergoing haploidentical (HAPLO) stem cell transplants. The choice between a HAPLO or a one-antigen HLA mismatched unrelated donor (9/10 MUD) for pts lacking an HLA-matched donor remains unclear. Methods: We conducted a prospective non-randomized phase 2 clinical trial with two parallel arms, HAPLO (n=60) and 9/10 MUD (n=46) transplants, for pts with advanced hematologic malignancies or aplastic anemia who lacked an HLA-matched unrelated donor type at 10 loci (HLA-A, -B, -C, -DRB1, and -DQB1) using a MEL-based reduced-intensity conditioning regimen. The regimen included a single intravenous dose of MEL 140 mg/m2 (day -7), thiotepa 5 mg/kg (day -6), and four daily IV doses of fludarabine 40 mg/m2 (day -5 to day -2) (FM140). Thiotepa was intermittently available and was replaced by total body irradiation at a dose of 2 Gy on day -1. Pts >55 years (yr) old or with significant comorbidities received a lower MEL dose (100 mg/m2) (FM100). All pts with CD20-positive lymphoma received rituximab (375 mg/m2) on days -13, -6, +1 and +8. GVHD prophylaxis consisted of PTCy 50 mg/kg on day +3 and +4, and tacrolimus and mycophenolate for 6 and 3 months (mo), respectively. The stem cell source was unmodified bone marrow for both arms. Results: Patient characteristics are shown in Table 1. The median follow-up duration was 24 mo in the HAPLO arm and 29 mo in the 9/10 MUD arm. The cumulative incidence (CI) of neutrophil (ANC) recovery at day 45 was 95% and 98% in the HAPLO and 9/10 MUD arm, respectively. The median time to ANC recovery was 18 days in both arms; the median time to platelet recovery was 25 days in the HAPLO arm and 28 days in the 9/10 MUD arm. Primary graft failure developed in two pts in the HAPLO arm (one due to anti-donor HLA antibodies) and one patient in the 9/10 MUD arm. One pt in both arms developed mixed donor chimerism at day 100; otherwise, all pts in both arms achieved full (>95%) donor chimerism. Bone marrow was the graft source in all pts except 2 in the HAPLO arm and 8 in the 9/10 MUD arm who received a peripheral blood graft. The 1-yr overall and progression free survival were 70% and 60%, respectively, in the HAPLO arm (Fig. 1A) and 60% and 47%, respectively, in the 9/10 MUD arm (Fig. 1B). Day 100 CI of grade II-IV aGVHD and III-IV aGVHD were 28% and 3%, respectively, in the HAPLO arm versus 33% and 13%, respectively, in the 9/10 MUD arm; the 2-yr CI of chronic extensive GVHD was 13% and 14% in the two groups, respectively. The 1-yr CI of non-relapse mortality was 21% in the HAPLO arm and 31% in the 9/10 MUD arm, while the 1-yr relapse rate was 19% and 25% in the two groups, respectively. Conclusions: This study establishes PTCy, tacrolimus, and mycophenolate as an effective regimen for GVHD prevention in mismatched transplantation using both haploidentical and mismatched unrelated donor sources. Melphalan-based reduced-intensity conditioning is an effective regimen for a broad range of hematologic malignancies. Prospective randomized studies comparing haploidentical and unrelated donor sources are needed. Table 1. HAPLO (n=60) 9/10 MUD (n=46) Median Age, years (Range) 45 (20-63) 51 (20-64) Sex (M/F) 29/31 23/23 KPS ³90 53 (88%) 40 (87%) <90 7 (12%) 6 (13%) HCT-CI 0-3 50 (83%) 38 (83%) >3 10 (17%) 8 (17%) Disease Risk Index* Very high 5 (8%) 3 (7%) High 18 (30%) 15 (33%) Intermediate 29 (48%) 12 (26%) Low 8 (13%) 12 (26%) NA 0 4 (9%)** Conditioning Regimen FM100 20 (33) 18 (39%) FM140 40 (67%) 28 (61%) Diagnosis AML/MDS 33 (55%) 18 (39%) ALL 7 (11%) 5 (11%) Lymphoma 10 (17%) 13 (28%) Others 10 (17%) 10 (22%) Disease Stage Acute Leukemia CR1/CR2 24 (66%) 9 (56%) CR3 or higher/ CRpx 6 (17%) 5 (31%) Active disease 6 (17%) 2 (13%) Lymphoma CR 3 (30%) 8 (62%) PR 5 (50%) 3 (23%) Chemoresistant 2 (20%) 2 (15%) *Disease Risk Index by Armand et al; xCRp: Complete Remission with incomplete count recovery; **Patients had aplastic anemia. Figure 1. Figure 1. Disclosures Brammer: Celgene: Research Funding. Lee:Ziopharm: Equity Ownership; Cyto-Sen: Equity Ownership; Intrexon: Equity Ownership. Rezvani:Pharmacyclics: Research Funding. Alousi:Therakos, Inc: Research Funding.

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