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Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia
Nagler, A., Kanate, A. S., Labopin, M., Ciceri, F., Angelucci, E., Koc, Y., Gulbas, Z., Arcese, W., Tischer, J., Pioltelli, P., et al
Haematologica. 2020
Abstract
Graft-versus-host disease (GVHD) prophylaxis for unmanipulated haploidentical hematopoietic cell transplantation (haplo-HCT) include post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG). Utilizing EBMT registry, we compared ATG versus PTCy based GVHD prophylaxis in adult acute lymphoblastic leukemia (ALL) patients undergoing haplo-HCT. Included were 434 patients; ATG (n=98) and PTCy (n=336). Median follow-up was ~2 years. Baseline characteristics were similar between the groups except that the ATG-group was more likely to have relapsed/refractory ALL (P=0.008), non-TBI conditioning (P<0.001), peripheral blood graft source (P=<0.001) and transplanted at an earlier time-period (median year of HCT 2011 vs. 2015). The 100-day grade II-IV and III-IV acute-GVHD was similar between ATG and PTCy, as was 2-year chronic-GVHD. On multivariate analysis (MVA), leukemia-free survival (LFS) and overall survival (OS) was better with PTCy compared to ATG prophylaxis. Relapse incidence (RI) was lower in the PTCy group (P=0.03), while non-relapse mortality (NRM) was not different. Advanced disease and lower performance score were associated with poorer LFS and OS and advanced disease with inferior GVHD-free/relapse-free survival (GRFS). Peripheral grafts were associated with higher GVHD compared to bone marrow grafts. In ALL patients undergoing unmanipulated haplo-HCT, PTCy for GVHD prevention resulted in lower RI and improved LFS and OS compared to ATG.
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Comparison of Haploidentical Bone Marrow versus Matched Unrelated Donor Peripheral Blood Stem Cell Transplantation with Post-transplant Cyclophosphamide in Patients with Acute Leukemia
Nagler, A., Labopin, M., Dholaria, B., Angelucci, E., Afanasyev, B., Cornelissen, J. J., Sica, S., Meijer, E., Ciceri, F., Van Gorkom, G., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020
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Editor's Choice
Abstract
BACKGROUND Post-transplant cyclophosphamide (PTCy) is increasingly being utilized as a principle graft-versus-host disease (GvHD) prophylaxis strategy in allogeneic hematopoietic cell transplantation (allo-HCT). A haploidentical (haplo) or matched unrelated donor (UD) are valid options in the absence of a matched related donor. EXPERIMENTAL DESIGN We compared the outcomes of patients with acute leukemia who underwent haplo bone marrow (haplo-BM, N=401) versus UD mobilized peripheral blood stem cells (UD-PB, N=192) transplantation in the setting of PTCy. RESULTS The median follow-up duration was 36 months in the haplo-BM group and 16.6 months in the UD-PB group, respectively (p<0.01). Myeloablative conditioning was used in 64.6% and 42.7% of haplo-BM and UD-PB patients, respectively (p<0.01). Cumulative incidence of neutrophil engraftment at day 30 was 87% in haplo-BM versus 94% in UD-PB, respectively (p =0.21). In the multivariate analysis, the risk of grade II-IV acute GvHD (HR=0.53, p=0.01) and chronic GvHD (HR=0.50, p=0.02) was significantly lower in the haplo-BM group compared to the UD-PB group. There was no significant difference between the study groups, with respect to relapse incidence, non-relapse mortality, leukemia-fee survival, overall survival or, GvHD-free, relapse-free survival. CONCLUSION The use of a haplo donor with a BM graft resulted in a lower incidence of GvHD compared to a UD-PB stem cell graft in the setting of PTCy for patients with acute leukemia. However, differences in GvHD did not translate into the difference in survival outcomes. Based upon these data, UD-PB or haplo-BM should be considered equally acceptable sources for allo-HCT.
PICO Summary
Population
Patients with acute leukaemia (n=593)
Intervention
Haploidentical bone marrow transplantation with post-transplant cyclophosphamide (PTCy) (haplo-BM, n=401)
Comparison
Matched unrelated donor transplantation with mobilised peripheral blood stem cells (UD-PB, n=192)
Outcome
The median follow-up duration was 36 months in the haplo-BM group and 16.6 months in the UD-PB group, respectively. Myeloablative conditioning was used in 64.6% and 42.7% of haplo-BM and UD-PB patients, respectively. Cumulative incidence of neutrophil engraftment at day 30 was 87% in haplo-BM versus 94% in UD-PB, respectively. In the multivariate analysis, the risk of grade II-IV acute GvHD and chronic GvHD was significantly lower in the haplo-BM group compared to the UD-PB group. There was no significant difference between the study groups, with respect to relapse incidence, non-relapse mortality, leukemia-fee survival, overall survival or, GvHD-free, relapse-free survival.
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Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation
Al Malki, M. M., Yang, D., Labopin, M., Afanasyev, B., Angelucci, E., Bashey, A., Socie, G., Karduss-Urueta, A., Helbig, G., Bornhauser, M., et al
Blood advances. 2020;4(9):2073-2083
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Editor's Choice
Abstract
We compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.
Clinical Commentary
Dr. Julia Wolf, University Hospitals Bristol and Weston NHS Foundation Trust
What is known?
Allogeneic stem cell transplant is a potentially curative treatment option for adults with acute lymphoblastic leukaemia (ALL). Transplant outcomes are, amongst other factors, dependent on optimal donor selection; despite a plethora of recent advances, donor availability is an area of unmet need for many patients. A fully HLA matched sibling donor is the preferred donor choice but is available in <30% of patients. Several studies have shown that comparable results can be achieved with a fully matched unrelated donor (MUD), but availability can be as low as 20% in non-Caucasian individuals. Haploidentical donor options are available for the vast majority of patients but historically their utility was limited by high rates of GvHD, treatment related morbidity and mortality and graft rejection. The addition of post-transplant cyclophosphamide (PtCy), calcineurin inhibitors (CNI) and mycofenolate mofetil (MMF) as GvHD prophylaxis has reduced these risks and is now a frequently employed approach for haploidentical haematopoietic stem cell transplant (HaploSCT) making it an attractive alternative to conventional donor transplant.
Several recent studies have compared MUD alloSCT and HaploSCT approaches in ALL in recent years. Most notably this has included an analysis of the European Bone Marrow Transplant (EBMT) group registry which included 1234 patients with ALL and shows comparable outcomes between HaploSCT and MUD alloSCT.
What did this paper set out to examine?
This retrospective multicentre cohort study aims to compare outcomes of HaploSCT & PtCy with MUD alloSCT in ALL in terms of engraftment, acute and chronic graft versus host disease (GvHD) incidence and severity, relapse free survival (RFS), non-relapse mortality (NRM) and overall survival (OS).
It is the first study to explicitly compare haploidentical allogeneic stem cell transplant (HaploSCT) with matched unrelated donor allogeneic stem cell transplant (MUD alloSCT) in terms of conditioning intensity, Philadelphia chromosome status and graft source. It also provides additional extensive, multinational data with matched pair analysis on outcomes of patients in both groups.
What did they show?
The authors compared data from 1461 adult patients (HaploSCT = 487 vs MUD = 974). Data from two separate registries was used: the EBMT registry alone was used for MUD alloSCT while the Haploidentical Transplant and Cellular Therapy Research Consortium (TCT-RC) was used in combination with Acute Leukaemia Working Party subgroup of the EBMT registry data for assessment of HaploSCT. The reason for using two databases is not explicitly stated although it is believed that this was done to increase sample size in the HaploSCT cohort.
Patients >18 years old with ALL over a 13.5-year period from January 2005 to June 2018 receiving their first alloSCT were included in the analysis. Exclusion criteria were fairly selected. GvHD prophylaxis was with PtCy, CNI and MMF in the HaploSCT group and with CNI and methotrexate or MMF in the MUD group. 64% of MUD patients also received ATG. Cohorts were matched at 1:2 (HaploSCT : MUD) for sex, cytogenetic risk, Philadelphia chromosome status, disease stage and intensity of conditioning (reduced intensity vs myeloablative). Statistical analysis was appropriate for the question to be answered.
RESULTS: HaploSCT and MUD alloSCT were comparable in terms of neutrophil engraftment, RFS and OS regardless of conditioning intensity, Philadelphia chromosome status and graft source. 3-year OS was 44% in the HaploSCT group vs 51% in the MUD group using myeloablative conditioning (p=5.56) with rates of 43% (HaploSCT) and 42% (MUD) for reduced intensity conditioning (p=5.6).
The overall incidence of acute and chronic GvHD was similar between the groups but there was an increased incidence in grade III-IV GvHD in HaploSCT when peripheral blood stem cells were used. Additionally, mortality form GvHD was higher in the MUD group. This is in keeping with results reported in the literature.
What are the implications for practice and for future work?
HaploSCT is becoming an increasingly attractive option for patients without matched sibling transplant. The comparable overall survival and now much more manageable GvHD risk will afford a previously difficult to manage cohort of patients a further option of curative treatment.
This study adds to the growing evidence base but did have some limitations. Firstly, the study is retrospective and uses registry-based data. While the registries used are of high quality, there are inherent concerns about missing data points and differences between the two databases used. The authors agreed that the variability of the condition regimes used added a further layer of complexity.
Prospective data with intention to treat analysis is required to further assess the comparability of HaploSCT and MUD for ALL patients.
PICO Summary
Population
Adult patients with acute lymphoblastic leukaemia (n=1461)
Intervention
HSCT from a haploidentical donor (n = 487)
Comparison
HSCT from a matched unrelated donor (n = 974)
Outcome
In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88%. The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% for aGVHD and 29% vs 31% for cGVHD; RIC, 31% vs 30% for aGVHD and 24% vs 29% for cGVHD. Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD. Corresponding rates after RIC were 43% and 42%.
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Haploidentical transplant with post-transplant cyclophosphamide for T-cell acute lymphoblastic leukemia: a report from the EBMT acute leukemia working party
Bazarbachi, A., Labopin, M., Angelucci, E., Gulbas, Z., Ozdogu, H., Arat, M., de Rosa, L., Pastano, R., Pioltelli, P., Montserrat, R., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
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Editor's Choice
Abstract
Allogeneic hematopoietic cell transplantation (HCT) is recommended in high-risk patients with T cell acute lymphoblastic leukemia (T-ALL). For patients with no HLA identical donor, haploidentical transplantation (haplo-HCT) is becoming the leading source of stem cell donation. However, data is scarce on predictive factors for outcome in that setting. We identified 122 adults (20% female; median age 31 years; range 18-68) with T-ALL who received a haplo-HCT with post-transplant cyclophosphamide (ptCy) between 2010 and 2017. Median follow-up of living patients was 23 months. The 2-year relapse incidence and non-relapse mortality were 45% and 21%, respectively. The 2-year leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 34%, 42% and 27%, respectively. The 2-year LFS and OS were highly influenced by disease status at transplant, being 49% and 55% respectively for first complete remission (CR1), 34% and 50% respectively for CR2, 8% and 12% respectively for patients with active disease. On multivariate analysis, only disease status affected LFS and OS. Transplantation in CR2 negatively affected LFS, whereas active disease at haplo-HCT negatively affected LFS and OS. In conclusion, haplo-HCT with ptCy produced encouraging results in this challenging disease, particularly when performed in CR. Despite the limitation of the small sample size, results were not affected by the type of conditioning, questioning the need for total body irradiation based-myeloablative conditioning (TBI-MAC) in that setting.
PICO Summary
Population
Adults with T cell acute lymphoblastic leukaemia (n=122)
Intervention
Haploidentical transplantation with post-transplant cyclophosphamide (ptCy)
Comparison
None
Outcome
The 2-year relapse incidence and non-relapse mortality were 45% and 21%, respectively. The 2-year leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 34%, 42% and 27%, respectively. The 2-year LFS and OS were highly influenced by disease status at transplant, being 49% and 55% respectively for first complete remission (CR1), 34% and 50% respectively for CR2, 8% and 12% respectively for patients with active disease. On multivariate analysis, only disease status affected LFS and OS. Transplantation in CR2 negatively affected LFS, whereas active disease at haplo-HCT negatively affected LFS and OS.
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Unmanipulated haploidentical versus HLA-matched sibling allogeneic hematopoietic stem cell transplantation in relapsed/refractory acute myeloid leukemia: a retrospective study on behalf of the ALWP of the EBMT
Battipaglia, G., Boumendil, A., Labopin, M., Ciceri, F., Tischer, J., Stelljes, M., Ehninger, G., Beelen, D., Finke, J., Van Lint, M. T., et al
Bone marrow transplantation. 2019
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Editor's Choice
Abstract
Refractory or relapsed acute myeloid leukemia (R/R-AML) has poor prognosis. Allogeneic hematopoietic stem-cell transplantation (HSCT) may provide cure in this scenario. We compared outcomes of HSCT from HLA-identical (HLA-id, n = 1654) sibling or haploidentical (Haplo, n = 389) donors in patients with R/R-AML, performed during the period 2007-2015. The Haplo group included patients receiving an unmanipulated graft (post-transplant cyclophosphamide, n = 278; in vivo T-cell depletion, n = 95; or both, n = 16). Median age at HSCT was 52 (range 18-74) years. Median follow-up was 16 and 22 months for HLA-id sibling and Haplo recipients, respectively (p = 0.11). Compared to MSD, Haplo HSCT were performed more recently (2013 vs 2011, p < 0.01), at longer interval from diagnosis (7 vs 5 months, p < 0.01), more frequently using bone marrow as stem cell source (47% vs 8%, p < 0.01) and with a reduced intensity conditioning regimen (50% vs 43%, p = 0.03). Engraftment was higher (93% vs 83%, p < 0.01) in HLA-id sibling. In multivariate analysis, Haplo HSCT was associated with lower GVHD/relapse-free survival, inferior LFS and OS and higher NRM, mainly due to a higher rate of infections (41% vs 25%, p < 0.01). For R/R-AML, HLA-id sibling donors remain the gold standard, when available, due to higher mortality in Haplo without significant gain in disease control.
PICO Summary
Population
Adults with refractory or relapsed AML, reported to the EBMT registry in the period 2007-2015
Intervention
Unmanipulated haploidentical allogeneic stem cell transplantation (n=389)
Comparison
HLA identical sibling allogeneic stem cell transplantation (n=1654)
Outcome
Engraftment was higher (93% vs 83%, p < 0.01) in HLA-id sibling. In multivariate analysis, Haplo HSCT was associated with lower GVHD/relapse-free survival, inferior LFS and OS and higher NRM, mainly due to a higher rate of infections.
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Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT
Shem-Tov, N., Peczynski, C., Labopin, M., Itala-Remes, M., Blaise, D., Labussiere-Wallet, H., Socie, G., Kroger, N., Mielke, S., Afanasyev, B., et al
Leukemia. 2019
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Editor's Choice
Abstract
Unmanipulated haploidentical allogeneic stem cell transplantation (Allo-SCT) has become an attractive alternative for patients lacking HLA-matched sibling or unrelated donors. However, data of outcome in ALL is still scarce. The outcomes of 1234 adult patients with ALL in first complete remission (CR1) who underwent Allo-SCT between 2007 and 2016 were analyzed. Comparison was done between haploidentical donor (Haplo) (136 patients), matched unrelated donor (MUD 10/10) (809 patients), and mismatched unrelated donor (MMUD 9/10) (289 patients). Univariate analysis showed similar outcomes in Haplo, MUD, and MMUD, including OS, LFS, RI, NRM, AGVHD, and CGVHD. In multivariate analysis, Haplo was not associated with worse outcomes compared to MUD 10/10 and MMUD 9/10. Indeed, compared to Haplo, the hazard ratio (HR) for LFS, OS, RI, NRM, AGVHD, and CGVHD were 1.1 (p = 0.7), 0.9 (p = 0.4), 1.35 (p = 0.2), 0.7 (p = 0.2), 1.1 (p = 0.8), and 0.8 (p = 0.2) for MUD, respectively, and 1.1 (p = 0.8), 1.0 (p = 1.0), 1.2 (p = 0.3), 0.8 (p = 0.4), 1.2 (p = 0.3), and 0.9 (p = 0.6) for MMUD, respectively. In conclusion, outcomes of adult patients with ALL in CR1 receiving Haplo Allo-SCT are comparable to MUD or MMUD transplants. Haplo should be considered as a clinically relevant option for patients lacking a matched sibling donor.
PICO Summary
Population
Adult patients with acute lymphoblastic leukaemia in first complete remission (n=1234)
Intervention
Haploidentical transplantation (n=136)
Comparison
Matched unrelated donor (n=809) or Mismatched unrelated donor (n=289)
Outcome
Univariate analysis showed similar outcomes in Haplo, MUD, and MMUD, including OS, LFS, RI, NRM, AGVHD, and CGVHD. In multivariate analysis, Haplo was not associated with worse outcomes compared to MUD 10/10 and MMUD 9/10.
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Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide
Shimoni, A., Labopin, M., Lorentino, F., Van Lint, M. T., Koc, Y., Gulbas, Z., Tischer, J., Bruno, B., Blaise, D., Pioltelli, P., et al
Leukemia. 2018
Abstract
Haploidentical stem cell transplantation with T cell-replete grafts and post-transplant cyclophosphamide (PTCy) is increasingly used with encouraging outcome. Natural killer (NK) cell alloreactivity, predicted by missing killer cell immunoglobulin-like receptor (KIR) ligands in the recipient that are present in their donor improves outcome of T cell-depleted haploidentical transplants. We explored the role of KIR ligand mismatching in 444 acute leukemia patients after T cell-replete transplants with PTCy. Thirty-seven percent of all patients had KIR ligand mismatching. Patients were in first remission (CR1) (39%), second remission (CR2) (26%), or active disease (35%). Stem cell source was peripheral blood (PBSC, 46%) or bone marrow (54%). The 2-year relapse, non-relapse mortality (NRM), and survival rates were 36.0% (95% confidence interval (CI), 31.4-40.7), 23.9% (20.0-28.0), and 45.9% (40.8-51.0), respectively. Multivariate analysis identified acute myeloid leukemia compared with acute lymphoblastic leukemia (hazard ratio (HR) 0.55, P = 0.002), female gender (HR 0.72, P = 0.04), and good performance status (HR 0.71, P = 0.04) as factors associated with better survival, while advanced age (HR 1.13, P = 0.04), active disease (HR 3.38, P < 0.0001), and KIR ligand mismatching (HR 1.41, P = 0.03) as associated with worse survival. KIR ligand mismatching was associated with a trend for higher relapse but not with graft-versus-host disease or NRM. The KIR ligand-mismatching effect was more prominent in patients given PBSC. In conclusion, there is no evidence that KIR ligand mismatching results in better outcome in the PTCy setting.
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Haploidentical versus unrelated allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukemia: A report of 1578 patients from the Acute Leukemia Working Party of EBMT
Brissot, E., Labopin, M., Ehninger, G., Stelljes, M., Brecht, A., Ganser, A., Tischer, J., Kroger, N., Afanasyev, B., Finke, J., et al
Haematologica. 2018
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Editor's Choice
Abstract
Primary refractory or relapsed acute myeloid leukemia is associated with dismal prognosis. Allogeneic stem cell transplantation is the only therapeutic option that offers prolonged survival and cure in this setting. In the absence of a matched sibling donor, transplantation from unrelated 10/10 or 9/10 and haploidentical donors are potential alternatives. The current study aimed to compare the outcomes of acute myeloid leukemia patients with active disease who received allogeneic stem cell transplantation from a haploidentical donor with post-transplant cyclophosphamide (n=199) versus an unrelated donor 10/10 (n=1111) and versus unrelated donor 9/10 (n=383) between 2007 and 2014 and reported to the EBMT registry. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups. The leukemia- free survival at 2 years was 22.8% for haploidentical donor, 28% for unrelated donor 10/10 and 22.2 % for unrelated donor 9/10 (p=NS). In multivariate analysis, there was no significant difference in leukemia-free survival, overall survival, relapse incidence, non-relapse mortality, neither graft-versus-host-disease-free relapse-free survival between the 3 groups. Two predictive factors were associated with a higher relapse incidence: first or second relapse compared to primary refractory acute myeloid leukemia and poor cytogenetics. Allogeneic stem cell transplantation may rescue about 25 % of acute myeloid leukemia patients with active disease. Importantly, the outcomes of transplants from haploidentical donor were comparable to those from 10/10 and 9/10 unrelated donor. Therefore, haploidentical donor is a valid option for acute myeloid leukemia patients with active disease.
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Unmanipulated haploidentical stem cell transplantation in adults with acute lymphoblastic leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT
Santoro, N., Ruggeri, A., Labopin, M., Bacigalupo, A., Ciceri, F., Gulbas, Z., Huang, H., Afanasyev, B., Arcese, W., Wu, D., et al
Journal of hematology & oncology. 2017;10(1):113
Abstract
BACKGROUND Allogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors. METHODS We performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014. RESULTS Median age at haplo-SCT was 32 years and median follow-up, 31 months. Forty-four percent of the patients were in first complete remission (CR1). Stem cell source was the bone marrow (BM) for 43% and peripheral blood (PB) for 57% of patients. Myeloablative conditioning (MAC) was used for 66% and reduced intensity regimen (RIC) for 34% of patients. GVHD prophylaxis was based on post-transplant cyclophosphamide (PT-Cy) for 118 (57%) or on anti-thymocyte-globulin (ATG) for 90 (43%) plus standard prophylaxis. One hundred eighty-four (92%) patients achieved engraftment. Cumulative incidence (CI) of grade II-IV acute-graft-versus-host-disease (GVHD) was 31%, grade III-IV 11%, and chronic GVHD 29%. Non-relapse mortality (NRM) and relapse-incidence (RI) were 32 and 37%, respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free-survival (GRFS) at 3 years were 33, 31, and 26%. For patients in CR1, OS, LFS, and GRFS were 52, 47, and 40%, respectively. Disease status was the main factor associated with transplant outcomes. Use of BM was independently associated with improvement in NRM, acute GVHD, GRFS, LFS, and OS. CONCLUSIONS Unmanipulated haplo-SCT may be considered a valid option for adult patients with high-risk ALL lacking HLA identical donor preferably in early disease status.
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Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT
Rubio, M. T., Savani, B. N., Labopin, M., Piemontese, S., Polge, E., Ciceri, F., Bacigalupo, A., Arcese, W., Koc, Y., Beelen, D., et al
Journal of hematology & oncology. 2016;9:25
Abstract
BACKGROUND Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. METHODS We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n=271) and MAC (n=425). Regimens were classified as MAC or RIC based on published criteria. RESULTS A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25%) patients in RIC and 125 (32%) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92%; p=0.58) and day 100 grade II to IV acute GVHD (24 vs. 29%, p=0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p=0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR=0.97, p=0.79) but a trend for worse OS with RIC in ALL (HR=1.44, p=0.10). The main factor impacting outcomes was disease status at transplantation (HR>1.4, p<0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p=0.02) without impact on relapse incidence (HR 0.99, p=0.94). CONCLUSIONS These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL.