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Bone marrow versus mobilized peripheral blood stem cell graft in T-cell-replete haploidentical transplantation in acute lymphoblastic leukemia
Nagler, A., Dholaria, B., Labopin, M., Savani, B. N., Angelucci, E., Koc, Y., Arat, M., Pioltelli, P., Sica, S., Gulbas, Z., et al
Leukemia. 2020
Abstract
The ideal stem cell graft source remains unknown in haploidentical haematopietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide (PTCy). This study compared outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for haplo-HCT in acute lymphoblastic leukemia (ALL). A total of 314 patients with ALL (BM-157; PB-157) were included in this study. The cumulative incidence of engraftment at day 30 was higher in the PB group compared with BM (93% vs. 88%, p < 0.01). The incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were not significantly different between the study cohorts. In the multivariate analysis, there were tendencies toward a higher incidence of grade II-IV acute GVHD (hazard ratio (HR) = 1.52, p = 0.07), chronic GVHD (HR = 1.58, p = 0.05), and nonrelapse mortality (NRM) (HR = 1.66, p = 0.06) in patients receiving PB versus BM graft, respectively. The use of PB grafts was associated with lower leukemia-free survival (LFS) (HR = 1.43, p = 0.05), overall survival (OS) (HR = 1.59, p = 0.02), and GVHD-free, relapse-free survival (GRFS) (HR = 1.42, p = 0.03) compared with BM grafts. There was no difference in relapse incidence (HR = 1.23, p = 0.41) between the study groups. In conclusion, use of BM graft results in better survival after haplo-HCT with PTCy in patients with ALL, compared with PB stem cell graft.
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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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CD34+ cell dose effects on clinical outcomes after T-cell replete haploidentical allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia using peripheral blood stem cells. A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Maffini, E., Labopin, M., Blaise, D., Ciceri, F., Gulbas, Z., Deconinck, E., Leblond, V., Chevallier, P., Socie, G., Araujo, M. C., et al
American journal of hematology. 2020
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Editor's Choice
Abstract
Previous observations have reported controversial conclusions regarding cell dose and survival endpoints after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a retrospective analysis on 414 adult patients (median age 54 years, range, 18-74) with acute myeloid leukemia (AML) in first and second complete remission who received a T-cell replete allogeneic HSCT from haploidentical donors, using peripheral blood stem cells, between 2006-2018. Median number of infused CD34+ was 6.58 x 10(6) /kg (range, 2.2-31.2). Graft-versus-host disease (GVHD) prophylaxis was post-transplant cyclophosphamide in 293 patients and anti-lymphocyte serum in 121 patients. Conditioning was myeloablative in 179 patients and reduced-intensity in 235 patients. After a median follow-up of 23.3 months (range, 12.1-41.8), 2-year overall survival (OS) was 64.5 % (95% CI 59.3-69.7) with leukemia-free survival (LFS) of 57.3 % (95% CI 51.8-62.7) and non-relapse mortality (NRM) of 23.3 % (95% CI 19-27.7). Grades III-IV acute GVHD day+100 incidence was 14.6 % while extensive chronic GVHD was 14.4% at 2-years. Thirteen (3.2%) patients experienced graft failure. We found the optimal CD34+/kg threshold defining high (n= 334) versus low cell dose (n= 80) at 4.96 x 10(6) . Recipients of > 4.96 x 10(6) /kg CD34+ cells experienced less NRM (Hazard ratio [HR] 0.48; 95% CI 0.30-0.76) and prolonged LFS (HR 0.63; 95% CI 0.43-0.91) and OS (HR 0.60; 95% CI 0.40-0.88) compared to those in the lower cell dose cohort. Larger cohort studies are needed to confirm these findings. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Patients with acute myeloid leukaemia (n=414)
Intervention
T-cell replete allogeneic HSCT from haploidentical donors, using peripheral blood stem cells, between 2006-2018
Comparison
None
Outcome
After a median follow-up of 23.3 months (range, 12.1-41.8), 2-year overall survival (OS) was 64.5% with leukemia-free survival (LFS) of 57.3% and non-relapse mortality (NRM) of 23.3 %. Grades III-IV acute GVHD day+100 incidence was 14.6 % while extensive chronic GVHD was 14.4% at 2-years. Thirteen (3.2%) patients experienced graft failure. We found the optimal CD34+/kg threshold defining high (n= 334) versus low cell dose (n= 80) at 4.96 x 10(6). Recipients of > 4.96 x 10(6) /kg CD34+ cells experienced less NRM and prolonged LFS and OS compared to those in the lower cell dose cohort.
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Haploidentical transplantation and posttransplant cyclophosphamide for treating aplastic anemia patients: a report from the EBMT Severe Aplastic Anemia Working Party
Prata, P. H., Eikema, D. J., Afansyev, B., Bosman, P., Smiers, F., Diez-Martin, J. L., Arrais-Rodrigues, C., Koc, Y., Poire, X., Sirvent, A., et al
Bone marrow transplantation. 2019
Abstract
In the absence of an HLA-matched donor, the best treatment for acquired aplastic anemia patients refractory to immunosuppression is unclear. We collected and analyzed data from all acquired aplastic anemia patients who underwent a haploidentical transplantation with posttransplant cyclophosphamide in Europe from 2011 to 2017 (n = 33). The cumulative incidence of neutrophil engraftment was 67% (CI95%: 51-83%) at D +28 and was unaffected by age group, stem cell source, ATG use, or Baltimore conditioning regimen. The cumulative incidence of grades II-III acute GvHD was 23% at D +100, and limited chronic GvHD was 10% (0-20) at 2 years, without cases of grade IV acute or extensive chronic GvHD. Two-year overall survival was 78% (64-93), and 2-year graft-versus-host disease-free survival was 63% (46-81). In univariate analysis, the 2-year OS was higher among patients who received the Baltimore conditioning regimen (93% (81-100) versus 64% (41-87), p = 0.03), whereas age group, stem cell source, and ATG use had no effect. Our results using unmanipulated haploidentical transplantation and posttransplant cyclophosphamide for treating refractory AA patients are encouraging, but warrant confirmation in a prospective study with a larger number of patients and longer follow-up.
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Outcomes of Salvage Haploidentical Transplant with Post-transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy
Prata, P. H., Resche-Rigon, M., Blaise, D., Socie, G., Rohrlich, P. S., Milpied, N., Turlure, P., Nguyen, S., Sirvent, A., Bulabois, C. E., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Editor's Choice
Abstract
Prognosis of patients with graft failure is dismal, and re-transplantation is the sole option for long-term survival. To address the interest of haploidentical transplantation as a salvage option in this context, we analyzed data from 24 patients with graft failure or loss re-transplanted with a haploidentical donor who received post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease prophylaxis (GvHD). Fludarabine-based reduced intensity conditioning was used in 23 patients, and 14 patients received the Baltimore regimen. The median delay between previous and salvage transplantation for graft failure was 63 (39-98) days. Besides PT-Cy, all patients received cyclosporine, and 22 patients also received MMF for GvHD prophylaxis. With a median follow up of 353 (16-2010) days, 1-year OS was 56% (95% CI: 38 - 81). Transplant complications accounted for 80% of deaths. The cumulative incidence of neutrophil engraftment was +30 was 79%. Cumulative incidence of grade II-IV acute GvHD at day-100 was 14%, and 1-year CI of chronic GvHD was 31%. One-year CI of relapse was 13%. Stem cell source did not impact on engraftment, GvHD, relapse nor overall survival. Salvage haploidentical transplant with PT-Cy for rescuing graft failure patients leads to an acceptable 1-year OS and might be a valid option in this poor situation.
PICO Summary
Population
Patients with graft failure or loss (n=24)
Intervention
Re-transplantation with a haploidentical donor who received post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease prophylaxis.
Comparison
None
Outcome
With a median follow up of 353 days, 1-year OS was 56%. Transplant complications accounted for 80% of deaths. The cumulative incidence of neutrophil engraftment was +30 was 79%. Cumulative incidence of grade II-IV acute GvHD at day-100 was 14%, and 1-year CI of chronic GvHD was 31%. One-year CI of relapse was 13%. Stem cell source did not impact on engraftment, GvHD, relapse nor overall survival.
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Evaluation of infectious complications after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning: a study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)
Fayard, A., Daguenet, E., Blaise, D., Chevallier, P., Labussiere, H., Berceanu, A., Yakoub-Agha, I., Socie, G., Charbonnier, A., Suarez, F., et al
Bone marrow transplantation. 2019
Abstract
Several approaches have been developed to overcome historical barriers associated with poor outcomes in the setting of HLA-haploidentical allogeneic transplantation (HaploSCT). Here, we examine the outcome of patients with various hematological disorders undergoing HaploSCT with high-dose, post-transplantation cyclophosphamide. We performed a retrospective study on 381 patients from 30 centers between January 2013 and December 2015. At the last follow-up, a total of 1058 infectious episodes were diagnosed, affecting 90.3% of the cohort. Median time to first infection was 13 days for bacterial, 32 days for viral and 20 days for fungal infections. Around 41% of these infections were of bacterial origin and 35% of viral origin, among which 48.8% of patients presented CMV reactivation. Median of GVHD relapse-free survival, progression-free survival and overall survival were 7.1 months, 19.9 months and 33.5 months, respectively. HSCT procedure was the primary or contributing cause of death (55.6%), followed by relapse of the original disease (34.2%). Infections accounted for 45.7% of the HSCT-related deaths. The present multicenter data on a large cohort of patients receiving HaploSCT with PTCy confirmed the feasibility of the procedure with an acceptable incidence of infectious complications, not different as compared to other haploidentical platforms or HLA-matched transplantation.
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Stem cell transplantation from a haploidentical donor versus a genoidentical sister for adult male patients with acute myelogenous leukemia in first remission: A retrospective study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation
Gorin, N. C., Labopin, M., Blaise, D., de Groot, M., Socie, G., Bourhis, J. H., Ciceri, F., Polge, E., Nagler, A., Mohty, M.
Cancer. 2019
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Editor's Choice
Abstract
BACKGROUND In adult patients with acute myeloid leukemia (AML), a matched sibling donor (MSD) is considered the first choice for an allogeneic transplantation. However, a female donor for a male recipient is a poor prognostic factor. The authors compared haploidentical (HAPLO) donors with female MSDs. METHODS In total, 834 men underwent allogenic transplantation from a female MSD, and 232 men underwent allogenic transplantation from a HAPLO donor. Of these, 86% of HAPLO recipients and 3% of MSD recipients received graft-versus-host disease (GVHD) prophylaxis posttransplantation with high-dose cyclophosphamide. A significant qualitative interaction was observed between donor type and cytogenetics, Therefore, the analyses were stratified on cytogenetics. RESULTS Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7; P = .02) and patient age for nonrelapse mortality and overall survival (HR, 1.22 [P = .02] and 1.15 [P = .02], respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43; P < 10(-4) ) but lower leukemia-free survival (HR, 1.7; P = .04). The GVHD/relapse-free survival (GRFS) was not different. Of the men with high-risk AML, 196 received transplantation from a female MSD, and 72 received transplantation from a HAPLO donor. By multivariate analysis, HAPLO recipients had a lower incidence of relapse (HR, 0.40; P = .004), better leukemia-free survival (HR, 0.46; P = .003), better overall survival (HR, 0.43; P = .003), and better GRFS (HR, 0.54; P = .006). CONCLUSIONS In men who have intermediate-risk AML, allogenic transplantation from a sister MSD or a HAPLO donor produces similar GRFS. However, in men who have high-risk AML, a HAPLO donor combined with prophylactic high-dose cyclophosphamide posttransplantation may be a better choice.
PICO Summary
Population
Adult male patients with acute myeloid leukaemia, undergoing allogeneic stem cell transplantation (n=1066)
Intervention
Haploidentical donor (HAPLO, n=232)
Comparison
Matched female sibling donor (MSD, n=834)
Outcome
Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7) and patient age for nonrelapse mortality and overall survival (HR, 1.22 and 1.15, respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43) but lower leukemia-free survival (HR, 1.7). The GVHD/relapse-free survival (GRFS) was not different. Of the men with high-risk AML, 196 received transplantation from a female MSD, and 72 received transplantation from a HAPLO donor. By multivariate analysis, HAPLO recipients had a lower incidence of relapse (HR, 0.40), better leukemia-free survival (HR, 0.46), better overall survival (HR, 0.43), and better GRFS (HR, 0.54).
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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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Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Salvatore, D., Labopin, M., Ruggeri, A., Battipaglia, G., Ghavamzadeh, A., Ciceri, F., Blaise, D., Arcese, W., Socie, G., Bourhis, J. H., et al
Haematologica. 2018
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Editor's Choice
Abstract
Allogeneic hematopoietic stem cell transplantation is the optimal care for patients with high-risk or intermediate acute myeloid leukemia. In patients lacking matched sibling donor, haploidentical donors are an option. We compared outcomes of unmanipulated haploidentical to matched sibling donor transplant in acute myeloid leukemia patients in first complete remission. Included were int- and high-risk acute myeloid leukemia in first complete remission undergoing haploidentical and matched sibling donor transplant from 2007-2015 and reported to the ALWP of the EBMT. A propensity score technique was used to confirm results of main analysis: 2 matched sibling donor were matched with 1 haplo. We identified 2654 pts (haplo =185; matched sibling donor =2469), 2010 with intermediate- acute myeloid leukemia (haplo=122; matched sibling donor =1888) and 644 with high-risk acute myeloid leukemia (haplo =63; matched sibling donor =581). Median follow up was 30 (range 1-116) months. In multivariate analysis, in intermediate - acute myeloid leukemia patients, haplo resulted in lower leukemia-free-survival (Hazard Ratio 1.74; p<0.01), overall-survival (HR 1.80; p<0.01) and GVH-free-relapse-free-survival (Hazard Ratio 1.32; p<0.05) and higher non-relapse-mortality (Hazard Ratio 3.03; p<0.01) as compared to matched sibling donor. In high-risk acute myeloid leukemia, no differences were found in leukemia-free-sruvival, overall-survival and GVH-free-relapse-free-survival according to donor type. Higher grade II-IV acute graft versus host disease was observed for haplo in both high-risk (Hazard Ratio 2.20; p<0.01) and int-risk (Hazard Ratio 1.84; p<0.01). A trend for a lower Relapse-Incidence was observed in haplo among high-risk acute myeloid leukemia (Hazard Ratio 0.56; p=0.06). The propensity score analysis confirmed results. Our results underline that matched sibling donor is the first choice for acute myeloid leukemia patients in first complete remission. On the other hand, results of haplo transplants are similar to matched sibling donor transplants in acute myeloid leukemia patients with high risk cytogenetics.