0
selected
-
1.
Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT
Sanz, J., Galimard, J. E., Labopin, M., Afanasyev, B., Sergeevich, M. I., Angelucci, E., Kröger, N., Koc, Y., Ciceri, F., Diez-Martin, J. L., et al
Journal of hematology & oncology. 2021;14(1):84
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). METHODS We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n?=?78), matched unrelated (MUD) (n?=?94) and haploidentical family (Haplo) (n?=?297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. RESULTS Median age of patients was 38 years (range 18-76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p?=?0.4); 13%, 15%, and 15% (p?=?0.8); 35%, 50%, and 42% (p?=?0.01); and 11%, 17%, and 21% (p?=?0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p?=?0.8); and 21%, 18%, and 21% (p?=?0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p?=?0.8); 66%, 69%, and 62% (p?=?0.8); and 46%, 44%, and 35% (p?=?0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. CONCLUSIONS Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia (ALL) receiving allogeneic transplant in CR1 with prophylaxis with post-transplant cyclophosphamide (PTCy) prophylaxis (n=469)
Intervention
Haploidentical transplantation (n=297)
Comparison
Matched unrelated donor (MUD, n=94); matched sibling donor (MSD, n=78)
Outcome
Median age of patients was 38 years (range 18-76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34%; 13%, 15%, and 15%; 35%, 50%, and 42%; and 11%, 17%, and 21%, respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% and 21%, 18%, and 21% for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51%; 66%, 69%, and 62%; and 46%, 44%, and 35%, respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better leukaemia free survival.
-
2.
Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., et al
Bone marrow transplantation. 2020
Abstract
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
-
3.
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
-
-
-
Free full text
-
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.
-
4.
Allogeneic stem-cell transplantation with sequential conditioning in adult patients with refractory or relapsed acute lymphoblastic leukemia: a report from the EBMT Acute Leukemia Working Party
Bazarbachi, A. H., Al Hamed, R., Labopin, M., Afanasyev, B., Hamladji, R. M., Beelen, D., Eder, M., Scheid, C., Wu, D., Bunjes, D., et al
Bone marrow transplantation. 2019
Abstract
Treatment of relapsed/refractory acute lymphoblastic leukemia (RR-ALL) remains a clinical challenge with generally dismal prognosis. Allogeneic stem-cell transplantation using sequential conditioning ("FLAMSA"-like) has shown promising results in relapsed/refractory acute myeloid leukemia, but little is known about its efficacy in RR-ALL. We identified 115 patients (19-66 years) with relapsed (74%) or primary-refractory (26%) ALL allografted from matched related (31%), matched unrelated (58%), or haploidentical donor (11%). Median follow-up was 37 (13-111) months. At day 100, cumulative incidences of grade II-IV/III-IV acute graft-versus-host-disease (GVHD) were 30% and 17%, respectively. Two-year cumulative incidence of chronic GVHD was 25% with 11% extensive cases. Two-year relapse incidence (RI) was 45%, non-relapse mortality was 41%. Two-year leukemia free survival (LFS) was 14%, overall survival (OS) 17%, and GVHD relapse-free survival (GRFS) was 14%. In multivariable analysis, Karnofsky score <90 negatively affected RI, LFS, OS, and GRFS. Conditioning with chemotherapy alone, compared with total body irradiation (TBI) negatively affected RI (HR = 3.3; p = 0.008), LFS (HR = 1.94; p = 0.03), and OS (HR = 2.0; p = 0.03). These patients still face extremely poor outcomes, highlighting the importance of incorporating novel therapies (e.g., BITE antibodies, inotuzumab, CAR-T cells). Nevertheless, patients with RR-T-cell ALL remain with an unmet treatment need, for which TBI-based sequential conditioning could be one of few available options.
-
5.
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.