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Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party
Duque-Afonso, J., Finke, J., Ngoya, M., Galimard, J. E., Craddock, C., Raj, K., Bloor, A., Nicholson, E., Eder, M., Kim, O., et al
Bone marrow transplantation. 2023
Abstract
Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m(2) (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m(2). We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with acute myeloid leukemia (AML) with intermediate/poor cytogenetic risk in first complete remission (CR) from the registry of the EBMT Acute Leukemia Working Party. Despite patients in the FBM/FTM group were older (64.1 years vs. 59.8 years, p < 0.001) and had a worse Karnofsky performance score (KPS < 90, 33% vs. 24%, p = 0.003), they showed a better overall survival (OS) (2 y OS: 68.3% vs. 58.1%, p = 0.02) and less non-relapse mortality (NRM) (2 y NRM: 15.8% vs. 22.2%, p = 0.009) compared to patients treated with FluMel. No significant differences were observed in relapse incidence (RI) (2 y RI: 24.9% vs. 23.7%, p = 0.62). In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning, improves OS in AML patients in first CR with intermediate/poor risk cytogenetics after allo-HCT.
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Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT
Giebel, S., Labopin, M., Socié, G., Aljurf, M., Salmenniemi, U., Labussière-Wallet, H., Srour, M., Kröger, N., Zahrani, M. A., Lioure, B., et al
Bone marrow transplantation. 2023
Abstract
In this registry-based study we retrospectively compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with acute lymphoblastic leukemia (ALL) following conditioning with total body irradiation (TBI) combined with either cyclophosphamide (Cy) or fludarabine (Flu). TBI 12 Gy + Cy was used in 2105 cases while TBI 12 Gy + Flu was administered to 150 patients in first or second complete remission. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with a reduced risk of relapse (HR = 0.69, p = 0.049) and increased risk of grade 2-4 acute graft-versus-host disease (GVHD, HR = 1.57, p = 0.03) without significant effect on other transplantation outcomes. In a matched-pair analysis the use of TBI/Cy as compared to TBI/Flu was associated with a significantly reduced rate of relapse (18% vs. 30% at 2 years, p = 0.015) without significant effect on non-relapse mortality, GVHD and survival. We conclude that the use of myeloablative TBI/Cy as conditioning prior to allo-HCT for adult patients with ALL in complete remission is associated with lower risk of relapse rate compared to TBI/Flu and therefore should probably be considered a preferable regimen.
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Fludarabine/TBI 8 Gy versus fludarabine/treosulfan conditioning in patients with AML in first complete remission: a study from the Acute Leukemia Working Party of the EBMT
Bug, G., Labopin, M., Niittyvuopio, R., Stelljes, M., Reinhardt, H. C., Hilgendorf, I., Kröger, N., Kaare, A., Bethge, W., Schäfer-Eckart, K., et al
Bone marrow transplantation. 2023
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Editor's Choice
Abstract
The optimal reduced intensity conditioning (RIC) regimen is a matter of debate. We retrospectively compared conditioning with fludarabine plus fractionated total body irradiation of 8 Gy (FluTBI) and fludarabine plus treosulfan 30, 36 or 42 g/m(2) (FluTreo) in 754 patients with AML above the age of 40 years undergoing an allogeneic hematopoietic stem cell transplant (HSCT) in first complete remission (CR). After balancing patient characteristics by propensity score matching of 115 patients in each group, FluTBI was associated with a significantly lower probability of relapse compared to FluTreo (18.3% vs. 34.7%, p = 0.018) which was counteracted by a higher non-relapse mortality (NRM, 16.8% vs. 5.3%, p = 0.02). Thus, overall survival and graft-versus-host disease-free and relapse-free survival at 2 years were similar between groups (OS 66.9% vs. 67.8%, GRFS 50.3% vs. 45.6%). Univariate analysis by age group demonstrated a higher NRM exclusively in patients ≥55 years of age treated with FluTBI compared to FluTreo (27.6% vs. 5.8%, p = 0.02), while a similarly low NRM was observed in patients <55 years in both groups (6.0% vs. 4.7%, p = ns). We conclude that both conditioning regimens are effective and safe, but FluTBI may better be reserved for younger patients below the age of 55 years.
PICO Summary
Population
Adults above the age of 40 years with AML, undergoing an allogeneic hematopoietic stem cell transplant (HSCT) in first complete remission and reported to the EBMT registry (n=754, pair matched to produce a population of 230)
Intervention
Conditioning with fludarabine plus fractionated total body irradiation of 8 Gy (FluTB, n=115)
Comparison
Conditioning with fludarabine plus treosulfan 30, 36 or 42 g/m(2) (FluTreo, n=115)
Outcome
After balancing patient characteristics by propensity score matching of 115 patients in each group, FluTBI was associated with a significantly lower probability of relapse compared to FluTreo (18.3% vs. 34.7%) which was counteracted by a higher non-relapse mortality (NRM, 16.8% vs. 5.3%). Thus, overall survival and graft-versus-host disease-free and relapse-free survival at 2 years were similar between groups (OS 66.9% vs. 67.8%, GRFS 50.3% vs. 45.6%). Univariate analysis by age group demonstrated a higher NRM exclusively in patients ≥55 years of age treated with FluTBI compared to FluTreo (27.6% vs. 5.8%), while a similarly low NRM was observed in patients <55 years in both groups (6.0% vs. 4.7%).
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Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis
Murthy, G. S. G., Kim, S., Estrada-Merly, N., Abid, M. B., Aljurf, M., Assal, A., Badar, T., Badawy, S. M., Ballen, K., Beitinjaneh, A., et al
Haematologica. 2023
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Editor's Choice
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (Fludarabine/busulfan=166, Fludarabine/melphalan=327) and 379 using MAC (Fludarabine/busulfan=247, Busulfan/cyclophosphamide=132). In multivariable analysis with RIC, Fludarabine/melphalan was associated with inferior overall survival (HR 1.80, 95% CI 1.15-2.81, p=0.009), higher early non-relapse mortality (HR 1.81, 95% CI 1.12-2.91, p=0.01) and higher acute graft versus host disease (GVHD) (grade II-IV- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade III-IV HR 2.21, 95%CI 1.28-3.83, p=0.004) compared to Fludarabine/busulfan. In the MAC setting, Busulfan/cyclophosphamide was associated with a higher acute GVHD (grade II-IV HR 2.33, 95% CI 1.67-3.25, p<0.001; grade III-IV HR 2.31, 95% CI 1.52-3.52, p<0.001) and inferior GVHD-free relapse-free survival (GRFS) (HR 1.94, 95% CI 1.49-2.53, p<0.001) as compared to Fludarabine/busulfan. Hence, our study suggests that Fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GVHD) and MAC (lower acute GVHD and better GRFS) in myelofibrosis.
PICO Summary
Population
Adults with myelofibrosis undergoing allogeneic HSCT between 2008-2019 and reported to the CIBMTR database (n=872)
Intervention
Reduced intensity conditioning (RIC) regimens (n=493): fludarabine/busulfan (n=166) or fludarabine/melphalan (n=327)
Comparison
Myeloablative conditioning (MAC) regimens (n=379): fludarabine/busulfan (n=247) or busulfan/cyclophosphamide (n=132).
Outcome
In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (HR 1.80, 95% CI 1.15-2.81), higher early non-relapse mortality (HR 1.81, 95% CI 1.12-2.91,) and higher acute graft versus host disease (GVHD) (grade II-IV- HR 1.45, 95% CI 1.03-2.03; grade III-IV HR 2.21, 95%CI 1.28-3.83) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GVHD (grade II-IV HR 2.33, 95% CI 1.67-3.25; grade III-IV HR 2.31, 95% CI 1.52-3.52) and inferior GVHD-free relapse-free survival (GRFS) (HR 1.94, 95% CI 1.49-2.53) as compared to fludarabine/busulfan.
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Impact of conditioning regimen intensity on outcomes of second allogeneic hematopoietic cell transplantation for secondary acute myelogenous leukemia
Nagler, A., Peczynski, C., Dholaria, B., Labopin, M., Valerius, T., Dreger, P., Kröger, N., Reinhardt, H. C., Finke, J., Franke, G. N., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Limited data is available on factors impacting the outcomes of second hematopoietic cell transplantation (HCT2) in patients with secondary acute myeloid leukemia (sAML). This study aimed to assess HCT2 outcome for sAML comparing reduced-intensity (RIC) to myeloablative (MAC) conditioning. Two hundred and fifteen patients were included: RIC (n = 134), MAC (n = 81). The median follow-up was 41.1 (95% CI: 26.7-69.3) and 28.5 (95% CI: 23.9-75.4) months, respectively. At two years, the relapse incidence (RI) was 58.3% versus 51.1% in RIC and MAC, respectively. The 2-year leukemia free survival (LFS) was 26.6% versus 26%, and the graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) was 16.4% versus 12.1%, while OS was 31.4% and 39.7%, for RIC and MAC respectively. MVA showed a significantly lower RI [hazard ratio (HR) = 0.46 (95% CI, 0.26-0.8, p = 0.006)] and improved LFS [HR = 0.62 (95% CI, 0.39-0.98, p = 0.042)] with MAC versus RIC. The choice of conditioning regimen did not impact non-relapse mortality [HR = 1.14 (95% CI, 0.52-2.5, p = 0.74)], overall survival (OS) [HR = 0.72 (95% CI, 0.44-1.17, p = 0.18)] or GRFS [HR = 0.89 (95% CI, 0.59-1.36, p = 0.6)]. In conclusion, MAC was associated with a lower RI and superior LFS. These results support the use of MAC for eligible patients with sAML who are being considered for HCT2.
PICO Summary
Population
Adult patients with relapsed secondary acute leukaemia (sAML) receiving a second hematopoietic cell transplant (HCT2) from mulitple centre registries across Europe (n=215)
Intervention
Reduced-intensity pre-HCT2 conditioning (RIC, n=134)
Comparison
Myeloablative pre-HCT2 conditioning (MAC, n=81)
Outcome
Median follow-up was 41.1 (RIC, 95% CI: 26.7-69.3) and 28.5 (MAC, 95% CI: 23.9-75.4) months. At two years, the relapse incidence (RI) was 58.3% versus 51.1% in RIC and MAC, respectively. The 2-year leukemia free survival (LFS) was 26.6% versus 26%, and the graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) was 16.4% versus 12.1%, while OS was 31.4% and 39.7%, for RIC and MAC respectively. Multivariate analysis showed a significantly lower RI [hazard ratio (HR) = 0.46 (95% CI, 0.26-0.8)] and improved LFS [HR = 0.62 (95% CI, 0.39-0.98)] with MAC versus RIC. The choice of conditioning regimen did not impact non-relapse mortality [HR = 1.14 (95% CI, 0.52-2.5)], overall survival (OS) [HR = 0.72 (95% CI, 0.44-1.17)] or GRFS [HR = 0.89 (95% CI, 0.59-1.36)].
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Comparison of fludarabine-melphalan and fludarabine-treosulfan as conditioning prior to allogeneic hematopoietic cell transplantation-a registry study on behalf of the EBMT Acute Leukemia Working Party
Duque-Afonso, J., Finke, J., Labopin, M., Craddock, C., Protheroe, R., Kottaridis, P., Tholouli, E., Byrne, J. L., Orchard, K., Salmenniemi, U., et al
Bone Marrow Transplantation. 2022;57(8):1269-1276
Abstract
In recent years considerable variations in conditioning protocols for allogeneic hematopoietic cell transplantation (allo-HCT) protocols have been introduced for higher efficacy, lower toxicity, and better outcomes. To overcome the limitations of the classical definition of reduced intensity and myeloablative conditioning, a transplantation conditioning intensity (TCI) score had been developed. In this study, we compared outcome after two frequently used single alkylator-based conditioning protocols from the intermediate TCI score category, fludarabine/melphalan 140 mg/m(2) (FluMel) and fludarabine/treosulfan 42 g/m(2) (FluTreo) for patients with acute myeloid leukemia (AML) in complete remission (CR). This retrospective analysis from the registry of the Acute Leukemia Working Party (ALWP) of the European Society of Bone Marrow Transplantation (EBMT) database included 1427 adult patients (median age 58.2 years) receiving either Flu/Mel (n = 1005) or Flu/Treo (n = 422). Both groups showed similar 3-year overall survival (OS) (54% vs 51.2%, p value 0.49) for patients conditioned with FluMel and FluTreo, respectively. However, patients treated with FluMel showed a reduced 3-year relapse incidence (32.4% vs. 40.4%, p value < 0.001) and slightly increased non-relapse mortality (NRM) (25.7% vs. 20.2%, p value = 0.06) compared to patients treated with FluTreo. Our data may serve as a basis for further studies examining the role of additional agents/ intensifications in conditioning prior to allo-HCT.
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Total body irradiation plus fludarabine versus thiotepa, busulfan plus fludarabine as a myeloablative conditioning for adults with acute lymphoblastic leukemia treated with haploidentical hematopoietic cell transplantation. A study by the Acute Leukemia Working Party of the EBMT
Swoboda, R., Labopin, M., Giebel, S., Angelucci, E., Arat, M., Aljurf, M., Sica, S., Pavlu, J., Socié, G., Bernasconi, P., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Optimal conditioning for adults with acute lymphoblastic leukemia (ALL) treated with haploidentical hematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide has not been established so far. We retrospectively compared outcomes for two myeloablative regimens: fludarabine + total body irradiation (Flu-TBI, n = 117) and thiotepa + iv. busulfan + fludarabine (TBF, n = 119). Patients transplanted either in complete remission (CR) or with active disease were included in the analysis. The characteristics of both groups were comparable except for patients treated with TBF were older. In univariate analysis the incidence of non-relapse mortality (NRM) at 2 years was increased for TBF compared to Flu-TBI (31% vs. 19.5%, p = 0.03). There was a tendency towards reduced incidence of relapse after TBF (p = 0.11). Results of multivariate analysis confirmed a reduced risk of NRM using Flu-TBI (HR = 0.49, p = 0.03). In the analysis restricted to patients treated in CR1 or CR2, the use of Flu-TBI was associated with a decreased risk of NRM (HR = 0.34, p = 0.009) but an increased risk of relapse (HR = 2.59, p = 0.01) without significant effect on survival and graft-versus-host disease. We conclude that for haplo-HCT recipients with ALL, Flu-TBI may be preferable for individuals at high risk of NRM while TBF should be considered in cases at high risk of relapse.
PICO Summary
Population
Adults with acute lymphoblastic leukemia (ALL) treated with haploidentical (n=haematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide (n=236)
Intervention
Fludarabine + total body irradiation conditioning (Flu-TBI, n=117)
Comparison
Thiotepa + iv. busulfan + fludarabine conditioning (TBF, n=119)
Outcome
In univariate analysis the incidence of non-relapse mortality (NRM) at 2 years was increased for TBF compared to Flu-TBI (31% vs. 19.5%). There was a tendency towards reduced incidence of relapse after TBF. Results of multivariate analysis confirmed a reduced risk of NRM using Flu-TBI (HR = 0.49). In the analysis restricted to patients treated in CR1 or CR2, the use of Flu-TBI was associated with a decreased risk of NRM (HR = 0.34) but an increased risk of relapse (HR = 2.59) without significant effect on survival and graft-versus-host disease.
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Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improves Transplant Outcomes in Older MDS Patients
Oran, B., Ahn, K. W., Fretham, C., Beitinjaneh, A., Bashey, A., Pawarode, A., Wirk, B., Scott, B. L., Savani, B. N., Bredeson, C., et al
Transplantation and cellular therapy. 2021
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Editor's Choice
Abstract
Reduced-intensity conditioning (RIC) regimens developed to extend allogeneic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the two most commonly used RIC regimens, intravenous use of fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in myelodysplastic syndrome (MDS). Through CIBMTR, we identified 1045 MDS patients aged = 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using RIC. CIBMTR's definition of RIC was used: a regimen that incorporated an intravenous busulfan total dose = 7.2 mg/kg, or a low-dose melphalan total dose of = 150 mg/m(2). The two groups, FluBu (n=697) and FluMel (n=448), were comparable for disease and transplant-related characteristics except for the more frequent use of anti-thymocyte globulin or alemtuzumab in the FluBu group (39% vs. 31%). The median age was 67 in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% vs. 44% (p=0.0001). Transplant-related mortality (TRM) was higher with FluMel compared with FluBu (26% vs. 16%, p=0.0001). Since the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was improved at 1-year and beyond with FluMel compared with FluBu (48% vs. 40% at 1 year, p=0.02, and 35% vs. 27% at 3 years, p=0.01). Overall survival (OS) was comparable at 1 year (63% vs. 61%, p=0.4) but significantly improved with FluMel compared with FluBu at 3 years (46% vs. 39%, p=0.03). Our results suggest that FluMel is associated with superior DFS compared with FluBu due to reduced RI in older MDS patients.
PICO Summary
Population
Patients with myelodysplastic syndrome aged >/=60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor, and were reported to the CIBMTR registry (n=1045)
Intervention
Reduced intensity regimen incorporating an intravenous busulfan total dose = 7.2 mg/kg (FluBu, n=697)
Comparison
Reduced intensity regimen incorporating a low-dose melphalan total dose of = 150 mg/m(2) (FluMel, n=448)
Outcome
The two groups were comparable for disease and transplant-related characteristics except for the more frequent use of anti-thymocyte globulin or alemtuzumab in the FluBu group (39% vs. 31%). The median age was 67 in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% vs. 44%. Transplant-related mortality (TRM) was higher with FluMel compared with FluBu (26% vs. 16%). Since the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was improved at 1-year and beyond with FluMel compared with FluBu (48% vs. 40% at 1 year, and 35% vs. 27% at 3 years). Overall survival (OS) was comparable at 1 year (63% vs. 61%) but significantly improved with FluMel compared with FluBu at 3 years (46% vs. 39%). Our results suggest that FluMel is associated with superior DFS compared with FluBu due to reduced RI in older MDS patients.
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Evaluation of six different types of sequential conditioning regimens for allogeneic stem cell transplantation in relapsed/refractory acute myelogenous leukemia - a study of the Acute Leukemia Working Party of the EBMT
Heinicke, T., Labopin, M., Polge, E., Stelljes, M., Ganser, A., Tischer, J., Brecht, A., Kröger, N., Beelen, D. W., Scheid, C., et al
Leukemia & lymphoma. 2020;:1-11
Abstract
The Acute Leukemia Working Party (ALWP) of the EBMT assessed the outcome of allogeneic stem cell transplantation (alloSCT) in patients with relapsed/refractory AML (r/rAML) evaluating six sequential conditioning regimens (SR) groups. A total of 2132 patients were included. LFS at 2 years was 28.9%, 33.6%, 35.3%, 20.6%, 24.4%, and 27% for the FLAMSA-TBI4, FLAMSA-Chemo, Mel-Flu-TBI8, Mel-Treo-Flu, Thio-ETO-Cy-Bu2-Flu, and Clo-ARAC-(Bu2/TBI4)-Cy groups, respectively. In patients <55 years of age Mel-Flu-TBI8 had the best LFS, which was statistically significant only in comparison to the Mel-Treo-Flu group, while in patients =55 years LFS was best with FLAMSA-Chemo without significant differences compared to FLAMSA-TBI4 and Mel-Flu-TBI8. Furthermore, best NRM rates were obtained with the two FLAMSA regimens groups. Our study suggests that in younger (<55 years) patients a more intense regimen might be used whereas in older (=55 years) patients the focus might be more on tolerability.
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10.
Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report
Zhou, Z., Nath, R., Cerny, J., Wang, H. L., Zhang, M. J., Abdel-Azim, H., Agrawal, V., Ahmed, G., Al-Homsi, A. S., Aljurf, M., et al
Blood advances. 2020;4(13):3180-3190
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Editor's Choice
Abstract
There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
PICO Summary
Population
Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 (n=1413)
Intervention
Fludarabine/busulfan reduced intensity conditioning regimen (FB, n=791)
Comparison
Fludarabine/melphalan reduced intensity conditioning regimen (FM, n=622)
Outcome
Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82), but was marginally superior beyond 3 months (HR = 0.87). LFS was better with FM compared with FB (HR = 0.89). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85). Long-term relapse was lower with FM (HR = 0.65). Analysis restricted to patients with CR showed comparable results.