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1.
Outcomes of patients with multiple myeloma and 1q gain/amplification receiving autologous hematopoietic stem cell transplant: the MD Anderson cancer center experience
Pasvolsky, O., Ghanem, S., Milton, D. R., Rauf, M., Tanner, M. R., Bashir, Q., Srour, S., Saini, N., Lin, P., Ramdial, J., et al
Blood cancer journal. 2024;14(1):4
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Editor's Choice
Abstract
The prognostic impact of additional copies of chromosome 1q (1q + ) on outcomes of newly-diagnosed multiple myeloma (NDMM) patients undergoing autologous transplantation (autoSCT) is unclear. We conducted a retrospective single-center analysis of NDMM patients with 1q21 gain/amplification (3 or ≥4 copies of 1q, respectively) that received autoSCT between 2008-2018. 213 patients were included (79% 1q gain; 21% 1q amplification). The most commonly used induction regimen was bortezomib, lenalidomide, and dexamethasone (41%). At day100 post-autoSCT and at best post-transplant response, 78% and 87% of patients achieved ≥VGPR, and 38% and 50% achieved MRD-negative ≥VGPR, respectively. Median PFS and OS for the entire cohort were 35.5 months and 81.4 months, respectively. On multivariable assessment for PFS, MRD negative ≥VGPR before autoSCT (HR 0.52, p = 0.013) was associated with superior PFS, whereas 1q amplification was associated with inferior PFS (2.03, p = 0.003). On multivariate analysis for OS, achieving MRD negative ≥VGPR at best post-transplant response was associated with superior survival (0.29, p < 0.001), whereas R-ISS III and concomitant del17p or t(4:14) were associated with inferior survival (6.95, p = 0.030, 2.33, p = 0.023 and 3.00, p = 0.047, respectively). In conclusion, patients with 1q+ NDMM, especially 1q amplification, have inferior survival outcomes compared to standard-risk disease after upfront autoSCT, though outcomes are better than other high-risk cytogenetic abnormalities.
PICO Summary
Population
Adults with newly-diagnosed myeloma (NDMM) patients with 1q21 gain/amplification (3 or >/=4 copies of 1q, respectively) that received autoSCT between from a single centre in USA (n=213)
Intervention
Assess the prognostic impact of additional copies of chromosome 1q (1q+) on autologous transplantation outcomes
Comparison
None
Outcome
At day100 post-autoSCT and at best post-transplant response, 78% and 87% of patients achieved very good partial response or better (>/=VGPR) and 38% and 50% achieved MRD-negative >/=VGPR, respectively. Median PFS and OS for the entire cohort were 35.5 months and 81.4 months, respectively. On multivariable assessment for PFS, MRD negative >/=VGPR before autoSCT (HR 0.52) was associated with superior PFS, whereas 1q amplification was associated with inferior PFS (2.03). On multivariate analysis for OS, achieving MRD negative >/=VGPR at best post-transplant response was associated with superior survival (0.29), whereas R-ISS III and concomitant del17p or t(4:14) were associated with inferior survival (6.95, 2.33, and 3.00, respectively).
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2.
Transplant Outcomes of Myelofibrosis with Busulfan and Fludarabine Myeloablative Conditioning
Joseph, J., Srour, S. A., Milton, D. R., Ramdial, J. L., Saini, N. Y., Olson, A. L., Bashir, Q., Oran, B., Alousi, A. M., Hosing, C., et al
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Outcomes of myelofibrosis with allogeneic stem cell transplantation (allo-SCT) have improved over the past decade and are partly related to advances in supportive treatments and conditioning regimens. Several factors are known to predict transplant outcomes. However, most studies lack homogeneity in the conditioning regimen used, which limits their ability to assess prognostic factors on transplant outcomes. OBJECTIVE We aimed to determine the risk factors that predict transplant outcomes in patients with myelofibrosis who underwent matched or mismatched allo-SCT using a uniform myeloablative conditioning regimen consisting of busulfan and fludarabine with tacrolimus and methotrexate-based graft-versus-host disease prophylaxis. STUDY DESIGN This single-center study included patients with myelofibrosis who underwent allo-SCT with a matched unrelated donor (MUD), matched related donor (MRD), or mismatched unrelated donor (MMUD) and received busulfan and fludarabine conditioning with methotrexate/tacrolimus-based GVHD prophylaxis. RESULTS Sixty-five patients with myelofibrosis met the criteria and were included in the study. At a median follow-up of 35.6 months, the 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and overall survival (OS) for all study patients were 27%, 20%, and 65%, respectively. In a multivariable analysis for CIR, prior use of JAK inhibitors was significantly associated with a decreased risk of relapse (HR [95% CI], 0.33 [0.11-0.99]; p = 0.048). For NRM, HCT-CI (≥3 vs. <3, 10.09 [2.09-48.76]; p=0.004) and donor type (MUD vs. MRD, 5.38 [1.14-25.30]; p=0.033 and MMUD vs. MRD, 10.73 [1.05-109.4]; p=0.045) were associated with an increased risk of mortality. Likewise for OS, HCT-CI (≥3 vs. <3, 3.31 [1.22-8.99]; p = 0.019) and donor type (MMUD vs. MRD, 5.20 [1.35-19.98]; p = 0.016) were significantly associated with inferior survival. Longer time from diagnosis to allo-SCT seemed to confer worse survival but this didn't reach statistical significance (>12 months vs. ≤12 months: NRM, 7.20 [0.96-53.94]; p=0.055 and OS, 2.60 [0.95-7.14]; p=0.06). CONCLUSIONS In a homogenous cohort of myelofibrosis patients uniformly treated with busulfan/fludarabine myeloablative conditioning and methotrexate-based GVHD prophylaxis, we showed that donor choice and HCT-CI are the two strongest predictors for improved survival after allo-SCT.
PICO Summary
Population
People with myelofibrosis who underwent allo-SCT with a matched unrelated donor (MUD), matched related donor (MRD), or mismatched unrelated donor (MMUD) at a single centre in USA (n=176)
Intervention
Cohort for analysis: all who received myeloablative conditioning regimen consisting of busulfan and fludarabine with tacrolimus and methotrexate-based graft-versus-host disease prophylaxis (n=65)
Comparison
None
Outcome
At a median follow-up of 35.6 months, the 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and overall survival (OS) for all study patients were 27%, 20%, and 65%, respectively. In a multivariable analysis for CIR, prior use of JAK inhibitors was significantly associated with a decreased risk of relapse (HR [95% CI], 0.33 [0.11-0.99]). For NRM, HCT-CI (>/=3 vs. <3, 10.09 [2.09-48.76]) and donor type (MUD vs. MRD, 5.38 [1.14-25.30] and MMUD vs. MRD, 10.73 [1.05-109.4]) were associated with an increased risk of mortality. Likewise for OS, HCT-CI (>/=3 vs. <3, 3.31 [1.22-8.99];) and donor type (MMUD vs. MRD, 5.20 [1.35-19.98]) were significantly associated with inferior survival. Longer time from diagnosis to allo-SCT seemed to confer worse survival but this didn't reach statistical significance (>12 months vs. </=12 months: NRM, 7.20 [0.96-53.94] and OS, 2.60 [0.95-7.14]).
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3.
Outcomes of Autologous Stem Cell Transplant in Patients with Ultra High-Risk Multiple Myeloma
Pasvolsky, O., Ghanem, S., Milton, D. R., Masood, A., Tanner, M. R., Bashir, Q., Srour, S., Saini, N., Lin, P., Ramdial, J., et al
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Multiple myeloma (MM) patients with high-risk cytogenetic abnormalities (HRMM) have inferior survival outcome and are under-represented in clinical trials. There is scarce data on MM patients with more than one high-risk cytogenetic aberration (i.e. ultra high-risk MM). OBJECTIVE To evaluate outcomes of newly diagnosed MM patients with ultra high-risk MM who underwent autologous stem cell transplant (autoHCT). STUDY DESIGN We conducted a retrospective single-center chart review analysis of adult patients with ultra high-risk MM who received autoHCT between 2008-2018 at MD Anderson Cancer Center. High-risk cytogenetics were defined as del17p, t(4;14), t(14;16) or 1q21 gain or amplification (1q+) by fluorescence in situ hybridization (FISH). Primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS Seventy-nine patients with two or more high-risk cytogenetic abnormalities were included in our analysis, with a median age of 61 (range 33.5-76.5) years and 57% were female. Sixty-seven patients had two HR cytogenetic abnormalities, while 12 patients had three. The most common combinations of HR abnormalities were [1q+, t(4:14)] (n=25, 32%) and [1q+, del17p] (n=21, 27%). The majority of patients received either bortezomib, lenalidomide and dexamethasone (VRD) (48%) or carfilzomib, lenalidomide and dexamethasone (KRD) (16%) as induction therapy. Prior to autoHCT, 52 (66%) patients achieved ≥VGPR, whereas 23 (29%) patients achieved MRD negative ≥VGPR. Fifty-six (71%) patients received post-transplant maintenance therapy. At day 100 post autoHCT and at best post-transplant response, 36 (46%) patients and 40 (51%) patients achieved MRD negative ≥VGPR, respectively. With a median follow-up in surviving patients of 38.3 (range 11.9 to 104.8) months, the median PFS and OS in the entire cohort were 22.9 and 71.5 months, respectively. For the subset of patients with three HR abnormalities, the median PFS and OS were 15.6 and 28.0 months, respectively. In multivariate analysis, achieving MRD negative ≥VGPR prior to autoHCT was associated with improved PFS (HR 0.42; p=0.045), while male gender (HR 0.15; p=0.009) and achieving MRD negative ≥VGPR post autoHCT (HR 0.27; p=0.026) were associated with improved OS. CONCLUSIONS MM patients with ultra high-risk MM have a median PFS of <24 months with the current standard of care that includes consolidation with autoHCT. These patients may benefit from earlier use of newer treatment modalities, such as CAR-T and bispecific antibodies.
PICO Summary
Population
Adults with multiple myeloma with two or more high-risk cytogenetic abonormalities from a single centre in USA (n=79)
Intervention
Upfront autologous transplant between 2008 and 2018.
Comparison
None
Outcome
At day 100 post transplant and at best post-transplant response, 36 (46%) patients and 40 (51%) patients achieved minimal residual disease (MRD)-negative >/=very good partial response (VGPR), respectively. With a median follow-up in surviving patients of 38.3 (range 11.9 to 104.8) months, the median progression free survival (PFS) and overall survival (OS) in the entire cohort were 22.9 and 71.5 months, respectively. For the subset of patients with three high-risk abnormalities, the median PFS and OS were 15.6 and 28.0 months, respectively. In multivariate analysis, achieving MRD negative >/=VGPR prior to autoHCT was associated with improved PFS (HR 0.42), while male gender (HR 0.15) and achieving MRD negative >/=VGPR post autoHCT (HR 0.27) were associated with improved OS.
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4.
Long-term outcomes of allogeneic hematopoietic cell transplantation in patients with newly diagnosed multiple myeloma
Afrough, A., Alsfeld, L. C., Milton, D. R., Delgado, R., Popat, U. R., Nieto, Y., Kebriaei, P., Oran, B., Saini, N., Srour, S., et al
Transplantation and cellular therapy. 2022
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Editor's Choice
Abstract
BACKGROUND Despite remarkable progress in survival with the availability of novel agents, an overwhelming majority of patients with multiple myeloma (MM) have disease that relapses. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative option for a subgroup of patients with high- risk disease. OBJECTIVE This study assesses the long-term outcome of MM patients who received allo-HCT at the first remission as consolidation treatment. METHODS/RESULTS Thirty-three patients with newly diagnosed MM who received allo-HCT as part of consolidation therapy from 1994 to 2016 were retrospectively reviewed. Of those, 70% received autologous HCT before allo-HCT. All patients were chemo-sensitive and achieved at least partial response before proceeding to allo-HCT. Most received nonmyeloablative/reduced-intensity conditioning (88%) and matched sibling donor (85%) grafts. Acute graft versus host disease (aGVHD) and chronic GVHD occurred in 30% and 61% of patients, respectively. The median follow-up was 64.1 months (range, 1.4 - 199.2) for all patients and 164.4 months (range, 56.0 -199.2) in survivors. The median progression-free survival (PFS) was 36 months (95% confidence interval (CI), 8.6 -73.0). The median treatment to progression (TTP) was 73.0 months (95% CI, 30.6 -not reached). The median overall survival (OS) was 131.9 months (95% CI, 38.4 -not reached). Of all patients, 39% were alive more than 10 years, with 46% (n=6) without progression or relapse. The cumulative incidence of relapse was 18% at 1-year, 39% at 5-years, and 46% at 10-year post-allo-HCT. The cumulative incidence of non-relapse mortality (NRM) was 3% at 100-day, 18% at 1-year, 21% at 3-years, and 24% at 5-year post-allo-HCT. On multivariable analysis, high-risk cytogenetics were associated with a shorter PFS (HR 2.7; 95% CI [1.01-7.21], p-value=0.047) and OS (HR 4.91, 95% CI [1.48-16.27], p-value=0.009). In addition, achieving complete remission after allo-HCT was also associated with longer PFS (HR 0.24, 95% CI [0.09-0.64], p-value=0.004) and OS (HR 0.23; 95% CI [0.07-0.72], p-value=0.012). CONCLUSIONS Allo-HCT may result in a survival advantage in a selected population of MM patients when performed early in the disease course. Additional data on the optimal patient selection who would benefit the most are needed.
PICO Summary
Population
Adults with newly diagnosed multiple myeloma at a single centre in Texas, USA (n=33)
Intervention
Allogeneic hematopoietic cell transplantation (allo-HCT)
Comparison
None
Outcome
Acute graft versus host disease (aGVHD) and chronic GVHD occurred in 30% and 61% of patients, respectively. Median follow-up was 64.1 months (range, 1.4 - 199.2) for all patients and 164.4 months (range, 56.0 -199.2) in survivors. Median progression-free survival (PFS) was 36 months (95% confidence interval (CI), 8.6 -73.0). Median treatment to progression (TTP) was 73.0 months (95% CI, 30.6 -not reached). Median overall survival (OS) was 131.9 months (95% CI, 38.4 -not reached). Of all patients, 39% were alive more than 10 years, with 46% (n=6) without progression or relapse. Cumulative incidence of relapse was 18% at 1-year, 39% at 5-years, and 46% at 10-year post-allo-HCT. Cumulative incidence of non-relapse mortality (NRM) was 3% at 100-day, 18% at 1-year, 21% at 3-years, and 24% at 5-year post-allo-HCT. On multivariable analysis, high-risk cytogenetics were associated with a shorter PFS (HR 2.7; 95% CI [1.01-7.21]) and OS (HR 4.91, 95% CI [1.48-16.27]). In addition, achieving complete remission after allo-HCT was also associated with longer PFS (HR 0.24, 95% CI [0.09-0.64]) and OS (HR 0.23; 95% CI [0.07-0.72]).
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9-year follow-up of patients with relapsed follicular lymphoma after nonmyeloablative allogeneic stem cell transplant and autologous transplant
Khouri, I. F., Milton, D. R., Gulbis, A. M., Jabbour, E. J., Nastoupil, L., Ledesma, C., Anderlini, P., Bashir, Q., Daher, M., Im, J. S., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021
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Editor's Choice
Abstract
PURPOSE To compare outcomes between patients with relapsed follicular lymphoma (FL) who received a nonmyeloablative allogeneic stem cell transplant (alloSCT) and those who received an autologous transplant (autoSCT). EXPERIMENTAL DESIGN We evaluated 194 patients with FL who received an alloSCT (n = 98) or autoSCT (n = 96) at MD Anderson Cancer Center. The transplant type used was based on donor availability and by Medicare reimbursement guidelines. AlloSCT patients were enrolled in 4 consecutive trials in which they received fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning. AutoSCT patients received R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan). RESULTS The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for alloSCT patients compared with autoSCT patients (62% vs. 46%; P = .048). Similarly, progression-free survival rates were 52% in alloSCT patients and 31% in autoSCT patients (P < .001), and the 8-year relapse rates were 11% and 43%, respectively (P < .0001). Only 3 patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2-4 acute graft-versus-host disease (GVHD), grade 3-4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Non-relapse mortality was similar between the 2 groups (15% vs. 11% at 8 years; P = .27). CONCLUSIONS This study shows that alloSCT is curative and confers superior survival compared with autoSCT in patients with FL.
PICO Summary
Population
Patients with follicular lymphoma at a single US centre (n=194)
Intervention
Nonmyeloablative allogeneic stem cell transplant, receiving fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning (alloSCT, n=98)
Comparison
Autologous transplant with R-BEAM conditioning: rituximab, carmustine, etoposide, cytarabine, and melphalan (autoSCT, n=96)
Outcome
The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for alloSCT patients compared with autoSCT patients (62% vs. 46%). Similarly, progression-free survival rates were 52% in alloSCT patients and 31% in autoSCT patients, and the 8-year relapse rates were 11% and 43%, respectively. Only 3 patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2-4 acute graft-versus-host disease (GVHD), grade 3-4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Non-relapse mortality was similar between the 2 groups (15% vs. 11% at 8 years).
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Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial
Bashir, Q., Thall, P. F., Milton, D. R., Fox, P. S., Kawedia, J. D., Kebriaei, P., Shah, N., Patel, K., Andersson, B. S., Nieto, Y. L., et al
The Lancet. Haematology. 2019
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Editor's Choice
Abstract
BACKGROUND Retrospective studies suggest that conditioning therapy with busulfan plus melphalan could result in longer progression-free survival compared with melphalan alone in patients with multiple myeloma undergoing autologous haemopoietic cell transplantation (auto-HCT). We aimed to test this hypothesis in a randomised trial. METHODS The primary objective of the study was to compare progression-free survival with conditioning of busulfan plus melphalan with melphalan alone in patients with multiple myeloma. Patients with newly diagnosed multiple myeloma who were eligible for cell transplantation, aged 70 years or younger, with at least stable disease, were randomly assigned (1:1) to treatment. Patients received either busulfan plus melphalan, with a test dose of busulfan 32 mg/m(2) followed by pharmacokinetically adjusted doses on days -7, -6, -5, and -4 to achieve a target daily area under the curve (AUC) of 5000 mmol-minute and melphalan 70 mg/m(2) per day on days -2 and -1 (total melphalan dose 140 mg/m(2)), or a melphalan dose of 200 mg/m(2) on day -2. Randomisation was performed via a Clinical Trial Conduct Website at the University of Texas MD Anderson Cancer Center. The accrual is complete and final results are presented here. The study is registered with ClinicalTrials.gov, number NCT01413178. FINDINGS Between Oct 12, 2011, and March 22, 2017, 205 patients were assessed for eligibility and randomly assigned to treatment. The primary analysis of progression-free survival was measured in 202 patients who received treatment: 104 patients in the busulfan plus melphalan group and 98 patients in the melphalan alone group. 90 days after auto-HCT, 102 (98%) of 104 patients given busulfan plus melphalan and 95 (97%) of 98 patients given melphalan alone achieved partial response or better. The median follow-up in the busulfan plus melphalan group was 22.6 months (IQR 15.2-47.1) and 20.2 months (IQR 8.8-46.6) in the melphalan alone group. Median progression-free survival was 64.7 months (32.9-64.7) with busulfan plus melphalan versus 43.5 months (19.9-not estimated) with melphalan alone (hazard ratio 0.53 [95% CI 0.30-0.91]; p=0.022). There were no treatment-related deaths by day 100 in either group. Grade 2-3 mucositis was observed in 77 (74%) of 104 patients in the busulfan plus melphalan group versus 14 (14%) of 98 patients in the melphalan alone group. INTERPRETATION These findings, if confirmed in other ongoing studies, suggest that busulfan plus melphalan could replace melphalan alone as the conditioning regimen for auto-HCT in patients with newly diagnosed myeloma. FUNDING This study was funded in part by the National Institutes of Health (NIH) through MD Anderson's Cancer Center Support Grant (CA016672).
PICO Summary
Population
Patients with newly diagnosed multiple myeloma who were eligible for cell transplantation, aged 70 years or younger, with at least stable disease (n=202)
Intervention
Busulfan plus mephalan conditioning prior to autologous transplantation (n=104)
Comparison
Melphalan conditioning alone (n=98)
Outcome
Median progression-free survival was 64.7 months with busulfan plus melphalan versus 43.5 months with melphalan alone. There were no treatment-related deaths by day 100 in either group. Grade 2-3 mucositis was observed in 77 (74%) of 104 patients in the busulfan plus melphalan group versus 14 (14%) of 98 patients in the melphalan alone group.
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7.
Allogeneic Transplantation after Myeloablative Rituximab/BEAM +/- Bortezomib for Patients with Relapsed/Refractory Lymphoid Malignancies: 5-Year Follow-up Results
Chamoun, K., Milton, D. R., Ledesma, C., Young, K. H., Jabbour, E. J., Alatrash, G., Anderlini, P., Bashir, Q., Ciurea, S. O., Marin, D., 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
Although bortezomib and rituximab have synergistic activity in patients with lymphoma, and can both attenuate graft-versus-host disease (GVHD), the drugs have not been used together in patients undergoing allogeneic stem-cell transplantation (alloSCT). In this phase 1/2 trial, we assessed the safety and activity of bortezomib added to the rituximab (R) plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. Bortezomib (1 - 1.3 mg/m(2) per dose) was administered intravenously on days -13, -6, -1, and +2. We performed inverse probability weighting analysis to compare GVHD and survival results to a historical control group that received R-BEAM without bortezomib. Thirty-nine patients were assessable for toxic effects and response. The median age was 54 years. The most common diagnosis was diffuse large B-cell lymphoma (41%). Twenty-two patients (56%) and 17 patients (44%) received their transplants from matched related and unrelated matched donors, respectively. The maximum tolerated bortezomib dose was 1 mg/m(2). The weighted cumulative incidences of grade II-IV and grade III or IV acute GVHD were 50% and 34%, respectively; these incidences and survival rates were not significantly different from those of the control group. Median survival has not been reached in patients age ≤50 years and who had a long follow-up time of 60.7 months. The R-BEAM regimen has a survival benefit in lymphoma patients age ≤50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.
PICO Summary
Population
Patients with relapsed lymphoma undergoing allo-SCT
Intervention
Bortezomib added to the rituximab plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen (n=39)
Comparison
Historical control group that received R-BEAM without bortezomib.
Outcome
The R-BEAM regimen has a survival benefit in lymphoma patients age </=50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.
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Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome
Kongtim, P., Parmar, S., Milton, D. R., Perez, J. M. R., Rondon, G., Chen, J., Chilkulwar, A. R., Al-Atrash, G., Alousi, A., Andersson, B. S., et al
Bone marrow transplantation. 2018
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Editor's Choice
Abstract
Outcomes after allogeneic stem-cell transplantation (AHSCT) are influenced by both disease- and patient-related factors. Here, we developed a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), by combining the refined disease risk index (DRI-R) and hematopoietic stem-cell transplant comorbidity/age index (HCT-CI/Age) to predict post-transplant survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The analysis included 942 AML/MDS patients treated with AHSCT. Patients were stratified into 4 HCT-CR risk groups: Low-risk-patients with low/intermediate DRI-R and HCT-CI/Age ≤3 (N = 272); Intermediate-risk-patients with low/intermediate DRI-R and HCT-CI/Age >3 (N = 168); High-risk-patients with high/very high DRI-R and HCT-CI/Age ≤3 (N = 284); and Very high-risk-patients with high/very high DRI-R and HCT-CI/Age >3 (N = 184). Compared with the low-risk group, intermediate, high, and very high-risk groups had a significantly increased risk of death [adjusted HR of 1.37 (P < 0.04), 2.08 (P < 0.001), and 2.92 (P < 0.001), respectively]. The concordance test showed that the HCT-CR model provided better discriminative capacity for OS prediction compared with all prior models independently, including cytogenetic risk group, DRI-R, and HCT-CI/Age model (C-indices: 0.62, 0.55, 0.60, and 0.54, respectively) (P < 0.001). In conclusion, combining disease- and patient-related factors provides better survival stratification for patients with AML/MDS receiving AHSCT.