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Impact of reduced-intensity conditioning regimens on outcomes in diffuse large B-cell lymphoma undergoing allogeneic transplantation
Epperla, N., Ahn, K. W., Khanal, M., Litovich, C., Ahmed, S., Ghosh, N., Fenske, T. S., Kharfan-Dabaja, M. A., Sureda, A., Hamadani, M.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
BACKGROUND Reduced-intensity conditioning (RIC) regimens are frequently used for allogeneic hematopoietic cell transplantation (allo-HCT) in diffuse large B-cell lymphoma (DLBCL). However, the RIC regimen with the best risk/benefit profile for allo-HCT in DLBCL is not known. This is particularly important, as patients with DLBCL undergoing allo-HCT in the future would be enriched for those whose lymphoma has failed chimeric antigen receptor T-cell (CAR-T) therapy or other novel immunotherapies, with potentially more advanced disease and suboptimal performance scores. Using the CIBMTR database, we report the outcomes of the three most commonly used allo-HCT RIC regimens in DLBCL. METHODS 562 adult DLBCL patients in the CIBMTR registry undergoing allo-HCT using matched related or unrelated donors, between 2008-2016 were included in the analysis. Patients received one of the three RIC regimens: fludarabine/i.v. busulfan (~6•4mg/kg) (Flu/Bu), fludarabine/melphalan (140mg/m(2)) (Flu/Mel140) or BCNU/etoposide/cytarabine/melphalan (BEAM). FINDINGS The study cohort was divided into three groups: Flu/Bu (n=151), Flu/Mel140 (n=296) and BEAM (n=115). Relative to Flu/Bu, the Flu/Mel140 (HR=2.33, 95%CI=1.42-3.82; p=0.001) and BEAM (HR=2.54, 95%CI=1.34-4.80; p=0.004) regimens were associated with a higher non-relapse mortality (NRM) risk. Although the risk of relapse with Flu/Mel140 was lower compared to Flu/Bu (HR=0.70, 95%CI=0.52-0.95; p=0.02), this did not translate in an improvement in progression-free (HR=1.04) or overall survival (HR=1.30). There was a significantly higher risk of grade 3-4 acute graft-versus-host disease with BEAM (HR=2.19, 95%CI=1.10-4.35; p=0.03) compared to Flu/Bu. In the chemosensitive subset, multivariate analysis showed a significantly higher mortality risk with Flu/Mel140 (HR=1.48, 95%CI=1.07-2.04, p=0.02) relative to Flu/Bu conditioning. CONCLUSIONS In the largest analysis comparing the impact of various RIC conditioning regimens on the survival of DLBCL patients undergoing allo-HCT, our results suggest that Flu/Bu is a better RIC choice in less fit or heavily pretreated patients due to lowest NRM risk.
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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.
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Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant
Ghosh, N., Ahmed, S., Ahn, K. W., Khanal, M., Litovich, C., Aljurf, M., Bacher, V. U., Bredeson, C., Epperla, N., Farhadfar, N., et al
JAMA oncology. 2020
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Abstract
Importance: Reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known. Objective: To investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT. Design, Setting, and Participants: This cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020. Interventions: Patients received 1 of 4 RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu), approximately 6.4 mg/kg (n = 458); fludarabine-melphalan (Flu-Mel140), 140 mg/m2 (n = 885); fludarabine-cyclophosphamide (Flu-Cy) (n = 391); or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI) (n = 89). Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes were nonrelapse mortality, incidence of relapse, progression-free survival, and the incidence of acute and chronic graft-vs-host disease (GVHD). Results: Of 1823 patients, 1186 (65%) were male, with a mean (SD) age of 54.8 (9.9) years. The 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001). After adjustment for age, Karnofsky performance score, HCT comorbidity index, NHL subtype, remission status at HCT, and the use of antithymocyte globulin or alemtuzumab, the regression analysis showed a significantly higher mortality risk associated with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P < .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P < .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P < .001) compared with the Flu-Bu regimen. Conclusions and Relevance: The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival.
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Impact of type of reduced-intensity conditioning regimen on the outcomes of allogeneic haematopoietic cell transplantation in classical Hodgkin lymphoma
Ahmed, S., Ghosh, N., Ahn, K. W., Khanal, M., Litovich, C., Mussetti, A., Chhabra, S., Cairo, M., Mei, M., William, B., et al
British journal of haematology. 2020
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Editor's Choice
Abstract
Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0.01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0.54), relapse/progression (P = 0.02) or progression-free survival (PFS) (P = 0.14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0.28; 95% CI = 0.10-0.73; P = 0.009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2.46; 95% CI = 0.1.32-4.61; P = 0.005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0.64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).
PICO Summary
Population
Adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for Hodgkin lymphoma (n=492)
Intervention
Reduced intensity conditioning with fludarabine/busulfan (Flu/Bu, n=102) or fludarabine/melphalan (Flu/Mel140, n=318)
Comparison
Reduced intensity conditioning with fludarabine/cyclophosphamide (Flu/Cy, n=72).
Outcome
There were no significant differences between regimens in risk for non-relapse mortality (NRM), relapse/progression or progression-free survival (PFS). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0.28), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2.46). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy, respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).
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PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL
Dreger, P., Sureda, A., Ahn, K. W., Eapen, M., Litovich, C., Finel, H., Boumendil, A., Gopal, A., Herrera, A. F., Schmid, C., et al
Blood advances. 2019;3(3):360-369
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Abstract
This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)-based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD-, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD-. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor.
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Impact of Conditioning Intensity of Allogeneic Transplantation for Acute Myeloid Leukemia With Genomic Evidence of Residual Disease
Hourigan, C. S., Dillon, L. W., Gui, G., Logan, B. R., Fei, M., Ghannam, J., Li, Y., Licon, A., Alyea, E. P., Bashey, A., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019;:Jco1903011
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Editor's Choice
Abstract
PURPOSE Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown. METHODS Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC). RESULTS No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive. CONCLUSION This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.
PICO Summary
Population
Adult patients with myeloid malignancy undergoing allo-HSCT while in remission (n=190)
Intervention
Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML prior to myeloablative conditioning (MAC recipients) (n=95)
Comparison
Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML prior to reduced intensity conditioning (RIC recipients) (n=95)
Outcome
No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%) and survival (3-year OS, 61% v 43) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95%), decreased relapse-free survival (HR, 2.94; 95), and decreased OS (HR, 1.97; 95%) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive.
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Outcomes of Medicare-age eligible NHL patients receiving RIC allogeneic transplantation: a CIBMTR analysis
Shah, N. N., Ahn, K. W., Litovich, C., Fenske, T. S., Ahmed, S., Battiwalla, M., Bejanyan, N., Dahi, P. B., Bolanos-Meade, J., Chen, A. I., et al
Blood advances. 2018;2(8):933-940
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Abstract
The application of allogeneic hematopoietic cell transplantation (allo-HCT) in non-Hodgkin lymphoma (NHL) patients ≥65 years in the United States is limited by lack of Medicare coverage for this indication. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report allo-HCT outcomes of NHL patients aged ≥65 years (older cohort; n = 446) compared with a cohort of younger NHL patients aged 55-64 years (n = 1183). We identified 1629 NHL patients undergoing a first reduced-intensity conditioning (RIC) or nonmyeloablative conditioning allo-HCT from 2008 to 2015 in the United States. Cord blood or haploidentical transplants were excluded. The median age was 68 years (range 65-77) for the older cohort vs 60 years (range 55-64) in the younger cohort. The 4-year adjusted probabilities of nonrelapse mortality (NRM), relapse/progression (R/P), progression-free survival (PFS), and overall survival (OS) of the younger and older groups were 24% vs 30% (P = .03), 41% vs 42% (P = .82), 37% vs 31% (P = .03), and 51% vs 46% (P = .07), respectively. Using multivariate analysis, compared with the younger group, the older cohort was associated with increased NRM, but there was no difference between the 2 cohorts in terms of R/P, PFS, or OS. The most common cause of death was disease relapse in both groups. In NHL patients eligible for allo-HCT, there was no difference in OS between the 2 cohorts. Age alone should not determine allo-HCT eligibility in NHL, and Medicare should expand allo-HCT coverage to older adults.
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Outcomes of reduced intensity conditioning allogeneic hematopoietic cell transplantation performed in the inpatient versus outpatient setting
Murthy, G. S. G., Hari, P. N., Szabo, A., Pasquini, M., Narra, R., Khan, M., Abedin, S., Chhabra, S., Dhakal, B., D'Souza, A., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
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Editor's Choice
Abstract
BACKGROUND Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced intensity conditioning (RIC) is commonly performed as an inpatient procedure. The feasibility and outcomes of RIC allo-HCT in the outpatient setting is not known. METHODS We performed a single center retrospective cohort study of patients aged ≥18 years with hematological malignancies who underwent RIC allo-HCT either in the inpatient or outpatient setting. Donor types included HLA matched sibling and well matched unrelated donors. The objectives were to compare the survival, complications, charges, and incidences of relapse, non-relapse mortality (NRM), and acute and chronic graft versus host disease (GVHD) between the two groups. RESULTS Between 2014-2017, 151 eligible patients were included with116 patients who underwent RIC allo-HCT in the inpatient setting and 35 patients who underwent this procedure in the outpatient setting. Baseline characteristics were comparable between the two groups except for a higher proportion of patients with myeloma in the outpatient cohort (inpatient 15.5% vs outpatient 37.1%). The cumulative incidence of grade 2-4 acute GVHD (inpatient 25.2% vs outpatient 25.7%), grade 3-4 acute GVHD (inpatient 10.4% vs outpatient 8.5%), chronic GVHD (inpatient 38.3% vs outpatient 51.6%), NRM at 1 year (inpatient 10.8% vs outpatient 3.2%), and relapse (inpatient 24.8% vs outpatient 33.2%) did not significantly differ between the two cohorts. One year progression free survival (inpatient 64.4% vs outpatient 63.6%, p=0.39) and overall survival (inpatient 73.8% vs outpatient 82.8%, p=0.93) were also not significantly different between the two groups. The proportion of patients who developed neutropenic fever (inpatient 25.8% vs outpatient 8.5%, p=0.03), mucositis (inpatient 50.8% vs outpatient 8.5%, p<0.001) and requirement of total parenteral nutrition (inpatient 20.6% vs outpatient 5.7%, p=0.04) were more frequent in the inpatient cohort. About 51.5% of the outpatient cohort never required hospital admission in the first 100 days. Outpatient HCT resulted in significantly lower charges than inpatient HCT in the first 100 days (Median charges -inpatient $339,621 vs outpatient $247,334, p<0.001). On multivariate analysis, site of the HCT (outpatient vs inpatient) was not a significant predictor of either overall or progression free survival. CONCLUSIONS Outpatient RIC allo-HCT is feasible and safe with daily outpatient evaluation and aggressive supportive care resulting in outcomes comparable to those who received the transplant in the inpatient setting.
PICO Summary
Population
Adults with haematological malignancies who underwent RIC allo-HCT
Intervention
Outpatient setting (N=35)
Comparison
Inpatient setting (N=116)
Outcome
The cumulative incidence of grade 2-4 acute GVHD, grade 3-4 acute GVHD, chronic GVHD, NRM at 1 year, and relapse did not significantly differ between the two cohorts. One year progression free survival and overall survival were also not significantly different between the two groups. The proportion of patients who developed neutropenic fever, mucositis, and requirement of total parenteral nutrition were more frequent in the inpatient cohort. About 51.5% of the outpatient cohort never required hospital admission in the first 100 days. Outpatient HCT resulted in significantly lower charges than inpatient HCT in the first 100 days. On multivariate analysis, site of the HCT (outpatient vs inpatient) was not a significant predictor of either overall or progression free survival.
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Rituximab-containing reduced-intensity conditioning improves progression-free survival following allogeneic transplantation in B cell non-Hodgkin lymphoma
Epperla, N., Ahn, K. W., Ahmed, S., Jagasia, M., DiGilio, A., Devine, S. M., Jaglowski, S., Kennedy, V., Rezvani, A. R., Smith, S. M., et al
Journal of hematology & oncology. 2017;10(1):117
Abstract
BACKGROUND In B cell non-Hodgkin lymphoma (B-NHL), rituximab-containing reduced-intensity conditioning regimens (R-RIC) have been shown to provide favorable outcomes in single-arm studies; however, large multicenter studies comparing R-RIC and non-rituximab-containing reduced-intensity conditioning regimens (nonR-RIC) have not been performed. Using the CIBMTR database, we report the outcomes of R-RIC versus nonR-RIC regimens in B-NHL. METHODS We evaluated 1401 adult B-NHL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who received nonR-RIC (n=1022) or R-RIC (n=379) regimens. Graft-versus-host disease (GVHD) prophylaxis was limited to calcineurin inhibitor-based approaches. RESULTS Median follow-up of survivors in the R-RIC and nonR-RIC groups was 47 and 37 months, respectively. On multivariate analysis, no difference was seen between the R-RIC and nonR-RIC cohorts in terms of acute GVHD grade II-IV (RR=1.14, 95%CI=0.83-1.56, p=0.43) or grade III-IV (RR=1.16, 95%CI=0.72-1.89, p=0.54), chronic GVHD (RR=1.15, 95%CI=0.92-1.46, p=0.22), non-relapse mortality (RR=0.90; 95%CI=0.67-1.22; p=0.51), relapse/progression (RR=0.79; 95%CI=0.63-1.01; p=0.055), and mortality (RR=0.84, 95%CI=0.69-1.02, p=0.08) risk. However, R-RIC was associated with a significantly improved progression-free survival (RR=0.76; 95%CI 0.62-0.92; p=0.006). On subgroup analysis, mortality benefit was noted in the R-RIC group patients not receiving busulfan-based RIC (RR=0.76; 95%CI=0.60-0.96; p=0.02) and with the use of a higher cumulative rituximab dose (RR=0.43; 95%CI=0.21-0.90; p=0.02). CONCLUSION Our analysis shows that inclusion of rituximab in RIC regimens improves progression-free survival in patients with B cell NHL. These data supports the use of R-RIC in B-NHL patients undergoing allo-HCT.
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10.
Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors
Kanate, A. S., Mussetti, A., Kharfan-Dabaja, M. A., Ahn, K. W., DiGilio, A., Beitinjaneh, A., Chhabra, S., Fenske, T. S., Freytes, C., Gale, R. P., et al
Blood. 2016;127(7):938-47
Abstract
We evaluated 917 adult lymphoma patients who received haploidentical (n = 185) or HLA-matched unrelated donor (URD) transplantation either with (n = 241) or without antithymocyte globulin (ATG; n = 491) following reduced-intensity conditioning regimens. Haploidentical recipients received posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, whereas URD recipients received calcineurin inhibitor-based prophylaxis. Median follow-up of survivors was 3 years. The 100-day cumulative incidence of grade III-IV acute GVHD on univariate analysis was 8%, 12%, and 17% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .44). Corresponding 1-year rates of chronic GVHD on univariate analysis were 13%, 51%, and 33%, respectively (P < .001). On multivariate analysis, grade III-IV acute GVHD was higher in URD without ATG (P = .001), as well as URD with ATG (P = .01), relative to haploidentical transplants. Similarly, relative to haploidentical transplants, risk of chronic GVHD was higher in URD without ATG and URD with ATG (P < .0001). Cumulative incidence of relapse/progression at 3 years was 36%, 28%, and 36% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .07). Corresponding 3-year overall survival (OS) was 60%, 62%, and 50% in the 3 groups, respectively, with multivariate analysis showing no survival difference between URD without ATG (P = .21) or URD with ATG (P = .16), relative to haploidentical transplants. Multivariate analysis showed no difference between the 3 groups in terms of nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). These data suggest that reduced-intensity conditioning haploidentical transplantation with posttransplant cyclophosphamide does not compromise early survival outcomes compared with matched URD transplantation, and is associated with significantly reduced risk of chronic GVHD. Copyright © 2016 by The American Society of Hematology.