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Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

There are limited data to guide the choice of high-dose therapy (HDT) regimen before autologous hematopoietic cell transplantation (AHCT) for patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL). We studied 4917 patients (NHL, n = 3905; HL, n = 1012) who underwent AHCT from 1995 to 2008 using the most common HDT platforms: carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) (n = 1730); cyclophosphamide, BCNU, and etoposide (CBV) (n = 1853); busulfan and cyclophosphamide (BuCy) (n = 789); and total body irradiation (TBI)-containing treatment (n = 545). CBV was divided into CBV(high) and CBV(low) based on BCNU dose. We analyzed the impact of regimen on development of idiopathic pulmonary syndrome (IPS), transplantation-related mortality (TRM), and progression-free and overall survival. The 1-year incidence of IPS was 3% to 6% and was highest in recipients of CBV(high) (hazard ratio [HR], 1.9) and TBI (HR, 2.0) compared with BEAM. One-year TRM was 4% to 8%, respectively, and was similar between regimens. Among patients with NHL, there was a significant interaction between histology, HDT regimen, and outcome. Compared with BEAM, CBV(low) (HR, .63) was associated with lower mortality in follicular lymphoma (P < .001), and CBV(high) (HR, 1.44) was associated with higher mortality in diffuse large B cell lymphoma (P = .001). For patients with HL, CBV(high) (HR, 1.54), CBV(low) (HR, 1.53), BuCy (HR, 1.77), and TBI (HR, 3.39) were associated with higher mortality compared with BEAM (P < .001). The impact of specific AHCT regimen on post-transplantation survival is different depending on histology; therefore, further studies are required to define the best regimen for specific diseases., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Cyclophosphamide (Cy) in combination with busulfan (Bu) or total body irradiation (TBI) is the most commonly used myeloablative conditioning regimen in patients with chronic myeloid leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CML in first chronic phase after myeloablative conditioning with Cy in combination with TBI, oral Bu, or intravenous (i.v.) Bu. Four hundred thirty-eight adults received human leukocyte antigen (HLA)-matched sibling grafts and 235 received well-matched grafts from unrelated donors (URD) from 2000 through 2006. Important differences existed between the groups in distribution of donor relation, exposure to tyrosine kinase inhibitors, and year of transplantation. In multivariate analysis, relapse occurred less frequently among patients receiving i.v. Bu compared with TBI (relative risk [RR], .36; P = .022) or oral Bu (RR, .39; P = .028), but nonrelapse mortality and survival were similar. A significant interaction was detected between donor relation and the main effect in leukemia-free survival (LFS). Among recipients of HLA-identical sibling grafts, but not URD grafts, LFS was better in patients receiving i.v. Bu (RR, .53; P = .025) or oral Bu (RR, .64; P = .017) compared with TBI. In CML in first chronic phase, Cy in combination with i.v. Bu was associated with less relapse than TBI or oral Bu. LFS was better after i.v. or oral Bu compared with TBI., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The best conditioning regimen before allogeneic transplantation for high-risk diffuse large B-cell lymphoma (DLBCL) remains to be clarified. We analyzed data from 396 recipients of allotransplants for DLBCL receiving myeloablative (MAC; n = 165), reduced intensity (RIC; n = 143), or nonmyeloablative conditioning (NMAC; n = 88) regimens. Acute and chronic GVHD rates were similar across the groups. Five-year nonrelapse mortality (NRM) was higher in MAC than RIC and NMAC (56% vs 47% vs 36%; P = .007). Five-year relapse/progression was lower in MAC than in RIC/NMAC (26% vs 38% vs 40%; P = .031). Five-year progression-free survival (15%-25%) and overall survival (18%-26%) did not differ significantly between the cohorts. In multivariate analysis, NMAC and more recent transplant year were associated with lower NRM, whereas a lower Karnofsky performance score (< 90), prior relapse resistant to therapy, and use of unrelated donors were associated with higher NRM. NMAC transplants, no prior use of rituximab, and prior relapse resistant to therapy were associated with a greater risk of relapse/progression. In conclusion, allotransplantation with RIC or NMAC induces long-term progression-free survival in selected DLBCL patients with a lower risk of NRM but with higher risk of lymphoma progression or relapse.

Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning.