Kharfan‐Dabaja, Mohamed A.

Abstract HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease–donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy–based Haplo-HCT vs MSD using calcineurin inhibitor–based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cell has changed the treatment landscape of B-cell non-Hodgkin’s lymphoma (NHL), especially for aggressive B-cell lymphomas. Single-center and multicenter clinical trials with anti-CD19 CAR T-cell therapy have shown great activity and long-term remissions in poor-risk diffuse large B-cell lymphoma (DLBCL) when no other effective treatment options are available. Two CAR T-cell products [axicabtagene ciloleucel (axi-cel) and tisagenlecleucel] have obtained US Food and Drug Administration approval for the treatment of refractory DLBCL after two lines of therapy. A third product, liso-cel, is currently being evaluated in clinical trials and preliminary results appear very promising. CAR T-cell-related toxicity with cytokine-release syndrome and neurotoxicity remain important potential complications of this therapy. Here, we review the s biology, structure, clinical trial results and toxicity of two commercially approved CAR T-cell products and others currently being studied in multicenter clinical trials in B-cell NHLs.

Key Points Compared with parous female sibling donors, male URDs confer more aGVHD in all patients and more cGVHD in females. There was no difference in survival, relapse, or transplant mortality between recipients of parous female sibling or male URD grafts.

Key Points There was no difference in overall survival after allogeneic transplant between patients aged 55-64 years and patients ≥65 years. Age alone should not be a determinant for allogeneic transplant eligibility among older non-Hodgkin lymphoma patients.

BACKGROUNDEarly treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high‐risk group of patients with an expected 5‐year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated.METHODSThis study compared autologous hematopoietic stem cell transplantation (auto‐HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo‐HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto‐HCT or allo‐HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression‐free survival, relapse, and nonrelapse mortality (NRM).RESULTSFour hundred forty FL patients had ETF (auto‐HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow‐up of 69 to 73 months, the adjusted probability of 5‐year OS was significantly higher after auto‐HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5‐year adjusted probability of NRM was significantly lower for auto‐HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5‐year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto‐HCT (58%; P < .0001).CONCLUSIONSPatients with high‐risk FL, as defined by ETF, undergoing auto‐HCT for FL have low NRM and a promising 5‐year OS rate (70%). MSD HCT has lower relapse rates than auto‐HCT but similar OS. Cancer 2018;124:2541‐51. © 2018 American Cancer Society.

Purpose To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS). Patients and Methods We examined 2,133 patients with MDS undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox multivariable model to identify factors prognostic of mortality in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was assigned to the remaining patients undergoing HLA-matched allo HCT (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched allo HCT. Results Blood blasts greater than 3% (hazard ratio [HR], 1.41; 95% CI, 1.08 to 1.85), platelets 50 × 109/L or less at transplantation (HR, 1.37; 95% CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI, 1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR, 1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to 2.35) were associated with increased hazard of death and assigned 1 point in the scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50 years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3-year overall survival after transplantation in patients with low (0 to 1 points), intermediate (2 to 3), high (4 to 5) and very high (≥ 6) scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort. Conclusion The proposed system is prognostic of outcome in patients undergoing HLA-matched and -mismatched allo HCT for MDS.

Summary For diffuse large B‐cell lymphoma ( DLBCL ) patients progressing after autologous haematopoietic cell transplantation (auto HCT ), allogeneic HCT (allo HCT ) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research ( CIBMTR ) database, we identified 503 patients who underwent allo HCT after disease progression/relapse following a prior auto HCT . The 3‐year probabilities of non‐relapse mortality, progression/relapse, progression‐free survival ( PFS ) and overall survival ( OS ) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status ( KPS ) <80, chemoresistance, auto HCT to allo HCT interval <1‐year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS <80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS , including KPS <80 (4 points), auto HCT to allo HCT interval <1‐year (2 points) and chemoresistant disease at allo HCT (5 points). This CIBMTR prognostic model classified patients into four groups: low‐risk (0 points), intermediate‐risk (2‐5 points), high‐risk (6‐9 points) or very high‐risk (11 points), predicting 3‐year PFS of 40, 32, 11 and 6%, respectively, with 3‐year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long‐term survival with allo HCT after a failed prior auto HCT .