Ahn, Kwang Woo

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.

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.

BACKGROUNDRace/ethnicity remains an important barrier in clinical care. The authors investigated differences in the receipt of autologous hematopoietic cell transplantation (AHCT) among patients with multiple myeloma (MM) and outcomes based on race/ethnicity in the United States.METHODSThe Center for International Blood and Marrow Transplant Research database was used to identify 28,450 patients who underwent AHCT for MM from 2008 through 2014. By using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 registries, the incidence of MM was calculated, and a stem cell transplantation utilization rate (STUR) was derived. Post‐AHCT outcomes were analyzed among patients ages 18 to 75 years who underwent melphalan‐conditioned peripheral cell grafts (N = 24,102).RESULTSThe STUR increased across all groups from 2008 to 2014. The increase was substantially lower among Hispanics (range, 8.6%‐16.9%) and non‐Hispanic blacks (range, 12.2%‐20.5%) compared with non‐Hispanic whites (range, 22.6%‐37.8%). There were 18,046 non‐Hispanic whites, 4123 non‐Hispanic blacks, and 1933 Hispanic patients. The Hispanic group was younger (P < .001). Fewer patients older than 60 years underwent transplantation among Hispanics (39%) and non‐Hispanic blacks (42%) compared with non‐Hispanic whites (56%). A Karnofsky score <90% and a hematopoietic cell transplantation comorbidity index score >3 were more common in non‐Hispanic blacks compared with Hispanic and non‐Hispanic whites (P < .001). More Hispanics (57%) versus non‐Hispanic blacks (54%) and non‐Hispanic whites (52%; P < .001) had stage III disease. More Hispanics (48%) versus non‐Hispanic blacks (45%) and non‐Hispanic whites (44%) had a very good partial response or better before transplantation (P = .005). Race/ethnicity did not impact post‐AHCT outcomes.CONCLUSIONSAlthough the STUR increased, it remained low and was significantly lower among Hispanics followed by non‐Hispanic blacks compared with non‐Hispanic whites. Race/ethnicity did not impact transplantation outcomes. Efforts to increase the rates of transplantation for eligible patients who have MM, with an emphasis on groups that underuse transplantation, are warranted. Cancer 2017;123:3141–9. © 2017 American Cancer Society.

BACKGROUNDPatients with FMS like tyrosine kinase 3 (FLT3)‐mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT).METHODSData from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes.RESULTSIn total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild‐type (WT) group (38% [95% confidence interval (CI), 30%‐45%] vs 28% [95% CI, 24%‐33%]; P = .04; relative risk, 1.60 [95% CI, 1.15‐2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia‐free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3‐year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%‐57%; WT group: 55%, 95% CI, 50%‐60%; P = .20).CONCLUSIONSThe current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long‐term survivors. Cancer 2016;122:3005‐3014. © 2016 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 .

Key Points In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.