Kate Mason

Second cancer risk in adults receiving autologous haematopoietic SCT for cancer: a population-based cohort study

Population-based evidence on second cancer risk following autologous haematopoietic SCT (HCT) is lacking. We quantified second cancer risk for a national, population-based cohort of adult Australians receiving autologous HCT for cancer and notified to the Australasian Bone Marrow Transplant Recipient Registry 1992–2007 (n=7765). Cancer diagnoses and deaths were ascertained by linkage with the Australian Cancer Database and National Death Index. Standardized incidence ratios (SIRs) were calculated and Cox regression models were used to estimate within-cohort risk factors treating death as a competing risk. During a median 2.5 years follow-up, second cancer risk was modestly increased compared with the general population (SIR 1.4, 95% confidence interval 1.2–1.6); significantly elevated risk was also observed for AML/myelodysplastic syndrome (SIR=20.6), melanoma (SIR=2.6) and non-Hodgkin lymphoma (SIR=3.3). Recipients at elevated risk of any second cancer included males, and those transplanted at a younger age, in an earlier HCT era, or for lymphoma or testicular cancer. Male sex, older age (>45 years) and history of relapse after HCT predicted melanoma risk. Transplantation for Hodgkin lymphoma and older age were associated with lung cancer risk. Second malignancies are an important late effect and these results inform and emphasize the need for cancer surveillance in autologous HCT survivors.

Validating the allogeneic stem cell transplantation disease risk index: sample size, follow-up, and local data are important.

Background Reporting allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes by disease and disease stage can limit statistical power. Recently, the disease risk index (DRI) was developed and validated to stratify clusters of patients with various combinations of disease and stage for overall survival (OS), progression-free survival (PFS), and cumulative incidence of relapse (CIR). However, the DRI has not been tested for smaller cohorts or cohorts with shorter follow-up. Methods Data from recipients of a first alloHSCT between 2000 and 2011 (n=466; median follow-up, 55.2 months) were extracted from our database. Each patient was assigned to one of four risk categories according to the DRI. Results The DRI was validated as being significantly predictive of OS, PFS, and CIR (P<0.001 for all). The OS, PFS, and CIR from a contemporaneous cohort (n=324) from our institution were superior to the original training cohort. Using randomized patient subsets, the DRI stratified a cohort of 100 patients (OS, P=0.010; PFS, P=0.016; CIR, P=0.027), but failed to stratify a cohort of 50 patients (OS, P=0.385; PFS, P=0.167; CIR, P=0.026). When simulating shorter follow-up, the DRI stratified a cohort (n=322) with a median follow-up of 40.6 months for OS and PFS, but failed to stratify a cohort (n=242) with a median follow-up of 33.1 months. Conclusion The DRI is a simple, robust pre-alloHSCT risk stratification tool. However, users should calibrate with local data before using the DRI to estimate absolute OS, PFS, and CIR and understand its limitations when applied to smaller cohorts or cohorts with shorter follow-up.

Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation: prognostic factors and impact of initial therapy of relapse

We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft‐versus‐host disease (GVHD) on OSR.

Prognostic Limitations of Donor T Cell Chimerism after Myeloablative Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes

Donor T cell chimerism is associated with relapse outcomes after allogeneic stem cell transplantation (alloSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, measures of statistical association do not adequately assess the performance of a prognostic biomarker, which is best characterized by its sensitivity and specificity for the chosen outcome. We analyzed donor T cell chimerism results at day 100 (D100chim) after myeloablative alloSCT for AML or MDS in 103 patients and determined its sensitivity and specificity for relapse-free survival at 6 months (RFS6) and 12 months (RFS12) post-alloSCT. The area under the receiver operating characteristic curve for RFS6 was .68, demonstrating only modest utility as a predictive biomarker, although this was greater than RFS12 at .62. Using a D100chim threshold of 65%, the specificity for RFS6 was 96.6%; however, sensitivity was poor at 26.7%. This equated to a negative predictive value of 88.5% and positive predictive value of 57.1%. Changing the threshold for D100chim to 75% or 85% modestly improved the sensitivity of D100chim for RFS6; however, this was at the expense of specificity. D100chim is specific but lacks sensitivity as a prognostic biomarker of early RFS after myeloablative alloSCT for AML or MDS. Caution is required when using D100chim to guide treatment decisions including immunologic manipulation, which may expose patients to unwarranted graft-versus-host disease.